Adaptive Immune System Notes

Adaptive Immune System

  • Identifies specific invaders and mounts an attack.
  • Response is variable and depends on the pathogen.
  • Two divisions:
    • Humoral immunity
    • Cell-mediated cytotoxic immunity.

Cells of the Adaptive Immune System

  • Two main types of lymphocytes:
    • B cells: Govern the humoral response.
    • T cells: Mount the cell-mediated response.
  • All immune cells are created in the bone marrow.
  • B cells mature in the bone marrow and spleen.
  • T cells mature in the thymus.
  • Adaptive immune response takes time so symptoms may take days to be relieved.

Humoral Immunity

  • Involves the production of antibodies. May take up to a week to become effective after initial infection.
  • Antibodies are specific to the antigens of the invading microbe.
  • Antibodies are produced by B cells, which originate and mature in the bone marrow, and are activated in the spleen and lymph nodes.
  • Antibodies (immunoglobulins or Ig) can be on the surface of cells or secreted into body fluids.
  • Response depends on the location of the antibody:
    • Antibodies in body fluids:
      • Opsonization: Attract other leukocytes to phagocytize antigens.
      • Agglutination: Cause pathogens to clump together, forming large insoluble complexes that can be phagocytized.
      • Neutralization: Block the ability of a pathogen to invade tissues.
    • Cell surface antibodies:
      • Binding of antigen to a B cell causes activation, proliferation, and formation of plasma and memory cells.
      • Binding of antigen to antibodies on a mast cell causes degranulation, releasing histamine and causing an inflammatory allergic reaction.
  • Antibodies are Y-shaped molecules with two identical heavy chains and two identical light chains, held together by disulfide linkages and noncovalent interactions.
  • Antigen-binding region (variable region domain) at the tips of the Y binds to a specific antigenic sequence. B cells undergo hypermutation of their antigen-binding region to find the best match; only those that bind with high affinity survive (clonal selection).
  • Constant region domain is recognized by cells like natural killer cells, macrophages, monocytes, and eosinophils, and can initiate the complement cascade.
  • Each B cell makes only one type of antibody. Antibodies come in five isotypes: IgM, IgD, IgG, IgE, and IgA, used at different times during the adaptive immune response.
  • Isotype switching: Cells can change which isotope they produce when stimulated by specific cytokines.
  • Naive B cells wait in the lymph nodes for their antigen. Upon exposure, they proliferate and produce:
    • Plasma cells: Produce large amounts of antibodies.
    • Memory B cells: Stay in the lymph node awaiting re-exposure.
  • Primary response: Initial activation takes approximately 7-10 days.
  • Secondary response: If the same microbe is encountered again, memory cells rapidly proliferate and differentiate into plasma cells, producing a more rapid and robust response.
  • Development of memory cells is the basis of vaccination.

Cytotoxic Immunity

  • Involves T cells, which mature in the thymus undergo:
    • Positive selection: Only cells that can respond to the presentation of antigen on MHC survive.
    • Negative selection: Causing apoptosis in cells that are self reactive, activated by proteins produced by the organism itself.
  • Thymosin, a peptide hormone secreted by thymic cells, facilitates T cell maturation.
  • Mature but naive T cells undergo clonal selection upon exposure to antigen.
  • Three major types of T cells:
    • Helper T cells (Th or CD4+ T cells): Coordinate the immune response by secreting lymphokines, which recruit other immune cells and increase their activity. Respond to antigens presented on MHC II molecules, effective against bacterial, fungal, and parasitic infections. In advanced HIV infection, also called acquired immunodeficiency syndrome, AIDS, even weak pathogens can cause devastating consequences as opportunistic infections.
    • Cytotoxic T cells (Tc or CTL, CD8+ T cells): Directly kill virally infected cells by injecting toxic chemicals that promote apoptosis. Respond to antigens presented on MHC I molecules. Effective against viral and intracellular bacterial or fungal infections.
    • Suppressor or regulatory T cells (Treg): Help tone down the immune response once the infection has been contained and turn off self-reactive lymphocytes to prevent autoimmune diseases (self-tolerance). Express CD4 and FOXP3.
  • Memory T cells: Lie and wait until the next exposure to the same antigen. When activated, they carry out a more robust and rapid response.

Activation of the Adaptive Immune System

  • Innate and adaptive immune systems interact.
  • Five types of infectious pathogens: bacteria, viruses, fungi, parasites (including protozoa, worms, and insects), and prions.
  • Immune system response depends on the pathogen, examples being extracellular and intracellular pathogen infections.

Bacterial Extracellular Pathogen Infections

  • Macrophages engulf bacteria and release inflammatory mediators.
  • Macrophages digest the bacteria and present antigens on their surfaces in conjunction with MHC II.
  • Cytokines attract inflammatory cells, including neutrophils and additional macrophages.
  • Mast cells are activated by the inflammation and degranulate, releasing histamine and increasing leakiness of capillaries.
  • Dendritic cells travel to the nearest lymph node and present the antigen to B cells.
  • B cells proliferate through clonal selection to create plasma cells and memory cells.
  • Antibodies travel through the bloodstream to the affected tissue where they tag the bacteria for destruction.
  • Dendritic cells also present the antigen to T cells, activating CD4+ T cells which come in two types:
    • Th1 cells: Release interferon gamma (IFN
      gamma), which activates macrophages and increases their ability to kill bacteria.
    • Th2 cells: Help activate B cells and are more common in parasitic infections.
  • After the pathogen has been eliminated, plasma cells die, but memory B and T cells remain, allowing for a faster secondary response upon exposure at a later time.

Viral Intracellular Pathogen Infections

  • Virally infected cells produce interferons which:
    • Reduce the permeability of nearby cells.
    • Reduce the rate of transcription and translation in these cells.
    • Cause systemic symptoms (malaise, muscle aching, fever).
  • Infected cells present intracellular proteins on their surface in conjunction with MHC I. CD8+ T cells recognize the MHC I and antigen complex as foreign and inject toxins into the cell to promote apoptosis.
  • If the virus down regulates the production and presentation of MHC I molecules, natural killer cells will recognize the absence of MHC I and cause apoptosis of these cells.
  • Memory T cells are generated for a faster response to a second exposure.

Recognition of Self and Non-self

  • Self-antigens are the proteins and carbohydrates present on the surface of every cell of the body and signal to immune cells that the cell is not foreign.
  • Autoimmunity: The immune system attacks cells expressing particular self-antigens.
  • Allergic reaction: The immune system misidentifies a foreign antigen as dangerous when it is not.
  • Autoimmunity and allergies are classified as hypersensitivity reactions.
  • T cells are educated in the thymus, where negative selection eliminates T cells that respond to self-antigens.
  • Immature B cells that respond to self-antigens are eliminated before they leave the bone marrow.
  • Autoimmune diseases can be treated with glucocorticoids, modified versions of cortisol.

Immunization

  • Active immunity: The immune system is stimulated to produce antibodies against a specific pathogen through:
    • Natural exposure: Antibodies are generated by B cells once an individual becomes infected.
    • Artificial exposure (vaccines): Injection or intra nasal spray containing an antigen that activates B cells to produce antibodies, includes weakened or killed forms of the microbe, or a part of the microbe's protein structure.
  • Passive immunity: Results from the transfer of antibodies to an individual, is transient, examples being:
    • Transfer of antibodies across the placenta during pregnancy.
    • Transfer of antibodies from the mother to her nursing infant through breast milk.
    • Intravenous immunoglobulin given to prevent the pathogen from spreading.