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Understanding Cellular Interaction: Cytokines and Molecules in Immunity

Explore the role of cytokines in cellular interactions, including lymphokines and monokines, and molecules involved in innate and adaptive immunity. Learn about adhesion and signal transduction molecules, immunoregulation, Tregs, tolerance induction, and autoimmune factors.

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Understanding Cellular Interaction: Cytokines and Molecules in Immunity

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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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