Type I Diabetes and Other Autoimmune Diseases Flashcards
What is the mechanism of Type I hypersensitivity reactions?
- Exposure to allergen activates TH2 cells which stimulate B cells to proliferate, undergo heavy-chain class switching to IgE, and differentiate into IgE-secreting plasma cells and memory B cells with IgE-specific receptors
- The secreted IgE antibodies bind to IgE-specific Fc receptors on basophils and mast cells
- Second exposure to allergen causes cross-linking of the IgE antibodies, causing degranulation (a signal cascade that leads to the release of mediators into the blood and tissue)
What are the mediators involved in Type I hypersensitivity reactions?
Histamine, heparin, proteases
Act on the surrounding tissues and other immune cells, causing allergy symptoms:
- Increased vascular permeability
- Vasodilation
- Smooth muscle contraction
What is a Type II hypersensitivity reaction?
Antibody-mediated destruction of cells by IgG and IgM
Provide 2 examples of Type II hypersensitivity reactions.
Transfusion reactions
Haemolytic disease of the newborn (erythroblastosis fetalis)
Explain transfusion reactions.
Individuals have different blood types (A, B, or O) which express different carbohydrate antigens
An individual with blood type A, for example, is tolerant of their own antigen (Type A). If they receive blood that is type B, anti-B antibodies are produced against the B carbohydrate antigen.
This causes destruction of the transfused RBCs.
Explain erythroblastosis fetalis.
Occurs when a Rh– mother carries a Rh+ foetus
When a Rh– mother is pregnant for the first time, she is not exposed to enough foetal blood cells to activate Rh-specific B cells
Upon time of delivery, the placenta is separated from the uterine wall, causing large amounts of Rh+ foetal blood to enter the mother’s bloodstream
- IgM antibodies clear the foetal RBCs from the mother’s blood (do not pose a threat as they don’t pass through the placenta)
- Memory B cells specific for the foetal Rh+ RBCs remain (poses a threat for subsequent pregnancies with Rh+ foetus)
Second pregnancy with Rh+ foetus leads to the activation of IgG-secreting plasma cells
- The secreted IgG can cross the placenta and damage Rh+ foetal RBCs
What is Type III hypersensitivity reaction?
Large numbers of immune (antibody-antigen) complexes that can lead to tissue damage, peculiarities in the antigen, or disorders in the phagocytic machinery
Arthus reactions are localised type III hypersensitivity reactions. Describe the mechanism in place.
Caused by insect bites or inhalation of fungal and animal proteins – the individual has antibodies for these antigens
Immune complexes are formed to facilitate the clearance of these antigens. However, large numbers of immune complexes can lead to deposition of immune complexes in the blood vessels
As a result, there is recruitment of complement components and neutrophils to the site - exhibited by tissue injury and inflammation of blood vessels in the skin or other tissue
What is type IV hypersensitivity reaction?
Also known as delayed type hypersensitivity (DTH)
The only hypersensitivity category that is purely cell mediated and not antibody mediated
Sensitised T cells (TH1 and TH2) release cytokines that activate macrophages or CTLs which mediate direct cell damage
Describe the sensitisation and effector phase of DTH.
Sensitisation
- After initial exposure to intracellular-derived antigen, CD4+ T cells proliferate and differentiate into TH1 cells
- TH1 cells release cytokines and chemokines
Effector
- The cytokines and chemokines (including IFN-gamma) recruit and activate macrophages + other inflammatory cells
- Activated macrophages are more effective in antigen presentation, perpetuating DTH response = Primary effector cell
Give three manifestations of DTH
Tuberculosis
Contact dermatitis
Type 1 Diabetes
- Autoimmune disease resulting from the body’s failure to produce insulin due to destruction of insulin producing beta cells in the pancreas
