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
the secreting cell  Autocrine
 Affecting nearby cells  Parecrine
 Affecting distant cells  Endocrine
 Affecting
Thee effects of the cytokines may be:
- Antagonistic
- Additive
- Synergistic
Chemokines
 Chemoatractant
4 types:
C
CC
CXC
CX3C
cytokines
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
• 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 (CTLA4+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: Contactdependent supression
- Induced Treg: Induced by antigen or TGFbeta 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: