Antigen recognition and immune response of T lymphocytes . Recognition of antigen by T lymphocytes. The course of T lymphocytes activation. Responses of effector T lymphocytes The course of immune response Antigen recognition specific binding of antigen to antigen receptor Immune response activation of lymphocytes and production of effector agents Immune reaction antigen elimination or neutralization by effector agents. Antigen recognition Characteristics of TCR antigen recognitionl recognize MHC-peptide complex on APC cellsl recognize linear amino acid antigen determinantslMHC restrictionCD4+T -MHC-II-peptideCD8+T -MHC-I-peptide() Nonspecific binding between T cell and APCNonspecific binding between T and APC () Specific binding between T cell and APCStable binding between T and APC low affinity binding between LFA-1and ICAM-1TCR and CD4 coreceptor recognize MHC-peptide complexTCR signaling enhance the affinity between LFA-1 and ICAM-1 T cellT cellT cellAPCAPCAPC()Binding of costimulatory molecules between T cell and APCCD28/B7、LFA-1/ICAM-1、CD2/CD58() immunological synapseRaft-like structure:Centre-TCR:MHC-peptide complexSurrounding -pairs of adhension molecules() The first signal.signals essential for the activation of T celldual recognition of CD4+T cell() The second signalCD28/B7LFA-1/ICAM-1 or ICAM-2CD2/LFA-3CD40/CD40Ldual signals in the activation of T cellCD28/B7, promotes the gene transcription of IL-2Without CD28/B7 ，T cell anergyCTLA4, high homology with CD28, with the affinity to B7 20 folds higher than that of CD28, restrict the over expansion of T cell through inhibitory signaling() cytokine promote the full activation of T cellIL-1、IL-2、IL-6、IL-12 . signal transduction in the activation of T lymphocytemultimerization:Clustering of TCR/CD3,CD4 or CD8 and CD45Immunoreceptor tyrosine-based activation motif, ITAMD/Exx YxxL/V x(711) YxxL/V Y：tyrosine L：leucine V：valine D：aspartic acid E：glutamic acid Signal transduction in T cell activation. transcription factor activation and gene expression() activation of transcription factors AP-1 (Fos、Jun) NF-B Oct-1 NFAT (nuclear factor of activated T cell )() gene expression of T cellncytokine gene expressionncytokine receptor gene expressionnadhesion molecule gene expressionnMHC() proliferation and diferentiation of T cellnCD4T cell proliferation and diferentiation nCD8T cell proliferation and diferentiation . Function of effector T cellTh0Th2humoral immunityTh1cell mediated immunityIL-12IL-4 Induced delayed type hypersencitivity, activate and recruit Mto local inflammation Enhanced expression of MHC and adhension molecules on APC Activate CD8T and NK cell，enhance killing activity1. Effects of Th1 CD4T cellEffect phase of TH1 immune responseTH1IL-2 IFN- TNF- GM-CSF IL-3 Macrophage,neutrophil activation,recruitment and local infiltrationDTHMacrophage activation,Expression of MHC-II and adhension moleculesAntigen presentationActivate MNK cellTc cellTH cellCell mediated effectsMemory THMechanism of Mactivation by Th1 T cellBiological roles of Th1 cell secreted cytokinesactivated Th1 cellIFN-and CD40LFasL or TGF-Lumen of blood vessel exudationchemoattractiveInfected siteactivate M to kill phagocyted bacteriaskill infected cell and released bacterias were killed by Minduce T cell proliferationinduce differentiation of bone marrow MInduce Mexudation by endothelial cell activationrecruitment of Mto local infected site2. Function of Th2 CD4T cell Regulate M(recruitment, inhibition：IL-10/FasL/TGF-) B cell activation, Ig isotype switchingInteraction between B and Th2 CD4+ T cellT cellB cellnecrosis、apoptosisActivation Induced Cell Death3.Effects of CD8CTLCD8+CTL cytotoxic effect recognitionproliferationdifferentiationcytotoxickillingactivation of naive T cellProliferation and differentiationKilling of infected cellT cellR release of granule substancesrelease of granule substancesperforinperforingranzymegranzyme release of TNFrelease of TNF switch on apoptosis signalingswitch on apoptosis signaling FasLFasL FasFas FADDFADDCaspase8 DNA incision enzymeCaspase8 DNA incision enzymeeffector phase of CD8+T cell mediated immune responseGranule-associated killing mechanism cytotoxic cellcytotoxic cellperforintarget celltarget cellvesicleenzymic polymerizationpolyperforin channelsenzyme releasecell damageT cell mediated immune response and immune effects antigenantigen： TD-AgTD-Ag cell cell： T cell and APCT cell and APC effect agent effect agent： ThTh/CTL/CTL（TcTc） immune effects: immune effects: anti-anti-intracellular infectionintracellular infectionanti-tumor anti-tumorimmunological injury immunological injurydelayed type de