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19.1 Hypersensitivities

  • An allergy is an adaptive immune response, sometimes life-threatening, to an allergen.
  • Type I hypersensitivity requires sensitization of mast cells with IgE, involving an initial IgE antibody response and IgE attachment to mast cells. On second exposure to an allergen, cross-linking of IgE molecules on mast cells triggers degranulation and release of preformed and newly formed chemical mediators of inflammation. Type I hypersensitivity may be localized and relatively minor (hives and hay fever) or system-wide and dangerous (systemic anaphylaxis).
  • Type II hypersensitivities result from antibodies binding to antigens on cells and initiating cytotoxic responses. Examples include hemolytic transfusion reaction and hemolytic disease of the newborn.
  • Type III hypersensitivities result from formation and accumulation of immune complexes in tissues, stimulating damaging inflammatory responses.
  • Type IV hypersensitivities are not mediated by antibodies, but by helper T-cell activation of macrophages, eosinophils, and cytotoxic T cells.

19.2 Autoimmune Disorders

  • Autoimmune diseases result from a breakdown in immunological tolerance. The actual induction event(s) for autoimmune states are largely unknown.
  • Some autoimmune diseases attack specific organs, whereas others are more systemic.
  • Organ-specific autoimmune diseases include celiac disease, Graves disease, Hashimoto thyroiditis, type I diabetes mellitus, and Addison disease.
  • Systemic autoimmune diseases include multiple sclerosis, myasthenia gravis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.
  • Treatments for autoimmune diseases generally involve anti-inflammatory and immunosuppressive drugs.

19.3 Organ Transplantation and Rejection

  • Grafts and transplants can be classified as autografts, isografts, allografts, or xenografts based on the genetic differences between the donor’s and recipient’s tissues.
  • Genetic differences, especially among the MHC (HLA) genes, will dictate the likelihood that rejection of the transplanted tissue will occur.
  • Transplant recipients usually require immunosuppressive therapy to avoid rejection, even with good genetic matching. This can create additional problems when immune responses are needed to fight off infectious agents and prevent cancer.
  • Graft-versus-host disease can occur in bone marrow transplants, as the mature T cells in the transplant itself recognize the recipient’s tissues as foreign.
  • Transplantation methods and technology have improved greatly in recent decades and may move into new areas with the use of stem cell technology to avoid the need for genetic matching of MHC molecules.

19.4 Immunodeficiency

  • Primary immunodeficiencies are caused by genetic abnormalities; secondary immunodeficiencies are acquired through disease, diet, or environmental exposures
  • Primary immunodeficiencies may result from flaws in phagocyte killing of innate immunity, or impairment of T cells and B cells.
  • Primary immunodeficiencies include chronic granulomatous disease, X-linked agammaglobulinemia, selective IgA deficiency, and severe combined immunodeficiency disease.
  • Secondary immunodeficiencies result from environmentally induced defects in B cells and/or T cells.
  • Causes for secondary immunodeficiencies include malnutrition, viral infection, diabetes, prolonged infections, and chemical or radiation exposure.

19.5 Cancer Immunobiology and Immunotherapy

  • Cancer results from a loss of control of the cell cycle, resulting in uncontrolled cell proliferation and a loss of the ability to differentiate.
  • Adaptive and innate immune responses are engaged by tumor antigens, self-molecules only found on abnormal cells. These adaptive responses stimulate helper T cells to activate cytotoxic T cells and NK cells of innate immunity that will seek and destroy cancer cells.
  • New anticancer therapies are in development that will exploit natural adaptive immunity anticancer responses. These include external stimulation of cytotoxic T cells and therapeutic vaccines that assist or enhance the immune response.
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