5 hypersensitivity and allergies Flashcards
What is immunopathology?
The study of immune system dysfunctions that can cause tissue damage when inappropriately activated.
How can the immune system be a “two-edged sword”?
It defends against infection but can also harm the host if improperly activated.
What determines the outcome of an immune response?
The type of immune response initiated (e.g., CD4 TH1, TH2, TH17, CD8).
What regulates immune responses?
Regulatory T cells (Tregs), which suppress inappropriate activation.
What is hypersensitivity?
An inappropriate immune response leading to tissue damage or symptoms.
What are the four types of hypersensitivity?
Type I: IgE-mediated (immediate),
Type II: Antibody-mediated (IgG/IgM),
Type III: Immune complex-mediated,
Type IV: T cell-mediated (delayed).
What is Type I hypersensitivity?
An immediate allergic reaction caused by allergen-specific IgE binding to mast cells.
What immune cell type drives Type I hypersensitivity?
CD4 TH2 cells.
What cytokines are involved in Type I hypersensitivity?
IL-4, IL-5, and IL-13.
How does an allergen trigger Type I hypersensitivity?
Allergen cross-links IgE on mast cells, causing degranulation.
What are pre-formed mediators released in Type I hypersensitivity?
Histamine, heparin, TNF-α.
What are newly synthesized mediators in Type I hypersensitivity?
Leukotrienes, cytokines, and chemokines.
What are common Type I allergens?
Pollen, house dust mites, food allergens, bee venom.
What is anaphylaxis?
A severe systemic allergic reaction with widespread mast cell degranulation.
What is the genetic component of Type I hypersensitivity?
Children of allergic parents are more likely to develop allergies; linked to genes like IL-4, IL-33, and FcεRI.
What is Type II hypersensitivity?
Antibody (IgG/IgM)-mediated destruction of cells or tissues.
What immune mechanisms cause tissue damage in Type II hypersensitivity?
Antibody-dependent cell-mediated cytotoxicity (ADCC), complement activation, frustrated phagocytosis.
What are examples of Type II hypersensitivity?
Transfusion reactions, haemolytic disease of the newborn, hyperacute graft rejection.
What is haemolytic disease of the newborn (HDN)?
A condition where maternal IgG anti-Rh antibodies attack fetal RBCs.
How can HDN be prevented?
By administering anti-RhD antibodies (RhoGAM) to the mother during pregnancy.
What is Type III hypersensitivity?
Immune complex (IC)-mediated tissue damage due to failure to clear antigen-antibody complexes.
What determines immune complex size and clearance?
The ratio of antigen to antibody.
What immune cells are involved in Type III hypersensitivity?
Neutrophils, mast cells, macrophages.
What happens when immune complexes deposit in tissues?
Complement activation, neutrophil chemotaxis, inflammation, and tissue damage.
Where do immune complexes commonly deposit?
Kidney (glomerulonephritis), skin (rash), joints (arthritis).
What is the Arthus reaction?
A local Type III hypersensitivity reaction following subcutaneous antigen exposure
What are some diseases caused by Type III hypersensitivity?
Serum sickness, systemic lupus erythematosus, rheumatoid arthritis
What is Type IV hypersensitivity?
A delayed T cell-mediated immune response.
What cells mediate Type IV hypersensitivity?
CD4 TH1, TH17, and CD8 cytotoxic T cells.
What is allergic contact dermatitis?
A Type IV reaction where small chemicals (haptens) modify self-proteins, triggering a T cell response.
How do haptens induce a T cell-mediated response?
They bind self-proteins, forming new antigens that activate CD4 T cells.
What cytokines are involved in Type IV hypersensitivity?
IFN-γ, TNF-α, IL-3, GM-CSF.
What are some examples of Type IV hypersensitivity?
Tuberculin reaction, poison ivy rash, chronic graft rejection.
Why is Type IV hypersensitivity delayed?
T cell activation and cytokine-mediated inflammation take time to develop.
What is the “hygiene hypothesis”?
Reduced early-life exposure to pathogens leads to an imbalance in immune responses, increasing allergy risk.
How prevalent are allergies?
Affect 20-30% of the population.
What is the skin prick test?
A diagnostic test for allergies where allergens are introduced into the skin, and a wheal-and-flare reaction is measured.
What are the phases of asthma?
Early phase: bronchoconstriction, mucus production.
Late phase: cytokine production, inflammation, chronic airway obstruction.
What causes food allergies?
Allergen-specific IgE cross-linking on mast cells in the GI tract.
What are common symptoms of food allergies?
Oral irritation, nausea, vomiting, anaphylaxis.
What is anaphylactic shock?
A life-threatening allergic reaction involving widespread histamine release, leading to cardiovascular collapse.
How is anaphylaxis treated?
Epinephrine injection, antihistamines, corticosteroids.
What are common treatments for allergies?
Antihistamines, corticosteroids, bronchodilators, epinephrine.
What is desensitization therapy?
Gradual exposure to increasing doses of an allergen to reduce IgE-mediated responses.
How does desensitization therapy work immunologically?
It shifts the immune response from IgE to IgG4 and induces regulatory T cells.
What is Omalizumab (Xolair)?
An anti-IgE monoclonal antibody that blocks IgE binding to mast cells
What are some new immunotherapy approaches for allergies?
Blocking cytokines involved in TH2 responses, enhancing Treg function.
Why do some allergies persist into adulthood?
Failure to develop tolerance, ongoing IgE production.
How does the environment influence allergy development?
Pollution, dietary changes, and reduced microbial exposure can increase allergy risk.
What role do eosinophils play in allergic responses?
They release toxic granules that contribute to tissue damage in chronic allergic inflammation.§
What are the pre-formed mediators released from mast cells in Type I hypersensitivity?
Histamine, proteases (tryptase, chymase), and heparin.
What are newly synthesised mediators produced after mast cell activation?
Prostaglandins (e.g., PGD2), leukotrienes (e.g., LTC4, LTD4, LTE4), and platelet-activating factor (PAF).
What effects do histamine have on the body?
Increases vascular permeability, causes vasodilation, and stimulates smooth muscle contraction.
What are the roles of prostaglandins and leukotrienes in Type I hypersensitivity?
Prostaglandins (e.g., PGD2) cause vasodilation and bronchoconstriction.
Leukotrienes (e.g., LTC4, LTD4, LTE4) enhance smooth muscle contraction and increase vascular permeability.
Which immune cells are recruited during the late-phase reaction in Type I hypersensitivity?
Eosinophils, basophils, and TH2 cells.
What do eosinophils release in allergic reactions?
Major basic protein (MBP), eosinophil peroxidase (EPO), and leukotrienes.
How does omalizumab work as a treatment for IgE-mediated allergies?
It is an anti-IgE monoclonal antibody that prevents IgE from binding to FcεR on mast cells.
