Hypersensitivity Reaction

Question 1

Define hypersensitivity. (3)

Answer 1

The antigen-specific immune responses that are inappropriate or excessive, and result in harm to the host.

Question 2

Briefly describe the four types of hypersensitivity reaction. (8)

Answer 2

I - immediate (Allergy) - IgE Reaction to environmental or non-infectious antigens
II - antiBody mediated - IgG or IgM against cell bound antigens.
III - immune Complex mediated - IgG or IgM against soluable antigens
IV - cell mediated (Delayed) - environmental or infectious agents, or self antigens.

Question 3

Describe the common phases of all hypersensitivity reactions. (4)

Answer 3

Sensitisation phas (no external reaction) - first encounter with the antigen, with the activation on APCs and memory cells. 
Effector phase (with external reaction) - pathological reaction on re-exposure to the antigen and activation on memory cells.

Question 4

Describe type I hypersensitivity. (4)
Time
Antigens

Answer 4

Usually happens within 30 minutes

Cal be local (inhaled or ingested) or systemic (IV), and is a reaction to environmental but non-infectious antigens.

Question 5

Describe the mechanism of type I hypersensitivity reactions, and explain how this differs from normal people. (7)

Answer 5

Normally, a TH1 reaction occurs without TH2 activation, so there’s no mast cell activation and no external reaction.
In those with allergies, there’s an abnormal TH2 response:
IL-4, IL-5 and IL-13 activation
IgE production from B cells
Activated mast cells in sensitised people

Question 6

Give three examples of cataegories of things that cause type I hypersensitivity reactions. Give an example for each category.
(6)

Answer 6

Seasonal - tree or grass pollen.
Perennial - dust mites, animal hair, fungal spores.
Accidental exposures - insect venom, medicines, chemicals (latex), foods.

Question 7

Describe the two hypothesis that try to explain why people have allergies. (6)

Answer 7

Hygiene hypothesis - children exposed to allergens in the post natal period are protected against certain allergic diseases - western culture has stopped this.
Old friends hypothesis - westernised lifestyle alters the symbiosis with parasites and bacteria that humans have, causing increased immune disease.

Question 8

Name the systems that can be affected in anaphylaxis. Give the signs in each system that would occur if that system was involved. (12)

Answer 8

CNS - lightheaded, LoC, confusion, headache, anxiety.
Respiratory - SoB, wheeze / stridor, pain on swallowing, cough.
Sensory - Swelling of the conjunctiva, swelling of the mouth, runny nose.
CVS - tachy- or bradycardia, hypotension.
Skin - hives, itchiness, flushing.
Urinary - incontinence.

Question 9

Describe the location of mast cells in the body. (3)

Answer 9

At mucosal and epithelial surfaces, and in proximity to blood vessels.

Question 10

Describe the things that can be targeted to reduce mast cell activation. (4)

Answer 10

Tryptase
Histamine
Leucotriene
Platelet activating factor

Question 11

Describe what happens to mast cells on the second exposure to an antigen in a sensitised individual. (12)

Answer 11

IgE forms cross links, forming the signal for mast cell degranulation. This causes:
Increased vascular permeability - angioedema (deep dermis - mediated by histamine and bradykinin)
Vasodilation - hypotension, cardiovascular collapse, urticaria (wheal and flare rash caused by histamine and leucotrienes in the epidermis).
Bronchial constriction - breathing difficulty.

Question 12

Explain the management for type I hypersensitivity reactions. (9)

Answer 12

Monitor pulse, ECG, and oximetry - check for any worsening of condition.
Give IM adrenaline - timesaver - reverses vasodilation, reduced oedema, alleviated hypotension, reverses bronchospasm, increases force of myocardial contraction, inhibits mast cell degranulation.

Question 13

Describe the treatments of type I hypersensitivity. (3)

Answer 13

Anti-IgE monoclonal antibody therapy.
Antihistamines or corticosteriods to prevent mast cell degranulation.
Allergen desensitisation.

Question 14

Describe the process of allergen desensitisation. (2)

Answer 14

Increasing doses of allergen extracts given over years to restore the balance between TH1 and TH2 response. .

Question 15

Describe type II hypersensitivity reactions. (3)
Time
Antigens

Answer 15

Usually develops in 5-12 hours, with IgG or IgM antibodies forming against cell bound antigens.

Question 16

Describe the mechanism of cell damage in type II hypersensitivity. (5)

Answer 16

In a sensitised individual, the antibody attached to the cell, causing compliment activation. This causes cell lysis through the membrane attack complex, neurophil recruitment (C3a / C5a) and opsonisation (C3b).

Question 17

Describe Haemolytic Disease of the Newborn. (7)

Answer 17

When a RhD- mother carries a RhD+ bab, some of the bab’s blood can cross into the mothers’ blood during delivery. This causes the mother to form anti-D antibodies (IgG).
When this mother carries her second RhD+ bab, her anti-D antibodies cross the placenta and lyse all the red blood cells in the bab, causing haemolytic anaemia.
This is an example of Type II hypersensitivity.

Question 18

Describe the consequences of haemolytic disease of the newborn. (3)

Answer 18

Kernicterus - bilirubin induced brain damage following birth when the placenta is not there to mop up the excess bilirubin.

Question 19

Describe the diagnosis of haemolytic disease of the newborn. (6)

Answer 19

Tested for with an amniocentesis or an umbilical vein sample.
Diagnosed with the Coombs Test - antibodies added that attach only to endogenous antibodies that are attached to red blood cells. This shows that there is some part of the immune system attacking red blood cells.
Can be direct (blood sample) or indirect (plasma sample).

Question 20

Describe the prevention of haemolytic disease of the newborn. (4)

Answer 20

Prevented by giving all RhD- mothers RhoGAM at 28 weeks, or with bleeding / miscarriage before 28 weeks.

Question 21

Describe transfusion reactions and name which type of hypersensitivity reaction they are. (4)

Answer 21

When someone is given the wrong blood type, and they form a type II hypersensitivity reaction to that, because it is not of them. Can cause shock, kidney failure, circulatory collapse, and death.

Question 22

Explain why mothers who have a different ABO blood type of their baby do not induce haemolytic disease of the newborn in their children. (2)

Answer 22

ABO antibodies are carried on IgM rather than the IgG of RhD antibodies, so they cannot cross the placental barrier like the RhD ones.

Question 23

Describe treatments for the cell damage caused by type II hypersensitivity reactions. (4)

Answer 23

Anti-inflammatory drugs targeting the compliment activation
Plasmapheresis
Splenectomy
IVIG

Question 24

Describe an example where receptor stimulation is the mechanism of a type II hypersensitivity reaction. (3)

Answer 24

Graves’ Disease - increased thyroid activity due to stimulation of TSH receptor.
Treated with anti thyroid drugs.

Question 25

Describe an example where receptor blockade is the mechanism of a type II hypersensitivity reaction. (4)

Answer 25

Myasthenia Gravis - impaired neuromuscular signalling due to IgG against nAChr.
Treated with acetylcholineesterase inhibitors or plasmapheresis.

Question 26

Describe type III hypersensitivity. (5)
Timing
Antibodies

Answer 26

Usually develops within 3-8 hours.
Immune complexes develop between IgM or IgG and soluable forgein antigens (infectious or endogenous). Tissue damage caused deposition of these complexes in tissues causing inflammation.

Question 27

Describe the pathogenesis of type III hypersensitivity reactions. (4)

Answer 27

Deposition of immune complexes in joints / kidneys / small vessels / skin.
Small complexes are RES cleared and large complexes are compliment cleared, but intermediate size can’t be cleared.

Question 28

Describe local tissue factors that affects the pathopathogenesis of type III hypersensitivity reactions. (5)

Answer 28

Haemodynamic - fiateation, bp, turbulence

Physiochemical factors - size, electrostatic.

Question 29

Describe the immune mechanisms that cause cell damage in a type III hypersensitivity reaction. (4)

Answer 29

Intermediate sized immune complexes deposited in tissues.
Complement activated
Neutrophil chemotaxis
Neutrophil adherence and degranulation

Question 30

Describe three examples of type III hypersensitivity reactions. (6)

Answer 30

RA - self antigen - antigen is portion of IgG called rheumatoid factor.
Glomerunephritis - infectious (bacterial endocarditis or Hep B) - immunocomplexes deposit in the kidney.
SLE - self antigen - dsDNA attacked leading to multi-organ inflammation.

Question 31

Describe type IV hypersensitivity. (3)
Timing
Antibody

Answer 31

Usually develops in 24-72 hours

Involves lymphocytes and macrophages - cell mediated.

Question 32

Describe three examples of exogenous types of IV hypersensitivity reactions. (9)

Answer 32

Contact hypersensitivity - 48-72h - epidermal reactions to exogenous proteins eg poison ivy, nickel.
Tuberculin hypersensitivity - 48-72h - dermal Reaction seen in Mantoux tests.
Granulomatous hypersensitivity - 21-48 days - common in TB, leprosy and schistosomiasis.

Question 33

Describe three examples of endogenous types of IV hypersensitivity reactions. (5)

Answer 33

DMII
RA
Hashimoto’s thyroiditis - TH1 prompts autorezctive B cells and CD8+ T cells that kill thyroid cells.

Question 34

Describe the mechanism of tissue destruction in type IV hypersensitivity. (3)

Answer 34

TH1 cells in a sensitised individual activate macrophages, which release toxic products to try to kill the thing. When this doesn’t happen, cytotoxic T cells and more macrophages are activated.

Question 35

Describe the treatments for both type III and type IV hypersensitivity reactions. (4)

Answer 35

Anti-inflammatory drugs - non-steroidal, corticosteriods, azathioprine.
Monoclonal antibodies - deplete T and B cells, block cytokines.