英文版-Indiana-University-Purdue-University-Fort-Wayne微生物学授课讲义-lecture-07课件.ppt

1、Lecture 7BIOL 5331Interactions of Phagocytes and Other Immunological CellsBIOL 533Lecture 7Medical MicrobiologyLecture 7BIOL 5332Production of Ab and Activation of Macrophages and Cytotoxic T Cells T-Dependent T-IndependentLecture 7BIOL 5333T-Dependent Activation Extracellular pathogens Digested by

2、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 fragmentAb Helper T cells(CD4+cells;TH1)produces IFN and activates macrophageLecture 7BIOL 5334T-Dependent Activation Intracellular patho

3、gens Digested when released from dying host cell Peptide Ag presented on MHC class I Proliferation of cytotoxic T cells(CD8+)Lecture 7BIOL 5335Processing CHO and Lipid Ag LPS interacts directly with B cells(independent of T cells)CHO Ag largely independent of T cells,but some involvement(production

4、of cytokines;necessary for maximal B cell activity)Lecture 7BIOL 5336T-Dependent Mechanism Macrophage 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 4-6 IL1 also stimulates hypothalamus to raise body t

5、emperature,enhancing T cell actionLecture 7BIOL 5337T-Dependent Mechanism IL2 4-6 stimulate T-helper cells to multiply These 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 multiplyLecture 7BIOL 5338T-Dependent Mechanism

6、 The 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 Ab Also B cell recognizes its Ag through its surface IgM receptor(signal#1 for B cell),subsequently triggered to proliferateplasma cells

7、AbLecture 7BIOL 5339T Cell Biology MHC molecules Major Histocompatibility Complex Found on plasma membrane Class I found on most nucleated body cells Class II found only on leukocytes involved in immune response(macrophage,Ag-presenting cells,B cells)Class I and II Ag processed differentlyLecture 7B

8、IOL 53310T Cell Biology Class I molecules bind to peptides found in cytosol(e.g.,replicating viruses)Endogenous proteins are digested by natural processes Peptides from cytosolendoplasmic reticulumLecture 7BIOL 53311T Cell Biology Within ER,class I MHC heavy chain synthesized and associates with 2 m

9、icroglobulin Dimer binds peptide plasma membrane If peptide is foreign,passing CD8+T cell(cytotoxic)recognizes,releases cytokines,destroys cellLecture 7BIOL 53312T Cell Biology Class II MHC bind to fragments arise from exogenous Ag Peptide recognized by CD4+T-helper cells Do not directly kill cell c

10、ells enlarge and dividemore CD4+cells Secrete cytokines(such as IL2)either directly inhibit pathogen or recruit other cells for immune response Lecture 7BIOL 53313MHC Genetics MHC gene complex located chromosome 6 ABCD co-dominant Individuals may have any combination of 8 different MHC molecules One

11、 gene of each pair code for MHCLecture 7BIOL 53314MHC Genetics Types of Genes Class IABC Class IID Class III Encode second component of complement(C2)classical pathway Factor Balternate pathway Two forms;4th complement components(C4a C4b)Lecture 7BIOL 53315Regulator T Cells T-helper CD4+TH1:IL2,IFN,

12、TNF;macrophage activation TH2:IL 4,5,10,13;humoral immunity TH0:not much known T-suppressorLecture 7BIOL 53316Regulator T Cells T-helper:two signals for stimulation by Ag Ag fragments presented to T cell by macrophage,dendritic,or activated B cell+MHC class II;needed for recognition by T-cell recept

13、or and CD4 protein on surface TH1 cell CD28 protein receptor on TH1 cells CD28 binds to CD80 on macrophage2nd signal;both go into cytoplasm of TH1 cellLecture 7BIOL 53317Regulator T Cells Signal 1 activates tyrosine kinase Adds phosphate groups to tyrosine in proteins Enzyme phospholipase CI cleaves

14、 phosphatidyl inositol bisphosphate in T cell helper membrane Two cleavage products;two pathways First diacyl glycerol activates protein kinase C Protein kinase C moves into nucleus catalyzes formation protein complex AP1Lecture 7BIOL 53318Regulator T Cells Second,inositol triphosphate causes Ca cha

15、nnel to open;Ca+ions rush in cytosol;activation of calmodulin,calcineurin,and nuclear factor of activated TH1Lecture 7BIOL 53319Regulator T Cells NF-ATnucleoplasm binds to AP-1 NF-AT/AP-1(transcription factor)Transcription factor binds to DNA specific gene sequence:IL2 m-RNA transcribed IL2m-RNAribo

16、somes where IL2 protein producedLecture 7BIOL 53320Regulator T Cells Signal 2 mediated CD28 receptor plus CD80 molecule activates another tyrosine kinaseformation transcription factor CD28RC;also stabilizes IL2 m-RNA;increases concentration of IL2 TH1 cells activated by 2 signals secrete large amoun

17、ts of IL2activates cytotoxic T cellsLecture 7BIOL 53321Regulator T Cells Signal 2 mediated,contd.Also secrete IFN which activates macrophages and enhances antimicrobial activity TH2 cells costimulated by Ag presentation and IL1,then release several cytokines that stimulate B cell proliferation and d

18、ifferentiation into Ab forming plasma cellsLecture 7BIOL 53322Cytotoxic T Cells CD8+Destroy target cells CD95 pathway(fas gene produces;apoptosis sequence)Perforin pathwaydirect cytolysis;secretion of perforin and granzyme proteinsLecture 7BIOL 53323Cytotoxic T Cells CD8+CD95 Pathway CD95 transmembr

19、ane fas protein receptor found in many eukaryotic cells CD95 coded fas gene;member of TNF family of genes Fas ligand binds CD95/CD95L complex activates several cytosolic proteinscellular suicide sequenceLecture 7BIOL 53324Cytotoxic T Cells CD8+Perforin pathway Ca+2 dependent sequence Microtubule assembly Movement of cytoplasmic granules Reorientation of Golgi apparatus Movement of microtubule organizing center T cell secretes pore-forming protein perforin T cell secretes granzymes(proteolytic enzymes further damage it),cause cytosisLecture 7BIOL 53325Lecture 7 Questions?Comments?Assignments.