Exam 3

Hypersensitivity:

• Describe the 3 Stages of Type 1 hypersensitivity

  The three stages of Type 1 hypersensitivity are:

1. Sensitization phase: Dendritic cells internalize antigens and activate Th2 cells, which secrete IL-4 and IL-13. This activates B cells to produce IgE, which attaches to the surface of mast cells.
2. Activation phase: When the allergens bind to the IgE on mast cells, crosslinking of Fc receptors initiates complex intracellular signaling events within the mast cell. This triggers the degranulation of mast cells and basophils in connective tissues.
3. Late phase: Mast cells and basophils synthesize other reactants from the breakdown of phospholipids in the cell membrane. These mediators are responsible for late-phase allergic reactions, occurring 6-8 hours after exposure to the allergen.

• Explain the degranulation process in mast cells and basophils
  • When an allergen binds to IgE on the surface of mast cells or basophils, it causes crosslinking of the Fc receptors on the cells.
  • This initiates complex intracellular signaling events within the cells, triggering the degranulation of histamine and other chemical mediators stored in the granules of the cells.
  • The degranulation process releases these chemical mediators into the surrounding tissues, leading to symptoms such as vasodilation, bronchoconstriction, and increased vascular permeability.
• Compare and contrast the cells, chemical mediators and antibodies involved in the 4 basic types of hypersensitivity reactions

• Explain the immunological mechanisms and pathologic features behind the 4 basic types of hypersensitivity reactions

  • Type I hypersensitivity, also known as immediate IgE hypersensitivity or anaphylactic, involves antigens triggering a Th2 cell-mediated immune response.
  • This results in the production of IgE antibodies, which attach to mast cells and basophils. When the allergen binds to the IgE on the mast cells, it initiates complex intracellular signaling events within the cells.
  • This triggers the degranulation of mast cells and basophils in connective tissues, releasing histamine and other chemical mediators that cause symptoms such as vasodilation, bronchoconstriction, and increased vascular permeability.
  • Type II hypersensitivity, also known as antibody-mediated cytotoxic hypersensitivity, is caused by antibodies IgG, IgM, or complement. IgG or IgM antibodies can coat cells, causing cell injury or death, while complement activation can lead to antibody-dependent cellular cytotoxicity (ADCC).
  • Type III hypersensitivity, or immune complex-mediated hypersensitivity, occurs when large amounts of antigen-antibody complexes form in blood.
  • Neutrophils and macrophages bind to immune complexes via Fc receptors and phagocytize the complexes. But if they deposit in capillaries or joints, they can cause inflammation via complement activation.
  • Type IV hypersensitivity, or T cell-mediated hypersensitivity, involves sensitized Th1 cells and no antibody involvement.
  • Activated Th1 cells secrete cytokines that induce a localized inflammatory reaction, causing inflammation and tissue damage.
  • This type of hypersensitivity is triggered by intracellular pathogens or contact antigens such as poison ivy, metals, hair dyes, cosmetics, and latex sensitivity.

• Describe any treatment options listed in the ppt

• Explain various types of testing used to diagnose the types of hypersensitivities: including the principles and interpretation of test results

  There are various types of testing used to diagnose the types of hypersensitivities. These include:

• IgE levels (allergen specific and total) testing: This includes RAST (radioallergosorbent test), RIST (radioimmunosorbent test), and the immunofluorescent EIA test. RAST and RIST measure total IgE levels, while the immunofluorescent EIA test measures specific IgE allergens.
• Skin testing: This includes percutaneous skin pricks for food or inhalation allergies and intradermal skin tests which are more sensitive and use more allergen.
• Direct antiglobulin test: This detects red cells that have been coated with antibodies or complement. It is used to detect transfusion reactions, HDFN, AIHA, and DIHA. It detects invivo Ag-Ab complexes.
• Indirect antiglobulin test: This is used to determine if an individual has an antibody in their plasma that will react with red cells. It is used to detect incompatibility from IgG antibodies and detects invitro Ag-Ab complexes.

  The interpretation of test results for IgE levels depends on the test used. For skin testing, a positive reaction is indicated by a wheal and flare reaction. The interpretation of direct and indirect antiglobulin tests depends on the presence or absence of invivo or invitro Ag-Ab complexes, respectively.

• Describe the principle and purpose of Interferon Gamma Release Assays
  • Interferon Gamma Release Assays (IGRAs) are an alternative to the traditional tuberculin skin test for detecting latent tuberculosis (TB) infections.
  • The principle of IGRAs is based on the detection of interferon-gamma (IFN-γ) released by T cells in response to stimulation with TB-specific antigens.
    • There are two types of IGRAs: the Quantiferon TB Gold Plus assay and the T-SPOT-TB test.
    • In the Quantiferon TB Gold Plus assay, patient blood is incubated in special tubes with TB antigens, and plasma is tested for IFN-γ by ELISA.
    • In the T-SPOT-TB test, patient mononuclear cells are incubated with TB antigens and tested for IFN-γ by ELISpot.
  • The purpose of IGRAs is to diagnose latent TB infections, which are not contagious but can develop into active TB if left untreated.