[User] Please transcribe this text

[Assistant] Our behavior is that behavior that is going to help us accomplish our goal. Our goal was to win a national championship. And so if you're upset with someone else on your team,


[User] Please transcribe this text

[Assistant] And the same thing with the Olympic team when I'm traveling, you know, we're traveling all over the world. I never had to pull someone in and say, hey, we need to talk about this. Everyone knew it was about winning a gold medal. And, you know, I think that, uhm,


[User] Please transcribe this text

[Assistant] I mean, I think that that's a communication, the importance of the communication from whether it's your head coach or, you know, leaders or team leaders and it's everyone really


[User] Please transcribe this text

[Assistant] Saying alright, I'm willing to sacrifice for this because we want this so badly.


[User] Please transcribe this text

[Assistant] That, uh, we sacrifice for each other, that we're unselfish and


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[Assistant] That we, uhm, that we work really hard for each other and a lot of it


[User] Please transcribe this text

[Assistant] Uh, that you don't want to let them down, uhm, and to develop this, uhm, culture of


[User] Please transcribe this text

[Assistant] Uhm, I will do what it takes and I will work extra so that we, uh, we experience kind of the highs together because uhm, it's, it is, uh, it is very, very competitive.


[User] Please transcribe this text

[Assistant] I'm sure that every field that each of you are in is extremely competitive.


[User] Please transcribe this text

[Assistant] Uhm, and to figure out what, you know, how do I get to the...


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[Assistant] Uhm, you know, coaching, during the summer, we've had 1,800, like, young girls, 8 to 18 come to basketball camp. And we have a room like this, over in the athletic department, there were 58 year olds sitting in the room. And I told them, I never played basketball when I was your age. They did not have teams. There was no such thing as


[User] Please transcribe this text

[Assistant] You know, bitty ball. There's no such thing as junior high basketball. Only the boys play.


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[Assistant] And I mean I went on about how there were no scholarships for girls, no teams to play on. My college team...


[User] Please transcribe this text

[Assistant] And they were, eight year olds were just in amazement. And one little eight year old raises her hand and says, why was it like that? And I was like,


[User] Please transcribe this text

[Assistant] You know, it was honestly, it was very painful for me as a young girl. I love to play. And I would take...


[User] Please transcribe this text

[Assistant] I saved my allowance, I went out and got a good basketball, and I would go and, you know, the time I was 10 years old, 11, 12, play with the boys.


[User] Please transcribe this text

[Assistant] And let's say they had an odd number. They're, I'm like, Tara, you're out. And I'm like, okay, that's my ball. If you want to play with that nice ball, I'm playing. You know, it's like, this little guy is out because I'm better than him. You know, so as I got older though, you know, it became,


[User] Please transcribe this text

[Assistant] So I thought, how am I going to get to the games? My parents, I was at a university school, my parents lived 20 miles away, so I...


[User] Please transcribe this text

[Assistant] Tried out to be the, uhm, mascot. So I was a bear. Imagine that. At Stanford, a bear. You know, so, and I would take the head off and watch the game, and I got fired in the middle of the season because I wasn't leading the cheers. I was watching the game. So,


[User] Please transcribe this text

[Assistant] But it was really, it was really painful as a young person not to have the opportunity to play. I, so I went out and I bought a 10 speed bike.


[User] Please transcribe this text

[Assistant] Uhm, it was, it was really painful and along comes Title IX in 1972 that basically is


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[Assistant] A law that was actually, uhm, Richard Nixon signed.


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[Assistant] Uhm, that basically said that, you know, universities and anyone that took federal money had to include


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[Assistant] Women in their sports programs. That's kind of the gist of it. There's, there's more to it. But, and the powers to be fought it. Uhm, because on college campuses, you as a student would pay


[User] Please transcribe this text

[Assistant] Uhm, at most schools you would pay a university fee, couple hundred dollars, it all went to the boys. And I'm like, this isn't right.


[User] Please transcribe this text

[Assistant] Can you ever look and say one thing totally changed the path of my life? Well that did for me. Because now all of a sudden there are jobs for women coaching basketball. My college coach, I went to Indiana, was a graduate student. She was a wonderful woman, uh, she was 25 years old, she had


[User] Please transcribe this text

[Assistant] You know, I have a full-time position with a video coordinator, three full-time assistants, uh, director of basketball, I mean there's...


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[Assistant] Uh, basketball in the United States and women's sports as much as anything.


[User] Please transcribe this text

[Assistant] I definitely think they were, they did go a little hand in hand and, you know, I, I, I think that


[User] Please transcribe this text

[Assistant] Uhm, some of the, uhm, obviously parents were really important, but I think that one of, uhm, I think the dads of daughters really


[User] Please transcribe this text

[Assistant] Are, were a lot of times the heroes of the story in that


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[Assistant] They would, you know, they'd have a son and when I, I call it the hot dogs and steak. When I would sit down at the dinner table, my mom and dad, I have one brother,


[User] Please transcribe this text

[Assistant] And my mom and dad would serve hot dogs to everybody.


[User] Please transcribe this text

[Assistant] Alright, or steak to everybody, not hot dogs to the girls and steak for the boys. You know, that wasn't how it worked.


[User] Please transcribe this text

[Assistant] But I look at it where, and a lot of times in sports, it was even worse than that. I mean, but


[User] Please transcribe this text

[Assistant] Now, I mean, and we still, we still have a long way to go in Title IX 1972, some, what's the math on that? You know, how many years ago was that? You know?


[User] Please transcribe this text

[Assistant] Yeah, it was a ways back and we still have a long way to go because when people have something they are slow to give it up.


[User] Please transcribe this text

[Assistant] You know, if you're used to having, as a football coach, if you're used to having unlimited scholarships, all of a sudden having 120,


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[Assistant] You know, we get used to a certain thing and then like, oh change is really hard. But uhm, one of the things I think with Stanford is that uhm,


[User] Please transcribe this text

[Assistant] You know, they recognized that early on they, they said we're gonna work hard to have, uhm, you know, women's sports and support women's sports and they, they are at Stanford. How many of you ever participated in college athletics at a university? Alright, so a lot of people.


[User] Please transcribe this text

[Assistant] At some level. How about, how many people play sports? Just, that's part of your life. You do something. Alright. I know a hockey player right here. Uhm.


[User] Please transcribe this text

[Assistant] And you, uhm, and you gain certain things from that activity, whether it's playing pickup.


[User] Please transcribe this text

[Assistant] Uh, at the gym or whether it's rock climbing or whatever it is, uhm, you know, it's a real important part.


[User] Please transcribe this text

[Assistant] of our, our, our lives and it keeps us in balance. So.


[User] Please transcribe this text

[Assistant] Women's rights, whether it's children's rights, I mean all, there are an incredible number of, of, whether it's battles or challenges, uhm, I think that uhm,


[User] Please transcribe this text

[Assistant] I think the most important thing is whatever you are in is be passionate about it and don't be afraid to commit wholly to what you believe in and you know just the thing I think that uhm,


[User] Please transcribe this text

[Assistant] You know, what I see, and I also, I think that whatever you do also, uhm,


[User] Please transcribe this text

[Assistant] You put your name on it and I tell our team this, you know, every day of practice or every paper you're working on or...


[User] Please transcribe this text

[Assistant] You know, the activities you're doing, you are signing your name to that and any great art, you know, it's like, well who did it?


[User] Please transcribe this text

[Assistant] Uhm, science happens to be John's medium and all of you are, you know, in the beginning of wonderful careers.


[User] Please transcribe this text

[Assistant] Uhm, and I would just say, you know, you've got to be totally into it. When I first came to Stanford, uhm,


[User] Please transcribe this text

[Assistant] I met a gentleman. He actually helped me recruit players. He was, uh, he was on the,


[User] Please transcribe this text

[Assistant] Staff, the medical staff, psychiatry was his specialty and I, I really felt like I needed it. Why did I take this job here sometimes?


[User] Please transcribe this text

[Assistant] But he really helped recruit players, and at one point he would take pictures at our games. Uhm, his name was Dr. Serenello. I don't know if anyone knows that name, but...


[User] Please transcribe this text

[Assistant] He would come to all of our games and he came into my office to show me pictures and I said, you know, Dr. Serenello, I just have one question for you. Is it bad for me as a coach to be so


[User] Please transcribe this text

[Assistant] They, they almost like teased me, they'd say, you know, video vanderbeer, cause they studied it so much, or I was so into it, and they would almost use it against me, that it would, and,


[User] Please transcribe this text

[Assistant] I mean, I, I don't know that I could do that then, but like now I take piano lessons and I...


[User] Please transcribe this text

[Assistant] Uhm, but that passion, I think, in whatever you're in, I think is really key. And I also think, one thing that Stanford, I don't know, I was uhm,


[User] Please transcribe this text

[Assistant] I think confidence is a real important thing, and I think it's an especially important thing for women. You know, there's, it's just amazing to me, uh, for, uh, you know, the young women that come up through basketball, uhm, they're, they're not always as confident as they should be.


[User] Please transcribe this text

[Assistant] And that's something that, uh, if you are in a situation where you can mentor women, whether you are male or female, uhm, but,


[User] Please transcribe this text

[Assistant] To bring out the best in the people that you're working with. Uhm, I think that for women, especially even maybe being at a place like Stanford, you are in the fast track and you are competing with the best and the brightest and then to be able to take that and carry it into whatever field you go in.


[User] Please transcribe this text

[Assistant] So I think passion and confidence are really two really key, uh, things that have, uhm, have helped me.


[User] Please transcribe this text

[Assistant] Why aren't there women coaching men's sports? That's a great question. I think that uhm, I think that part of it is the


[User] Please transcribe this text

[Assistant] The culture that young boys grow up with, and a lot of it is not respecting women, uhm, they have a lot of


[User] Please transcribe this text

[Assistant] Uh, one parent families where they love their mothers and they have a lot of female teachers, but the message from a lot of their coaches when they're young, male coaches, uh, is not respectful about women and if you had a woman as a coach, you would somehow be being shortchanged. It's not that women can't do the job. Uhm, you know, there used to be this, uh, this little


[User] Please transcribe this text

[Assistant] And the doctor said, I can't operate. That's my son. Who was the doctor?


[User] Please transcribe this text

[Assistant] I mean, like, well, was it a dot, you know, it's like, but,


[User] Please transcribe this text

[Assistant] Uhm, you know, we haven't had a, a female president of the United States. There are leaders in other, our countries, but uhm, sports in a lot of ways is the absolute, uh, last frontier. Uhm, there are,


[User] Please transcribe this text

[Assistant] Uhm, you know, things that have happened in every other field throughout the world that have not happened in sports and in male sports. Uhm, so, uh, I think women are capable, uhm, but it would, uhm, you know,


[User] Please transcribe this text

[Assistant] It would be interesting, like there was a woman that actually coached at Stanford and she coached boys high school and the attitude was don't lose to that skirt. You know, that was how other coaches, male coaches would


[User] Please transcribe this text

[Assistant] You know, and it's interesting also that a lot of men coach women. Over half of the division one coaches of women's basketball are men.


[User] Please transcribe this text

[Assistant] And it's interesting the dynamics, the, just how men relate to women, you know, uhm, it's


[User] Please transcribe this text

[Assistant] It's interesting. A lot of, some of the men coaches of women could never coach men because of how they treat women. They could never get away with that, treating men that way.


[User] Please transcribe this text

[Assistant] So it, it's interesting for discussion. Yes, I saw your hand.


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[Assistant] Uh, the question is, uhm, in professional athle- athletics, there's discord between sometimes the stars and the, uhm,


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[Assistant] Not, not stars, subs. How do I work with that in our own team situation?


[User] Please transcribe this text

[Assistant] Make decisions, uhm, based on what's best for our team. You know, so it's not always you individually. Uhm, but.


[User] Please transcribe this text

[Assistant] They're extenuating circumstances. I would listen in the same way that I would listen to the non-star players extenuating circumstances. So uhm, I try to rule or, or be uhm, make decisions based on what's best for our team.


[User] Please transcribe this text

[Assistant] And by individual situations that happen.


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[Assistant] You know, some of it too is that everyone has a chance to be a star. A lot of times people don't work as hard. They really are not as committed and they might not be as talented. So my challenge is you be the best player you can be, you know, and


[User] Please transcribe this text

[Assistant] Realize our potential individually and collectively, which uhm, you know, is hard to do.


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[Assistant] But I also think that it's how the players relate to each other. Is if...


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[Assistant] You know, one person's a star and they don't recognize that you are working against them every day in practice and getting them better. Uhm, you know, that...


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[Assistant] The inner, inner workings of the team I think can take care of those dynamics.


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[Assistant] And one thing that's very different professionally is the pay scale. At Stanford, as an example, uhm, a student athlete on our basketball team has a full scholarship, so they are, they are basically clearing tax free about 52 or 53 thousand dollars.


[User] Please transcribe this text

[Assistant] So that's a full scholarship to go to undergraduate at Stanford. Uh, whereas on a pro team, you might have one key player, LeBron James, you know, what is he making? 25 million. And then there's someone else's at the, at the rookie salary. So there are very, you know, big discrepancies, but uhm,


[User] Please transcribe this text

[Assistant] I don't know that there's actually dissension on the team. I think the guys on those teams, they know the deal.


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[Assistant] You know, I think that uhm, some of them just want to be a star in their own right and they're not, so then they go on a different team. I don't know that there's the issues with, they're happy when the star wins because then everyone gets some of the bonus.


[User] Please transcribe this text

[Assistant] Let me work my way back, alright? Go ahead, in the front, in the front.


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[Assistant] Okay. Alright, so this is a Stanford recording, when the Stanford women's team wins against second billing. I don't, I probably should follow the paper more carefully than I do, but uhm, I haven't seen it always that way. Uhm, in the old days, I would say yes. It wouldn't even be in a paper. Uhm, but uhm, I think that what, when things are in fact, if, if that's how you see it, I would write to the paper. And I think that


[User] Please transcribe this text

[Assistant] You know, as the coach of the team, I feel like sometimes there are just so many battles I can fight and...


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[Assistant] It's not that that's not important, it is. Because it, again, that's perception, that's men here, women here. Uhm.


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[Assistant] And there is, we, we live in, in that world a lot. But you know, I would say this, look at our, our men's volleyball team just won a national championship. Did anybody see that, the match? It was phenomenal. I had to look on the back page for them, you know.


[User] Please transcribe this text

[Assistant] So it's uhm, it's not always male, female. It might be sometimes a sport.


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[Assistant] But uhm, I would encourage you to write to, whether it's the Stanford Daily. I mean, it happens all the time, like with the sports on TV.


[User] Please transcribe this text

[Assistant] They'll show St. Mary's men will have twice as many people at our game.


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[Assistant] Uh, so I won't say I don't notice it and I won't say it doesn't affect me at some level, but it's worn me down too, you know, because I'm in my 30-something year of a head coach and I'm kinda like,


[User] Please transcribe this text

[Assistant] Like, uhm, we had, we had a great player, Jane Appel, for our team. Was a great center. Candace Wiggins, phenomenal.


[User] Please transcribe this text

[Assistant] Players. At anything you do. It's the same thing with an orchestra. You've gotta have great talent. Great, but you have to have someone who can listen and say, wow, that player plays really well. You know, and at a real high level, the differences are small.


[User] Please transcribe this text

[Assistant] Business. So if you're in business, you know, if all these people in the room give you the resume, you've got to be able to look at a resume and say, wow, this, this person is someone I want to, cause that's, you'll probably start with that and then you'll interview them.


[User] Please transcribe this text

[Assistant] And you might, you know, so you have to develop a way of saying, well, this person is really going to bring great skills to my business. You know, and that's the difference.


[User] Please transcribe this text

[Assistant] We looked at players early on, uh, and my assistant coach does a great job at this. She has a great ability to watch people play as young players and be able to project this is going to be a great player, you know, down the road.


[User] Please transcribe this text

[Assistant] And then it's as, as a coach, how you develop the talent.


[User] Please transcribe this text

[Assistant] Uhm, and how you, how you use your time. We're allowed 20 hours a week. And we use, we have to use our time very well. And we have people that will come and watch.


[User] Please transcribe this text

[Assistant] at sanford.edu and you're welcome to come watch a practice and see how it's organized. It moves.


[User] Please transcribe this text

[Assistant] People are, I mean, not wasting any time and develop and just, like, how do you use your meetings? How do you use your meeting time? Uhm, you know, maximizing your time. Did I answer your question? Alright, I'm working my way back there. I'm coming to you next.


[User] Please transcribe this text

[Assistant] I don't know that, I don't know that I'm a, I'm not a great motivator, but this is my attitude. I'm gonna outwork you. So I want players who are competitive.


[User] Please transcribe this text

[Assistant] And, like, I got, I got mad if they're in the gym before me. Now I gotta get over there, cause I'm gonna be there ready.


[User] Please transcribe this text

[Assistant] And so I think that what I can do is I can model good motivation. And I am motivated. I like...


[User] Please transcribe this text

[Assistant] Winning, I'll tell you that. It beats the heck out of losing. Losing is painful. Winning is fun.


[User] Please transcribe this text

[Assistant] Uhm, and so it's getting great players who understand, well, this is how we're going to be successful as a team.


[User] Please transcribe this text

[Assistant] That they're motivated to buy into kind of the program, our practice, our off-season practice, our, and you know, some aren't, but uhm,


[User] Please transcribe this text

[Assistant] And then recognizing your losses, if, if this isn't a fit, I'll say, you know,


[User] Please transcribe this text

[Assistant] I walk in, one of my, you know, I just walk in and I'll say, you know, how's it going today? Great. I mean, surround yourself with upbeat, positive,


[User] Please transcribe this text

[Assistant] Interesting, enthusiastic, knowledgeable people.


[User] Please transcribe this text

[Assistant] And then recruit those kind of people. And if somewhere along the way...


[User] Please transcribe this text

[Assistant] You know, that's why I think it's so key to get them to begin with, but if you make a mistake, hey, kiss and part friends. Goodbye, this isn't working. You know, I need, I need somebody else. Uhm, but I, I really, I mean, I just think that getting


[User] Please transcribe this text

[Assistant] You know, I mean it's beautiful and great opportunities. Yes.


[User] Please transcribe this text

[Assistant] So, how do you know you're good at math? Because you have had success at math, right? Uh, I know I'm not good at math, alright? Like, I can't balance my checkbook, math, no. But, to build confidence in something,


[User] Please transcribe this text

[Assistant] Nothing succeeds like success.


[User] Please transcribe this text

[Assistant] You know, what's, what's that, Shamu or something? I guess he had a problem, but, you know, jumping over that, uh, rope. How do they get him to do that? You know?


[User] Please transcribe this text

[Assistant] They put the rope on the bottom of the pool. And they put a piece of fish over here so the whale swims over and gets a fish. Then they move the rope up.


[User] Please transcribe this text

[Assistant] You know, then the fish is over here, you've got to go up over there. And, but the confidence to do something starts with success at a low level.


[User] Please transcribe this text

[Assistant] I try not to put them in the biggest game and then they lose their confidence because keeping their confidence is real important. And what I'd say as a coach is, you know,


[User] Please transcribe this text

[Assistant] Honestly, I'm not really concerned with your confidence in yourself. I'm concerned with my confidence in you.


[User] Please transcribe this text

[Assistant] I mean, it's just like anybody, if you see someone do it, you know, if, if as an example, you know, like John,


[User] Please transcribe this text

[Assistant] Makes his free throws in practice every day and I miss them every day if you're


[User] Please transcribe this text

[Assistant] $10,000 bonus depends on John making that free throw. Who do you want at the free throw line, me or John? You've watched him make it every day.


[User] Please transcribe this text

[Assistant] You know what I mean? So it's like, then you have confidence in him and not in me.


[User] Please transcribe this text

[Assistant] But uhm, as far as, again, my, I don't know, my confidence in myself is uhm, it's challenging myself and kind of winning these little battles like, you know, just coming to Stanford.


[User] Please transcribe this text

[Assistant] You know, I don't like to sit in front of the mayor and go, well damn, I'm good. You know? But I do, I do say, well, you know what? Uhm, I know I can coach. Because it, because of the situation building up to it. And I, I do have confidence in myself.


[User] Please transcribe this text

[Assistant] And at the same time, when I go to the gym and there are 7,000 people there, I'll come to you next, okay? Uhm, everyone there knows more than me. Cause they'll tell me so. Yes.


[User] Please transcribe this text

[Assistant] Well, the, the, the question is about one of our freshmen, how she developed confidence in her, her game and how, or how she kept it. Uhm, what's funny is, uhm,


[User] Please transcribe this text

[Assistant] Uhm, you obviously have watched our team play. Jane Appel was a senior All-American and she might have been out. And then Jocelyn was a freshman who, you know,


[User] Please transcribe this text

[Assistant] Sometimes we want, she didn't know the place. We didn't know if she knew which basket we were shooting at sometimes because it was a little overwhelming. It was stressful. You know, and I, I think about this like uhm, you know, if, if this table were a lot longer between John and I,


[User] Please transcribe this text

[Assistant] How many people could walk on this table from this chair to that chair? Everybody, right?


[User] Please transcribe this text

[Assistant] Could anyone not walk on this table? I'm assuming that it's sturdy. We could all do it, right? But if we put this up ten stories, you know, across two buildings, then it would change. And that's what we, what we do.


[User] Please transcribe this text

[Assistant] Every day when we challenge people and like in a game, in a big game, we put it up there and now we expect, and I use the analogy with our team, I am your net. I am here for you.


[User] Please transcribe this text

[Assistant] You know, now I'm asking you to walk across that and to perform, you know, in front of these people, but


[User] Please transcribe this text

[Assistant] We're, we don't go to the Final Four without her making this running basket, which thankfully she knew which basket she was shooting at. Uhm, but, you know.


[User] Please transcribe this text

[Assistant] But it's, uhm, it's understanding, I think, having a background in developing people and not putting people in situations where they can't be successful.


[User] Please transcribe this text

[Assistant] That, that, that's a great question. How, how do, how do, how are the students on the team leaders?


[User] Please transcribe this text

[Assistant] And now, has anyone read the book Brothers and Keepers? Her dad, John Wideman, uh, is an accomplished author. And, uh, Jamila was just an incredible young lady on our team.


[User] Please transcribe this text

[Assistant] And she amazed me every day. So I have learned a lot of leadership from different players on our team.


[User] Please transcribe this text

[Assistant] I learned a lot from Jamil all through her four years at Stanford. Uhm, but the one, the one time I learned the most was we played a team. Our team was very close and we played a game.


[User] Please transcribe this text

[Assistant] Uh, against a team, Old Dominion. And it was in the semifinal game of the NCAA.


[User] Please transcribe this text

[Assistant] And in this particular game, we went into overtime and Jamila had the last shot that she was fouled on, but it wasn't called. And, you know, I'm biased because this is my player.


[User] Please transcribe this text

[Assistant] Players on the team were just laying on the floor sobbing.


[User] Please transcribe this text

[Assistant] In 10 minutes, when you play in an NCAA game, in 10 minutes, they open the doors for the press to come in.


[User] Please transcribe this text

[Assistant] And you're supposed to then, you know, answer these questions and be all, oh, okay. Our team was devastated. And so...


[User] Please transcribe this text

[Assistant] I kinda got up, they're crying, so I got up and I just, you know, I just said, okay, you know, you guys, you know, I don't even remember what I said. No one heard me, no one listened, you know, they're still crying. Jamila got up and said, pick your heads up.


[User] Please transcribe this text

[Assistant] She just, and she was a, as a freshman she was captain of our team. I mean she just had this presence where you had eye contact with her and


[User] Please transcribe this text

[Assistant] That was, that's, that's, she, I just remember that and I was like, woah. So I think that as, you know, you have,


[User] Please transcribe this text

[Assistant] Whatever, I mean, someone made some really bad mistakes down in, uh, you know, the Gulf of Mexico with this oil thing. Someone all along the line, there were mistakes.


[User] Please transcribe this text

[Assistant] Someone needed to stand up and say, hey, no, we need a safety valve here. We need this. You know, someone had, had to put this up on that. And that's where I think, you know, young people, you're coming from Stanford, you have the opportunities to, to make some really valuable contributions. Yes. Can I come back to you? Cause he hasn't answered the question. Yes, sir.


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[Assistant] She was a high school All-American. She would have been a phenomenal player to come to Stanford.


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[Assistant] She came here and I'm taking her around campus, she's going like this. I'm like, what are you looking for? She goes, the nerds. I'm like, oh boy, this is a problem.


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[Assistant] She, but she was just like, you can't get enough of players like me to win. And I said, do you think God broke the mold on you? You know, I was like, we did run into that, but we were able to get enough


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[Assistant] Good players, Jennifer Azee, who liked, so I had to sell the challenge. I said, you know, you have an opportunity to be a difference maker.


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[Assistant] Along with Sonia Henning, along with other, you know, and then it, and then it grew and...


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[Assistant] You know, when I took Jennifer into the, uh, Maples Pavilion, I said,


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[Assistant] You know, and we did not even pull out the bleachers across the way.


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[Assistant] And she kinda teases me about that. But, but we didn't even pull out the bleachers across the way and I told her, I said, Jennifer, picture someone in each corner. We are going to fill this arena.


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[Assistant] I think that was it. And the fact that then when they got here, it was fun. The challenge was fun. You know, we're gonna win the Pac-10. We're gonna win a national championship. Uhm, and we,


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[Assistant] And they won a national championship. In their freshman year, they were 500.


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[Assistant] And not letting go of that, no matter what other people said. And honestly, we outworked people. Uhm, that answer your question?


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[Assistant] They were, but it was really different, like you didn't have the internet then, you didn't have all this scouting services then, uhm.


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[Assistant] You know, we had, uh, it's really different now. I mean, we pay over a thousand dollars for a scouting service where, you know,


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[Assistant] People go out and watch all these kids play and they rank them and, you know, we know the best sixth grader.


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[Assistant] You know, it's like, you got a right to that sixth grader, and you got seventh and eighth graders already committing. It's crazy, but, you know. So, that, that was different. Yes, sir.


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[Assistant] Uhm, and I think that, I think a big part of that is probably looking at the success of the team.


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[Assistant] Uh, and so what is success? Uhm, part of it is winning games. Uhm, I think it's graduation. Uhm, players graduating.


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[Assistant] And probably a lot of it for women's basketball is, uhm, more so in women's basketball is that players are happy.


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[Assistant] They either go somewhere else or, you know, that's about it. But if the team is losing...


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[Assistant] I think, uhm, the other thing at Stanford might be really important is that you don't get in trouble with the NCAA, uh, rules violations, uhm.


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[Assistant] You know, and there might be a breakdown of, uhm, are you a strong administrator? They have, you know, budgeting, things like that, staying within your budget. But most, mostly I think it's, uhm, that the players have a very positive experience. And I think that's, that's important too.


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[Assistant] I don't know that I can do justice to answer. The question is, uhm, about


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[Assistant] A lot of them, they want to graduate. A lot of them just get passed along as young athletes. And I think that we, I think in some ways you can't, uh,


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[Assistant] Maybe, you know, just point out whether it's a college or a coach or an athletic department, it's the, the problem is much more systemic.


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[Assistant] And it goes back to the school systems and the programs all along the way. Uhm, I don't know that that would actually fix it.


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[Assistant] Uhm, but I, I do think it is an issue that, uhm, players are used basically for their athletic talent.


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[Assistant] And then when their eligibility or their, you know, a lot of them decide they're just not gonna, you know, continue to play.


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[Assistant] Uhm, then they, but they have at least had the opportunity to go to school and, and some of it is at, at a university giving the, uh, the kind of support, life skills, a lot of the young.


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[Assistant] Uhm, players coming up need life skills. And again, it might not be quite applicable to Stanford. Uhm, but life skill programs, uhm, tutoring, things like that.


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[Assistant] Uhm, and not just putting, you know, putting money into things that won't help him graduate.


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[Assistant] They are visiting all parts of the country They will be arriving here tomorrow


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[Assistant] They will be coming by train and most of the young people in the town will be meeting them at the station


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[Assistant] The Greenwood Boys will be staying for five days.


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[Assistant] During this time they will give 5 performances.


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[Assistant] As usual, the police will have a difficult time. They will be trying to keep order. It is always the same on these occasions.


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[Assistant] That's the first time we'd seen, they were catching queenies because there was a lot of baitfish. And it's the first time we had seen big fish caught off the beach. So that's what brought us here.


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[Assistant] Thank you, Sherry, and thank you again, John, for, uh,


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[Assistant] Yeah, and, and thanks for championing graduate education. It's really wonderful to see. So uhm, I'm gonna


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[Assistant] Pretend I'm David Letterman here and these are going to be flying around so you'll just have to indulge me. This is a new skill for me or not. So it's 2009, right? Can we fast forward to 2034 and could you say what you hope?


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[Assistant] Who were role models or mentors when you were a child or a teenager in school or family?


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[Assistant] So this is an audience of graduate students and post-docs. If you think back to when you were a graduate student.


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[Assistant] What do you wish somebody had told you about leadership that might have saved you a lot of pain and suffering over the last few years?


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[Assistant] Since, for example, when you were a graduate student to now.


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[Assistant] Multiple alternative futures for themselves and often it comes down to corporate or academic.


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[Assistant] You voted with your feet. You decided to return full-time to Stanford. Can you talk a little bit about


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[Assistant] So among the individuals out here, we have historians, we have chemists, we have engineers,


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[Assistant] Et cetera, et cetera, right across the spectrum of the university, which is very different from probably the kinds of people you had at MIPS.


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[Assistant] I've got two more questions and then we'll open it up to the audience.


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[Assistant] Do you think only a few people have the innate ability to be a leader?


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[Assistant] The people who don't feel that they maybe have all those innate abilities, what advice would you give to them about how to learn to be a leader?


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[Assistant] What program you're in, for example, whether you're a graduate student and so on with the program or postdoc.


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[Assistant] And I, I can't resist making the plug. That's what we're trying to do today is to, is to


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[Assistant] We had John till 3.15 and we wanted to have a reception and just making communication with some of my colleagues here. We thought let's just keep going with the questions.


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[Assistant] And use up some of that reception time. So we've done that and I hope that was in everybody's best interest. Thank you all very much for great


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[Assistant] Questions, they were really good, right on the money. Two important announcements. One is that the next


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[Assistant] A tremendous individual, former vice president of Google, uhm,


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[Assistant] So I encourage you all to come. That's February 23rd at 4.15.


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[Assistant] We love to get very brief input just to know who did we reach? How did we reach you? Is this a good idea or not?


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[Assistant] Well, oddly enough, they thought, the first four years or so, there's almost no, there's almost no sickness.


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[Assistant] They didn't realise when they started to get supply ships in from Timor that they were bringing malaria with them. And at one stage everybody except one man on the settlement had malaria.


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[Assistant] Well, it just outlived its usefulness. It'd been here for 11 years, it attracted no settlers, it attracted no trade, it was too far away to act as a, a port of refuge for shipwrecked sailors from the Torres Strait.


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[Assistant] And by now there was quite a pair of the French had no more interest in Australia. So they simply pulled out.


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[Assistant] You've learned how to implement exponentially weighted averages. There's one technical detail called bias correction that can make your computation of these averages more accurately. Let's see how that works.


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[Assistant] In the previous video, you saw this figure for beta equals 0.9, this figure for beta equals 0.98.


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[Assistant] But it turns out that if you implement the formula as written here, you won't actually get the green curve when, uh, say beta equals 0.98. You actually get the purple curve here. And you notice that the purple curve starts off really low.


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[Assistant] So let's see how to fix that. When you're implementing a moving average, you initialize it with v0 equals 0.


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[Assistant] Theta 1. But v0 is equal to 0, so that term just goes away. So v1 is just 0.02 times theta 1.


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[Assistant] So that's why if the first day's temperature is, uhm, say 40 degrees Fahrenheit, then V1 will be 0.02 times 40, which is 0.8. So you get a, you know, much lower value down here. So it's not a very good estimate of the first day's temperature.


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[Assistant] V2 will be 0.98 times V1 plus 0.02 times theta 2. And if you plug in, you know, V1, which is this, down here,


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[Assistant] And multiply it out, then you find that V2 is actually equal to 0.98 times 0.02 times theta 1.


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[Assistant] Theta 2. So again, you know, assuming theta 1 and theta 2 are positive numbers, when you, uh, compute this, V2 will be much less than theta 1 or theta 2. So V2 isn't a very good estimate of, you know, the first two days' temperature of the year.


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[Assistant] So it turns out that there's a way to modify this estimate that makes it much better, that makes it more accurate, especially during this initial phase of your estimates, which is that instead of taking vt, take vt divided by 1 minus beta to the power of t, where t is the current day that you're on.


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[Assistant] So let's take a concrete example. When t is equal to 2, 1 minus beta to the power of t is, uhm, 1 minus 0.98 squared. And it turns out that this is 0.0396.


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[Assistant] And so your estimate of the temperature on day two becomes V2.


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[Assistant] 9, 6 and so this becomes a weighted average of theta 1 and theta 2 and this removes this bias.


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[Assistant] So you notice that uhm, as t becomes large, beta to the t will become, will


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[Assistant] You're still warming up your estimates when bias correction can help you to obtain a better estimate of the temperature. And it's this bias correction that helps you go from the purple line to the green line.


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[Assistant] So in machine learning, for most implementations of the exponentially weighted average


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[Assistant] Uhm, people don't often bother to implement bias corrections because most people would rather just wait that initial period and have a slightly more biased estimate and go from there. But if you are concerned about the bias during this initial phase while your exponentially weighted moving average is still warming up,


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[Assistant] Then bias correction can help you get a better estimate early on.


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[Assistant] So with that, you now know how to implement exponentially weighted moving averages. Let's go on and use this to build some better optimization algorithms.


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[Assistant] I don't reckon there are many experiences that beat this. It's just mile after mile after mile of smooth driving through incredible scenery.


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[Assistant] But a hundred years ago, reaching the isolated towns scattered along this coast was no easy task. Particularly if you weren't keen to take to these notoriously treacherous seas.


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[Assistant] Basically you had one option. Travelling along awful bush tracks like this one. But that was all about to change.


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[Assistant] In 1918, World War I was drawing to a close. Over 400,000 Australian men had enlisted to fight for their country.


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[Assistant] Back in Victoria, one man had a plan to honour the dead and wounded diggers and provide work for those who would make it home.


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[Assistant] He was Howard Hitchcock, the mayor of Geelong, and he wanted to build a road.


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[Assistant] But not just any road. One that would cling to the coastline. In many places, it would be cut out of sheer cliff faces. So he set up a trust and started fundraising. In 1919, the work began. But the job ahead would be incredibly demanding.


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[Assistant] And I'm meeting historian Ian Grant to explore the reasons why.


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[Assistant] G'day Ian. Raymond, how are ya? Very, very good. Great to meet you. Thank you.


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[Assistant] Living under canvas, the men toiled five and a half days a week, in all conditions.


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[Assistant] Many had left the trenches of World War I for this.


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[Assistant] With rope attached to them and to a tree. And once they're here they would start to make a foothold into the side of the cliff.


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[Assistant] And then from that, they would continue their way into the hillside, just making a V. I can't even believe that this is the way they did it.


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[Assistant] The work progressed steadily, and in 1922, the first section


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[Assistant] Between lawn and eastern view, opened. Complete with a toll.


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[Assistant] Each passenger costs extra. And as we know, everyone hates paying a toll.


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[Assistant] So in order to save a bit of cash, sometimes they would stop the car just before the toll gate. One of the passengers would get out, walk along the beach and try and join them on the other side. There was just one problem.


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[Assistant] Doug Sterling had first-hand experience with the Toll Dodgers and their fate at the hands of the notorious and much feared toll collector, Mrs. Wright.


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[Assistant] A bit like an encounter with Mrs. Wright, the new road wasn't for the faint-hearted.


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[Assistant] In 1936, the road was fully handed over to the state, and the tolls removed.


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[Assistant] Today the Great Ocean Road stretches 243 kilometres from Allensford near Warrnambool to Torquay and in 2011 it was added to the Australian National Heritage List in recognition of its iconic status.


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[Assistant] Above all though, it remains a premium Australian touring experience, thanks to the diggers of World War I.


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[Assistant] Yeah, well you see it all the time. You see wild crocodiles, you pull them out to the river. And they are missing an arm or they've got some giant gash down their stomach.


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[Assistant] We can actually. We can do a really, really simple test, which hopefully will work. So what I'm gonna need is some crocodile blood.


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[Assistant] But I'm also going to need some of your blood. I want to show you just how effective crocodile blood is against your blood, which is going to be pretty useless in comparison.


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[Assistant] I'm going to put it onto these agar plates. Now each one of these


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[Assistant] Uh, has got a colony of bacteria on it, evenly spread. Put one drop there on the crocodile side, and then also do the same with the human serum here. What will happen is, if there's any antibacterial properties,


[User] Please transcribe this text

[Assistant] Uh, in the serum, then it will kill the bacteria adjacent to the spot.


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[Assistant] Haneda's gonna be shut down for a while. We need to get a handle on this situation as soon as possible.


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[Assistant] So the plane was crushed? Do we know how many were on board?


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[Assistant] Already tipsy, huh? And now Asano's here.


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[Assistant] Fine. So they're choosing to work over taking a vacation.


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[Assistant] Yeah, they're all big jobs, but I doubt they're big enough for him.


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[Assistant] This program is brought to you by Stanford University. Please visit us at stanford.edu


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[Assistant] The Clayman Institute for Gender Research at Stanford University, creating a more equal society for women and men through data-driven research and public education.


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[Assistant] The preceding program is copyrighted by Stanford University. Please visit us at stanford.edu.


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[Assistant] So today we're going to, uh, start talking about some of the specific details of the innate immune response. Uhm, and so I'm kind of thinking about in general, uhm, aspects of, uhm, the


[User] Please transcribe this text

[Assistant] Uh, this part of the course is where we're kind of building the immune system a bit. So uhm, we're going to see the, and build aspects of the innate immune response uhm, today as well as next week.


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[Assistant] I will also tell you that uhm, some students by the end of this class, uhm, because of some of the stuff that comes up in this particular, uh, class,


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[Assistant] Start freaking out about like, exams and stuff, and they're like, oh my gosh, how could I ever handle that on an exam?


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[Assistant] Uhm, but uhm, that's one reason why this weekend I'm gonna make sure my, all my old exams and in fact even old problems on this exact topic are posted. Uhm, and the inquisitive also is about this particular topic. Uhm, so if it, if there are a couple places where you feel like


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[Assistant] Oh my gosh, the details today. Know that you can actually both have the inquisitive as


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[Assistant] I mentioned to you last time the fact that we can divide up the immune system into, uhm, lots of different categories.


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[Assistant] Particularly thinking about, um, these different layers of immunity, either the barrier defenses, the innate immune response or the adaptive immune response.


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[Assistant] And for today and for next week, we're really going to be zooming in on innate immunity.


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[Assistant] We can do other types of divisions to kind of make sense or classify, uh, different aspects of the, um, immune system as well.


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[Assistant] And the aspect of the innate immune system that we're going to talk about today, uhm,


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[Assistant] Here you can see I listed as the humoral response.


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[Assistant] That was originally a name that was given when it seemed like the liquid of the blood was active.


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[Assistant] And really what it means is that we're looking at some proteins. And so today we're largely thinking about


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[Assistant] Proteins of the innate immune system that are basically pre-made.


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[Assistant] Your body has them right now, and so if...


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[Assistant] If a microbe were to enter your body, those innate immune proteins could start to act immediately. So this is sort of the first thing that might happen. If a microbe were to enter your body.


[User] Please transcribe this text

[Assistant] Uhm, you don't actually even need to do any transcription or translation. These proteins are all ready.


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[Assistant] Ready to go waiting in your body to start trying to combat microbes.


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[Assistant] Uhm, and so you can see that this is really uhm, part of this very immediate response.


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[Assistant] Uhm, where perhaps our pathogen will invade. Uhm, and we have these preformed proteins.


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[Assistant] That might be able to eliminate the pathogen and it might be done there. We might not ever get to any further parts of immune responses. We might not ever get to really much of any tissue damage, much of any disease.


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[Assistant] This is going to uhm, really be helpful in acting against those microbes.


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[Assistant] Even when the microbe is not totally controlled by these proteins, which is the part of this figure that I waited out and I'm not showing you here because we're doing that later, uhm, these proteins are really important.


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[Assistant] In terms of knocking down numbers of microbes and making sure that those microbes are not increasing exponentially, uhm, so that we have a chance.


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[Assistant] Generally these innate immune proteins are going to be acting against extracellular pathogens.


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[Assistant] They are going to be acting against things that are outside of cells, uhm, either because they live outside of cells or because they have not yet made it to inside of cells to be intracellular pathogens.


[User] Please transcribe this text

[Assistant] And so the things that we're looking at right now are largely, like I said, early and preformed as well as largely acting against extracellular pathogens.


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[Assistant] This also, uhm, will, is a place.


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[Assistant] Where my nice perfect little description of layers of the immune response already starts to get a little weird because in fact,


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[Assistant] One thing to know about some of these antimicro-, these, these innate immune proteins, sometimes also mentioned as antimicrobial peptides, is that they are a common feature at the barrier organs.


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[Assistant] So one of the things that's great about the barrier organs, like skin, gut, lungs, et cetera, is that they all have a lot of antimicrobial peptides.


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[Assistant] So that we can immediately start to...


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[Assistant] Combat microbes at those barriers because those barriers are in contact with the every- with everyday life.


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[Assistant] Uhm, they're not only found in barrier organs. There are many, for example, that circulate in the blood.


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[Assistant] But uhm, this is already one place where uhm, sometimes the distinction can get a little gray.


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[Assistant] You see here that I have these listed as antimicrobial peptides. And in reality,


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[Assistant] There are tons of different antimicrobial peptides. I'm going to highlight.


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[Assistant] Some particularly interesting or important antimicrobial peptides, but know that the ones I am telling you about are examples.


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[Assistant] Out of a really big set of potential proteins or peptides.


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[Assistant] A specific slide about, but that I would just will point out here, just cause it's cool and I like it, uhm, is one called Lactoferrin.


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[Assistant] Uhm, you can see that lactoferrin is in a number of barrier tissues, though it can be in a number of other places as well.


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[Assistant] Need iron to reproduce? They want to steal it from you.


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[Assistant] So basically lactoferrin just hides all the iron so the microbes can't have it.


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[Assistant] Really fun actually, when microbes use, try to steal your iron. Technically that strategy is called iron piracy.


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[Assistant] Uhm, and so they're trying to, so you just have a protein that basically soaks up all your iron, so the microbes can't get it.


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[Assistant] There are tons of different ways that that can work. You might imagine that lactoferrin


[User] Please transcribe this text

[Assistant] Uhm, it's probably going to be pretty broad in its action against many microbes.


[User] Please transcribe this text

[Assistant] Other antimicrobial peptides are, can be a bit more specific.


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[Assistant] Uhm, because this is actually a great experiment, it makes a good, important point, but I also worry that you're going to somehow tell Dr. Miller that I told you to do this. I did not, do not do this. No, no, no, no, no.


[User] Please transcribe this text

[Assistant] Uhm, in this experiment, we have a person who actually put some bacteria on their bare hands, on their skin. Uhm, either staph aureus,


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[Assistant] Uhm, or E. coli. Staph aureus being a gram positive organism, E. coli being a gram negative. And then the individual let their hands just sit for 30 minutes.


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[Assistant] And the idea was to see if that Staph aureus or that E. coli remained on the skin.


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[Assistant] When we look, when they looked, they saw that Staph aureus was still, uh, still grew while the E. coli did not.


[User] Please transcribe this text

[Assistant] And the idea here, and in fact the reasoning behind this is that you have a large number of antimicrobial peptides on the skin.


[User] Please transcribe this text

[Assistant] And in this case, these antimicrobial peptides tend to be more specific. They're not necessarily acting against all microbes. They don't act against staph aureus and many gram positives, but they might act against gram negatives.


[User] Please transcribe this text

[Assistant] Depending on which of this huge list of antimicrobial peptides we are talking about, they could be very


[User] Please transcribe this text

[Assistant] Uhm, broad, like lactoferrin, or they could be more specific, like you might imagine in that example I have just shown you.


[User] Please transcribe this text

[Assistant] Um, immunologists think about antimicrobial peptides. There are a few really critical antimicrobial peptides that we think about.


[User] Please transcribe this text

[Assistant] One of the most famous examples of an antimicrobial peptide is called lysozyme.


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[Assistant] Note that lysozyme has zyme at the end of its name. Uhm, that's because it's an enzyme. It has enzymatic activity.


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[Assistant] Later in the semester, we will talk about an organelle called the lysosome.


[User] Please transcribe this text

[Assistant] Lysosome, S-O-M, and lysozyme, Z-Y-M, are not the same thing. One's an organelle, one's an enzyme, so be careful on that. Uhm, and lysozyme,


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[Assistant] Specific enzymatic activity is that it cleaves a particular chemical linkage called the beta-14 linkage. The reason why you care about that is that different bacteria


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[Assistant] We'll have specific cell wall structures as shown here that can include, uhm, this molecule peptidoglycan as a major part of the cell wall. Different microbes have different amounts of peptidoglycan, but many of them do have peptidoglycan. Lysozymes specific enzymatic activity breaks


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[Assistant] A particular chemical linkage, the beta one four linkage in peptidoglycan in order to destroy the prokaryotic cell wall.


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[Assistant] And once that cell wall is destroyed, that can make it very easy for the microbe to be lysed by osmotic lysis.


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[Assistant] Uhm, and so this will lead to lysis of the cell. Uhm, lysozyme is found in many mucosal secretions, uhm, in many of your, uhm,


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[Assistant] Different, uh, barrier organs. Two of the best places if you decided what you really wanted to do was purify a whole bunch of lysozyme.


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[Assistant] The two places that you would actually be able to get it from the best are saliva and tears.


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[Assistant] Uhm, so there's tons of this trying to, uhm,


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[Assistant] Sort of inhibit, uh, potential microbial growth in uh, saliva and tears.


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[Assistant] Another really critical group of antimicrobial peptides are a group of peptides known as the defensins.


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[Assistant] Again, there are many defensens. I'm just gonna say defensens.


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[Assistant] But there are, for example, people whose lives work is human beta defensin 3. Or something like that. I'm just going to say defensins.


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[Assistant] You can see that they can be made by a number of different cell types, some immune cells, like our neutrophils, some sort of more nonimmune cells. You can see that they can be present in


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[Assistant] Many different tissue types. Uhm, many of them are barrier organs, though uhm, we can see them in some other places as well.


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[Assistant] And what you can notice is that in most situations, they are made constitutively.


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[Assistant] Meaning, they're being made all the time 24-7.


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[Assistant] Um, so you always have them to potentially stop, um, microbial replication no matter what. This is sort of that, you know.


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[Assistant] First few minutes after exposure, this is going to be, these are going to be helping you against microbial replication. That's why they're constitutive. They're there all the time, ready to go.


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[Assistant] One of the places that they are very commonly found or very famously found is in the GI tract.


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[Assistant] Uhm, so if you look at a GI tract, you have, uhm, your, uh, these villi as part of the intestine, and there are these sort of deeper areas called crypts.


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[Assistant] Many of the cells in the crypt actually make tons of antimicrobial peptides, particularly defensins, uhm, in order to stop or control microbial replication in the GI tract.


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[Assistant] Uhm, defensins have a mechanism of action that's also pretty straightforward. Uhm,


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[Assistant] So, defensins really just act, uh, because they are charged, little charged proteins. So you can see they are these proteins with a positive charge.


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[Assistant] And the way that they work is that they are able to actually insert into plasma membranes and make pores. So they poke holes in plasma membranes.


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[Assistant] Uhm, to allow for uhm, osmotic lysis. Basically, water comes in, cytoplasm goes out.


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[Assistant] Uhm, the cell no longer has structural integrity, cell's dead. It's really all that happens with defensins. Sometimes people look at defensins and say, okay, I get this, I get how that kills a cell, I can see how this would be useful against microbes, but what I don't understand is how in the world does this not kill all of my other cells too?


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[Assistant] How can my intestine make some defensins kill the microbial cells and not kill the intestine cells? Cause my, my cells have plasma membranes too.


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[Assistant] And the way that that works actually is that ourselves, uhm,


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[Assistant] And move all of the phospholipids with negative charges to the inside of the plasma membrane. Uhm, when you were in Bio250 with Dr. Dunaway, you might have learned about flip bases.


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[Assistant] Uhm, that's what flip bases are doing, is that they're making sure that all of the negatively charged phospholipids are on the inside.


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[Assistant] Uhm, we use that for lots of reasons that I am not gonna deal with right now. But it just so happens we do that.


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[Assistant] Microbes don't sort of organize their phospholipids in the same way. They've got negative charges on both the in or the outside. And so these positively charged defensins can bind to those negative head groups.


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[Assistant] On prokaryotic cells and destroy their membranes while not destroying the membranes of our eukaryotic cells because of the sorting we have done on those phospholipids.


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[Assistant] Uhm, I mention this because most of the time this is what we say about defensins. We're like, oh yea, they just insert into membranes and make holes.


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[Assistant] Tada! And uhm, I know that I have had many times where students have been like, that seems pointless. Why would we do that? Uhm, and so this is the reason why we would do that.


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[Assistant] One other thing to point out about antimicrobial peptides in general is that sometimes they can also act not just in terms of microbial replication, but they might also stop different types of microbial processes that are involved in disease. So many microbes, uh,


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[Assistant] Induced disease partially because of specific proteases. So many microbes have proteases that can cleave stuff of yours.


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[Assistant] Like alpha 2 macroglobulin, which is pretty cool. Alpha 2 macroglobulin basically has a protease substrate in the middle of it. It's like bait for proteases from microbes.


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[Assistant] And if a protease tries to cleave alpha-2 macroglobulin, the protein undergoes a conformational change.


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[Assistant] Closes off the protease and inactivates it, but also basically sequesters that protease. So you can see the protease tries to cleave alpha 2 macroglobulin and alpha 2 macroglobulin actually


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[Assistant] Uhm, a better strategy than trying to get rid of all microbes ever. Just get rid of anything that might be dangerous.


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[Assistant] And so this is another strategy we see with antimicrobial peptides.


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[Assistant] Students will see different mechanisms that we learn throughout this semester.


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[Assistant] Uhm, and one of the places that they will sort of be a little confused is, okay awesome, we have


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[Assistant] A semester's worth of all these fancy aspects of our immune system that are protecting us from microbial infection.


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[Assistant] And protecting us from microbial disease, why the heck do we ever get sick?


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[Assistant] Uhm, and so I just want to also point out that


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[Assistant] We are in an evolutionary arms race with microbes. They are trying to evolve to evade all of these things. There are plenty of microbes that evade antimicrobial peptides.


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[Assistant] Show you evasion mechanisms, uhm, but basically everything we talk about this semester, there are microbes that have evolved ways to evade.


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[Assistant] Uhm, so I wanted to also point out, uhm, because some,


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[Assistant] Uh, someway when we finish some of the things we talk about today, students are like, why isn't that not it? Isn't this-


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[Assistant] We had some cells the other day, we had some proteins, that seems like enough. Uhm, and part of the reason why this is not enough is because


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[Assistant] of microbes trying to evade everything that we're doing.


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[Assistant] To, uhm, an immunologist, one of my colleagues from grad school.


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[Assistant] Their mind would go to a very specific place. They would be like, oh, I know what she's going to talk about today.


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[Assistant] Because when we think about proteins of the innate immune system that help to combat microbes, there is one particular set of proteins outside of the ones I've already told you about that are super famous.


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[Assistant] And so everybody, any immunologist who saw this would be like, okay, that's what we're, that's what this is about today. And the rest of the time today, I'm going to talk about that group of proteins.


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[Assistant] These proteins are known as the complement proteins.


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[Assistant] There is much to be said about complement proteins. So, when I started, uhm, you know, taking immunology, when I started TA-ing immunology, complement was


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[Assistant] Really, like, the short straw that no one ever wanted to think about and talk about. And we would all be like, really, do we even have to talk about it?


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[Assistant] We would joke as TAs, like, who gets the short straw of having to actually talk about compliment? No one wants to do this. Everyone hates it. Uhm, it was described really early in the history of immunology, uhm, and sort of seemed really, I guess, old and dusty when I was starting grad school.


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[Assistant] What we have realized over the years?


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[Assistant] In a lot of ways, this is a little perspective piece talking kind of about this.


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[Assistant] Are all of the things that compliment is actually really important in the body that we maybe never thought of before.


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[Assistant] Uhm, so this is an example of actually an eyeball of a person with macular degeneration.


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[Assistant] All of these little clumps are actually the things occluding the eye to stop this person's vision. They are all clumps of compliment.


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[Assistant] We have realized that compliments is actually a major contributor to pathology in arthritis, particularly osteoarthritis.


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[Assistant] Uhm, there have been some really beautiful papers showing that complement is actually, uh, critically responsible for synapse pruning in the nervous system.


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[Assistant] Uhm, and on and on and on. And so compliment keeps getting, uhm, related to things that maybe we didn't even originally know were immune related. Uhm, and it's, uhm, importance is particularly, uh,


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[Assistant] Sort of obvious, but you will notice there are a few kind of really weird old timey phrases that come up when we talk through compliment because it was described such a long time ago.


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[Assistant] Uhm, I'll also tell you why it has the name compliment.


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[Assistant] Once upon a time, people, and you'll see why this is, uhm, people realized that if you were trying to do certain experiments with antibodies, you could


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[Assistant] Add this stuff, and it would make the antibodies better. It would complement them. Would improve them.


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[Assistant] We often talk about, uhm, we'll sometimes refer to complement as C prime. Uhm, so if in a paper you ever see something that's just like, and then we added C prime, that's, I mean I'll just speak for complement. And we often talk about this thing called the fixation of complement.


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[Assistant] I don't know why they picked that term. That term was picked.


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[Assistant] I don't know, before my, probably before my grandparents were born. Definitely before my parents were born, I would say. So, I don't know why I picked it. Uhm, but the basic idea for complement is that there is some complement protein.


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[Assistant] Most of the complement proteins have very creative names like C3.


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[Assistant] You can see that protease activity happening here.


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[Assistant] To make a couple of different fragments. And one of those fragments will be small and will float away and do something.


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[Assistant] And one of those fragments will actually get attached to the microbe.


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[Assistant] Uhm, a bacteria has complement fixed to it if we've attached a piece of a complement fragment to the bacteria.


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[Assistant] And so really the very broad overview of what we're going to see when we think about complements is a bunch of proteins getting activated by a protease.


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[Assistant] Part floating away and doing stuff, part getting stuck on things.


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[Assistant] Sometimes people can get a little overwhelmed thinking about what's going on with compliment.


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[Assistant] I really like this figure from your textbook.


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[Assistant] Uhm, because it helps us understand big picture what's going on with compliment.


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[Assistant] So big picture what's going on with compliment.


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[Assistant] Is that there are three different ways it can get started. There are three different initiation pathways.


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[Assistant] All three of those initiation pathways then meet up at one common similar point. So, at that point,


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[Assistant] Uhm, as described here, is activating something called C3b.


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[Assistant] Uhm, so specifically cleaving C3 into...


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[Assistant] C3A and C3B. So, but we'll just say getting to doing something to C3.


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[Assistant] So really the initiation pathways are how do you get to C3?


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[Assistant] Once we've gotten to C3, there are a few different ways we can deal with the pathogen. So once we get to C3,


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[Assistant] We have a few different ways we can deal with the pathogen. So when you're thinking about different parts of the complement cascade,


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[Assistant] One of the things you should be aware of is, are we talking about initiation? Are we trying to figure out which of these top things we're doing to get us to C3? Or are we thinking about an effector function?


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[Assistant] It wasn't until I was interviewing for professor jobs that I learned that people who are not immunologists don't use that word. We use it so much that I'm like, what do you mean? Everyone knows that word.


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[Assistant] Uhm, factor function means how you do stuff, how you have an effect, how you get rid of the microbe.


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[Assistant] So one thing to, to be aware of as we talk about different parts of this is are we talking about part, an initiation type of part, or are we talking about an effect or function type of part?


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[Assistant] Each of the different effector functions that we see could happen following any different initiation pathway. So you could go like here and then here, go here and then here.


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[Assistant] Usually you go here and then like multiple of them. Okay.


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[Assistant] So the way that I'm going to talk through this today is I'm going to first talk through one initiation pathway and get us to see three.


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[Assistant] Then we're going to talk about the effector functions, sort of the things that could happen.


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[Assistant] Once we've done that, I'm going to go back up to the top and show you the two other ways we could have gotten to C3.


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[Assistant] So that's kind of the overall view of what we're doing here. This is a nice figure from your textbook.


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[Assistant] Uhm, that gives you an overview of exactly what I'm going to be talking about, this exact process, and divides it up in the same way. Uhm, just for your studying purposes later, uhm, I've put in the same


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[Assistant] Uhm, concept figure from a different textbook.


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[Assistant] Uhm, it has some pictures instead of just words. So when you're studying later...


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[Assistant] Uhm, whichever of these two figures makes more sense to you, uhm, they're both here for you. So the, uhm,


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[Assistant] Version of, uh, compliment initiation that I'm going to start with is called the classical pathway.


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[Assistant] The classical pathway was named the classical pathway because it was the first one we discovered and like understood. So it was kind of the first way we understood it. We now know


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[Assistant] That, this one was actually probably the last one to evolve. Uhm, and in a lot of ways, uhm, it's probably, you know, not the one that...


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[Assistant] If it happens first, it's probably not the one that even happens last in your body. But, it's the one that was described first. To me, it makes the most sense to start with the description of the classical pathway.


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[Assistant] Because the classical pathway starts with an antibody binding to the surface of a pathogen.


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[Assistant] The antibodies are drawn here as these Y-shaped proteins. And we are going to see so much more about antibodies going forward. So you can see these Y-shaped antibody proteins.


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[Assistant] A thing that is really, really, really important to know.


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[Assistant] Is that antibodies are products of the adaptive immune system. They're not usually thought of as part of the innate immune system. So the classical pathway


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[Assistant] Actually requires the adaptive immune system to do something, even though we are totally in an innate immunity day.


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[Assistant] So one of the things that's really, that's sort of unique about the classical pathway is that it starts with an antibody binding to our microbe.


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[Assistant] And so you can see that antibody, uh, binding here.


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[Assistant] Uhm, the specific geometry of the antibody binding to the microbe is actually kind of important.


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[Assistant] Uhm, then the complement pathway is initiated, uhm, with our first, with the first of these complement proteins.


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[Assistant] And the first complement protein that's involved in the classical pathway is called C1.


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[Assistant] See, because of the way the numbers go in this one, that's why I like to do this one first. We start with C1. Uhm, so there is this protein that's called C1.


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[Assistant] And you can see a cartoon version of C1 from your textbook on the left as well as a microscopy image of C1 on the right to show you that that is really what it looks like structurally.


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[Assistant] And we usually describe C1 as looking something like an upside down bouquet of flowers. So, you can see that, looking at C1.


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[Assistant] Can bind to that antibody that's on the surface of our pathogen. So we started the classical pathway with an antigen or the antibody bound. Um, C1 can now go ahead and bind to that antibody.


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[Assistant] The geometry again is a little important just to make it fit C1, but we're not going to get super into that.


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[Assistant] Is bound to antibodies as is shown on this slide.


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[Assistant] It gains the ability to act as a protease.


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[Assistant] And when it gains the ability to act as a protease.


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[Assistant] It cleaves the next protein in the complement, uh, the classical pathway.


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[Assistant] The classical pathway is where you learn that immunologists can't count. So we'd love to go from C1 to C2, but we don't. Instead, C1 activates C4.


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[Assistant] C4 activates C2, and that activates C3. So it's actually 1, 2, 3, 4. It just 4s in the wrong place.


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[Assistant] Uhm, so you can see this, uhm, on these slides as well. So fir- the first thing that will happen is C1 will bind. That will allow it to interact with, uhm, C4 and C2. Uhm, it's actually 4 first then 2. Little piece- pieces of them. You can see that C2 was shown here before it was cleaved. It's a little smaller after it's cleaved. Uhm, same thing with C4.


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[Assistant] C4 and C2 will now both have pieces that get stuck.


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[Assistant] Or fixed onto the surface of the microbe.


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[Assistant] And that protease cleaves the next one in the line, C3. So you can see that here.


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[Assistant] Uhm, once we have C4 and C2 on the surface of the cell, we can activate C3.


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[Assistant] Oh my gosh, C3 was the middle part I already told you about before. We're done. We're there. We got there. All good. Uhm.


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[Assistant] It does turn out that there is one other way that you could start the classical pathway. Uhm, and that's a good thing because


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[Assistant] The classical pathway as shown here requires an antibody to start that process.


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[Assistant] Antibodies are part of the adaptive immune response. Maybe you don't have a great antibody response at the beginning.


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[Assistant] The first time you've ever seen a new microbe, you may not have an antibody response.


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[Assistant] Uhm, there are some other proteins. A famous one is called C-reactive protein.


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[Assistant] Uhm, C1 and do the whole, the same thing. So C-reactive protein.


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[Assistant] Uhm, is made by the liver as our, most of our complement proteins.


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[Assistant] It can bind specifically to microbial surfaces and start this process as well.


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[Assistant] Kind of described, uh, later. We didn't really understand it as well, and it's sort of not the, the famous way of doing it. If you, so C-reactive protein, like I mentioned, uhm, and many of these other, uh, complement proteins are made by the liver. If, uhm, you,


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[Assistant] Are going to have blood work done. If you remember, we talked yesterday that you might have someone check your white blood cell counts to see if you have too many white blood cells. Sometimes you also will have your C-reactive protein levels checked.


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[Assistant] Again to see if you are making, uh, if your liver has been turned on to start.


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[Assistant] No, it can occur anytime, uhm, that C-reactive protein does have the ability only to bind to microbial surfaces.


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[Assistant] We can now do something about our micro.


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[Assistant] Uhm, your textbook shows three different potential effector functions that can happen, and I will talk about all three of those. I am going to briefly mention a fourth.


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[Assistant] Just to say that it's a thing, I'm not gonna go into further detail on it.


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[Assistant] So the one that many people think a lot about, when I think of compliment, I will admit this is usually the first one my brain goes to.


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[Assistant] Is formation of the membrane attack complex, or the MAC, uhm,


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[Assistant] There was some song when I was younger about Return of the Mac, and now it'll be in my head for the rest of the day.


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[Assistant] Uhm, since I had to return to the Mac slide today. Uhm, so once C3 is active,


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[Assistant] It can activate C5, which is not shown here. When I was actually putting to these, uhm, I was putting these slides together.


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[Assistant] ...was unimpressed with how they dealt with C5 in this version of your textbook. They just kind of were like...


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[Assistant] And didn't really get into it. Usually C3 activates C5.


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[Assistant] Uhm, I actually sometimes draw this layer as the C3, C5 layer. Uhm, whatever. C5. It's a thing.


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[Assistant] It, just like every other piece of, uh, one of these complement proteins, gets cleaved into two pieces. So it will get cleaved into a small piece and a big piece.


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[Assistant] Uhm, an A and a B. You can see that here as well for C3. So C3, uhm,


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[Assistant] And C3b is actually the one that was bound to the surface of the microbe. C3a is the little one that floated away. The exact same


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[Assistant] Thing happens with C5. C5 gets, uhm,


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[Assistant] Uh, stuck to the microbe, C3A, or C5B gets stuck, C3, C5A goes away.


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[Assistant] So here you can see C5b getting stuck to the microbe and it brings along its friends 5, 6, 7, 8, 9.


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[Assistant] We're basically counting for this one. That's why I like to do this one first. And that makes a pore in the surface of the microbial cell.


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[Assistant] So, C9 is this little pore-forming protein. We get lots of them and make a pore.


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[Assistant] Which are actually easily visible under a microscope. So here you can actually see pores in a bacterial cell that have been poked by C5.


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[Assistant] You can also see a cylinder right here on the side of this microbial cell, this little tube. That is C5. Uhm, in a side view on this cell. And as a result, our bacteria is laced. Uhm, so we have laces of our cell.


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[Assistant] So one thing that we can do with Complement is we can basically put all of these little sticky notes on the bacteria and eventually start lysing at that sticky note spot.


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[Assistant] We can also do some other things. So if you recall, I mentioned that.


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[Assistant] C3b was getting stuck to the surface of our microbe, as was C5b.


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[Assistant] Also have a particular role. One thing I forgot to say on this slide.


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[Assistant] Is that if you go look at that animation I mentioned, uhm, the chapter two animation that's on Moodle.


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[Assistant] It's linked from Moodle. It basically is starting from here and going through here.


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[Assistant] And it's just a video of each of these steps with someone telling you about that. So you can see it again there.


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[Assistant] Uhm, but C3A and C5A, the little pieces that are cut off, have an important job. And those two proteins can induce inflammation.


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[Assistant] Uhm, so they can do things like change blood vessel permeability.


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[Assistant] Have these smaller proteins uhm, act as alarm bells. They say, hey, hey, we got a problem right here. Can you please send over some white blood cells to this location?


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[Assistant] That's basically what C3A and C5A are doing. They can actually act on a number of our different innate immune cells by binding to receptors with the overall


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[Assistant] Um, role of them is to lead to inflammation.


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[Assistant] We're going to talk a lot more about other aspects of inflammation next week.


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[Assistant] Uhm, sometimes people refer to C3A and C5A as the anaphylatoxins, so if you see that word, it just means they're little proteins that induce inflammation. Uhm, it's a word that every so often you might see, so I'm just gonna tell you what it means, even though I'm not gonna be super into it.


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[Assistant] The third thing that complement proteins can do is called opsonization. Opsonization is one that is near and dear to my heart.


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[Assistant] Those of you who've taken micro have already heard my optimization story, but you get to hear my optimization story again.


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[Assistant] I have in my office the, uh, I still have my first ever immunology exam from my first undergraduate immunology class.


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[Assistant] And on that exam there was a place where there were some terms and we had to define them. And optimization was one of the terms. And I got it wrong. And the reason why I got it wrong


[User] Please transcribe this text

[Assistant] Was because my professor had actually taught us a sort of analogy to help us remember opsonization.


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[Assistant] And I could remember the analogy, but couldn't think how to describe it otherwise, so I just wrote the analogy, or something related to it, and I got it wrong.


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[Assistant] I'm gonna actually tell you that same analogy now to help you understand opsonization, but, but don't write it on the exam.


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[Assistant] Uhm, lots of people now write me random jokes related to it. Uhm, next to writing their real answer. Uhm,


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[Assistant] The other reason why this actually cracks me up is because I've been telling that story for years when I teach immunology and a former member of my lab went to graduate school in immunology at the same university where I was an undergrad. And in one of her graduate school courses,


[User] Please transcribe this text

[Assistant] The person who taught it to me taught it to them with that same analogy.


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[Assistant] And she sort of like couldn't handle herself, uhm, that she was in that same class hearing that same analogy. It was crazy. So people still use this analogy to this day.


[User] Please transcribe this text

[Assistant] So with opsonization, we are thinking about those fragments of our complement proteins that are attached to the microbial surface like C3b. So you can see.


[User] Please transcribe this text

[Assistant] Here, the protein's being attached to the surface. And whenever we think about opsonization, because it does come up in some other places in immunology, part of it means something getting coated with stuff.


[User] Please transcribe this text

[Assistant] Whatever the coding thing is, in this case, it's complement proteins.


[User] Please transcribe this text

[Assistant] Those coding things can be bound by a receptor. Here, it's a complement receptor.


[User] Please transcribe this text

[Assistant] That's on some kind of cell. So we've got our complement proteins binding to a complement receptor on a particular cell. Oftentimes it is a macrophage.


[User] Please transcribe this text

[Assistant] And now that macrophage will phagocytose that bacteria and destroy it. Basically what has happened here is that we have marked


[User] Please transcribe this text

[Assistant] This bacteria to be phagocytosed. We have marked it for phagocytosis.


[User] Please transcribe this text

[Assistant] Uhm, the way that my professor explained it to me was that we have put a coating on that bacteria to make it more likely to get eaten.


[User] Please transcribe this text

[Assistant] Or we put a coating on it to make it look extra tasty. And so, opsonization is like butter.


[User] Please transcribe this text

[Assistant] It's like putting butter on something to make it more likely to get eaten, or to make it more tasty.


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[Assistant] And yes, I wrote butter was the definition of opsonization, uh, on that exam.


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[Assistant] Uhm, so it's like butter in that it's a coating that makes something more likely to get eaten and label something as a thing to be eaten, but it is not actually butter.


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[Assistant] Uhm, the other thing that I will tell you that does happen following compliment fixation


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[Assistant] Also has to do with complement receptors, just like opsonization does. Uhm, it's slightly different complement receptors, but uhm, the


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[Assistant] Sort of thing I just want you to know is that there are also some complement receptors that are on adaptive immune cells.


[User] Please transcribe this text

[Assistant] And complement can also start to activate the adaptive immune response. So we can also help the adaptive immune response by coding things with complement. So we will also turn on adaptive immunity.


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[Assistant] Uhm, I'm not gonna say any more than that. I just want to point out that yes, in fact, uhm, that can, uh, happen.


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[Assistant] Uhm, so at this point, we have started with one initiation pathway.


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[Assistant] For the complement cascade, we've gotten to our section of C3, where all of these complement initiation pathways come together, and we have gone through multiple different ways that we could eliminate the infecting pathogen.


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[Assistant] As your textbook says, and as I mentioned before, the classical pathway is likely the last to be activated. And we now understand


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[Assistant] That if we look in terms of evolution, it is probably the last one to have evolved. Uhm, in fact, if we look at different groups of animals,


[User] Please transcribe this text

[Assistant] Only mammals, birds, reptiles, amphibians.


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[Assistant] We're only seeing classical pathway there, while these other pathways of complement initiation are found throughout animal phyla.


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[Assistant] Uhm, so in fact they probably evolved first, and Classical Pathway was like an add-on.


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[Assistant] I still find it easier to explain classical first.