The Immune System Innate ·Acquired(Adaptive) ·Antimicrobial -B Lymphocytes Peptides Antibody ·Phagocytes (Macrophages,PMNs, -T Lymphocytes Monocytes,DCs) Cytotoxicity Help”Antibody 。Alternative Cytokine Secretion Complement System BDC
The Immune System • Innate • Antimicrobial Peptides • Phagocytes (Macrophages, PMNs, Monocytes, DCs) • Alternative Complement System • Acquired (Adaptive) -B Lymphocytes Antibody -T Lymphocytes Cytotoxicity “Help” Antibody Cytokine Secretion BDC
B and T Lymphocyte Antigen Receptors VB Va y E CB Co CH2 CH2 Iga/IgB CH3 CH3 Iga/IgB fyn Blk,Fyn or Lyn φ派 2 light chains(orK) 2 Chains a/B(95%)ory/(5%) 2 heavy chains(5 isotypes:IgG,M,A,D,E) 2 Binding sites(Divalent) 1 Binding site(Monovalent) Secreted into circulation Membrane Bound,Not Secreted Binds Soluble Antigen Binds Antigen Complexed with MHC BDC
2 light chains ( or ) 2 heavy chains (5 isotypes: IgG, M, A, D, E) 2 Binding sites (Divalent) Secreted into circulation Binds Soluble Antigen 2 Chains / (95%) or / (5%) 1 Binding site (Monovalent) Membrane Bound, Not Secreted Binds Antigen Complexed with MHC Zap 70 fyn lck e z V V C C CH1 CH2 CH3 CH2 CH3 CH1 CL CL VL VL VH VH e z Ig/Ig Ig/Ig Blk, Fyn or Lyn B and T Lymphocyte Antigen Receptors BDC
XPID:X-linked polyendocrinopathy, immune dysfunction and diarrhea ·XLAAD:“Autoimmunity Allergic Dysreg Scurfin gene (Foxp3/JM2) Immunopathogenesis:Th2 Cytokines, abnormal activation (I1-4,5,13) -Scurfy+Nude:No Autoimmunity -CD4+into Nude:Disease -Bone Marrow into irradiated:No Disease -Require Antigen Stimulation for Disease -Mixed Chimera:No Disease BDC
XPID: X-linked polyendocrinopathy, immune dysfunction and diarrhea • XLAAD: “Autoimmunity Allergic Dysreg” • Scurfin gene (Foxp3/JM2) • Immunopathogenesis: Th2 Cytokines, abnormal activation (Il-4,5,13) -Scurfy+Nude: No Autoimmunity -CD4+ into Nude: Disease -Bone Marrow into irradiated: No Disease -Require Antigen Stimulation for Disease -Mixed Chimera: No Disease BDC
J.Noble HLA Human Leukocyte Antigen human MHC cell-surface proteins important in self vs.nonself distinction present peptide antigens to T cells CLASS I:A.B.C CLASS II:DR,DQ,DP
Human Leukocyte Antigen human MHC cell-surface proteins important in self vs. nonself distinction present peptide antigens to T cells CLASS I: A,B,C CLASS II: DR,DQ,DP HLA J. Noble
The Human Leukocyte Antigen Complex (6p21.31) Class Ill Class ll (1.1 Mb) (0.7Mb) Class I (2.2Mb) DP DO DR B C elomere Frequent Class I-like genes Recombination Complement and pseudogenes and Cytokines Recombination Recombination is Rare is Rare BDC
The Human Leukocyte Antigen Complex (6p21.31) DP DQ DR B C A Class II (1.1 Mb) Class III Class I (2.2Mb) Complement and Cytokines Class I-like genes and pseudogenes Frequent Recombination Recombination is Rare Telomere Centromere Recombination is Rare (0.7Mb) BDC
HLA Class I and ll Molecules Have a Distinct Structure and Function .Binds 8-10mers ·Binds13-25mers .Expressed on most .Expressed on APCs, Nucleated cells Macs,B cells,activated .Presents Cytosolic T cells Proteins to CD8+T cells .Presents Vesicular Proteins to CD4+T cells 02 a1β1 B2 02 B2 ClassI Class ll BDC
2 3 1 2 1 2 1 2 •Binds 8-10mers •Expressed on most Nucleated cells •Presents Cytosolic Proteins to CD8+ T cells •Binds 13-25mers •Expressed on APCs, Macs, B cells, activated T cells •Presents Vesicular Proteins to CD4+ T cells Class I Class II HLA Class I and II Molecules Have a Distinct Structure and Function BDC
Cis and Trans-Class ll Dimerization DQA1 DOB1 Maternal 0501 0201 cis 做 DQA1*0501/DQB1*0201 0301 0302 CIS Paternal trans DQA1*0301/DQB1*0302 黛 打滋 DQA1*0301/DQB1*0201 DQA1*0501/DQB1*0302 BDC
0501 0201 0301 0302 cis cis DQA1 DQB1 trans DQA1*0301/DQB1*0201 DQA1*0501/DQB1*0302 DQA1*0501/DQB1*0201 DQA1*0301/DQB1*0302 Maternal Paternal Cis and Trans- Class II Dimerization BDC
DQB1*0402 a -chain Leu56β B-chain Asp57B BDC
DQB1*0402 Asp57 Leu56 -chain -chain BDC BDC
HLA-Peptide:TCR a2 Helix NH3+ a1 Helix TCR CDR1 alpha CDR3 CDR2 CDR2 CDR3 TCR beta BDC COO-
HLA-Peptide: TCR NH3+ COOTCR alpha TCR beta 2 Helix α1 Helix BDC
() L-10 Co-Stimulation TGFB CTLA-4- B7 CD28+ T CD154 CD40 APC (CD40L) Cell CD2 CD58 TCR-MHC (+)IL-1,IL-6,TNFa BDC
Co-Stimulation T Cell APC CTLA-4 - CD28 + CD154 (CD40L) CD2 CD58 CD40 B7 (+)IL-1, IL-6, TNF IL-10 TGF (-) TCR-MHC BDC