immunology07 上課定稿t cells

1、Lymphocytes(T cells)Maturation of lymphocytesderive from HSC（hemopoietic stem cell）in bone marrow T cells develop and mature in thymus and B cells in Bone marrow migrate to, and function in, the peripheral lymphoid organs and tissuesLymphocytesT LymphocytesB lymphocytesNatural cellskiller(NK)T lymph

2、ocytescell surface markers on T LymphocytesSubsetsof functionsTlymphocytesandtheirheterodimerTCR/CD3 compleximmunoreceptor tyrosine- based activation motifprotein tyrosine kinaseInhibition of T cell activation by CTLA-4Cell surface markers of T lymphocytes and their functionsTCR/CD3 complex:TCR(hete

3、rodimer): antigen recognization; CD3:signal transductionCD4 and CD8: T cell co-receptorCo-stimulatory molecules: CD28/CTLA4(for T), CD40L(for B)adhesion molecules: LFA-1、LFA-2cytokine receptors：IL-1R, IL-2R, IL-4R, IL-6R etc. mitogen receptorsfor PHA、Con A and PWMOthers：FcR (IgG、IgM)、complement rece

4、ptor(CR1) etc.T lymphocytescell surface markers on LymphocytesSubsetsof functionsTlymphocytesandtheirSubsets of T lymphocytesdistribute in skin and mucosa tissues Most gdT cells are double negative.Cytokine profile of CD4+ Th cell subsetsTh0Th1Th2High IL-2 Low IL-4 IFN-gIL-3 GM-CSFIL-3 GM-CSFIL-2 IF

5、N-g TNFa TNF-bIL-4 IL-5 IL-6 IL-10TGF-bInduction of Th1 cellsUncommitted Th cellTIL-12Th1MacrophageInduction of Th2 cellsUncommitted Th cellTIL-4Th2BRoles of Th1 cell cytokinesTh1IL-3GM-CSFGrowth of progenitor haemopoeitic cellsMyelopoiesis.IL-2 IFN-gT cell growth. Macrophage activation. Induction o

6、f MHC class II. Inhibition of Th2 cells CTL induction Macrophage activation Cytotoxicity.Macrophage activation. Neutrophil activation.TNFa TNF-bEffector functions of Th1 cellsIFN-gTh1MacrophageTh1 cellActivated macrophageIL-12Killing of intracellular bacteriaHelping B cell to produce antibodiesIFN-g

7、Th1BIL-12IFN-gIg-producing B cellComplement fixing muIgG2a muIgG 3?huIgG?Activated macrophageHelping pCTL to differentiate into effector CTLIL-2Th1IFN-gpCTLCTLLysis of targetInduction of CTL differentiation1. The functions of Th1 cellscytokines, such as IL-2、IFN-、TNF- etc；releaseactivate macrophages

8、 to kill intracellular pathogens;helpBcellstoproduceantibody(e.g.IgG2a),promoting phagocytosis by macrophages;help precursor of CTL differentiate into effector CTL;mainlymediatecellularimmunitytoagainstintracellular pathogens;involved in immunity to virus, antitumor, DTH, graft rejection and organ-s

9、pecific autoimmune diseases.Roles of Th2 cytokinesTh2IL-3GM-CSFGrowth of progenitor haemopoeitic cellsMyelopoiesis.IL-4B cell activation and growth. IgE isotype switch.Induction of MHC class II.T cell growth. Macrophage inhibition Eosinophil growthIgA isotype switch B cell growthAcute phase protein

10、releaseInhibits macrophage activation Inhibits Th1 cellsInhibits macrophage activationIL-5IL-6IL-10TGF-bEffector functions of Th2 cellsTh2Differentiation and developmentMast cellEosinophilEffector functions of Th2 cellsCD40-CD40L+ IL-4Th2Th0Ig isotype switch factorIgGCeIgEBIL-4 also enhances IgE, hu

11、IgG4 and muIgG1 isotype switchVDJCeVDJCg2. The functions of Th2 cells:IL-4、IL-5、IL-6、secreteIL-10；cytokines,suchasHelp B cells to produce antibodies (IgG1, IgG,Eetc.)Helpeosinophilandmastcellswithproliferation and differentiation；chieflymediatehumoralimmunitytocombatfree-living microorganisms;involv

12、ed in immunity to parasites, allergy and non-organ-specific autoimmune diseases.3. CD8+ CTLs or Tc cellsMostCTLsareCD8+andrecognizeantigenicpeptidespresentedonMHCclassI.Theyuseavarietyofdifferentmechanisms to kill their target cells:*Perforin/granzymepathway:inducenecrosis and apoptosis* Fas/FasL pa

13、thway: induce apoptosis*Cytokines: IFN-g, TNF-a and lymphotoxinCTL kill target cells by release of perforin and granzymesCTL induces apoptosis of target cells by FasL expressionFasLTarget cell infected by virusFasL expression by activated T cellInteraction of Fas- FasL induces target cell apoptosisO

14、ther Effector MechanismIFN-：inhibit viral replicationincrease expression of MHCTNF/：directlykill target cells4. Suppressor T cells (Ts)CD4+T suppressor cells：Tr: secrete IL-10 Th3: secret TGF-bTh1-Th2: they inhibit each otherIFN-gTh1Th2IL-4inhibitCD8+Tsuppressorcells:theantibodyproduction by B cells;DNTsuppressorcells:playanimportantrolein tolerance.SummaryCell surface markers: TCR/CD3, CD4/CD8,CD28, LFA-1 etc.T ce