Clinical use of immune modulators.

Question 1

Why is pharmacological control necessary in the immune system?

Answer 1

• Suppression of the immune system to prevent allograft rejection and for treating autoimmune disease.
• Stimulation of the immune system to treat immune depression, cancer and infections.

Question 2

What is an autoimmune disease?

Answer 2

• Immune system can fail to recognise self antigens
• Leads to disease due to destruction of tissue by immune system.
• Can be triggered by infection or can be mediated by drugs.

Question 3

List examples of auto-immune diseases.

Answer 3

1. Lupus erythematosus
   - Antibody to DNA histone complex ie anti-nuclear factor
2. Rheumatoid arthritis
   - Due to formation of rheumatoid factor which is an antibody to IgG leading to complement activation
3. Myasthenia gravis
   - Due to antibody formation to nicotinic acetylcholine receptors
4. Thyroiditis
   - Hashimoto’s disease due to antibodies to thyroid tissue
   - Graves disease due to increased thyroid hormone production due to antibodies to TSH receptor
5. Haemolytic anaemia
6. Thrombocytopenia

Question 4

Treatment of organ failure.

Answer 4

• Artificial organs e.g. dialysis machines, heart lung machines and artificial heart.
• The alternative is organ transplantation
• Animal donors cannot be used due to complement formation
• Compatible human donors required.

Question 5

How is organ trafficking prevented?

Answer 5

• Declaration of Istanbul.

Question 6

Discuss the difficulties associated with organ transplantation.

Answer 6

• Difficult getting perfect match which can lead to immune rejection.
  -The antigens involved are histocompatible antigens
• Lymphocytes from the donor may attack tissue of the recipient ie, graft versus host reaction and vice versa.

Question 7

What are the alternatives to organ donation?

Answer 7

• Xenograft from humanised animals eg pig
• Synthetic organs from stem cells
• Artificial skin
• Artificial heart

Question 8

Complications associated with a transgenic pig.

Answer 8

1. Hyper-acute rejection
   - Due to complement formation
   - Pigs have no galactose on the cell surface
   - Pigs express CD46 which is a co-factor for complement factor I: Inactivates C3b/C4b
2. Delayed xenograft rejection
   - Due to loss of anti-coagulant factors on endothelial cells
   - Add in genes?
3. Long-term rejection
   - T-cell based
   - Immune suppressants

Question 9

Discuss the pathology of multiple sclerosis.

Answer 9

• Autoimmune disease where brain-reactive T-cells cause demyelination and destruction of neurons.
• Evidence of a role for B-cells as well.
• Leads to paralysis and death.
• Presence of “scars” on brains.

Question 10

Discuss the pathology of Crohn’s disease.

Answer 10

• Auto-immune disease.
• Form of inflammatory bowel disease affecting all layers of the intestine
  -Associated with diarrhea, cramps, bloody stools and weight loss

Question 11

Discuss the pathology of psoriasis.

Answer 11

• Autoimmune skin disease.
• Involves epidermal hyper-proliferation, abnormal differentiation of epidermal keratinocytes, and inflammation with immunologic alterations in the skin.

Question 12

How do drugs target the immune system?

Answer 12

1. Reduce the number of immune cells
2. Prevent activation of immune cells
3. Alter function of immune cells
4. Prevent extravasation of immune cells
5. Enhance immune cell activation

Question 13

Drugs that reduce the number of immune cells

Answer 13

• Cytotoxic agents
• Inhibitors of immune cell replication
• Cell depletion therapies
• Prevent immune cells entering circulation

Question 14

Drugs that prevent activation of immune cells.

Answer 14

• Inhibitors of pro-inflammatory cytokines
• Inhibitors of co-stimulation

Question 15

Drugs that alter function of immune cells.

Answer 15

• Th 1-2 switching

Question 16

Drugs that enhance immune cell activation.

Answer 16

• Pro-inflammatory cytokines
• Inhibitors of co-inhibition