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Cell-Mediated immune
          responses
           (Basic Immunology)



15/07/52
scope
-Phases of T Cell Responses
-Antigen Recognition and Costimulation
-Functional Responses of T Lymphocytes to
 Antigens and Costimulation
-T Cell Signal Attenuation
-Migration and retention of effector T cells at
 site of infection
Phases of T Cell Responses
Antigen Recognition and
     Costimulation
TCR complex and its restriction
Components of TCR complex
Ag receptor of γδT cells
-TCR γ & δ chain consist of extracellular Ig-like
V & C regions, hydrophobic transmembrane
segment, short cytoplasmic tail เช่นเดียวกับ TCR
  αβ
But not express CD4/CD8
-มักพบใน epithelial tissue (intraepithelial
  lymphocyte)
-recognition : hypothesis
  recognize Ag ที่พบบ่อยบน epithelial boundaries
  between host & external environment
Structure of CD4 and CD8 coreptor
Costimulatory receptors of CD28 &
    CD2 families &their ligand
Role of costimulators in T cell
              activation
-2nd signal
-absense : fail to respond & die by apoptosis or
 enter state of unresponsiveness (anergy)
-increase production of IL-2 & stabilize IL-2
 mRNA
-promote survival of T cell
Role of costimulators in T cell
              activation
1).CD28 bind to B7-1(CD80), B7-2(CD86) on
  APC (dendritic cell, macrophage), B cell

2).ICOS(inducible costimulator) : activate
production of IL-10

3)CTLA-4(CD152) : self tolerance
Others accessory molecule on T cells
-CD44 acidic sulfated membrane glycoprotein :
   mature T cell, thymocyte, B cell, macrophage,
   granulocyte, erythrocyte, fiboblasts
-bind to hyaluronate : retention T cell in extravascular
                       tissue at infection site
-binding of activated & memory T cell to endothelium
 at site of inflammation, in mucosal tissue
Others accessory molecule on T cells
                (con.)
-CD40 ligand express บน activated CD4 T cell
bind to CD40 บน B cell, macrophage, dendritic
cell, endothelial cell

-Ligand for Fas (CD95)
  -apoptosis
  -important for eliminating T cell that are
   repeated stimulated by Ag
Accessory molecules of T lymphocyte
Ligand-receptor pairs involved
     in T cell activation
Regulation of integrin avidity
Clonal expansion (proliferation)
Signal transduction pathways
      in T lymphocyte
Early tyrosine phosphorylation events
          in T cell activation
Early tyrosine phosphorylation events
          in T cell activation
T cell signaling downstream of
             PLCγ1
Ras-Map kinase pathway in
     T cell activation
Activation of transcription factors in T
                  cell
T cell signal attenuation
ทำำได้ 3 วิธี
  1).activation inhibitory receptor of CD28
  2).tyrosine-phospatases (SHP-1)
  3).protein known as E3 ubiquitin ligases
T cell signal attenuation
Ubiquitin ligase Cbl-b in terminating T
             cell responses
Differentiation of naïve T cell into
           effector cell
Development of Th1 and Th2 subset
Cytokine signaling by the Jak-STAT
             pathway
Characteristics of subsets of
       CD4+ T cell
Effector function of Th1 cells
Effector function of Th2 cells
Activation of CD8+ T cells
Differentiation of CD8 T cell into
                 CTL
-ต้องกำร IL-12
-transcription factor :
      T-bet & eomesodermin
-differentiated CTL secrete cytokine,
 mostly IFN-γ, lymphotoxin, TNF
-cascade in differentiation same as
 CD4
Effector of CD8+ T cell
steps in CTL-mediated lysis of target cell
Mechanisms of CTL-mediated lysis
         of target cells
Action and functions of
 macrophages in CMI
Migration and retention of effector
    T cells at site of infection
Migration of naïve and effector
        T lymphocytes
Recruitment of leukocyte
    at infection site
T cell homing receptors and their
            ligands
Thank you for your attention

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