Lecture 18

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astigmo
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49071
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Lecture 18
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2010-11-11 23:10:38
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immunity
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Immune Response I: Third Level of Defense
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  1. Immunity
    Specific protection against particular pathogens.
  2. 3 key features- The "essence of the immune response"
    1.
    Recognition of self
    Must distinguish and react only to what is foreign.
  3. 3 key features- The "essence of the immune response"
    2.
    Specificity
    Must also distinguish different foreign entities and react to them separately.
  4. 3 key features- The "essence of the immune response"
    3. Memory
    At second and subsequent encounters, must "remember" and act appropriately.
  5. Anatomy of the immune system
    • An intricate system of lymphatic vessels which are similar to blood vessels that begin as blind ended capillaries in the tissues. Lymph(tissue fluid) and lymphocytes enter the vessels and are transported back to the blood. Lymph nodes filter the lymph, while the spleen filters blood. These are secondary lymphoid organs, where most immune responses occur. The bone marrow and thymus are primary lymphoid organs, and the respective sites of B cell and T cell maturation. Very early in development, potentially harmful (self-reactive) lymphocytes are deleted or inactivated and potentially useful (non-self reactive) cells are allowed to develop. The result is a state of immune tolerance(ability to no respond to self, & ability to respond to nonself) that allows reactivity against non-self and specific non-reactivity against self (self tolerance).
    • -lymph nodes & spleen are secondary lymphoid organs.
  6. Humoral immunity
    • the protection provided by antibody (Ab) molecules, which are proteins that recognize and bind to specific Ags. Ab binding enhances non-specific antimicrobial activities phagocytosis,
    • inflammation, C') and may neutralize cell-free viruses, toxins and other soluble Ags.
    • soluble proteins
    • produced by B lymphocytes which differentiate to plasma cells.
    • identify and bind to antigens
  7. Cell-mediated immunity (CMI)
    • protection by specialized T lymphocytes that regulate immune responses or react directly against cellular antigen by non-phagocytic cytotoxic mechanisms. T cells are especially active against intracellular infections, cancer cells, and foreign (grafted/transplanted) tissue.
    • specialized cells that act by a variety of nonphagoctic mechanisms.
    • respond to infected, cancerous, and foreign cells
  8. Antigen (Ag)
    • foreign molecules that stimulate the immune system. Antigens (Ags) are usually proteins(almost always protein).
    • (Ag) antigen means "antibody generating"
  9. Antibodies (Immunoglobulins)
    "Y-shaped" molecules produced by B cells.
  10. Ab molecules are composed of 2 pairs of
    identical polypeptide chains held together by disulfide bonds:


    • 1 pair of light chains: either kappa (k) or lambda (l) and,
    • 1 pair of heavy chains: delta (d), mu (m), alpha (a), gamma (g), or epsilon (e).
  11. Each Ab molecule has
    2 identical binding sites (Fab) and a constant (Fc) region. The binding sites form a pocket with a specific three dimensional shape and bind Ag like a "lock and key". Ab binding alone cannot kill bacteria or other cells. However, specific Ab bound to Ag can act as opsonin or activate C' lysis. Ab may also neutralize toxins and cell-free virus.
  12. Antibody function
    • Identification Molecule - No direct activity
    • agglutination
    • Opsonization (enhancement of phagocytosis)
    • Activate Complement (C')
    • Neutralization soluble proteins & viruses
  13. 5 Classes of immunoglobulins
    IgG
    ~80% of all Ab in the serum. Can cross placenta. Expresses all biological activities. (g heavy chains)
  14. 5
    Classes of immunoglobulins
    IgM
    5-10% of serum Ab. Pentamer structure held together by a J chain (joining chain). First Ab's to appear in response to infection and most efficient at fixing C'. (m heavy chains).
  15. 5 Classes of immunoglobulins
    IgA (secretory antibody)
    10-15% of serum Ab, but most abundant in body because of presence in mucous membranes. Exists as monomers in serum, and as dimers in mucous secretions. (a heavy chains)
  16. 5 Classes of immunoglobulins
    IgD
    Rare in serum. Serves as surface receptor on B cells. (d heavy chains)
  17. 5 Classes of immunoglobulins
    IgE
    • Least abundant in serum. Binds by Fc to mast cells and basophils.
    • Involved in allergic reactions and mediates responses to parasitic infections. (e heavy chains)
  18. Bcells
    (Proliferate in response to Ag and a "cosimulatory signal")
    • Each B cell produces only 1 kind of Ab, which is expressed as a surface receptor on virgin cells, those that have never encountered Ag. Initial exposure to Ag stimulates the B cells to proliferate clonally and to differentiate to plasma cells, which secrete soluble Ab. This clonal expansion of B cells also produces memory B cells, that do not immediately differentiate to plasma cells (Fig 17.5). Memory cells are very long-lived and can expand and differentiate on subsequent exposure to Ag, only at a much faster rate than virgin B cells. Abs also remain in the blood, and the level (titer) may be an indication of immune status.
    • *cytokines, T cell make cytokine goes to B cell
  19. T dependent and T independent antigens
    B cells require T cell "help" in order to produce antibodies to most antigens. Specialized antigen-specific T lymphocytes bind to Ag and B cells, activating them to secrete soluble B cell growth and differentiation factors. Ags that require T cell help for B cell responses are T dependent antigens. B cells do not require T cell help to respond to some antigens (usually long chain polysaccharides). These are T independent antigens.
  20. Antibody diversity
    • There may be as many as 1015 different B cells (and 1015 different Abs) in an individual. This tremendous diversity is a consequence of rearrangement of germline genes that code for the variable regions of Ab heavy and light chains and subsequent mutational events.
    • *Genes for these are formed through rearrangements of the germline DNA and later modified by mutational events.

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