on the surface of mast cells. activation of mast cells following engagement of fcεri results in a process called degranulation, whereby the mast cell releases preformed molecules from its cytoplasmic granules; these are a mixture of compounds including histamine, proteoglycans, and serine proteases. activated mast cells also synthesize and secrete lipid-derived mediators (such as prostaglandins, leukotrienes, and platelet-activating factor) and cytokines (such as interleukin 1, interleukin 3, interleukin 4, interleukin 5, interleukin 6, interleukin 13, tumor necrosis factor-alpha, gm-csf, and several chemokines. these mediators contribute to inflammation by attracting other leukocytes. on eosinophils large parasites like the helminth (worm) schistosoma mansoni are too large for ingestion by phagocytes. they also have an external structure called an integument that is resistant to attack by substances released by macrophages and mast cells. however, these parasites can become coated with ige and recognized by fcεrii on the surface of eosinophils. activated eosinophils release preformed mediators such as major basic protein, and enzymes such as peroxidase, against which helminths are not resistant. the interaction of the fcεrii receptor with the fc portion of helminth bound ige causes the eosinophil to release these molecules in a mechanism similar to that of the nk cell during adcc. on t lymphocytes cd4+ t cells (mature th cells) provide help to b cells that produce antibodies. several subsets of activated effector cd4+ t cells are observed in disease pathology. earlier studies summarized by sanders and lynch in 1993 suggested critical roles for fcrs in cd4+ t cell mediated immune responses and proposed the formation of a joint signaling complex among fcrs and tcr on the cell surface. chauhan and coworkers reported the colocalization of the labeled ics with the cd3 complex on activated cd4+ t cell surface, which thus suggest the coexistence of fcrs together with tcr complex. both of these receptors are observed forming an apical structure on the membrane of activated cd4+ t cells, suggesting the lateral movement of these receptors. co-migration of fcrs with tcr and bcr complex is observed on the cells surface and t:b cell cytoconjugates show this coexistence at the point of contact. an earlier review suggested that the expression of fcrs on cd4+ t cells is an open question. this established the current paradigm that t cells do not express fcrs and these findings were never challenged and experimentally tested. chauhan and coworkers showed binding of immune complexes (ics), the fcr ligand to activated cd4+ t cells. cd16a expression is induced in the activated human naïve cd4+ t cells, which express cd25, cd69, and cd98 and ligation to ics leads to generation of effector memory cells. cd16a signaling is mediated by phosphorylation of syk (psyk). a study now suggests induced expression of cd32a upon activation of human cd4+ t cells, similar to cd16a. cd32a expression on cd4+ t cells was also suggested by three independent studies from hiv-1 researchers. the expression of cd16a and cd32a in a subset of activated cd4+ t cells is now confirmed. fcrs on the cell surface upon binding to ics composed of nucleic acids trigger cytokine production and upregulate nucleic acid sensing pathways. fcrs are present both on the cell surface and in the cytosol. cd16a signaling upregulate the expression of nucleic acid sensing toll-like receptors and relocate them to cell surface. cd16a is a new costimulatory signal for human cd4+ t cells, which successfully substitute the cd28 requirement during autoimmunity. in an autoimmune background cd4+ t cells bypass the requirement of cd28 cosignaling to become fully activated. furthermore, the blockade of cd28 cosignaling does not inhibit the development of tfh cells, a key subset for the generation of autoantibody producing autoreactive plasma b cells. a balance among costimulatory and inhibitory signals is required for immune homeostasis. excessive costimulation and/or insufficient co-inhibition leads to the tolerance-breakdown and autoimmunity. cd16a mediated costimulation provides a positive signal in the activated cd4+ t cells and not in the quiescent cells which lack fcγr expression.