Immuno Intro/Antibody (1/2)

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Immuno Intro/Antibody (1/2)
2013-10-05 21:14:30

Exam 3
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  1. innate vs. adaptive immunity
    • 1. age: innate has been around longer; adaptive immunity
    • evolved ~500 million years ago
    • 2. time to be useful: innate is the 1st line of defense, & takes minutes to hours to kick in; adaptive immunity kicks in after days/weeks
    • 3. recognition: innate recognizes pathogens in a non-specific, broad fashion (eg. microbes), whereas adaptive immunity recognizes HIGHLY specific ANTIGENS
  2. innate immunity recognizes __________, whereas the adaptive immune system recognizes __________________
    innate immunity recognizes PATHOGENS/MICROBES, whereas the adaptive immune system recognizes THINGS THAT AREN'T YOU
  3. innate immunity examples
    • 1. physical barriers (eg. skin, mucous membr)
    • 2. biologically active substances
    • -lysosomes
    • -anti-microbe proteins
    • -cytokines (IL-1, 6 & TNF-alpha)
    • -complement activation (lectin/alternative pathways)
    • 3. CELLS (NK cells, phagocytes [macrophages + neutrophils])
    • *present ALL the time
    • *recognizes groups of similar pathogens (NOT antigen specific)
    • *no memory: doesn't increase responsiveness with repeated exposure to pathogen
  4. white blood cells EXCEPT for __________ comprise your innate immune system
    WBCs except for lymphocytes = innate immune system
  5. Hematopoiesis
    • the generation of the cellular components of blood: red blood cells, white blood cells, & platelets
    • white blood cells (also called leukocytes) are the blood cells which function in immunity
  6. What are the two main cell lineages that can be derive from the common bone marrow stem cell?
    myeloid and the lymphoid lineages
  7. myeloid lineage cells
    • Basophils
    • Eosinophils
    • Neutrophils
    • Granulocytes
    • Dendritic cells (DC)
    • Mast cells
    • Monocytes
    • Macrophages
    • (BEN GD MMM)
  8. Basophils
    • circulate in the blood and are thought to have a function similar to mast cells
    • (Basophils in the Blood; mast cells in the tissue)
  9. Eosinophils
    • leukocytes important in the defense against parasitic infections
    • also related to IgE mediated functions, fighting off parasites, and the allergic reaction response
  10. Neutrophils
    phagocytic leukocytes that have an important role in engulfing and destroying extracellular pathogens, primarily bacteria; often referred to as polymorphonuclear leukocytes (PMN), or simply “polys”, due to their multi-lobed nucleus
  11. Granulocytes
    • include neutrophils, basophils, and eosinophils
    • named for their conspicuous cytoplasmic granules
  12. Dendritic cells (DC)
    • the part of the innate immune system that RECOGNIZES recognize there's an infection and TELLS the adaptive immune system to respond!
    • take up and transport an antigen to peripheral lymphoid organs where they function as potent activators of T cells (adaptive immune system)
    • found in most tissues, including lymphoid tissue
  13. Mast cells
    congregate in tissues and release various soluble mediators such as histamine when activated; play a major role in allergic responses
  14. Monocytes
    phagocytic leukocytes found in the blood; macrophage tissue precursors
  15. Macrophages
    phagocytic leukocytes found in tissues derived from blood monocytes
  16. How are neutrophils and monocytes recruited from the blood to sites of infection?
    by chemoattractants – chemokines - produced in response to the infection
  17. Lymphoid Lineage Cells
    • B cells
    • Lymphocytes
    • NK cells (Natural killer cells)
    • T cells
    • (BLuNT)
  18. B cells
    • produce antibodies which target primarily extracellular pathogens, especially bacteria
    • antibodies circulate in the bloodstream and lymphatic system to target antigens
    • B cells mediate humoral (bodily fluid) immunity
  19. Lymphocytes
    • includes BOTH B lymphocytes (B cells) and T lymphocytes (T cells) express antigen-specific receptors and mediate the adaptive/acquired immune response
    • histology: small cells composed mostly of nucleus with only a thin rim of cytoplasm
  20. Natural killer cells (NK cells)
    • derived from the lymphoid progenitor but do NOT exhibit antigen specificity (are distinct from B cells and T cells)
    • part of the innate immune response
    • are large granular lymphocyte-like cells that can DETROY virus-infected & tumor cells WITHOUT prior stimulation
    • main effectors in cellular cytotoxicity
  21. T cells
    • don't produce antibodies and can be divided into two sub-populations: CD4+ T cells and CD8+ T cells
    • CD4+ T cells secreting cytokines
    • CD8+ T cells recognize & destroy infected & tumor cells
  22. pattern recognition receptors (PRR)
    • innate immune system receptors for pathogens
    • eg. TLR-4 (toll-like receptor 4)
    • when TLR-4 sees LPS, innate immune cells activate macrophages and dendritic cells; they're alerted to the fact that there's a microbe --> adaptive immune system is SET OFF
  23. pathogen associated molecular pattern (PAMP)
    • the microbial product recognized by a PRR; this is usually the something the bug REQUIRES for survival
    • EG. LPS (lipopolysaccharide; in gram -bacteria)
    • innate immune system PRRs recognize microbial PAMPs paradigm #2)
  24. two subgroups of adaptive immune system:
    • 1. Humoral Immunity: mediated by antigen-specific antibodies produced by activated B lymphocytes (plasma cells)
    • antibodies can be transferred to non-immune (naïve) recipients by antiserum (immune serum)
    • 2. Cell-mediated Immunity (CMI): responses involving antigen-specific T lymphocytes (T cells)
    • CMI can be transferred to naïve recipients by T cells, but NOT by immune serum
    • humoral = B cells + antibodies, CMI = T cells
  25. How is humoral immunity measured?
    by the TITER (concentration) of serum antibodies specific for a particular antigen
  26. Lymphocytes in the blood are approximately __% B cells and __% T cells
    Lymphocytes in the blood are approximately 20% B cells and 80% T cells
  27. Clonal Selection (paradigm #1)
    • a single progenitor cell gives rise to a large number of lymphocytes (either B or T cell), each with a DIFFERENT specificity
    • self-reactive (anti-self) immature lymphocytes are removed by clonal DELETION
    • a pool of mature (anti-foreign), naive lymphocytes results
  28. Clonal Selection of B Cells
  29. Primary Lymphoid Organs
    • Bone Marrow (where B cells are made)
    • Thymus (where T cells are made)
  30. Secondary Lymphoid Organs
    • where CLONAL EXPANSION happens (eg. swollen lymph node)
    • Adenoid
    • Tonsil
    • Lymph Nodes
    • Spleen
    • Peyer's Patches
  31. Multiple Myeloma
    a plasma cell tumor, or a neoplasitic antibody secreting cell
  32. tumor cells are almost always derived from a single cell, so plasma cell tumor will produce only one particular antibody called a Mab (monoclonal antibody)
    • malignant plasma cells (myeloma cells) in bone marrow DISRUPT normal hematopoiesis, results in
    • lowered white cell counts, increased susceptibility to infection, decrease RBC formation, & anemia
  33. What indicates a patient might have myeloma?
    • on a gel electrophoresis that separates serum proteins by charge, instead of heterogenous group of antibodies one would see a LOT of one single antibody (dark, thick band)
    • in a graph called a monoclonal spike

  34. Are an antibody's antigen-binding sites identical?
    YES - because they are composed of identical heave and light chain combinations
  35. epitope (antigenic determinant)
    shape on the antigen that's actually CONTACTED/recognized by an antibody
  36. avidity
    • the strength of antibody-antigen interactions involving multiple antigen-binding sites
    • can be several orders of magnitude greater than the affinity of a single antigen-binding site
  37. CDRs (complimentary determining regions)
    • extremely changeable regions of the antibody variable region ("between" heavy and light chain parts) WHERE antigen actually binds
    • "loops" or "3 fingers" that tightly bind the epitope

  38. Immunoglobulin Classes (Isotypes)
    • exist because the constant region of the heavy chain is only relatively constant --> has 5 major isotypes in humans
    • mnemonic: GAMED (there are actually 9 different possibilities)
    • IgA & IgG have different heavy chain subclasses: gamma 1-4 & alpha 1, 2
    • a particular antibody will have one of the nine possible heavy chain constant regions

  39. What determines the class of an antibody?
    • the CONSTANT region of the heavy chain
    • by having different constant regions of the heavy chain, you change how the antibody can respond to different antigens because the Fc region is what's CHANGING
  40. What are the two types of light chain antibodies?
    • kappa (60%) or lambda (40%)
    • DOES not change the effector function (how it gets rid of a microbe) of the antibody
  41. Which two antibodies exist as homodimers in the body?
    • Pentameric IgM
    • Dimeric IgA - monomer in the blood, dimer on mucosal surfaces
    • one J chain polypeptide initiates polymerization and binds polymeric antibodies together

  42. BCR
    • B cell membrane receptor
    • all B cells have an antigen-specific receptor consisting of a monomeric Ig molecule (two H-chains and two L- chains) plus a heterodimer of Ig alpha and Ig beta (initiate signal transduction)
    • Naïve B cells: have BOTH IgM and IgD BCRs
    • Memory B cells: IgG, or IgA or IgE BCRs (only ONE class per cell)
  43. major functions of antibodies
    • virus/toxin neutralization - IgG & IgA
    • bacterial adhesion inhibition - IgM & IgG
    • opsonization - IgG
    • cellular cytotoxicity (ADCC, antibody-dependent cellular cytotoxicity) - IgG
    • activation of mast cells - IgE
    • (opsonization, ADCC, & mast cell activation require FcRs)
  44. opsonization
    • Fc-gamma receptors exist on some cell membranes (eg. macrophages)
    • they won't recognize free antibodies, however antibodies that bind to bacterial surfaces and CLUSTER may activate Fc-gamma receptors and PROMOTE macrophages to engulf the bound bacteria
    • IgG = OPSONIN (another opsonin is C3b, which mediates opsonization via phagocyte's C3b-receptor)
  45. Antibody-dependent cellular cytotoxicity (ADCC)
    • 1. antibody binds antigens on the surface of target cells
    • 2. Fc receptors on NK cell surface recognize bound antibody
    • 3. cross-linking of Fc receptors signal NK cells to kill target cell
    • 4. target cell dies --> apoptosis
  46. where Ig's are present in the body:
    • IgG: highest concentration antibody - crosses placenta and gives newborn protection several months after birth (found in circulation, tissue fluid)
    • IgM: CONFINED to circulation (too large)
    • IgA: dimeric found on mucosal surfaces (mammary glands) - secretory antibody
  47. Mechanism by which IgA gets onto mucosal surfaces
    • -IgA is covalently bound to poly-Ig receptor
    • -only want to release IgA dimer at the apical face of epith. cell is to CUT the receptor --> most of the receptor is still bound to the antibody when it's released (secretory)

  48. common mucosal immune system
    • immune responses that occur at one mucosal site can result in IgA secreting cells migrating, via the lymphatics and blood, to distant mucosal sites
    • if you have an infection at one mucosal site and make IgA in response to that infection, the plasma cells you make at that infection will travel through the lamina propiera to ALL mucosal sites and make antibody --> transmits immunity to ALL mucosal sites
  49. What class do you make the most of?
    • IgA - mostly all it does is neutralize
    • you wouldn't want antibodies in gut to activate an inflammatory response

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