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 เช่�นเดี�ยวกับ TCR αβBut not express CD4/CD8-มักัพบใน epithelial tissue (intraepithelial
lymphocyte)-recognition : hypothesis
recognize Ag ที่��พบบ�อยบน 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, dendriticcell, 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 pathwaysin T lymphocyte
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
ที่��ไดี� 3 ว�ธี�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
-ต้�องกั�ร IL-12
-transcription factor :
T-bet & eomesodermin
-differentiated CTL secrete cytokine,
mostly IFN-, lymphotoxin, TNF
-cascade in differentiation same as
CD4
Effector of CD8+ T cellsteps 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
