Cell-mediated immune responses

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