heavy chains and two light chains. the unique variable region allows an antibody to recognize its matching antigen. most large molecules, including virtually all proteins and many polysaccharides, can serve as antigens. the parts of an antigen that interact with an antibody molecule or a lymphocyte receptor, are called epitopes, or antigenic determinants. most antigens contain a variety of epitopes and can stimulate the production of antibodies, specific t cell responses, or both. a very small proportion (less than 0.01%) of the total lymphocytes are able to bind to a particular antigen, which suggests that only a few cells respond to each antigen. for the acquired response to "remember" and eliminate a large number of pathogens the immune system must be able to distinguish between many different antigens, and the receptors that recognize antigens must be produced in a huge variety of configurations, in essence one receptor (at least) for each different pathogen that might ever be encountered. even in the absence of antigen stimulation, a human can produce more than 1 trillion different antibody molecules. millions of genes would be required to store the genetic information that produces these receptors, but, the entire human genome contains fewer than 25,000 genes. myriad receptors are produced through a process known as clonal selection. according to the clonal selection theory, at birth, an animal randomly generates a vast diversity of lymphocytes (each bearing a unique antigen receptor) from information encoded in a small family of genes. to generate each unique antigen receptor, these genes have undergone a process called v(d)j recombination, or combinatorial diversification, in which one gene segment recombines with other gene segments to form a single unique gene. this assembly process generates the enormous diversity of receptors and antibodies, before the body ever encounters antigens, and enables the immune system to respond to an almost unlimited diversity of antigens. throughout an animal's lifetime, lymphocytes that can react against the antigens an animal actually encounters are selected for action—directed against anything that expresses that antigen. the innate and acquired portions of the immune system work together, not in spite of each other. the acquired arm, b, and t cells couldn't function without the innate system input. t cells are useless without antigen-presenting cells to activate them, and b cells are disabled without t cell help. on the other hand, the innate system would likely be overrun with pathogens without the specialized action of the adaptive immune response. acquired immunity during pregnancy the cornerstone of the immune system is the recognition of "self" versus "non-self". therefore, the mechanisms that protect the human fetus (which is considered "non-self") from attack by the immune system, are particularly interesting. although no comprehensive explanation has emerged to explain this mysterious, and often repeated, lack of rejection, two classical reasons may explain how the fetus is tolerated. the first is that the fetus occupies a portion of the body protected by a non-immunological barrier, the uterus, which the immune system does not routinely patrol. the second is that the fetus itself may promote local immunosuppression in the mother, perhaps by a process of active nutrient depletion. a more modern explanation for this induction of tolerance is that specific glycoproteins expressed in the uterus during pregnancy suppress the uterine immune response (see eu-feds). during pregnancy in viviparous mammals (all mammals except monotremes), endogenous retroviruses (ervs) are activated and produced in high quantities during the implantation of the embryo. they are currently known to possess immunosuppressive properties, suggesting a role in protecting the embryo from its mother's immune system. also, viral fusion proteins cause the formation of the placental syncytium to limit exchange of migratory cells between the developing embryo and the body of the mother (something an epithelium can't do sufficiently, as certain blood cells specialize to insert themselves between adjacent epithelial cells). the immunodepressive action was the initial normal behavior of the virus, similar to hiv. the fusion proteins were a way to spread the infection to other cells by simply merging them with the infected one (hiv does this too). it is believed that the ancestors of modern viviparous mammals evolved after an infection by this virus, enabling the fetus to survive the immune system of the mother. the human genome project found several thousand ervs classified into 24 families. immune network theory main article: immune network theory a theoretical framework explaining the workings of the acquired immune system is provided by immune network theory, based on interactions between idiotypes (unique molecular features of one clonotype, i.e. the unique set of antigenic determinants of the variable portion of an antibody) and 'anti-idiotypes' (antigen receptors that react with the idiotype as if it were a foreign antigen). this theory, which builds on the existing clonal selection hypothesis and since 1974 has been developed mainly by niels jerne and geoffrey w. hoffmann, is seen as being relevant to the understanding of the hiv pathogenesis and the search for an hiv vaccine. stimulation of adaptive immunity one of the most interesting developments in biomedical science during the past few decades has been elucidation of mechanisms mediating innate immunity. one set of innate immune mechanisms is humoral, such as complement activation. another set comprises pattern recognition receptors such as toll-like receptors, which induce the production of interferons and other cytokines increasing resistance of cells such as monocytes to infections. cytokines produced during innate immune responses are among the activators of adaptive immune responses. antibodies exert additive or synergistic effects with mechanisms of innate immunity. unstable hbs clusters band-3, a major integral red cell protein; antibodies recognize these clusters and accelerate their removal by phagocytic cells. clustered band 3 proteins with attached antibodies activate complement, and complement c3 fragments are opsonins recognized by the cr1 complement receptor on phagocytic cells. a population study has shown that the protective effect of the sickle-cell trait against falciparum malaria involves the augmentation of acquired as well as innate immune responses to the malaria parasite, illustrating the expected transition from innate to acquired immunity. repeated malaria infections strengthen acquired immunity and broaden its effects against parasites expressing different surface antigens. by school age most children have developed efficacious adaptive immunity against malaria. these observations raise questions about mechanisms that favor the survival of most children in africa while allowing some to develop potentially lethal infections. in malaria, as in other infections, innate immune responses lead into, and stimulate, adaptive immune responses. the genetic control of innate and acquired immunity is now a large and flourishing discipline. humoral and cell-mediated immune responses limit malaria parasite multiplication, and many cytokines contribute to the pathogenesis of malaria as well as to the resolution of infections. evolution the acquired immune system, which has been best-studied in mammals, originated in jawed fish approximately 500 million years ago. most of the molecules, cells, tissues, and associated mechanisms of this system of defense are found in cartilaginous fishes. lymphocyte receptors, ig and tcr, are found in all jawed vertebrates. the most ancient ig class, igm, is membrane-bound and then secreted upon stimulation of cartilaginous fish b cells. another isotype, shark igw, is related to mammalian igd. tcrs, both α/β and γ/δ, are found in all animals from gnathostomes to mammals. the organization of gene segments that undergo gene rearrangement differs in cartilaginous fishes, which have a cluster form as compared to the translocon form in bony fish to mammals. like tcr and ig, the mhc is found only in jawed vertebrates. genes involved in antigen processing and presentation, as well as the class i and class ii genes, are closely linked within the mhc of almost all studied species. lymphoid cells can be identified in some pre-vertebrate deuterostomes (i.e., sea urchins). these bind antigen with pattern recognition receptors (prrs) of the innate immune system. in jawless fishes, two subsets of lymphocytes use variable lymphocyte receptors (vlrs) for antigen binding. diversity is generated by a cytosine deaminase-mediated rearrangement of lrr-based dna segments. there is no evidence for the recombination-activating genes (rags) that rearrange ig and tcr gene segments in jawed vertebrates. the evolution of the ais, based on ig, tcr, and mhc molecules, is thought to have arisen from two major evolutionary events: the transfer of the rag transposon (possibly of viral origin) and two whole genome duplications. though the molecules of the ais are well-conserved, they are also rapidly evolving. yet, a comparative approach finds that many features are quite uniform across taxa. all the major features of the ais arose early and quickly. jawless fishes have a different ais that relies on gene rearrangement to generate diverse immune receptors with a functional dichotomy that parallels ig and tcr molecules. the innate immune system, which has an important role in ais activation, is the most important defense system of invertebrates and plants. types of acquired immunity immunity can be acquired either actively or passively. immunity is acquired actively when a person is exposed to foreign substances and the immune system responds. passive immunity is when antibodies are transferred from one host to another. both actively acquired and passively acquired immunity can be obtained by natural or artificial means. naturally acquired active immunity – when a person is naturally exposed to antigens, becomes ill, then recovers. naturally acquired passive immunity – involves a natural transfer of antibodies from a mother to her infant. the antibodies cross the woman's placenta to the fetus. antibodies can also be transferred through breast milk with the secretions of colostrum. artificially acquired active immunity – is done by vaccination (introducing dead or weakened antigen to the host's cell). artificially acquired passive immunity – this involves the introduction of antibodies rather than antigens to the human body. these antibodies are from an animal or person who is already immune to the disease. naturally acquiredartificially acquired active – antigen enters the body naturallyactive – antigens are introduced in vaccines. passive – antibodies pass from mother to fetus via placenta or infant via the mother's milk.passive – preformed antibodies in immune serum are introduced by injection.