148 - Hypersensitivity 3

Question 1

Two broad outcomes of type II hypersensitivity

Answer 1

– Injury due to activation of effector mechanisms
• C’activation
• Recruitment of inflammatory cells
• Activation via Fc Receptor

– Abnormal physiological response (Graves & MG)
• Binding to receptors or proteins interfering with function
• Activation or inhibition.

Question 2

Example of TIIH

Answer 2

ABO blood group mismatch.

Leads to RBC haemolysis, shock, nausea, vomiting and pain

Question 3

Example of a rare TIIH against erythrocytes
1
2
3

Answer 3

1) Type II mediated drug allergies (rare)
eg penicillin, quinidine, methyldopa
2) Some produce antibodies against these drugs.
The drug becomes bound to red blood cells or platelets, which are then the target of anti-drug antibodies.
3) Splenic macrophages phagocytose the cells, resulting in haemolytic anaemia or thrombocytopenia

Question 4

Haemolytic disease of the newborn

Answer 4

Due to preformed maternal IgG antibodies which react
against the child’s Rh antigens on their RBC’s in utero
→ removal of RBC via complement activation.

More of a problem for the second child, as mother will have a secondary adaptive response against Rh

Question 5

How is haemolytic disease of a newborn treated?

Answer 5

Anti-Rh antibodies within 24 hrs of delivery remove foetal RBC’s in maternal circulation

Question 6

Goodpasture’s syndrome

Answer 6

Antibodies are made against a variant of collagen type IV, a major component of basement membranes (EG: lining vasculature in kidney, blood vessels).

Antibodies can get stuck in glomeruli, which activates C’. This leads to glomerular disease.

Question 7

What do people with Goodpasture’s syndrome present with/

Answer 7

Nephritis

Question 8

Grave’s disease antibodies

Answer 8

Stimulatory antibodies against thyroid-stimulating hormone receptors in thyroid.

Question 9

Thyroid gland role

Answer 9

Thyroid gland essential for regulating metabolism through the production of thyroid hormones.

Pituitary gland releases TSH, which leads to thyroid hormone release. Thyroid hormone negatively regulates release of TSH.

Question 10

Effect of Grave’s disease

Answer 10

Hyperthyroidism

Question 11

Myasthenia gravis

Answer 11

Ab against ACh receptors on motor endplates.

This leads to internalisation, degradation of ACh receptors

Question 12

How can antibody binding to an allergen cause injury?
1)
2)
3)

Answer 12

1) C’ activation
2) Recruitment of inflammatory cells
3) Activation via Fc receptor

Question 13

Haemolytic disease of a newborn
1)
2)
3)
4)

Answer 13

1) When a Rh+ baby is delivered from a Rh- mother
2) During delivery, baby’s RBCs enter mother’s bloodstream
3) Mother produces anti-Rh IgG - is now sensitised
4) If the mother has another child who is Rh+, maternal IgG cross the placenta, bind to foetus RBCs, cause C’ removal of them

Question 14

How is haemolytic disease of a newborn treated?
1)
2)

Answer 14

1) During delivery of the first child, administer anti-Rh antibodies to mother within 24 hours of delivery
2) These clear Rh+ RBCs from mother, so mother doesn’t produce anti-Rh antibodies

Question 15

What causes type III hypersensitivity?

Answer 15

Immune complexes formed from antibodies and antigens (self or foreign), that are either overproduced or improperly cleared

Question 16

How are immune complexes normally removed?

Answer 16

Covered in C3b, which RBCs with C3bR bind to.

Removed by splenic macrophages

Question 17

What determines the pathology of type III hypersensitivities?

Answer 17

Where the immune complexes deposit.

EG: Cationic complexes can deposit on blood vessel walls and the kidney glomeruli

Question 18

Mechanism of type III hypersensitivity
1) 
2) 
3)
4)
5)
6)
7)

Answer 18

1) Immune complexes aren’t cleared (low Ab affinity, excess antigen, inefficient C’ activation)
2) Complexes deposited on blood vessel walls
3) Deposition eventually leads to C’ activation
4) Anaphylatoxins are generated (C3a, C4a, lead to neutrophil, mast cell degranulation)
5) Macrophage cytokine release stimulated
6) Immune complexes directly activate platelets, basophils, mast cells
7) Vasoactive amines lead to increased vascular permeability

Question 19

Immune complex-mediate damage
1) 
2) 
3)
4)

Answer 19

1) Immune complexes deposit on vascular wall, lead to disrupted blood flow, turbulence
2) Vasculitis
3) Glomerulitis (form deposition in kidney basement membrane)
4) Arthritis (deposition in joint synovium, vessels)

Question 20

What affects clearance from circulation of immune complexes?

Answer 20

Size.
Larger complexes activate C’ better, better at binding FcR.
–> are removed from the circulation more effectively

Question 21

Examples of situations where immune complex clearance could be impaired
1
2
3

Answer 21

1) Complexes don’t form properly (too small to be effectively cleared)
2) Excessive antigens and antibodies, leads to overload mononuclear phagocyte system
3) Poor C’ activation

Question 22

Possible sources of antigen leading to TIIIH
1
2
3

Answer 22

1) Persistent infection (can’t clear infection, EG with hepatitis B or C, HIV)
2) Autoimmune
3) Inhaled antigen (EG mould, plant or animal antigen)

Question 23

Farmer’s lung

Answer 23

Exposure to hay dust or bacteria (Actinomyces) leads to alveolitis from type III hypersensitivity.
Stimulation of IgG, complex formation in alveoli leading to inflammation and fibrosis

Question 24

Example of an autoimmune TIIIH

Answer 24

Systemic lupus erythematosus

Question 25

Systemic lupus erythematosus

Answer 25

Anti-DNA autoantibodies produced.
Immune complexes deposited in the kidneys (basement membranes).
Multiple body systems are involved.
B-cell hyper-reactivity.

Question 26

Two forms of immune tolerance generation

Answer 26

• Central Tolerance
– Occurs during development in primary
lymphoid organs
– Removes self-reactive lymphocytes
during development

• Peripheral Tolerance
– Occurs in the periphery
– Controls self-reactive lymphocytes