青岛大学基础医学院医学免疫学课件cha2
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1、Chapter 21 Immunodeficiency Disease Immunodeficiency DiseaseTopics on medical immunology Endoscopic imaging of the duodenum shows multiple prominent nodules 35 mm in size,consistent with nodular lymphoid hyperplasiaA child with severe combined immunodeficiency showing skin lesions due to infection w
2、ith vaccinia gangrenosum resulting from smallpox immunization.Lesions were widespread over the whole body.1.X-linked SCID,XSCID1.X-linked SCID,XSCID2.Autosomal recessive heredity SCID2.Autosomal recessive heredity SCIDMHC-I derangementsMHC-I derangementsMutation of TAP geneEndogenous Ag cant be tran
3、sported on endoplasmic reticulumMHC-II derangements(Bare lymphocyte syndrome,BLS)MHC-II derangements(Bare lymphocyte syndrome,BLS)Gene derangement in C II TA,RFX5,or RFXAPChronic viral infection in respiratory tractDTH,little Ab to TD-Ag,susceptibility to virus3.Other SCIDs3.Other SCIDsWiskott-Aldri
4、ch syndrome,WASWiskott-Aldrich syndrome,WASX-linkedX-linkedAtaxia telangiectasia syndrome,ATSAtaxia telangiectasia syndrome,ATSARARBreak in TCR&Ig heavy chain genesDefective DNA repair mechanismGene derangement in PI3-KImmune defectsReduced T cell-numbers and functions(PHA,con-A responses)Low IgG an
5、d IgANon immune defectsLack of coordinationTelangiectasisIg levels in Ataxia-telangiectasia4Hereditary angioedemaHereditary angioedemaC1-INH deficiencyParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaPig-GPICD55CD59MACImmune hemolysisComplementComplement5Acquired Immunodeficienc
6、y Disease,AIDDAnd AIDSImmunodecifiency caused by infectious agentsMany bacterial,viral and parasitic agents compromise the host immune functions,most prominent among theses is HIV infectionImmunodeficiency resulting from aging and malnutritionA number of immune functions become less efficient with a
7、gingImmunodeficiency during malignancy and other diseasesIatrogenic causesAIDS and HIVThe virus-HIVOverview of the HIV replication cyclePathogenesis of HIVPathogenesis of HIVThe necessity for CD4 antigen expression for entry of HIV into a human cell.HeLa cells do not have CD4 antigen and are not inf
8、ected.HeLa cells transfected with CD4 gene are infected Chemokine receptors are involved,in association with CD4 antigen,in infection by HIV(left).The chemokine can block attachment of the virus to its receptors(middle).Mutations in the chemokine receptor can lead to resistence to HIV infection(righ
9、t)HIV-binding to CCR or CXCRHIV-binding to CCR or CXCRVirus titer,CD4 cell number and anti-gp120 titer during the course of HIV infection 1.Budding causes cell lysis Some possible mechanism for the loss of T4 cells after HIV infectionMost CD4 T cells Most CD4 T cells are notare not HIVHIV+,but,but c
10、ould“sweep up”could“sweep up”uninfect T cellsuninfect T cellsuninfected CD4 cellGp120 negativeCells FuseInfected CD4 cellGp120 positiveSyncytia may be poor Syncytia may be poor or ineffective at or ineffective at immune response.immune response.2.Killing of CD4 cells-Syncytia formationCytotoxic T cell3.Killing of CD4 cells -Cytotoxic T cell-mediated lysisHAART:highly active antiretroviraldrug therapyFactors affecting HIV progression.Therapeutic strategies for controlling AIDSHighlyActiveAnti-RetroviralTherapyHAART:两种脱氧核苷类似物逆转录酶抑制剂和一种蛋白酶抑制剂Now also:两种脱氧核苷类似物逆转录酶抑制剂和一种非核苷
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