T细胞亚群医学知识课件.ppt
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1、Classes of lymphocytesv T 细胞亚群细胞亚群v T 细胞活化分子机制细胞活化分子机制v T 细胞免疫应答及其效应细胞免疫应答及其效应v 自身免疫和超敏反应自身免疫和超敏反应v T cell subsetsq T cells and T cells q CD4+T cells and CD8+Tq Nave T cells(初始(初始T细胞)细胞)Effector T cells(效应(效应T细胞)细胞)Memory T cells(记忆(记忆T细胞)细胞)q T helper(Th)辅助性辅助性CD4+T细胞细胞 Cytotoxic T cells(CTLs)细胞毒性细
2、胞毒性CD8+T细胞细胞 Regulatory T cells(Tregs)调节性调节性CD4+T细胞细胞T Cell subsetsClassFunctionsAntigen receptor and specificitySelected markersPercent of total lymphocytes(human)T lymphocytes BloodLymph nodeSpleen CD4+helper T lymphocytesB cell differentiation(humoral immunity)Macrophage activation(cell-mediated
3、immunity)heterodimersDiverse specificities for peptide-class II MHC complexesCD3+,CD4+,CD8-50-60*50-6050-60 CD8+cytotoxic T lymphocytesKilling of cell infected with microbes,killing of tumor cells heterodimersDiverse specificities for peptide-class I MHC complexesCD3+,CD4-,CD8+20-2515-2010-15Regulat
4、ory T cellsSuppress function of other T cells(regulation of immune responses,maintenance of self-tolerance)heterodimersCD3+,CD4+,CD25+(Most common,but other phenotypes as well)Rare1010 T lymphocytesHelper and cytotoxic functions(innate immunity)heterodimersLimited specificities for peptide and nonpe
5、ptide antigensCD3+,CD4,and CD8 variable T cells express a limited number of TCRs abundant in epithelial tissues of certain species:in the small bowel mucosa and in the skin of mouse.In the skin,known as a dendritic epidermal T cell(DETC)do not recognize MHC-associated peptide antigens and are not MH
6、C restricted.may bind to conserved ligands whose expression is triggered by cell injury or stress,such as microbial heat shock proteins.may represent an important bridge between innate and adaptive immunity,functioning as lymphocytes that enhance the first line of defense against a range of pathogen
7、s.Jensen,K.D.et al.Thymic selection determines T cell effector fate:antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon Immunity 29,90100(2008).p Epithelial T cell and Peripheral T cell p CD27-IL-17+T cells and CD27+IFN-+T cells Subsets of T cells Developmental prog
8、ramming of T cell subsets.Cua DJ,et al.Nature review Immunology,2010u Martin B et al.IL-17-Producing T cells Selectively Expand in Response to Pathogen Products and Environmental Signals.Immunity 31,321330(2009).They show that T-17 cells additionally express IL-23R,and the innate receptors TLR2 and
9、dectin-1,which recognize archetypical and fungal constituents.These T-17 cells use these receptors to rapidly produce IL-17 in response to bystander cell-derived IL-23 and to bacteria and fungi without concomitant TCR stimulation.One of the roles of T-17-derived may be indirect or direct amplificati
10、on of IL-17 production in Th17 cells.u Sutton,C.E.et al.Interleukin-1 and IL-23 induce innate IL-17 production from T cells,amplifying Th17 responses and autoimmunity.Immunity 31,331341(2009).This report shows that T cells have an early role in promoting CNS inflammation.The authors suggest that inn
11、ate cell-produced IL-17 directly enhances development of MOG-specific Th17 cells.A major innate source of IL-17Innate Activation of IL-17-Production by a Specialized T Cell SubsetKapsenberg ML.Immunity,2009u Witherden,et al.The junctional adhesion molecule JAML is a costimulatory receptor for epithe
12、lial T cell activation.Science 2010 SepIdentify an epithelial T cells-specific costimulatory molecule,JAMLu Petermann F,et al.T cells enhance autoimmunity by restraining regulatory T cells responses via an IL-23-dependeng mechanism.Immunity,2010 Sep IL-23-activated render effector T cells refractory
13、 to the suppressive activity of Treg cells and also prevented the conversion of conventional T cells into Foxp3+Treg cells in vivo.Two new papers about T Cell published in this monthq Nave T cells Mature T cells that have not previously encountered antigen;Preferential migration to secondary lymphoi
14、d organs(lymph nodes),where they recognize antigenq Effector T cells Activated T cells capable of performing the functions required to eliminate foreign antigens Preferential migration to sites of infection or inflammation Short-livedq Memory T cells Long-lived,functionally silent cells;Mount rapid
15、secondary immune responses to the same antigen exposure Heterogenous(central and effector)Based on the history of antigen encounter and the stage of T cell activation.Naive T cellsEffector T cellsMemory T cellsMigrationPreferentially to peripheral lymphoid tissuesPreferentially to inflamed tissuesPr
16、eferentially to inflamed tissues,mucosal tissuesFrequency of cells responsive to particular antigenVery lowHighLowEffector functionsNoneCytokine secretion;cytotoxic activityNoneCell cyclingNoYes+/-Surface protein expression High-affinity IL-2 receptorLowHighLowPeripheral lymph node homing receptor(L
17、-selectin,CD62L)HighLowLow or variableAdhesion molecules:integrins,CD44LowHighHighChemokine receptor:CCR7HighLowVariableMajor CD45 isoform(humans only)CD45RACD45ROCD45RO;variableMorphologySmall;scant cytoplasmLarge;more cytoplasmSmallu Central memory T cells express CCR7 and L-selectin,and home to l
18、ymph nodes.limited capacity to perform effector functions when they encounter antigen generate many effector cells upon antigen challenge u Effector memory T cells do not express CCR7 or L-selectin,and home to peripheral tissues,especially mucosa.produce effector cytokines upon antigenic stimulation
19、 do not proliferate much.Based on their homing properties and effector functions.Subsets of memory T cells CD4+CD8+CD4+Th1-Th2 hypothesis 1986 Coffman and Mossman Th17 2006Discovery of CD4+Th cell subsetsThe subsets of CD4+Th cells How they are induced,What cytokines they produce What effector mecha
20、nisms they activate Th0q Cytokines Stimuli that influence the pattern of Th cell differentiationq High doses of antigen without adjuvants q Different subsets of dendritic cells may existq The genetic makeup of the host Properties of CD4+Th1 and Th2 subsetsDifferentiation of Th1 Subsetv Stimulated by
21、 intracellular microbes that infect or activate macrophages or NK cells Listeria,mycobacteria and Leishmaniav Important cytokines for the Th1 differentiationv Important transcription factors(TF)for the Th1 differentiation IL-12 IFN-IL-18 type I IFNs (in human)T-bet:master regulator STAT4 STAT1The mo
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