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

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

Chemokines  Chemoatractant cytokines 4 types: CCCCXCCX3C

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

Molecules involved in adaptive immunity  IL-2  IL-4  IL-5  TGF-beta

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

Cluster of differentiation molecules  > 250 molecules  CD4  CD8  CD3 (TCR)

Signal transduction molecules  JAK-STAT pathway:  RAS-MAP KINASE pathway:

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

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

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

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

 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

 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.

 INDUCTION OF THE TOLERANCE - Clonal deletion - Clonal anergy - Clonal ignorence - Anti-idiotype antibodies

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

 - Sequestered antigens:  Clonal escape of autoreactive T cells  Lack of Treg  İnfluence of infections: