Cellular Immune response Jianzhong Chen, Ph.D Institute of immunology, ZJU
Concept of adaptive immune response T cell-mediated adaptive immune response
I. Concept of immune response A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
1. Phases of T cell responses The response of T cells to antigens consist of a series of sequential steps that result in an increase in the number of antigen-specific T cells and the conversion of naïve T cells to effector T cells.
Three phases Antigen recognition phase Activation and differentiation phase Effector phase
2. Antigen recognition 1) Substances that induce T cell activation antigen (presented by APC) Superantigen mitogen (PHA, ConA, etc.) mab (anti-t cell surface molecules)
2) Double signals for T cell activation The first signal TCR-antigen peptide-mhc (double recognition) CD4-MHC II or CD8-MHC I The second signal (co-stimulatory signal) Interactions between co-stimulatory molecules on APC and corresponding receptors on T cells CD28/CTLA-4 B7, LFA-1 ICAM-1, LFA-2 LFA-3
Ligand-receptor pairs involved in T cell activation
Important properties of the major accessory molecules
The role of costimulation in T cell activation (A)
Anergic T cell The role of costimulation in T cell activation (B)
3. Signal transduction in T cell activation
gene expression of T cell cytokine gene expression cytokine receptor gene expression adhesion molecule gene expression MHC
4. Proliferation and differentiation of T cells 1) CD4 + T cells: Th, Tr, Tm regulated by cytokines 2) CD8 + T cells: Tc Th-dependent Th-independent: virus infected DC that highly express co-stimulatory molecules can directly stimulate CD8 + T cells.
Activation of CD8 + T cells
Cytokines are required in T cell proliferation and differentiation Activated T cells can produce cytokines (IL-2, 4, 7, 10, etc.) and express cytokine receptors, that promote T cells to proliferate and differentiate.
5. Effector functions of activated T cells 1) CD4 + T cells Th1: secrete IFN-γ, etc. Activate macrophages express CD40L express FasL, kill Fas + target cells effect on lymphocytes: IL-2 effect on neutrophil: TNF-α,β Th2: promote B cell growth and Ig production mediate hypersensitivity
activated Th1 cell IFN-γand CD40L FasL or TGF-β Lumen of blood vessel exudation chemoattractive Infected site activate Mφ to kill phagocyted bacterias kill infected cell and released bacterias were killed by Mφ induce T cell proliferation induce differentiation of bone marrow Mφ Induce Mφexudation by endothelial cell activation recruitment of Mφto local infected site Biological roles of Th1 cell secreted cytokines
Function of Th2 CD4 + T cell Regulate Mφ recruitment, inhibition:il-10/fasl/tgf-β B cell activation, Ig isotype switching
Function of Th17 CD4 + T cell Secret:IL-17/IL-22/IL-21 Inflammation,infection disease, autoimmune disease
Function of Tfh CD4 + T cell IL-21;CD40L,ICOS B cell activation, Ig isotype switching
2) CD8 + T cells Cytotoxicity: kill target cells a. necrosis: perforin and granzyme b. apoptosis: granzyme, FasL Characteristics of CD8 + T cell cytotoxicity a. Specificity b. MHC I restriction c. High efficiency
Mechanisms of killing of infected cells by CD8 + CTLs Downloaded from: StudentConsult (on 1 June 2006 03:50 PM) 2005 Elsevier
Two types of cell-mediated immunity
Cell-mediated immunity against intracellular microbes
T cell mediated immune response and immune effects antigen: TD-Ag cell: T cell and APC effect agent: Th/CTL(Tc) immune effects: anti-intracellular infection anti-tumor immunological injury DTH graft exclusion reaction autoimmune disease
6. Generation of memory T cells 1) CD45RA - CD45RO +, 2) Long-lived memory to specific antigen 3) Mediate faster, stronger and more effective immune response 4) Mechanism: remains elusive
Development of memory T cells.
7. Activation induced cell death, AICD 1) Activation induced cell death Activated T cells express FasL that induce apoptosis of Fas positive T cells. 2) Passive cell apoptosis Ag, survival signals and growth factors