Regulation of the immune response

Signalling in the immune system involves cell-cell interactions, but this is not unique to the immune system. Cell-cell interactions are also involved in signalling and cellular differentiation in the nervous system, establishing the interconnectivity of neurons. 

Antigen-specific activation of T and B lymphocytes follows, in principle, a pattern not much different from activation of cells by growth factors and cytokines. The antigen is the 

The major difference between T cells and B cells is that the former recognize antigens only when they are displayed on the surface of another cell, whereas B cells accept cell free, particulate and soluble antigens. Here the focus will be on T cells. 

Differentiation of lymphocytes produces cells with different functions, such as B cells, and T helper and killer cells. The former produce and secrete antibodies, releasing them into Ijrmph and blood, the latter are responsible for the cellular immune response. The response of T cells is antigen-spedfic, just like the response of B cells. But, T cells interact with another cell in the body, the antigen-presenting cells (APCs), which have taken up and processed the foreign antigen. Helper T cells react with APCs and killer T cells 

MHC molecules are polymorphic. Each individual has five or more gene loci encoding MHC molecules. Each dimeric MHC molecule binds only one ligand. Although there is only a limited number of structures of MHC molecules, perhaps 20, MHC molecules are able to bind to every conceivable structure, to a very large number of different peptides and carbohydrates and unnatural, synthetic molecules. The X-ray crystallographic structure helps to explain this (Fig. 14.2). i° 

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King, C.L. and Nutman, T.B. (1991) Regulation of the immune response in lymphatic filariasis and onchocerciasis. Immunology Today 12, A54-58. 

Maizels RM, Yazdanbakhsh M Regulation of the immune response by helminth parasites cellular and molecular mechanisms. Nat Rev Immunol 2003 3 733-743. 

Alexander WS, Hilton DJ. 2004. The. role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Ann Rev Immunol. 22 503-529. 

Anti-idiotypic and antiergotypic Treg cells are activated after T-cell vaccination and are regulators of the immune response. The Treg cells induced by activated... 

R7. Reinherz, E. L., and Schlossman, S. F., Current concepts in immunology Regulation of the immune response—Inducer and suppressor T-lymphocyte subsets in human beings. N. Engl. J. Med. 303, 370-373 (1980). 

Another role for PKs was revealed in hematopoiesis and in regulation of the immune response and in cardiomiocytes survival. They promote survival and differentiation of the granulocytic and monocytic lineage as well as stimulate hematopoietic cell mobilization. PKs, via Akt activation, protect cardiomyocytes against oxidative stress and rescue the myocardium against myocardial infarction in mouse model (Urayama et al., 2007). 

Metz, C. N., and Bucala, R. (1997). Role of macrophage migration inhibitory factor in the regulation of the immune response. Adv. Immunol. 66, 197-223. 

Weber RJ, Ikejhi B, Rice KC, Pert A, Hagan A A (1987) Opiate receptor mediated regulation of the immune response in vivo. NIDA Res Mono Ser 48 341—348. 

Morgan EL, Thoman ML, Weigle WO, Hugh TE (1983) Ana-phylatoxin-mediated regulation of the immune response 11. C5a-mediated enhancement of human humoral and T cell-mediated immune responses. 1 Immunol 130 1257-1261. 

D. H. Irvine and M. A. Savagean, Network regulation of the immune response modulation of suppressor lymphocytes by alternative signals including contrasuppression. J Immunol 134(4) 2117-2130 (1985). 

Berdyshev et al. (1997) examined the effects of anandamide, palmitoylethanolamide and THC on the production of TNF-a, IL-4, IL-6, IL-8, IL-10, IFN-y, p55, and p75 TNF-a soluble receptors expressed by stimulated human peripheral blood mononuclear cells as well as [ H]-arachidonic acid release by non-stimulated and N-formyl-Met-Leu-Phe (fMLP)-stimulalcd human monocytes. Anandamide diminished IL-6 and IL-8 production at low nanomolar concentrations and inhibited the production of TNF-a, IFN-y, IL-4, and p75 TNF-a soluble receptors at higher concentrations (i.e., micromolar levels). Palmitoylethanolamide inhibited IL-4, IL-6, and IL-8 synthesis and the production of p75 TNF-a soluble receptors at concentrations similar to those of anandamide but did not affect TNF-a and IFN-y production. Neither anandamide nor palmitoylethanolamide influenced IL-10 synthesis. THC, on the other hand, exerted a biphasic effect on pro-inflammatory cytokine production. TNF-a, IL-6, and IL-8 synthesis was inhibited maximally by 3 nM THC but stimulated by 3 pM THC. A similar effect was observed for IL-8 and IFN-y. The level of IL-4, IL-10, and p75 TNF-a soluble receptors was diminished by 3 pM THC. [ H]-Arachidonate release was stimulated only by high THC and anandamide concentrations. Based on these observations, the investigators suggested that the inhibitory properties of anandamide, palmitoylethanolamide, and THC are determined by the activation of peripheral-type cannabinoid receptors (i.e., CB2) and that various endogenous fatty acid ethanolamides also participate in the regulation of the immune response. 

Irvine, D. H. Savageau, M. A. (1985a). Network regulation of the immune response alternative control points for suppressor modulation of effector lymphocytes. J. Immunol. 134,2100-2116. 

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