hypersensitivity

Question 1

define hypersensitivty

Answer 1

immune reactions that are damaging rather than helpful to the host. over-reactions.

Question 2

how many types of hypersensitivity and their mediator?

Answer 2

4 types, the first due to antibody, the fourth by T cells.

Question 3

the cause of type 1?

Answer 3

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.

Question 4

define Atopy

Answer 4

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.

Question 5

3 examples of type 1 hypersensitivity

Answer 5

1 - hayfever (allergic rhinitis)
2 - eczema
3 - asthma

Question 6

give 5 groups of common allergens and specific examples of each

Answer 6

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

Question 7

common characteristics of allergens?

Answer 7

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

Question 8

how do you determine sensitivity to allergens?

Answer 8

a skin-prick test. a “wheal and flare” will appear at site within about 30mins.
wheal is swelling/edema, redness is falre/erythema.

Question 9

incidence of type 1 sensitivity in the population?

Answer 9

abotu 20-30%

Question 10

serum IgE in atopic individuals?

Answer 10

raised to 10-100 times normal level?

Question 11

potential selective advantage of atopy?

Answer 11

orprotect against parasites ie in tropical countries - muscular contractions are needed to expel them from the GI.

Question 12

define systemic anaphylaxis. treatment?

Answer 12

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.

Question 13

cause of type 2 hypersensitivity?

Answer 13

IgM or IgG binding to cells or tissue antigens.

Question 14

penicillin hypersensitivity?

Answer 14

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.

Question 15

blood transfusion hypersensitivity?

Answer 15

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.

Question 16

ABO structure and prevalence?

Answer 16

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%

Question 17

universal donor?

Answer 17

OO

Question 18

whats the rhesus reaction?

Answer 18

reaction to the rhesus RBC antigen. you’re either Rh+ or Rh-. can cause haemolytic disease of the newborn

Question 19

what is haemolytic disease of the newborn?

Answer 19

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.

Question 20

describe a type 3 hypersensitivity reaction

Answer 20

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.

Question 21

examples of type 3 hypersensitivity?

Answer 21

post infection complications such as arthritis and glomerulonephritis.

Question 22

what’s an arthus reaction?

Answer 22

a local type 3 hypersensitivity reaction. triggered in the skin of sensitised individuals who have IgG against the sensitising antigen.

Question 23

what is serum sickness?

Answer 23

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

Question 24

describe type 4 hypersensitivity

Answer 24

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.

Question 25

what is contact hypersensitivity?

Answer 25

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

Question 26

what orchestrates a type 4 hypersensitivity reaction? how?

Answer 26

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

Question 27

difference of timescales between types of hypersensitivity reaction?

Answer 27

1 - 2-30mins - IgE mediated
2 - 5-8hours - antibody mediated cytotoxic
3 - 2-8 hours - immune complex mediated
4 - 24-72 hours- cell mediated