Week 5 - Hypersensitivity

Question 1

What is a Hypersensitivity Reaction?

Answer 1

= An injurious or pathological immune reaction -> excessive immune response

Question 2

When do hypersensitive reactions occur?

Answer 2

• response to foreign antigens
• response to self antigens (autoimmunity)

Question 3

What are the 4 types of Hypersensitivities?

Answer 3

Type 1:
- IgE, Mast cells, Th2 cells, Basophils, Eosinophils
Type 2 & 3:
- IgG, IgM, IgA, Complement and Fc receptors
Type 4:
- T cells, Macrophages

Question 4

Describe Immediate Hypersensitivity (Type 1)

Answer 4

Mechanism:
- Th2 immunity, IgE, Mast cell degranulation, eosinophilic influx
Diseases:
- Anaphylaxis, Atopic diseases, Asthma, Allergies

Question 5

Describe sensitisation and re-exposure in Type 1 Hypersensitivity

Answer 5

Sensitisation:
1. Exposure to allergen -> DC drive differentiation of Th2 cells
2. Th2 cells secrete IL-4 -> drives B cells to switch isotype and secrete IgE
3. IgE will bine to Fce on surface of mast cells
Re-exposure:
1. Upon repeat exposure, Vasoactive amines and leukotrienes get released causing immediate reaction
2. Cytokines can cause late phase reaction

Question 6

Mast Cell Degranulation:

Answer 6

Question 7

Summary of Allergic Diseases

Answer 7

Question 8

Summary of Th2 cells and what they do

Answer 8

Question 9

Why does there need to be a balance between Th1 and Th2?

Answer 9

more Th2 than Th1 leads to hypersensitive responses so need Th1 to balance that out

Question 10

What are treatments for allergic diseases?

Answer 10

• Antihistamines
• B-2 agonists
• Corticosteroids
• Allergen immunotherapy -> repeated exposure to allergen inhibiting Th2 response and promoting Th1 response

Question 11

Describe Mediated Hypersensitivity (Type 2)

Answer 11

Mechanism:
- IgG and IgM Ab directed against the cell surface
- usually against self antigens
Diseases:
- Graves disease, Mysanthia gravis, etc.

Question 12

What happens in Immune Complex Mediated Hypersensitivity (Type 3)?

Answer 12

Immune complexes of antibody and circulating antigen deposit in tissues giving rise to complement and Fc receptor activation

Diseases:
- Drug allergies, serum sickness, lupus, etc

Question 13

How do Fc receptors mediate antibody-dependent cellular cytotoxicity?

Answer 13

1. Ab binds antigens on surface of target cell
2. Fc receptors on NK cells recog bound Ab
3. Cross-linking of Fc receptors signals the NK cell to kill the target cell
4. Target cell dies by apoptosis

Question 14

Can Fc receptors detect immune complexes?

Answer 14

Yes

Binding of Fc receptors to immune complex activates phagocytes leading to:
- Pro-inflamm cytokine production
- Phagocytosis and oxidative burst
- Degranulation

Question 15

Pro-inflamm Cytokines summary

Answer 15

Question 16

What is Complement activation and what does it lead to?

Answer 16

Complement proteins are proteases which cleave on another to form the complement cascade -> inflammation, opsonisation and bacterial lysis

Question 17

Describe T cell mediated Hypersensitivity

Answer 17

Mechanism:
- Th1 and/or Th17 cells activate and recruit macrophages and neutrophils

Diseases:
- Contact hypersensitivity, Type 1 diabetes, MS

Question 18

How do Th1 cells protect us from intracellular pathogens?

Answer 18

• Th1 cells secrete IFN-gamma to activate macrophages
• Th1 cells also activate Cytotoxic T lymphocytes which will cause tissue damage

Question 19

What do macrophages release and what do they do?

Answer 19

Macrophages release Pro-inflamm cytokines that:
- Activate vascular endothelium
- Chemotactically attract macrophages
- Mobilise monocyte production in bone marrow