hypersensitivity Flashcards
6 pages - lecture 11
define hypersensitivty
immune reactions that are damaging rather than helpful to the host. over-reactions.
how many types of hypersensitivity and their mediator?
4 types, the first due to antibody, the fourth by T cells.
the cause of type 1?
contact to an antigen to which the host has a pre-existing IgE antibody. mast cells activated by crosslinking FcetaR1 via antigen binding to the bound IgE, causing degranulation of histamine/serotonin, increased vascular permeability, smooth muscle contraction and synthesis of secondary inflammatory mediators. (leukotrienes, prostaglandins, cytokines.
define Atopy
Atopy or atopic syndrome is a predisposition toward developing certain allergic hypersensitivity reactions. Atopy may have a hereditary component, although contact with the allergen must occur before the hypersensitivity reaction can develop.
3 examples of type 1 hypersensitivity
1 - hayfever (allergic rhinitis)
2 - eczema
3 - asthma
give 5 groups of common allergens and specific examples of each
1 - pollens - oli seed rape 2 - foods - nuts/eggs/seafood 3 - drugs - penicillin, aspirin 4 - insect products - bee venom/ house dust mite 5 - animal hair - cat hair and dander
common characteristics of allergens?
1 - often proteases, generally low MW and highly soluble (hence readily diffusible), generally stable and can survive as a desiccated particle. contain peptides that bind MHC2 to prime T cells. low dose may favour IL4, Th2 responses
how do you determine sensitivity to allergens?
a skin-prick test. a “wheal and flare” will appear at site within about 30mins.
wheal is swelling/edema, redness is falre/erythema.
incidence of type 1 sensitivity in the population?
abotu 20-30%
serum IgE in atopic individuals?
raised to 10-100 times normal level?
potential selective advantage of atopy?
orprotect against parasites ie in tropical countries - muscular contractions are needed to expel them from the GI.
define systemic anaphylaxis. treatment?
increased permeability of blood vessels resulting in extreme blood pressure drop and anaphylactic shock. treat with antihistamine, corticosteroids and avoidance of allergen. In some cases desensitisation may be achieved by gradual exposure to increasing doses to convert a Th1 to a Th2 response.
cause of type 2 hypersensitivity?
IgM or IgG binding to cells or tissue antigens.
penicillin hypersensitivity?
type 2.
haemolytic anaemia or thrombocytopenia. (RBCs or platelet destruction)
the drug binds the cell surface in a minority and triggers clearance by spleen tissue macrophages via Fcgamma receptors, or by complement lysis.
blood transfusion hypersensitivity?
type 2.
the ABO blood group is special as its the only histocompatability alloantigen for which a preexisting antibody is present in naive recipients.
induced by natural exposure to similar antigenic determinants on microorganisms in the gut.
ABO structure and prevalence?
all have a core H antigen. o = unmodified a = terminal N-acetylgalactosamine b = terminal galactose ab= both a - 40% b - 11% ab - 4% o = 45%
universal donor?
OO
whats the rhesus reaction?
reaction to the rhesus RBC antigen. you’re either Rh+ or Rh-. can cause haemolytic disease of the newborn
what is haemolytic disease of the newborn?
a type 2 rhesus reaction.
mother is negative, child is positive, RBCs leak into maternal circulation at birth, adaptive response, then IgG can cross the placenta and compromise the subsequent baby. countered by giving anti-Rh antibody to the mother before she reacts to her child’s RBCs.
describe a type 3 hypersensitivity reaction
soluble antigen in high quantities (low causes IgE) causing IgG response. immune complexes deposit in tissues, trigger mast cells via the low affinity FcgammaRIII receptor. complement activated, polymorphs attracted, local tissue damage and inflammation.
examples of type 3 hypersensitivity?
post infection complications such as arthritis and glomerulonephritis.
what’s an arthus reaction?
a local type 3 hypersensitivity reaction. triggered in the skin of sensitised individuals who have IgG against the sensitising antigen.
what is serum sickness?
used to result from high doses of horse serum to treat pneumonia. rarely seen now but serum injection still used as anti-snake venom.
causes fever, vasculitis, arthritis and nephritis
describe type 4 hypersensitivity
delayed type hypersensitivity.
mediated by T cells, release cytokines, recruit mononuclear cells. effect maximal in 48-72 hours.
classical example is the mantoux test to TB. amount of antigen required is generally 10-100 times more than for antibody mediated hypersensitivity.
what is contact hypersensitivity?
cutaneous, type 4 hypersensitivity to haptens, which form stable complexes with host proteins. ie poison ivy, metal salts and small reactive chemicals. often damage is via Th1 cells activating macrophages they present antigen to T cells and amplify the response and release inflammatory mediators
what orchestrates a type 4 hypersensitivity reaction? how?
Th1 CD4 cells respond to antigen when presented by tissue macrophages.
release cytokines eg:
1 - chemokines - recruit macrophages
2 - IFNgamma - induce expression of vascular adhesion molecules. activate macrophages, increase release of inflammatory mediators.
3 - TNFalpha/beta - local tissue destruction. increase vessel adhesion molecule expression.
4 - IL3/GM-CSF : stimulate monocyte produciton by bone marrow cells
difference of timescales between types of hypersensitivity reaction?
1 - 2-30mins - IgE mediated
2 - 5-8hours - antibody mediated cytotoxic
3 - 2-8 hours - immune complex mediated
4 - 24-72 hours- cell mediated
