Hypersensitivities Flashcards
As a doctor, what allergies are important to ask about ?
Latex
Iodine
Elastoplast
Explain how type II hypersensitivity occurs.
IgG antibody binding to components of cell membranes or ECM. These components can be self (e.g. self proteins), or exogenous.
Give examples of type II hypersensitivity reactions.
Goodpasture’s Syndrome (antibodies bind to self component): antibodies bind to collagen type IV in basement membrane, which causes glomerulonephritis in the kidney, and sometimes pulmonary haemorrhage.
Reaction to penicillin (antibodies bind to extraneous component): penicillin forms bond with surface protein of RBC. This modified protein forms a neo-antigen which can be taken up by macrophages and degraded into fragments. T cells will then be activated by recognition of antigen displayed on macrophage. T cell activation results in B cell priming producing antibodies against neoantigen. These B cells will wait in the lymph nodes until next administration of penicillin, at which point, they will produce IgG which will bind to penicillin-modified protein on RBC and result in a) activation of complement system, and therefore RBC lysis, (by formation of membrane attack complex), or b) phagocytosis of RBC (by macrophages etc.). These can lead to (heamolytic, since some lysis) anaemia.
What kind of hypersensitivity is hypersensitivity to penicillin ?
Can be type I or type II
Explain how type III hypersensitivity occurs.
-Usually IgG (but also sometimes IgM), directed to soluble antigens.
-Excess immune complex present leads to deposition in tissues, where they can elicit complement activation, resulting in localised inflammation (and thus tissue lesions) and vasodilation.
(formation of said antibody-antigen complexes is normal).
In normal physiology, how does immune complex deposition, and clearance occur ?
-Formed from the integral binding of an antibody to a soluble antigen. At the start of immune response, more antigens than antibodies, small immune complexes (at this stage cannot be cleared). At intermediate stages (after B cells are primed), comparable numbers of antibodies and antigens (can be cleared). Later, more antibodies than antigens (can be cleared).
-Usually cleared by activation of: Reticuloendothelial system (RES): macrophages, neutrophils in liver spleen and bone marrow that ingest and degrade immune complexes
Identify the sites in the body where immune complexes get deposited and cause type III hypersensitivity.
NOT necessarily the sites from where the antigen is derived!
1) Glomeruli: IC deposited because of filtration process, causing damage due to complement activation
2) Blood vessel walls: IC deposited in walls of arteries and veins, causing vasculitis (seen as skin lesions if present close to surface)
3) Skin: causes rashes
4) Systemic sites: for instance systemic lupus erythematosus, where IC deposited in kidney, joints, skin, vasculature, muscle and other organs.
5) Synovial membranes: In rheumatoid arthritis, IgG in immune complex itself becomes an antigen itself, causing IgM Rheumatoid factor antibodies to develop, causing localised joint damage.
Explain how type IV hypersensitivity occurs.
-Entirely cell-mediated and complements do NOT contribute
-Most Type IV reaction due to CH4+ delayed (i.e. 2 to 4 days after antigen exposure) type hypersensitivity (DTH) reactions:
CD4+ Th1 helper T cells recognize foreign antigen on the surface of antigen-presenting cells. CD4+ T cells secrete cytokines (e.g. IL-2 and interferon gamma) which act on vascular endothelium. Recruitment of T cells, phagocytes, fluid, and proteins to the site of antigen injection causes visible lesion.
Macrophages that cause damage are not specific, harm infected and non-infected tissue
This all results in a presentation of chronic inflammation, including walling off of the infectious sites, granulomas (remnants of these granulomas are the tubercles seen in tuberculosis)
Identify pathogens associated with DTH.
M. tuberculosis, Listeria, M. leprae,
Give examples of contact sensitivities/dermatites.
- Heavy metal sensitivity
- Poison Ivy (reaction in skin to catechols)
- Elastoplast
Define contact dermatitis, and its symptoms.
Special kind of DTH reaction called contact sensitivities (i.e. contact dermatitis)- antigen not an infectious agent, but a chemical binding to cell surface
Classically it presents as red blistered skin.
Identify autoimmune diseases which an be classified in same way as hypersensitivity type II reactions. Also name the consequences of each autoimmune disease identified.
♣ Autoimmune hemolytic anemia- Destruction of RBCs, anaemia
♣ Autoimmune thrombocytopenic purpura- Abnormal bleeding
♣ Goodpasture’s syndrome- glomerulonephritis, lung haemorrhage
♣ Pemphigus vulgaris- Skin blisters
♣ Acute rheumatic fever- arthritis, myocarditis, valve scarring
Identify autoimmune diseases which an be classified in same way as hypersensitivity type III reactions. Also name the consequences of each autoimmune disease identified.
♠ Mixed essential cyoglobulinemia (cold temperatures result in complement activation): systemic vasculitis
♠ SLE: glomerulonephritis, vasculitis, rash
♠ Rheumatoid arthritis: Joint inflammation and destruction
Identify autoimmune diseases which an be classified in same way as hypersensitivity type IV reactions. Also name the consequences of each autoimmune disease identified.
♦ (Type 1) Insulin Dependant Diabetes Mellitus: β-cell destruction
♦ Rheumatoid arthritis (cell-mediated aspect of it): Joint inflammation and destruction
♦ Multiple Sclerosis (T cells damage coat surface of nerve cells): NS damage
