For normal functioning of organism inhibition of the immune system is as much required as activation. The following examples are to elucidate this statement. After pathogen elimination and excretion from the organism the immune response subsides in a natural way: immune response suppression is being developed. As for immune response to self tissues, it is prevented by immunological tolerance. Inhibition of the immune system is very important for such human interventions as organ and tissue transplantations.
INHIBITORY RECEPTORS
At least 15 membrane molecules are known as negative coreceptors, i.e. able to modulate (inhibit) cell activation stimulated by other Rc. Inhibitory Rc comprise a family of Signal-Regulatory Proteins (SIRP) of immunoglobulin superfamily.
• Tyrosine-based inhibitory sequences. All Rc of SIRP family contain in their cytoplasmic sites 1-4 Immunoreceptor Tyrosine-based Inhibitory Motifs (ITIM). These negative receptors accompany all Rc for growth factor as well as Rc for hormones (e.g. insulin) interacting with tyrosine kinase within a cell.
• The following inhibitory receptors are known:
♦ PIR-B (Paired Immunoglobulin-like Receptors of B-lymphocytes). PIR-B on B-lymphocytes and CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) on T-lymphocytes are bound by SHP-1/2 inhibitory phosphatase blocking activation of Tec kinase-family and PLCy phospholipase.
♦ KIR (Killer cell immunoglobulin-like Receptor). Rc of KIR family on CTL and NK recognize MHC-I molecules and inhibit various types of cytotoxicity.
♦ FcyRIIB-1/2 on B-lymphocytes and leukocytes of myeloid lineage recognize IgG-Ag complexes and inhibit AB production and leukocyte activation.
APOPTOSIS
Apoptosis (from Greek word 'apoptosis' - leaf-fall) is programmed (regulated) cell death by degradation of its components (including chromatin condensation and DNA fragmentation) and further phagocytosis by