《微生物学美国IndianaUniversityPurdueUniversity授课07》由会员分享，可在线阅读，更多相关《微生物学美国IndianaUniversityPurdueUniversity授课07（25页珍藏版）》请在金锄头文库上搜索。
1、Lecture 7微生物学美国IndianaUniversityPurdueUniversity授课07Stillwatersrundeep.流静水深流静水深,人静心深人静心深Wherethereislife,thereishope。有生命必有希望。有生命必有希望Lecture 7Production of Ab and Activation of Macrophages and Cytotoxic T CellsT-DependentT-IndependentBIOL 5332Lecture 7T-Dependent ActivationExtracellular pathogensDige
2、sted by macrophageAg complexed MHC class II (present only in macrophage and few other cell types)Stimulates helper T cells (TH2) to find B cells, recognize particular peptide fragmentAbHelper T cells (CD4+ cells; TH1) produces IFN and activates macrophageBIOL 5333Lecture 7T-Dependent ActivationIntra
3、cellular pathogensDigested when released from dying host cellPeptide Ag presented on MHC class IProliferation of cytotoxic T cells (CD8+)BIOL 5334Lecture 7Processing CHO and Lipid AgLPS interacts directly with B cells (independent of T cells)CHO Ag largely independent of T cells, but some involvemen
4、t (production of cytokines; necessary for maximal B cell activity)BIOL 5335Lecture 7T-Dependent MechanismMacrophage presents part of Ag and own class II MHC to T-helper cell (signal #1)Also makes IL1 6 (signal #2)IL1 6 stimulates T cell clone to divide and make IL2 4-6IL1 also stimulates hypothalamu
5、s to raise body temperature, enhancing T cell actionBIOL 5336Lecture 7T-Dependent MechanismIL2 4-6 stimulate T-helper cells to multiplyThese T cells associate with B cells that have correct Ag MHC II complex and secrete B cell growth factors (BCGF) that cause B cells to multiplyBIOL 5337Lecture 7T-D
6、ependent MechanismThe number of B cells increase, T-helper cells produce other cytokines (BCDF)These cause some B cells to stop dividing, differentiating into plasma cells and produce AbAlso B cell recognizes its Ag through its surface IgM receptor (signal #1 for B cell), subsequently triggered to p
7、roliferateplasma cellsAbBIOL 5338Lecture 7T Cell BiologyMHC moleculesMajor Histocompatibility ComplexFound on plasma membraneClass I found on most nucleated body cellsClass II found only on leukocytes involved in immune response (macrophage, Ag-presenting cells, B cells)Class I and II Ag processed d
8、ifferentlyBIOL 5339Lecture 7T Cell BiologyClass I molecules bind to peptides found in cytosol (e.g., replicating viruses)Endogenous proteins are digested by natural processesPeptides from cytosolendoplasmic reticulumBIOL 53310Lecture 7T Cell BiologyWithin ER, class I MHC heavy chain synthesized and
9、associates with 2 microglobulinDimer binds peptide plasma membraneIf peptide is foreign, passing CD8+ T cell (cytotoxic) recognizes, releases cytokines, destroys cellBIOL 53311Lecture 7T Cell BiologyClass II MHC bind to fragments arise from exogenous AgPeptide recognized by CD4+ T-helper cellsDo not
10、 directly kill cellcells enlarge and dividemore CD4+ cellsSecrete cytokines (such as IL2) either directly inhibit pathogen or recruit other cells for immune response BIOL 53312Lecture 7MHC GeneticsMHC gene complex located chromosome 6ABCD co-dominantIndividuals may have any combination of 8 differen
11、t MHC moleculesOne gene of each pair code for MHCBIOL 53313Lecture 7MHC GeneticsTypes of GenesClass IABCClass IIDClass IIIEncode second component of complement (C2)classical pathwayFactor Balternate pathwayTwo forms; 4th complement components (C4a C4b)BIOL 53314Lecture 7Regulator T CellsT-helper CD4
12、+TH1: IL2, IFN, TNF; macrophage activationTH2: IL 4, 5, 10, 13; humoral immunityTH0: not much knownT-suppressorBIOL 53315Lecture 7Regulator T CellsT-helper: two signals for stimulation by AgAg fragments presented to T cell by macrophage, dendritic, or activated B cell + MHC class II; needed for reco
13、gnition by T-cell receptor and CD4 protein on surface TH1 cellCD28 protein receptor on TH1 cellsCD28 binds to CD80 on macrophage2nd signal; both go into cytoplasm of TH1 cellBIOL 53316Lecture 7Regulator T CellsSignal 1 activates tyrosine kinaseAdds phosphate groups to tyrosine in proteinsEnzyme phos
14、pholipase CI cleaves phosphatidyl inositol bisphosphate in T cell helper membraneTwo cleavage products; two pathwaysFirst diacyl glycerol activates protein kinase CProtein kinase C moves into nucleus catalyzes formation protein complex AP1BIOL 53317Lecture 7Regulator T CellsSecond, inositol triphosp
15、hate causes Ca channel to open; Ca+ ions rush in cytosol; activation of calmodulin, calcineurin, and nuclear factor of activated TH1BIOL 53318Lecture 7Regulator T CellsNF-ATnucleoplasm binds to AP-1 NF-AT/AP-1 (transcription factor)Transcription factor binds to DNA specific gene sequence: IL2 m-RNA
16、transcribedIL2m-RNAribosomes where IL2 protein producedBIOL 53319Lecture 7Regulator T CellsSignal 2 mediatedCD28 receptor plus CD80 molecule activates another tyrosine kinaseformation transcription factor CD28RC; also stabilizes IL2 m-RNA; increases concentration of IL2TH1 cells activated by 2 signa
17、ls secrete large amounts of IL2activates cytotoxic T cellsBIOL 53320Lecture 7Regulator T CellsSignal 2 mediated, contd.Also secrete IFN which activates macrophages and enhances antimicrobial activityTH2 cells costimulated by Ag presentation and IL1, then release several cytokines that stimulate B ce
18、ll proliferation and differentiation into Ab forming plasma cellsBIOL 53321Lecture 7Cytotoxic T Cells CD8+Destroy target cellsCD95 pathway (fas gene produces; apoptosis sequence)Perforin pathwaydirect cytolysis; secretion of perforin and granzyme proteinsBIOL 53322Lecture 7Cytotoxic T Cells CD8+CD95
19、 PathwayCD95 transmembrane fas protein receptor found in many eukaryotic cellsCD95 coded fas gene; member of TNF family of genesFas ligand bindsCD95/CD95L complex activates several cytosolic proteinscellular suicide sequenceBIOL 53323Lecture 7Cytotoxic T Cells CD8+Perforin pathwayCa+2 dependent sequ
20、enceMicrotubule assemblyMovement of cytoplasmic granulesReorientation of Golgi apparatusMovement of microtubule organizing centerT cell secretes pore-forming protein perforinT cell secretes granzymes (proteolytic enzymes further damage it), cause cytosisBIOL 53324Lecture 7Lecture 7Questions?Comments?Assignments.BIOL 53325
