PRINCIPLES OF TOXICOLOGY - Biology East Borneo

192 IMMUNOTOXICITY: TOXIC EFFECTS ON THE IMMUNE SYSTEMTABLE 10.1 Cytokines and their FunctionsCytokineProduced byIL1(IL1-α andIL1-β)Several cell types, includingneutrophils andmacrophagesFunction(s)Variety of effects, including neutrophil and macrophageactivation, T- and B-cell chemotaxis, and increased IL2and IL6 productionIL2 T cells Stimulates replication of T cells, NK cells, and B cellsIL3 T cells Involved in regulation of progenitor cells for severaldifferent cell types, including granulocytes, macrophages,T cells, and B cellsIL4 Activated T cells Activates T and B cells; suppresses synthesis of IL1 andTNFIL5 T cells and activated B cells Increases secretion of immune globulins by B cellsIL6Several cell types, including Tand B cellsImportant in inflammatory reactions and in differentiationof B cells into Ig-secreting cellsIL7 Bone marrow stromal cells Important in regulating lymphocyte growth anddifferentiationIL8Activated monocytes andmacrophagesActivates neutrophils; important for chemotaxis ofneutrophils and lymphocytesIL9 TH cells Stimulates growth of TH cellsIL10 B cells Stimulates growth of T cells in the presence of IL2 and IL4TNF-α Variety of cells, primarily Important in inflammatory responses; effects similar to IL1activated macrophagesTGF-β Variety of cells Inhibits T-cell proliferation and suppresses inflammatoryresponsesTNF-β Activated CD4+ cells (TH) Important in mediating cytotoxic immune responses, celllysisInterferonsLeukocytes (INF-α),fibroblasts (INF-β), andlymphocytes and NK cells(INF-γ)(INF): Neoplastic growth inhibitor; activates macrophages;protects against viral infections by interfering with viralprotein synthesisis afforded by long-lived cells that become activated only following repeat exposure to the antigen orimmunization. While it has been assumed that “ memory cells” last indefinitely following a singleantigen contact, recent evidence suggests the life-span of memory cells may be related to repeat contactwith antigen.In order to be recognized by the immune system, antigens must be of appreciable size. Someof the smallest antigens, for example, are natural substances with molecular weights in the lowthousands. There are circumstances where much smaller molecules can elicit an immune response,but this requires the participation of a large molecule to serve as a carrier. For example, somemetals, drugs, and organic environmental and occupational chemicals too small to be recognizedby the immune system can become antigenic when bound to a macromolecule such as a protein.Once the immune response has been initiated, antibodies will recognize and bind the smallmolecule even when it is not bound to the carrier molecule. In situations such as this, the smallmolecule is called a hapten.The antibodies themselves are glycoproteins, the basic unit of which consists of two pairs ofpeptide chains (see Figure 10.1) connected by disulfide bonds. The longer peptide chain is termedthe heavy (or H) chain and the shorter is the light (or L) chain. There are five main types ofantibodies, or immunoglobulins (Ig): IgG, IgM, IgA, IgE, and IgD. They differ both in structureand function. IgG is present in the greatest concentration in serum, has a molecular weight ofaround 150,000 (there are four subtypes of somewhat different sizes), and is important insecondary immune responses. IgM is a primary response antibody, meaning that it is increased