Immuno 10-15

Immuno 10-15

1. T-Cell

   • MHC Restricted
   • Processed Linear Peptide Antigen
   • TCR never Secreted
   • TCR + CD28 Receptor=> APC MHII + B7 (CD80/86)
     • Highly Regulated

2. B-Cell

   • See's Epitopes on Unprocessed Antigen free in Solution
   • Secreted BCR = Antibody
     • Ab= BCR - Membrane Anchor
     • Ab Identical to plasma cell's BCR
   • T-Dependent Antigens
     • Require Th direct contact
       • Immunologic Memory
       • Soluble Protein antigens
   • T-Independent Antigens

3. Source

   • Fetal Liver=>
   • Bone Marrow
   • Yolk Sac =>
   • Primary Lymphoid Organ:Development
     • Primary Lymphoid Organs=  Education/Maturation with self antigen 
     • Thymus
       • All T-Cells Mature here
       • Somatic TCR Gene Rearrangement = Diversity
       • Central Tolerance
         • Positive Selection
           • Recognize self - MHC Molecules
             • Survival
           • Don't Recognize MHC = Apoptosis
         • Negative Selection
           • DC's Present Self-Antigen
             • Binding Self Antigen = Apoptosis
             • Mature T-Cell Leaves Thymus
               • Remain in thymus 4-5 days.
               • CD3+/CD4+
               • CD3+/CD8+
                 • ImmunoPhenotyping
     • Bursa
       • Only in Birds
       • Birds: Maturation B-Cells
     • Peyer's Patches
       • Bursa Equivalent in Mammals. Small Intestines 
     • Bone Marrow
       • BCR Repertoire Generation (Gene rearrangement
     • Secondary Lymphoid Organs: Response Arena
       • Secondary Lymphoid Organs:   Differentiation after foreign antigen exposure
       • Lymph Nodes
       • Peyer's Patches
         • GALT
           • Gut Associated Lymphoid Tissue
       • Spleen
       • Tonsils
         • BALT
           • Bronchus Associated Lymphoid Tissue
       • 1) Site of Foreign Antigen Presentation
         • B+T Cells undergo Differentiation => "Effector" Cells
           • B-Cells = Plasma Cells
             • Antibody Producers
             • CD79: Signal Transducer
           • Effector T-Cells
             • Cytotoxic T-Lymphocytes (CTL's; CD8 + T-Cells)
               • Kill infected cells + Tumor Cells
                 • Infected cells w/ MHC-1 presentation -Tumor w/ Tumor Antigens w/ MHC1 -MHC Incompatible Cells 
             • T-Helper Cells (CD4+ T-Cells)
               • B Cells and T Cells
               • TH1 = Cell Mediated Immunity
                 • IL-2: Helps Activate Cells
                   • T-Cells (Also Th Cells)
                     • CTL activation
                       • Binds Target Cell
                         • TCR
                         • CD3
                         • CD8
                         • Endogenous Ag- MHC1
                       • Destruction of Target Cells: Apoptosis
                   • B-Cells
                     • Prod. Opsonin
                     • Produce C1 Binding Ab
                   • NK cells
                 • Interferon-y: INFy
                   • Also made by other cells
                   • Activates Macrophages
                   • Promotes CMI = Resist Intracellular Pathogens
                     • Inhibit Th2 Differentiation
                 • Cell-Mediated Immunity
                   • 1) Th1 Cells direct the CTL's   2) Delayed-type hypersensitivity (DTH) response: Marophages directed by Th1 cells 
                   • Primary CMI Response
                     • Response to NOVEL Ag: First exposure
                     • Secondary CMI Response
                       • Memory Effector T-Cells
                       • Long-Lived
               • TH2 = Humoral Immunity
                 • IL-4 and 5
                   • B-Cell Proliferation
                     • Monoclonal Response
                     • Polyclonal Response
                   • Antibody Secretion
                     • Positive Charge Electrophoresis: most Ig migrates to negative cathode: Gamma
                     • Can:  1) Act as Opsonin 2) Activate Classical Complement Cascade 3) Bind Pathogens, Neutralize 4) Blocking of Attachment 5) Aggregation 
                     • Anti- " " Ig@
                       • Anti-Human IgM = Human IgM antibody injected into mouse, mouse plasma cells make antibody against human IgM
                       • Body Makes antibodies against other antibodies
                     • Fab = Binding
                     • Fc = Constant
                       • Complement Binds here
                         • Classical Complement Cascade
                           • IgG and IgM allow binding of complement to Fc region
                       • Determines "Class"
                         • IgA
                           • Mucosal Surfaces
                         • IgG
                           • Main Ab of Secondary Response
                             • Affinity maturation
                           • Highest concentration in Colostrum (and Blood)
                         • IgE
                           • Histamine: Inflammatory response
                           • Type 1 Hypersensitivity
                           • Immunity to Parasitic Worms
                         • IgM
                           • Opsonization
                           • Primary Immune Response
                             • High level = Recent Primary Exposure to Antigen
                             • Class Switching
                         • IgD
                       • Phagocytic cells have receptors for....
                 • Why We Assess??
                   • If Exposed
                   • If able to Respond
                   • Level/Kind of Antiibody Response
                   • How??
                     • Measure CFS/Joint anitbody
                     • Mostly Check Serum
                     • Amount/Kind of Antibody
                     • Check total amount in serum
               • Immune profiling
             • CD3: Signal Transducer
               • Signaling event AFTER antigen binding
                 • Activates T-Cell
                 • Enters Cell Cycle: Proliferates
                 • Secretes cytokines
                 • Signal 1: TCR => MHC
                   • Signal 2: Costimulators CD28=>B7
                     • Trigger T-Cell entry into G1 of Cell Cycle
                       • IL-2 + IL-2R PROLIFERATIOn
                   • CD3 Signal Generated
     • 1) Acquire Repertoire of Antigen-Binding Receptors
       • TCR + BCR
         • Only Somatic Cells w/ Gene Rearrangement
           • Gonadal Cells
       • 2) Select Receptors w/ foreign Antigen Recognition
         • Delete Self-Antigen Recognizers
         • 3) Maturation + Education
           • Don't Encounter Foreign Antigen

4. Somatic Gene Rearrangement

   • RAG Proteins
     • Recombination Activating Gene Protein
     • V, D, J Gene Segments

5. Regulate Lymphocyte Function

   • 1) Receptor Molecules
     • Antigen Receptors (TCR/BCR)
     • Cytokine Receptors
     • Antibody Receptors: FcR
       • NK cells
       • Macrophages
       • Neutrophils
     • Complement Protein Receptors
   • 2) Adherence Molecules
     • Integrins
   • 3) MHC Molecules: Antigen Presentation
   • 4) Co-Stimulatory Molecules
     • Stimulated on APC side by exposure to PAMPS or Cytokines -Not antigen specific  1st signal = MHC/Ag - TCR 2nd signal = APC: CD80 (B7) =>Tcell CD28  
     • Link between innate and Adaptive
     • REQUIRED for full T/B Activation