Week 32 - Immunopathology

• Problems with the immune system

  • Hypersensitivity
  • Deficient immune response
  • Autoimmunity
• Hypersensitivity, or an overactive immune system may respond to foods or pollen, leading to allergic and other responses
• The immune response may be deficient from birth or after infection (such as with HIV)
• The immune response may mutiny and start attacking the body damaging vital tissues. This is called autoimmunity
• An allergic response is triggered when an IgE antibody becomes cross-linked with an allergen on the surface of a mast cell
• Cross-linking in allergic response

  1. Allergen, such as pollen, binds two adjacent IgE molecules

  2. Mast cells contain secretory granules packed with histamine and other inflammatory molecules
• Allergic diseases

  • Asthma
  • Eczema
  • Hay fever
  • Rhinitis
  • Anaphylaxis
• Genes, the environment, and atopic (allergic) disease development are important determinants
• The “hygiene hypothesis” suggests that exposure to some infectious agents in childhood drives the immune system to a general state of Th1 responsiveness and no allergy development
• With allergy genes, a very clean environment, and a certain composition of gut bacteria, some children mount mainly Th2 responses which can lead to many allergic responses leading to eczema and asthma symptoms
• Steps that generate an allergic response to pollen

  1. Previous exposure to the allergen

  2. Production of IgE by B cells and arming of mast cell with pollen-specific IgE antibodies

  3. Re-exposure to the same pollen leads to a hay fever response (acute rhinitis) as the IgE antibody gets cross-linked with pollen on the surface of the mast cell
• Degranulation of mast cells


  Binding to antigen from a microbe such as a parasite worm or from an allergen such as house dust mite
• Immunodeficiency diseases

  • Primary immunodeficiency
  • Secondary immunodeficiency
• Primary immunodeficiency is the “inherited” version and secondary immunodeficiency is due to an infection
• In SCID, children are born without working B and T lymphocytes and 1/30,000 children are affected
• A tissue matched bone marrow transplant is the only cure for SCID, but a recent paper has used a disabled virus to get a working copy of the defective gene into the body. Of 16 children given this treatment, 14 are now living normal lives
• Acquired Immunodeficiency is caused by an infectious agent, even before birth. HIV infection, which leads to the development of AIDS (acquired immunodeficiency syndrome) is an infamous example
• Acquired Immunodeficiency is a disease caused by an infectious agent, even before birth. HIV infection leads to the development of AIDS (acquired immunodeficiency syndrome)
• The course of HIV infection (without anti-retroviral treatment) which leads to AIDS

  1. Clinical symptoms indicative of AIDS typically do not appear till about 8 years after infection

  2. From this point onwards, levels of CD4+ T helper cells are reaching extremely low levels

  3. This leads to a very sharp increase in viral load and many opportunistic infections will take hold in the patient as they are now severely immunocompromised
• Example of antigen mimicry

  • Between a structurally similar streptococcal Group A cell wall epitope and an epitope found on heart valves
• Selective destruction of pancreatic β cells in type 1 diabetes by cytotoxic T lymphocytes

  1. Highly specific cytotoxic T cells destroy just the β cells producing insulin in the pancreatic islets

  2. The morphology of the islet structure is disrupted by the loss of the β cells and the massive invasion of cytotoxic T lymphocytes
• Autoantibodies block normal acetylcholine receptor function in the disease Myasthenia gravis


  1. Autoantibodies in blue bind to the acetylcholine receptors (in green)

  2. These antibodies block the binding of sodium ions (purple dots) to the acetylcholine receptors

  3. Complement is also activated which damages the muscle end plate

  4. The number of acetylcholine receptors decreases as the disease progresses due to receptor internalisation
• Transplantation Immunology

  1. Grafted tissue taken from one site to another on the same person is termed an autograft and are always accepted with no rejection

  2. Grafts between genetically non-identical members of the same species are called allografts and are rejected unless immunosuppressive therapy is given

  3. Grafts between members of a different species, e.g. mouse to rabbit, is called a xenograft and are rapidly rejected