Disorders of Immune System

Question 1

TYPE I HYPERSENSITIVITY:
What is it usually due to?

e.g. Pollen
1. What occurs in the Sensitisation Phase?
→ What do the Th2 cells then do? What does this lead to?

2. What occurs in the Effector Phase?
3. What then occurs on the Second exposure to Pollen?
   → What does this cause?
4. What occurs in the Late Phase?

Answer 1

• Exaggerated/Inappropriate immune response, resulting in tissue damage
• Pollen, Insect bites, Foods (Peanuts), Penicillin

1. First exposure to pollen causes B cells to recognise, internalise, and present the antigen to Th2 cells
→ Th2 cells secrete IL4, which induces the B cells to switch class to produce IgE

2. IgE travels in the blood, and its Fc region binds to the Fc receptors on MAST cells
3. Pollen binds to the Antigen-binding sites of the IgE on the Mast cell
   → Causes Degranulation of Mast cells for Histamine release and Cross-linking of the IgE molecules
4. Mast cells produce other Cytokines, which stimulates Th cells to produce more Cytokines = Prolonged allergic reaction

Question 2

TYPE II HYPERSENSITIVITY:
What is it initiated by? Which Ig’s mediate it?

What are some examples of conditions that this occurs in? How does it happen?

Answer 2

• Initiated by Antigen-Antibody interactions - IgM and IgG mediated
• • Myasthenia Gravis - Autoantibodies block Ach receptors at NMJ
  • Haemolytic Disease of the Newborn (Rhesus Isoimmunisation) - Rh-ve mother and Rh+ve foetus
  • Grave’s Disease - Autoantibodies bind to TSH receptor, to stimulate TH release = Hyperthyroidism

Question 3

TYPE III HYPERSENSITIVITY:
What does the immune system target here?

What condition does this occur in? How does it happen
→ What can these Complexes then do?

Answer 3

• Soluble self/foreign, circulating antigens
• Systemic Lupus Erythematosus (SLE) - Autoantibodies against Self DNA, Histones, and Ribosomes to form Immune Complexes
  → Can activate complement system (↑tissue damage) and can get trapped in Kidney, leading to Glomerulonephritis

Question 4

TYPE IV HYPERSENSITIVITY:
What is it also called? What is it mediated by?

What Test can be used here? What does it lead to if Positive?

How does this occur in T1DM?

Answer 4

• Delayed hypersensitivity - T cell-mediated
• Mantoux test - Patient injected with foreign antigen into skin
  o Macrophages present the antigen to activate CD4+ Th cells = Cytokine release, which activates even more Macrophages = Firm Red Swelling forms
• β-cells act as an Autoantigen and is taken up by APCs, which present them on MHC II to stimulate CD4+ Th cells for the release of Cytokines, which then activates Cytotoxic CD8+ T cells = ↓β-cells

Question 5

Coeliac Disease:
What is primarily affected?
→ What changes occur here?

Inflammatory Bowel Disease:
What are the 2 main types? What is affected in each?

Psoriasis:
What is it characterised by?

Which cells are most active here?

Answer 5

• Small Intestine
  → Villous Atrophy and Malabsorption
• IgA Anti-Gliadin, Antiendomysium and Antireticulin antibodies
• • Ulcerative Colitis - Affects Mucosal layer of Colon
  • Crohn’s Disease - Affects any part of the GIT
• Lots of Ig production at the site, Deposition of complement components in mucosa causing ↑IL levels
• Red plaques covered by Silverly scales
• CD4+ Th cells

Question 6

Autoimmunity:
What is it?

Immunodeficiency:
What can cause Primary Immunodeficiency?

What can cause Secondary Immunodeficiency?

Answer 6

• Acquired immune response to self-antigens
• Immunodeficiency, Age, Gender, Genetics, Infections, Drugs
• Genetic - Deficiency in Complement, Phagocytes (e.g. Chediak-Higashi syndrome), B and T cell deficiencies
• HIV infection, Malnutrition, Tumours, Radiotherapy/Chemotherapy