Review

Question 1

Describe type I hypersensitivity reactions

Answer 1

1) Mast cell activation is induced by the secretion of IgE antibodies
2) Initial exposure to the antigen causes the priming of Th2 cells, and their release of IL-4 causes the B cells to switch their production of IgM to IgE antibodies
3) IgE antibodies are antigen-specific -> bind to mast cells & basophils, sensitising them
4) When antigen enters the body again, it cross links the IgE bound to the sensitised cells, causing the release of mediators -> leads to widespread vasodilation, bronchoconstriction & increased permeability of vascular endothelium

Question 2

Describe type II hypersensitivity reactions

Answer 2

Mediated by antibodies targeting antigens on cell surfaces
Antibodies binding to cells can activate the complement system -> leads to destruction of the cell
Destruction of host cells in this way can lead to tissue-specific damage

Question 3

Describe type III hypersensitivity reactions

Answer 3

Mediated by antigen-antibody complexes in the circulation that may be deposited in and damage tissues
Once lodged, immune complexes rapidly and significantly activate the complement chain -> cause local inflammation and activation of leucocytes

Question 4

Describe the pathophysiology of rheumatoid arthritis

Answer 4

Antigen-antibody complexes circulating in the bloodstream end up in the filtration systems responsible for maintaining the levels of synovial fluids at synovial joints
Lodged immune complexes can cause a local inflammatory response, leading to stiffness and pain in affected joints

Question 5

Describe type IV hypersensitivity reactions

Answer 5

Mediated by antigen-specific activated T cells
Activated macrophages release pro-inflammatory factors & also secrete lysosomal elements and reactive oxygen species -> local tissue damage
CD8+ T cells may be involved in type IV reactions where a foreign antigen is detected on a cell (eg. organ rejection) = cell mediated cytotoxicity

Question 6

List examples of transitory autoimmune disease in the newborn

Answer 6

Neonatal lupus
Transient myasthenia gravis
Neonatal Graves’ disease

Question 7

List an example of an infection that can trigger autoimmune diseases

Answer 7

EBV and measles can both trigger multiple sclerosis

Question 8

How are monoclonal antibodies produced?

Answer 8

1) Immunise a mouse against a specific epitope on an antigen & then harvest the B-lymphocytes from the spleen of the mouse
2) B-lymphocytes are then fused with an immortal myeloma cell line not containing any other immunoglobulin-producing cells
3) Resulting hybridoma cells are then cultured in vitro so only hybridomas survive
4) Selected hybridomas are found making a specific desired clonal antibody

Question 9

List three examples of monoclonal antibodies

Answer 9

1) Rituximab, targets CD20, treats B cell lymphoma
2) Trastuzumab, targets HER-2, treats breast cancer
3) Bevacizumab, targets VEG-F, treated multiple cancers eg. colon & lung cancer

Question 10

Describe the clinical presentation of myasthenia gravis

Answer 10

Droopy eyelids
Double vision
Difficulty making facial expressions
Problems chewing and difficulty swallowing
Slurred speech

Question 11

Describe the pathophysiology of myasthenia gravis

Answer 11

Abnormal antibodies to AChR are produced, circulate in the blood & bind to nicotinic receptors on the muscle end plates
When antibodies are bound to AChR, the receptors are not available to be activated by the ACh that is released physiologically -> no APs or contraction in the muscle

Question 12

Describe the treatment for myasthenia gravis

Answer 12

Pyridostigmine – acetylcholinesterase inhibitor that binds to acetylcholinesterase & therefore reduces binding and degradation of ACh at the muscle end plate
Increases its synaptic concentration and thus prolonging its action
The longer the muscle end plate is exposed to high concentrations of ACh, the greater the likelihood that APs and contraction in the muscle will occur

Question 13

What is the Coombs’ test?

Answer 13

Direct Coombs’ test – looking directly at RBCs found in a sample of blood (used for suspected haemolytic anaemia)
Indirect Coombs’ test – looks at the plasma part of the blood (used to make sure blood that has been donated is compatible with the patient who is going to receive it & to check that a pregnant mother’s blood does not contain antibodies that might cause her baby harm)
Both types are looking for antibodies which may attack RBCs & lead to them being destroyed