18. IMMATURE
DC
Antigen capturing
phenotype
Encounter with Ag
MATURE DC
Antigen
presenting
phenotype
•LOSS OF PHAGOCYTOSIS AND LARGE SCALE
PINOCYTOSIS
•GAIN OF ANTIGEN PRESENTING FUNCTION
•GAIN OF EXPRESSION OF COSTIMULATORY
MOLECULE
22. T-Lymphocyte
• TCR- only processed Ag, typically peptides
• MHC- The processed Ag have to be bound to
this cell membrane Glycoprotein complex:
CD4+ with MHC class II, CD8+ with MHC class I
• Activation of T-cell
23.
24. Three signals are required for activation of a naïve T cell.
1. The TCR/MHC-peptide interaction, along with CD4 and CD8 co-receptors and
adhesion molecules, provide Signal 1.
2. Co-stimulation by a separate set of molecules, including CD28 provide Signal 2.
3. Together, Signal 1 and Signal 2 initiate a signal transduction cascade that results
in activation of transcription factors and cytokines (Signal 3) that direct T-cell
proliferation (IL-2) and differentiation (polarizing cytokines).
(Cytokines can act in an autocrine manner, by stimulating the same cells that produce them,
or in a paracrine manner, by stimulating neighbouring cells.)
25.
26. Regulation of Immune system
TOLERANCE
CENTRAL
PERIPHERAL
ANTIGEN
SEQUESTRATION
IMMUNE
PRIVILEGED
IMMUNOSUPPRESSIVE
MICRO-ENVIRONMENT
28. May be induced to have increased
FOXP3 expression l/t development
of iTREG cells
-Cytokines eg TGFβ in
GALT
-Chr Ag exposure eg gut
flora or food
-Lack of co-stimulation
-Presence of immature
dendritic cells
29. REGULATORY T-CELL
CD4+ Treg cells
• Express high levels of IL-2Rα
aka CD25 which is a low
affinity receptor for IL-2
• It prevents binding of IL-2 with
other high affinity IL-2
receptors
• It also discourages expansion
of local immunostimulatory
effector T-cells
• Acts against both self and
non-self anigen
CD8+ Treg cells
• Some T-cells, from
Thymocytes, when come to
peripheral blood, they
increase expression of
FOXP3 being stimulated by
cytokines eg. TGF-β
• Minority of CD8+ cells
directly become nTreg cell
30. COSTIMULATORY SIGNAL
• T-cell activation signaling is manifold.
• Two-signal hypothesis (Quill and Schwartz,
1987)- TCR-MHC interaction of a naïve T-cell in
absence of functional APC renders T-cell non-
responsive – ANERGY
• Clonal Anergy results if a Costimulatory
Signal Is Absent
31.
32. • CD28 acts as co-stimulatory receptor and
CD80/86 its ligand;
• Negative co-stimulator receptor: CTLA-4, PD-1,
BTLA
• Effector T-cells up-regulate negative co-
stimulatory receptors at the end of an immune
response, when proliferation is no longer
advantageous, whereas naïve Ts don’t.
35. In next class we will find answer of
• How this complex immune system fails, and
auto-immune response ensues?
• Where lies the problem?
• What are various of auto-immune disorders?
• Why women are more susceptible than men?
and ………………………………….. many newer aspects
