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MOLECULES INVOLVED IN CELLULAR INTERACTION

MOLECULES INVOLVED IN CELLULAR INTERACTION. CYTOKINES. Low molecular Soluble protein messengers Common subunit receptors (heterodimers) Lymphocyte derived  lymphokine Monocyte derived  Monokine Involved ın leukocyte interaction  Interleukines.

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MOLECULES INVOLVED IN CELLULAR INTERACTION

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  1. MOLECULES INVOLVED IN CELLULAR INTERACTION

  2. CYTOKINES • Low molecular • Soluble protein messengers • Common subunit receptors (heterodimers) Lymphocyte derived  lymphokine Monocyte derived  Monokine Involved ın leukocyte interaction  Interleukines

  3. Affecting the secreting cell  Autocrine • Affecting nearby cells  Parecrine • Affecting distant cells  Endocrine Thee effects of the cytokines may be: • Antagonistic • Additive • Synergistic

  4. Chemokines • Chemoatractant cytokines 4 types: C CC CXC CX3C

  5. Molecules involved in innate immunity • TNF-alpha • IL-1 • IL-10 • IL-12 • Type I interferons • IFN-gamma • Chemokines

  6. Molecules involved in adaptive immunity • IL-2 • IL-4 • IL-5 • TGF-beta

  7. Adhesion molecules •  Stable cell contact • Types: • Integrines: Combinations of alpha and beta chains interacting with molecules of IG-superfamily • Selectins and addressins: Trafficking leukocytes to certain tissue and/organs

  8. Cluster of differentiation molecules • > 250 molecules • CD4 • CD8 • CD3 (TCR)

  9. Signal transduction molecules • JAK-STAT pathway: • RAS-MAP KINASE pathway:

  10. Immunoregulation • Anergy (absence of co-stimulation during the antigen recognition) • Downregulation of the T cell activation (CTLA-4+B7) • Activities of the cytokines • Idiotype-anti-idiotype interactions

  11. Soluble ABsoccupy B cell receptors • AB-AG complex  bind to Fcreceptors of B cells  Inhibitory signals for B cells

  12. Tregs • CD4+CD25+FoxP3 • 5-10 % of peripheral CD4 + cells • Selected ın tymus • Naturally occuring Treg: Contact-dependent supression • Induced Treg: Induced by antigen or TGF-beta or IL-10 ( Tr1 cells) • CD8+ Treg (supressor T cells – Ts): Can be induced by IL-10 or antigen

  13. TOLERANCE • Self tolerance: Positive and negative selection in tymus (clonal deletion) • Non-self tolerance: May be induced (different Ag administration route; induction by mo.)

  14. Large, aggegated, complex molecules, SC or IM administration, optimal dose, older or mature host, presence of fully differantiated cells (memory B and T cells) - favor immune response

  15. Soluble, smaller, less complex Ag, Ag not presented y APC or processed by cells without MHC class II, oral or IV administration, large doses, immature or new-borne host, relatively undifferentiated cells - favor tolerance.

  16. INDUCTION OF THE TOLERANCE • Clonal deletion • Clonal anergy • Clonal ignorence • Anti-idiotype antibodies

  17. Autoimmunity • Breakdown of self tolerance • Genetic predispositin (HLA B8, B27, Dr2, Dr3, Dr4, Dr5,…)

  18. - Sequestered antigens: • Clonal escape of autoreactive T cells • Lack of Treg • İnfluence of infections:

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