hypersensitivity

Question 1

hypersensitivity

Answer 1

immune response that is exaggerated or inappropriate in response to an immunological stimuli

Question 2

type 1

Answer 2

immediate reaction mediated by IgE and mast cells
- cause vascular leakage, mucus secretion, inflammation

Question 3

mechansim of type 1

Answer 3

1. sensitisation
   - on exposure to allergen, Th2 and Tfh activated to stimulate class switching to IgE
   - IgE bind to FceR1 receptor on mast cell and mast cells are sensitised
   - activated mast cells upregulate CD40 ligand expression to bind to CD40 receptor for B cell activation, leading to IgE production (positive feedback)
2. activation of mass cells
   - sensitised mast cells exposed again, causing cross linking of IgE receptors to antigen that is bound to FceR1 receptor on mast cell
   - cross linking triggers signal cascade that leads to degranulation of mast cells which release mediators that characterise allergic rxn + cause upregulation of IgE receptors (greater chance of antigen binding to IgE and cross linking so its easier to get allergic rxn)

histamine -> vasodilation, vasopermeability, smooth muscle contraction

protease -> tryptase and chymae which cause tissue damage and destruction

lipids
- prostaglandin: vasodilation, chemotaxis, neutrophil attraciton
- leukotriene: smooth muscle contraction
- platelet activating factor: bronchoconstriction

cytokines
- IL4.13: B cell activation
- TNF-alpha: activate endothelial cells
- IL5: activate eosinophil

3. late phase reaction (8-12h later)
   - cytokines trigger recruitment of immune cells like eosinophil, neutrophil, basophil, Th2 cell
   - continous synthesis and release of inflammatory mediators by mast cells

Question 4

effects of type 1

Answer 4

airway -> bronchoconstriction, increased mucus secretion => congestion

GIT -> smooth muscle contraction (peristalsis) + increase fluid secretion => diarrhoea, vomitting

blood vessels -> vasodilation + increase vasopermeability => oedema (fluid accumulation in extravascular tissue)

Question 5

anaphylaxis

Answer 5

1. urticaria + itching
2. swelling
3. bronchocontriction
4. fall in BP, fainting

Question 6

condition related to type 1

Answer 6

asthma -> mast cell located in submucosal
allergic rhinitis -> mast cell located below nasal epithelium

allergic conjunctivitis, systemic anaphylaxis

Question 7

type 2

Answer 7

antibody bind to antigen on cell surface or ECN (antigen in fixed location)

antibody binds and causes localised effects

Question 8

type 3

Answer 8

antigen are freely floating and antibody binds to form immune complex

immune complex travel to any part of body and symptoms occur wherever immune complex deposits

Question 9

mechanism of type 2 and 3

Answer 9

1. complement activation and Fc receptor mediated inflammation by recruiting neutrophils
2. opsonisation and phagocytosis
3. abnormal response without injury
   - antibody stimulates receptor without hormone (graves disease)
   - autoantibodies bind to Ach receptor to prevent Ach from binding -> no signal transduction across NMJ -> no muscle contraction

Question 10

type 2 examples

Answer 10

1. Graves disease
   - antibody stimulates TSH receptor to produce T4 (cause hyperthyroidism)
2. myasthenia gravis
   - autoantibody binds to Ach receptor to block binding of neurotransmitter to receptor -> no signal transduction -> no muscle contraction -> fatigue, muscle weakness
3. haemolytic disease of the newborn
   - in a Rh- mother, during 2nd pregnancy, anti-Rh antibodies cross placenta to destroy foetal RBC
   - symptom: enlarged spleen and liver, elevated bilirubin, facial haemorrhaging

Question 11

type 3 examples

Answer 11

1. Arthus reaction
   - in repeated vaccine recipients due to local vasculitis
   - antibody formed at local site -> local immune complex formation
2. serum sickness
   - injection of foreign serum proteins cause large amount of immune complex deposition

Question 12

therapy for type 2,3

Answer 12

• corticosteroids (limit inflammation)
• plasmapheresis (reduce antibodies or immune complex but only severe case)
• intravenous IG (healthy antiboides compete with pathogenic Ab for binding to Fc receptors -> reduce half-life of Ab)
• anti CD 20 (deplete B cells)
• anti CD 40/ anti CD 40L (inhibit Ab production)

Question 13

type 4

Answer 13

delayed hypersensitivity mediated by T cell against environmental antigens
- 48-72h later
- Th1: macrophage activation
- Th2: IgE production, eosinophil activation
- Cd 8: cytotoxicity

environmental antigens: contact sensitivity to chemical including drugs, plants (poison ivy), microbial proteins

Question 14

examples of type 4

Answer 14

• tuberculin skin test: Th1 recognise antigen and release cytokines, causing recruitment of phagocytes and plasma to site of infection
• contact dermatitis: foreign agents penetrate skin and bind to self protein, making them seem foreign. langerhan cells take up foreign agent and present to Th1 which activate macrophage

Question 15

therapy for type 4

Answer 15

corticosteroids, TNF antagonist -> reduce inflammation

anti-B7, cytokine antagonists -> inhibit T cell response

Question 16

steps to neuromuscular transmission

Answer 16

1. An action potential is propagated down the motor neuron until the presynaptic terminal is depolarized.
2. Depolarisation of the presynaptic terminal causes voltage gated Ca2+ channels to open and Ca2+ flow into the nerve terminal.
3. Uptake of Ca2+ into the nerve terminal causes exocytosis of Ach into the synaptic cleft.
4. Ach diffuses across the synaptic cleft to the muscle end plate where it binds to nicotinic Ach receptors.
5. Nicotinic receptor is an ion channel for Na and K and the channel opens when Ach binds, allowing Na and K to flow down their electrochemical gradients, causing depolarisation