MOLECULES INVOLVED MOLECULES INVOLVED IN CELLULAR IN CELLULAR INTERACTIONINTERACTION

CYTOKINESCYTOKINES

Low molecularLow molecular Soluble protein messengersSoluble protein messengers Common subunit receptors (heterodimers)Common subunit receptors (heterodimers)

Lymphocyte derived Lymphocyte derived lymphokinelymphokine

Monocyte derived Monocyte derived MonokineMonokine

Involved ın leukocyte interaction Involved ın leukocyte interaction InterleukinesInterleukines

Affecting the secreting cell Affecting the secreting cell Autocrine Autocrine Affecting nearby cells Affecting nearby cells Parecrine Parecrine Affecting distant cells Affecting distant cells Endocrine Endocrine

Thee effects of the cytokines may be:Thee effects of the cytokines may be:- AntagonisticAntagonistic- AdditiveAdditive- SynergisticSynergistic

ChemokinesChemokines

Chemoatractant cytokinesChemoatractant cytokines

4 types:4 types:

CC

CCCC

CXCCXC

CX3CCX3C

Molecules involved in innate Molecules involved in innate immunityimmunity

TNF-alphaTNF-alpha IL-1IL-1 IL-10IL-10 IL-12IL-12 Type I interferonsType I interferons IFN-gammaIFN-gamma ChemokinesChemokines

Molecules involved in adaptive Molecules involved in adaptive immunityimmunity

IL-2IL-2 IL-4IL-4 IL-5IL-5 TGF-betaTGF-beta

Adhesion moleculesAdhesion molecules

Stable cell contactStable cell contact Types:Types:• Integrines: Combinations of alpha and Integrines: Combinations of alpha and

beta chains interacting with molecules of beta chains interacting with molecules of IG-superfamilyIG-superfamily

• Selectins and addressins: Trafficking Selectins and addressins: Trafficking leukocytes to certain tissue and/organsleukocytes to certain tissue and/organs

Cluster of differentiation moleculesCluster of differentiation molecules

> 250 molecules> 250 molecules CD4CD4 CD8CD8 CD3 (TCR)CD3 (TCR)

Signal transduction moleculesSignal transduction molecules

JAK-STAT pathway:JAK-STAT pathway: RAS-MAP KINASE pathway: RAS-MAP KINASE pathway:

ImmunoregulationImmunoregulation

Anergy (absence of co-stimulation during the Anergy (absence of co-stimulation during the antigen recognition)antigen recognition)

Downregulation of the T cell activation (CTLA-Downregulation of the T cell activation (CTLA-4+B7)4+B7)

Activities of the cytokinesActivities of the cytokines Idiotype-anti-idiotype interactionsIdiotype-anti-idiotype interactions

Soluble ABsSoluble ABsoccupy occupy B cell receptorsB cell receptors

AB-AG complex AB-AG complex bind to Fcreceptors of bind to Fcreceptors of B cells B cells Inhibitory Inhibitory signals for B cellssignals for B cells

TregsTregs

CD4+CD25+FoxP3CD4+CD25+FoxP3 5-10 % of peripheral CD4 + cells5-10 % of peripheral CD4 + cells Selected ın tymusSelected ın tymus- Naturally occuring Treg: Contact-Naturally occuring Treg: Contact-

dependent supressiondependent supression- Induced Treg: Induced by antigen or TGF-Induced Treg: Induced by antigen or TGF-

beta or IL-10 (beta or IL-10 ( Tr1 cells) Tr1 cells) - CD8+ Treg (supressor T cells – Ts): Can CD8+ Treg (supressor T cells – Ts): Can

be induced by IL-10 or antigen be induced by IL-10 or antigen

TOLERANCETOLERANCE

Self tolerance: Positive and negative Self tolerance: Positive and negative selection in tymus (clonal deletion)selection in tymus (clonal deletion)

Non-self tolerance: May be induced Non-self tolerance: May be induced (different Ag administration route; (different Ag administration route; induction by mo.)induction by mo.)

Large, aggegated, complex molecules, SC Large, aggegated, complex molecules, SC or IM administration, optimal dose, older or or IM administration, optimal dose, older or mature host, presence of fully mature host, presence of fully differantiated cells (memory B and T cells) differantiated cells (memory B and T cells)

-- favor immune response favor immune response

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

INDUCTION OF THE TOLERANCEINDUCTION OF THE TOLERANCE- Clonal deletionClonal deletion- Clonal anergyClonal anergy- Clonal ignorenceClonal ignorence- Anti-idiotype antibodiesAnti-idiotype antibodies

AutoimmunityAutoimmunity

Breakdown of self toleranceBreakdown of self tolerance Genetic predispositin (HLA B8, B27, Dr2, Genetic predispositin (HLA B8, B27, Dr2,

Dr3, Dr4, Dr5,…)Dr3, Dr4, Dr5,…)

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