Hypersensitivity reactions

Question 1

Define hypersensitivity:

Answer 1

An inappropriate innume response/inflammatory response that has deleterious effects resulting in tissue damage or death

Question 2

Hypersensitivity reactions can develop in the course of either:

Answer 2

humoral or cell-mediated responses

Question 3

Classify hypersensitivity reactions:

Answer 3

Type I: immediate (soluble antigen)
Type II: cytotoxic (cell-associated antigen)
Type III: immune complex (soluble antigen)
Type IV: delayed (soluble or cell-associated antigen)

Question 4

Which immunoglobulin is involved in type I hypersensitivity reactions?

Answer 4

IgE

Question 5

What happens during type I hypersensitivity reactions?

Answer 5

IgE antibodies bind to Fc receptors on mast cells (sensitisation). If the individual is re-exposed to the antigen, cross-linkage of the membrane bound IgE occurs.
This results in immediate release of mediators (histamine etc.)
- vasodilation, smooth muscle contraction, oedema, mucus secretion, blisters

• genetic predisposition

Question 6

How is diagnosis of type I hypersensitivity reactions performed?

Answer 6

• Skin test (prick test)
  Intradermal inoculation of antigen
• vasoactive molecules –> redness (erythema) due to capillary dilation, as well as oedema

Question 7

What are in vitro techniques for testing of type I hypersensitivity?

Answer 7

Blood: elevation of IgE and eosinophilia (but this can also be parasite infection).
‘‘Basophil activation test’’ can also be used.

Question 8

What is used for testing of allergen-specific IgE in blood serum?

Answer 8

ELISA or immunoblot

Question 9

Describe the basophil activation test:

Answer 9

incubation of heparinised blood with allergen.
CD63 and CD203c are expressed only on activated basophils.

Question 10

What happens in type II hypersensitivity reactions?

Answer 10

IgG or IgM antibodies bind to cellular antigen. Complement activation leads to cell lysis. IgG can also mediate ADCC with NK cells, macrophages and neutrophils.

Question 11

Name example of type I hypersensitivity reactions:

Answer 11

Atopic dermatitis
Food allergy
Drug allergy
Systemic anaphylaxis

Question 12

Name example of type II hypersensitivity reactions:

Answer 12

RBC destruction after transfusion with mismatched blood types or haemolytic disease of newborn.
Drug induced haemolytic anaemia.
Autoimmune haemolytic anaemia.

Question 13

How is type II hypersensitivity reactions diagnosed?

Answer 13

Cross-matching to avoid transfusion reactions.
- anticoagulant + clotted blood samples are taken from both, 2.5% suspension of washed erythrocytes in saline solution is added to undiluted serum
- incubation 30 min
If the donor erythrocytes are lysed or agglutinated by patient’s serum, no transfusion should take place

Question 14

What is the direct antiblogulin test (Coombs test)?

Answer 14

It is used to detect antibodies that already attached to the surface of red blood cells in blood from patients with haemolytic anaemia.

Question 15

How is Coombs test performed?

Answer 15

RBCs are incubated with Coombs reagent (antiglobulins)
Positive=agglutination
- autoimmune haemolytic anaemia

Question 16

What is indirect Coombs test used for?

Answer 16

Circulating (unbound) anti-erythrocyte antibodies in the serum
Screen antibodies in transfusion cross matching
Detection of antibodies in diagnosis of immune-mediated haemolytic anaemia

Question 17

What happens in type III hypersensitivity reactions?

Answer 17

• Immune complex-mediated.
  Antigen-antibody complexes are deposited in tissues. Complement activation provides inflammatory mediators and recruits neutrophils. Enzymes released from neutrophils damage tissue.

Question 18

Example of type III hypersensitivity reactions:

Answer 18

Serum sickness
Post-infectiousw glomerulonephritis
Rheumatoid arthritis

Question 19

What happens in type IV hypersensitivity deactions?

Answer 19

Th1 cells secrete cytokines, which activate macrophages and cytotoxic T cells

Question 20

Example of type IV hypersensitivity reactions:

Answer 20

Contact dermatitis
Tuberculin reaction
Granuloma formation
Diabetes mellitus type I

Question 21

How is type III hypersensitivity diagnosed?

Answer 21

Latex agglutination: for rheumatoid factor [RF]^94.

Question 22

What is used for detection of deposition of immune complexes in patients with autoimmune diseases?

Answer 22

Indirect immunofluorescence, immunoblotting or ELISA

Question 23

What happens in precipitation of immune complexes?

Answer 23

Serum is precipitated with polyethylene glycol, for detection of presence of circulating immune complexes.
Intensity of turbidity is proportional to the amount of circulating immune complexes.

Question 24

What is type IV hypersensitivity reactions referred to as?

Answer 24

Delayed-type hypersensitivity

Question 25

How is type IV hypersensitivity diagnosed?

Answer 25

Patch test - contact dermatitis
Tuberculin reaction (Mantoux Skin Test)
Mallein Test

Question 26

Describe tuberculin reaction (type IV hypersensitivity)

Answer 26

Purified protein derivative tuberculin is used to extract M. bovis or M. avium to skin test animals for tuberculosis.
Intradermal injection into a sensitised animal –> swelling, inflammation after 12-24 hours.
Mediated by T cells.

Question 27

Positive reaction in the tuberculin skin test in cattle:

Answer 27

presence of clinical signs or thickening of skin more than 4 mm