Session 13

• Innate immunity


  An individual's genetically predetermined resistance to certain diseases
• Adaptive immunity


  Ability of the body to react to specific microbial infection
• Adaptive immunity

  • Antigen specific, has memory
  • Made up of two branches: Humoral Immunity (B cell mediated) and Cellular Immunity (T cell mediated)
  • Collaborates with innate immunity
  • Has ability to ignore healthy "self" molecules (tolerance)
• Antigen (Ag)


  A substance that causes the body to produce specific antibodies or sensitized T cells
• Antibody (Ab)


  Proteins made in response to an Ag; can combine with that Ag
• Serology


  The study of reactions between antibodies and antigens
• Antiserum


  A generic term for serum because it contains Ab
• Globulins


  Serum proteins
• Immunoglobulins (= Gamma (γ) globulins)


  Serum antibodies
• Complement


  Serum proteins
• Antibodies recognize and react with antigenic determinants or epitopes on an antigen
• Haptens


  Small separable part of an antigen that reacts specifically with an antibody but is incapable of stimulating antibody production except in combination with a carrier protein molecule
• Immunoglobulin Structure


  • 4 polypeptide chains (2 heavy and 2 light)
  • Variable regions
  • Constant regions
• Antibody Classes


  • IgG
  • IgM
  • IgA
  • IgE
  • IgD
• IgG

  Monomer, 80% of serum antibodies, Activate complement, In blood, lymph, and intestine, Cross placenta, Enhance phagocytosis; neutralize toxins and viruses; protects fetus and newborn, Half-life = 23 days
• IgM


  Pentamer, 5-10% of serum antibodies, Fix complement, In blood, lymph, and on B cells, Agglutinates microbes; first Ab produced in response to infection, Half-life = 5 days
• IgA


  Dimer, 10-15% of serum antibodies, In secretions, Mucosal protection, Half-life = 6 days
• IgE


  Monomer, 0.002% of serum antibodies, On mast cells, basophils, and in blood, Allergic reactions; lysis of parasitic worms, Half-life = 2 days
• IgD


  Monomer, 0.2% of serum antibodies, In blood, lymph, and on B cells, On B cells, initiate immune response, Half-life = 3 days
• B cells and Humoral Immunity


  • Effective against free antigen (toxins, bacterial surface structures, viruses in between cells)
  • B cell receptors (mostly IgM and IgD)
  • Activated B-cells go through clonal expansion leading to Plasma cells (effector cell for antibody production) and Memory cells
• Clonal Selection


  1. B cells internalize antigen and present it to T-helper cell in combination with MHC class II molecules

  2. If T cell recognizes antigen it activates B cell → clonal expansion → plasma cells and memory cells
• B cells require help of T cells for most protein antigens (T-dependent ag)
• No T-helper cells involved in response to T-independent Antigens (Polysaccharides and LPS)
• Young children react poorly to T-independent Antigens
• Antibody Diversity


  • 10^15 different B-cell receptors
  • Mechanism: Somatic recombination (during embryonic development) primarily through gene rearrangement (mix and match)
• Affinity


  Strength of bond between Ag and Ab
• Specificity


  Ab recognizes a specific epitope
• Antibody Functions


  • Agglutinate and precipitate
  • Opsonize
  • Neutralize (immobilize and prevent adherence)
  • Activate complement
  • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) via NK cells and eosinophils
• Protective outcome ⇒ disposal of antigen (based on antigen-antibody binding)
• T Cells and Cellular Immunity


  • T cells have TCR on surface
  • TCR does not recognize free antigen, Ag must be presented in association with MHC on an antigen-presenting cell (APC)
  • Antigens are processed by APC and positioned on the surface of the APC
• Antigen Presenting Cells (APCs)

  • B cells
  • Dendritic Cells
  • Macrophages
• Activated macrophages


  Macrophages stimulated by ingesting Ag or by cytokines
• Helper T Cells (CD4, TH)


  • Activated by antigen presented by MHC class II
  • After binding to Ag presented by APC, CD4 cells secrete cytokines activating other T cells and B cells
  • TH1 cells activate cells involved in cellular immunity
  • TH2 stimulate production of eosinophils, IgM, and IgE (⇒ associated with allergic reactions and parasitic infections)
• Cytotoxic T Cells (CD8, TC, CTL)


  • Activated by endogenous antigens and MHC class I
  • When activated transform into CTLs and memory cells
  • CTLs lyse target cell or induce apoptosis
• MHC Class I


  On all nucleated cells
• MHC Class II


  On surface of APCs (Macrophages, B-cells, dendritic cells)
• Mechanism of Action of CTL

  1. Perforin molecules create protein channels in target cell membrane

  2. Granzymes enter and trigger apoptosis in target cell
• Natural Killer (NK) Cells

  Granular leukocytes, Not immunologically specific, Lyse virus-infected and tumor cells, Kill target cell in absence of MHC-I (early stages of virus infection and tumor cells), Similar mechanism to CTLs
• Antibody-Dependent Cell Mediated Cytotoxicity (ADCC)


  NK cells and macrophages lyse antibody-coated cells (protozoans and helminths)
• Antibody Titer


  Amount of antibody in serum