Natural Inhibition of Immune Response

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Natural Inhibition of Immune Response

  • After coming to the peak of highest intensity, immune reactions gradually fade. Clonal expansion of immunocytes results in the formation of long-living memory T- and B cells that come into a dormant state until the next antigenic challenge. This dampens overexuberant or detrimental immune reactivity thus preventing autoimmune disorders.
  • There are numerous versatile mechanisms of natural inhibition and restriction of the immune response.
  • Normally all secreted cytokines are short-living substances. They render discernible activity only within the limited space affecting the cell itself and/or neighbouring cells. This prevents undesirable immune expansion.
  • Furthermore, multiplex interrelationships within the cytokine network are characterized by reciprocal suppression of their actions.
  • For instance, IL-4 precludes Th1 differentiation and next cell-mediated response, whereas IL-12 inhibits Th2 thereby down-regulating humoral immunity; IL-10 blocks literally all pro-inflammatory cytokines; potent inhibitory activity is proven for TGF-beta (transforming growth factor-beta) cytokine.
  • In addition, cell activation terminates after the change of superficial costimulatory molecules. While CD80/86 promotes Th differentiation via CD28, later substitution of CD80/86 with CD152 inhibits further proliferation of T helpers.
  • And finally, many of activated cell subsets (e.g., plasma cells) raise the expression of apoptosis receptor CD95. It causes their programmed death, for example, after interaction with regulatory T lymphocytes, bearing specific CD95L.
  • It has been established quite recently that the group of regulatory T cells includes diverse T cell populations endowed with powerful suppressive function.
  • After coming to the peak of highest intensity, immune reactions gradually fade. Clonal expansion of immunocytes results in the formation of long-living memory T- and B cells that come into a dormant state until the next antigenic challenge. This dampens overexuberant or detrimental immune reactivity thus preventing autoimmune disorders.
  • There are numerous versatile mechanisms of natural inhibition and restriction of the immune response.
  • Normally all secreted cytokines are short-living substances. They render discernible activity only within the limited space affecting the cell itself and/or neighbouring cells. This prevents undesirable immune expansion.
  • Furthermore, multiplex interrelationships within the cytokine network are characterized by reciprocal suppression of their actions. For instance, IL-4 precludes Th1 differentiation and next cell-mediated response, whereas IL-12 inhibits Th2 thereby down-regulating humoral immunity; IL-10 blocks literally all pro-inflammatory cytokines; potent inhibitory activity is proven for TGF-beta (transforming growth factor-beta) cytokine.
  • In addition, cell activation terminates after the change of superficial costimulatory molecules. While CD80/86 promotes Th differentiation via CD28, later substitution of CD80/86 with CD152 inhibits further proliferation of T helpers.
  • And finally, many of activated cell subsets (e.g., plasma cells) raise the expression of apoptosis receptor CD95. It causes their programmed death, for example, after interaction with regulatory T lymphocytes, bearing specific CD95L.
  • It has been established quite recently that the group of regulatory T cells includes diverse T cell populations endowed with powerful suppressive function.
  • The number of adaptive regulatory T cells is activated directly after antigenic challenge. Among them are CD4(+) Tr1 lymphocytes, producing IL-10, Th3 cells, secreting TGF-beta, and some others.
  • Another substantial part of T lymphocytes (more than 3% of total T cell count) is primarily differentiated as regulatory suppressor cells. They demonstrate striking inhibitory capacity contributing to immune reactions as natural regulatory T cells (T regs). Molecular markers of this cell type are CD4 and CD25 that are co-expressed together upon the cell membranes.
  • Unlike other lymphocytes, natural regulatory T cells contain an active form of specific transcriptional factor Foxp3. It is encoded by X chromosome foxp3 gene Н – a special molecular label for this cell subset.
  • During recognition of Ags presented by DCs natural regulatory T cells expose inhibitory molecule CTLA-4 (CD-152). This leads to silencing of cell activation and prevents effective co-stimulation of other T cells by APCs.
  • Furthermore, natural regulatory lymphocytes produce large amounts of suppressive cytokines TGF-beta and IL-10 that averts the proliferation of reactive cell populations.
  • Another way of immune control is realized by idiotypic network regulation. Any antigen that encounters with the immune system triggers a polyclonal immune response, i.e., stimulates the production of specific Abs and TCRs by various cell clones.
  • They display similar but not identical specificity and affinity. It means that generated Abs and receptors have minor structural differences in their antigen-binding sites.
  • Therefore, active sites of newly appeared Abs and receptors would bear unique antigenic determinants (named idiotopes) that specify only one certain clone of immune cells. The total number of idiotopes carried by a single molecule of antibody was termed idiotype.
  • The first generation of Abs raised against specific Ag during the immune response was named idiotypic (i.e. bearing idiotype). Once appeared, idiotypic Abs start to trigger the second generation of Abs against their own active sites (so-called anti-idiotypic Abs). The latter inhibits overexpression of primary idiotypic Abs, receptors and cell clones.
  • Number of adaptive regulatory T cells is activated directly after antigenic challenge. Among them are CD4(+) Tr1 lymphocytes, producing IL-10, Th3 cells, secreting TGF-beta, and some others.
  • Another substantial part of T lymphocytes (more than 3% of total T cell count) is primarily differentiated as regulatory suppressor cells. They demonstrate striking inhibitory capacity contributing to immune reactions as natural regulatory T cells (T regs). Molecular markers of this cell type are CD4 and CD25 that are co-expressed together upon the cell membranes.
  • Unlike other lymphocytes, natural regulatory T cells contain an active form of specific transcriptional factor Foxp3. It is encoded by X chromosome foxp3 gene Н – a special molecular label for this cell subset.
  • During recognition of Ags presented by DCs natural regulatory T cells expose inhibitory molecule CTLA-4 (CD-152). This leads to silencing of cell activation and prevents effective co-stimulation of other T cells by APCs.
  • Furthermore, natural regulatory lymphocytes produce large amounts of suppressive cytokines TGF-beta and IL-10 that averts the proliferation of reactive cell populations.
  • Another way of immune control is realized by idiotypic network regulation. Any antigen that encounters with the immune system triggers a polyclonal immune response, i.e., stimulates the production of specific Abs and TCRs by various cell clones.
  • They display similar but not identical specificity and affinity. It means that generated Abs and receptors have minor structural differences in their antigen-binding sites.
  • Therefore, active sites of newly appeared Abs and receptors would bear unique antigenic determinants (named idiotopes) that specify only one certain clone of immune cells. The total number of idiotopes carried by a single molecule of antibody was termed idiotype.
  • The first generation of Abs raised against specific Ag during the immune response was named idiotypic (i.e. bearing idiotype).
  • Once appeared, idiotypic Abs start to trigger the second generation of Abs against their own active sites (so-called anti-idiotypic Abs). The latter inhibits overexpression of primary idiotypic Abs, receptors and cell clones.