Regulation of the immune response--lessons from transgenic models.
Generation of the immune antigen receptor repertoire by means of semi-random recombination requires a mechanism for ensuring that self reactivity is constrained. A model is presented which accounts not only for the generation of self tolerance during ontogeny but also for regulation of tolerance and immunity in peripheral immune responses. The model proposes a hierarchy of immune regulation in which antigen presenting cells (APCs) determine the responses of T cells and T cells those of B cells. APCs respond to environmental triggers such as microbes, particulate antigen and tissue injury by becoming highly immunogenic for T cells. At other times, APCs can either be non-stimulatory or tolerogenic, depending on their environment. The model suggests that during ontogeny T and B cells mature in a tolerogenic environment in the thymus and bone marrow, thus ensuring that immunological tolerance results from early contact with self antigen.
Fazekas de St Groth
B
B
Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW.
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics* / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D011948:Receptors, Antigen, T-Cell