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2011-12-03 14:30:18
F2 Blood

F2 Blood
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  1. Adaptive Immunity Overview
  2. B cell antibodies
    • Each B cell typically makes only 1 type of unique antibody
    • The antibody is expressed on the cell surface, and later on, when needed, can be secreted into the blood.
    • Combinations of heavy and light chains
    • 10^11 - 10^14 different types of antibodies
  3. Plasma Cells
    • terminally differentiated B cells that undergo an immune response,
    • Secreted antibody (immunoglobulin) vs. surface Abs
    • IgM, IgG, IgA, IgE, IgD
    • histological pic (bottom middle): has nucleus off to one site, and purplish cytoplasm (bc there are many antibody proteins being produced
  4. Secreted antibodies
    • 1) neutralize- antibodies bind to and neutralize,
    • 2) opsonization- make bacteria more tasty to be phagocytosed, and
    • 3) complement activation- for lysing bacterial cells
  5. TCR
    • T Cell Receptor (never secreted)
    • Membrane bound 'antennae'
    • Binds differently than Ig
    • Combinations of a and b chains
    • Combination of g and d in the gut
    • 10^18 different types of TCRs
    • in contrast to Abs, the TCR only bind to fragments of foreign objects (such as microbes) which are expressed on the surface of antigen presenting cells (APCs) in the context of MHC surface molecules
  6. Host Defense System
    • body will ramp up its host defense when necessary; see axis
    • 1) skin (barrier function) can host off a variety of potential infections
    • 2) but if there are small infections, there is inflammation & neutrophils/resident macrophages will be called into play
    • 3) if pathogen can gain a foothold in a tissue, some of the bigger guns are called into play
    • 4) the more infection is able to gain a foothold, the more body takes notice & recruits more potent defense mechanisms
  7. Innate Host Response & Acute Inflammation
    • Immediate
    • neutrophils (kill via lysosomal enzymes and oxidative enzymes, seen upper right)
    • macrophages
    • Circulating PMNs respond to chemotactic factors along gradient
    • Secreted defenses e.g., Defensins, multi-reactive IgM
    • Serum protein activation e.g., Complement, coagulation
    • Stimulated cellular response (Recruiting factors)
    • -Phagocytosis and release of reactive oxygen metabolites
    • -Phagocytosis and lysosomal enzymes
    • -Prostaglandins and leukotrienes
    • -Cytokines
  8. Antigen Specific (Adapative) Immunity
    • Kicks in when organism escapes innate host defenses
    • Major players
    • -Lymphocytes (B and T cells)
    • -Antigen presenting cells (e.g., macrophages, and dendritic cells)
  9. Langerhans (Dendritic cells) and macrophages
    • eat microorganisms
    • Langerhans cells will act to phagocytize and present antigens;
    • can be in dermis/hypodermis, as well as macrophages
    • both types of cells will eat infectious agents, degrade bacteria into peptide components, and then present the peptides as antigens on their cell surfaces
  10. APC action
    • digested the bacteria
    • expressed bacteria peptides on its cell surface in conjunction with a membrane protein MHC
    • travel by the lymphatic system to regional lymph nodes and, most likely to the spleen as well.
    • -peptide antigens presented as part of MHC Class II complex
    • -migrate to nearest lymph node they can find, via lymphatic system
  11. Lymph Node
    • Small encapsulated oval structures
    • Lymph and blood vessels flow in and out
    • Arterial blood in; venous blood out
    • Afferent lymph in; efferent blood out
    • Filter for Lymph (and blood)
    • A site of an immune response
    • Present throughout body
    • Including tonsils
  12. Lymph Node Cortex
    • Foreign material, microbes, dendritic cells enter node through afferent lymphatics
    • enter the subcapsular sinus and the cortical sinus
    • APC will exit the sinus and go to both the paracortex region as well as the cortex region
    • T cells stay around the paracortex; B cells migrate to the cortex.
  13. Lymph Node Paracortex
    • Lymphocytes enter node through High Endothelial venules (HEV)
    • In the paracortex, the APC will bind to, activate, and promote the proliferation of the T cell that recognizes the bacterial antigen
    • T cells stay around the paracortex; B cells migrate to the cortex.
  14. T Cells (lymphocyte)
    • Regulator of Immune response
    • Regulator of Inflammation
    • Regulator of Antibody response
    • -By B cells
    • proliferation and activation of this T cell clone in the paracortex
  15. T Cell-Mediated Immunity
    • One of every 104-106 T cells will express the correct T cell receptor
    • Activated T Cells Undergo Clonal Proliferation / Differentiation
    • T cell can now direct and amplify an all-out attack
    • secretion of factors that produce more T cells, as well as production of other factors that affect other branches of the host defense system
    • T cells can help expand an immune response
    • e.g., Can help B cells produce specific antibodies
    • T cells can promote an inflammatory response
    • T cells can sometimes directly kill
    • i.e., Cytotoxic T cells (CD8+ T cells)
    • Recognize our own cells which are infected with virus
    • Bind to the infected cell and kill
  16. types of T cells
    • Helper cells (of type 1 and 2 flavors; these can orchestrate and amplify a defense response),
    • Tregulatory cells (which can help modulate, regulate, and turn down an immune response), and
    • CTL (direct killer)
    • Activates macrophages
    • Induces B cells to make opsonizing Ab
    • secrete factors
    • Sometimes harmful, chronic inflammation
  18. B Cell (antibody) Response
    • B Cell Meets Specific TH Cell -> Humoral Immunity
    • Cortex
    • Follicles:
    • 1o: B Cells
    • 2o: Proliferating B cells
    • - Immune response
    • B cells mutate and modify their antibody further so that it will bind tighter to the foreign antigen
  19. Germinal Center
    • cluster of proliferating / differentiating B cells (which have been specifically stimulated by TH cell) in a follicle of resting B cells.
  20. Mantle Zone
    Resting B Cells
  21. follicular dentritic cells
    B cells in general, are summonsed to follicles by cells called "follicular dentritic cells" (not to be confused with a "dendritic" or Langerhans cells, which are different).