Lymphokine

One component of the age-ielated decline in immune function is decreased production of the lymphokine that promotes the growth of T-ceUs, interleukin 2 (IL-2). Administration of recombinant-derived IL-2, both in vitro and in vivo, appears to restore certain immune functions in aged mice. Recovery of T-regulatory effects on B-ceU differentiation has been reported in human cells from elderly patients treated with IL-1 and/or IL-2 (42). Similar effects have been observed in the presence of the pentapeptide thymopentin [69558-55-0] (Arg Lys Asp Val Tyr), a weU-known IL-2 inducer. Recombinant IL-2 adrninistered to aged mice for three weeks has been shown to correct the T-ceU functional deficiency associated with antigen-specific immunoglobulin production by certain lymphoid tissue (43). 

Tissue plasminogen activators Human growth hormone Neuroactive peptides Regulatory peptides Lymphokines Human serum albumin Gamma globulin Antihemophilic factors Monoclonal antibodies... 

In addition to effects mediated through glucocorticoid secretion (stress-related), a hypothetical mechanism for direct immunotoxicity of organophosphates is the inhibition of esterases and stabilization of the lysosomal membrane of lymphocytes, thus blocking release of lymphokines (Sharma and Reddy 1987). 

Walker CM, Levy JA (1989) A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication. Immunology 66 628-630 Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, Lehman SF, Palensky J, Wittes J, Davey RT, Falloon J, Polls MA, Ko-vacs JA, Broad DF, Levine BL, Roberts MR, Masur H, Lane HC (2000) Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96 467 74... 

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

These are supplied by the secretion of peptide molecules (termed cytokines or lymphokines) fiom a subset of the T-cell family (the helper T cells, TH cells). These peptide molecules (interleukins (IL) 2,4,5 and 6) stimulate the B cells to proliferate, undergo clonal expansion and mature into plasma cells which secrete antibody and also into the longer-hving, non-dividing memory cells. 

These are the eentral eells of the immune system as they are essential for activation of the other eells assoeiated with an effeetive immune response hy the secretion of peptide mediators termed eytokines. Cytokines produeed hy macrophages and monocytes are termed monokines whilst those produeed hy lymphocytes are termed lymphokines. TH eells express CD4 on their surfaee. 

T cells responsible for delayed-type hypersensitivity seerete lymphokines whieh recruit and activate non-specific cells like maerophages into the area of the reaetion. Examples of some of these lymphokines are listed below. 

A macrophage chemotactic factor (MAC) which causes an aeeumulation of mononuclear phagoeytes at the site of the antigen-mediated lymphokine release. 

The Arthus reaction. The phenomenon is a local one and occurs if a soluble antigen is introduced into the body when there is a great excess of antibody. The union between the two results in an acute inflammatory reachon which may involve complement, polymorphs, lymphokines or platelet aggregation, all of which enhance the inflammatoiy response. 

In humans, the structural gene locus is on chromosome 19 (M17), and the gene spans over 40 kilobases (kb) including 18 exons and 17 introns (W2, X2). Neu-roleukin, a protein that acts as both a neurotrophic factor and a lymphokine, has been isolated from mouse salivary glands (G7), and subsequently the primary structure of neuroleukin was found to be identical to that of GPI by comparison of the cDNA sequences (C7, FI). The cDNA sequence encodes 558 amino acid residues. The enzyme consists of two identical subunits with a molecular weight of approximately 63,000 and neuroleukin is active as a monomer. 

Grencis, R.K, Hiiltner, L. and Else, K.J. (1991) Host protective immunity to Trichinella spiralis in mice activation of Th cell subsets and lymphokine... 

Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A. and Coffman, R.L. (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. Journal of Immunology 136, 2348-2357. 

Seder, RA., Paul, W.E., Davis, M.M. and Farekas de St Groth, B. (1992b) The presence of interleukin 4 during in vitro priming determines the lymphokine producing potential of CD4+ T cells from T cell receptor transgenic mice. Journal of Experimental Medicine 176, 1091—1098. 

These are called delayed hypersensitivity reactions since they normally occur 6-24 hours after exposure. A cell-mediated allergy involves the interaction of food allergens with sensitised lymphocytes, which usually occurs in the gastrointestinal tract. The sensitised lymphocytes produce lymphokines and the generation of cytotoxic T lymphocytes. These latter cells destroy other intestinal cells, including the epithelial cells that are critical for absorption. 

The term cytokine was first introduced in the mid 1970s. It was applied to polypeptide growth factors controlling the differentiation and regulation of cells of the immune system. The interferons and interleukins represented the major polypeptide families classified as cytokines at that time. Additional classification terms were also introduced, including lymphokines (cytokines such as IL-2 and IFN-y, produced by lymphocytes) and monokines (cytokines such as TNF-a, produced by monocytes). However, classification on the basis of producing cell types also proved inappropriate, as most cytokines are produced by a range of cell types (e.g. both lymphocytes and monocytes produce IFN-a). 

A third biological activity of IL-2 pertinent to immunostimulation is its ability to promote the growth of NK cells. It also promotes further differentiation of NK cells, forming lymphokine-activated killer (LAK) cells, which exhibit an enhanced ability to kill tumour cells or virally infected cells directly. NK cells express the P and y IL-2 receptor subunits only thus, their stimulation by IL-2 requires elevated concentrations of this cytokine. NK cells are also activated by a variety of additional cytokines, including all interferons and TNF. 

Immunoglobulins (Igs) can activate the complement system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. The processed antigen is recognized by the major histocompatibility complex proteins on the lymphocyte surface, resulting in activation of T and B cells. 

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