1. Hypersensitivity Reactions

Question 1

What is the definition of hypersensitivity?

Answer 1

The antigen-specific immune responses that are either inappropriate or excessive and result in harm to host

Question 2

Give examples of exogenous antigens that can cause hypersensitivity

Answer 2

Non infectious substances (innocuous)
Infectious microbes
Drugs (penicillin)

Question 3

Give examples of intrinsic antigens that can cause hypersensitivity

Answer 3

Infectious microbes (mimicry)
Self antigens (auto-immunity)

Question 4

What are the broad types of hypersensitivity reactions?

Answer 4

Type I/immediate (allergy)
Type II/antibody mediated
Type III/immune complexes mediated
Type IV/cell mediated (delayed)

Question 5

What is the sensitisation phase?

Answer 5

First encounter with the antigen. Activation of APCs and memory effector cells. A previously exposed individual to the antigen is said to be sensitised

Question 6

What is the effector phase?

Answer 6

Pathologic reaction upon re-exposure to the same antigens and activation of the memory cells of the adaptive immunity

Question 7

How long after exposure does type II hypersensitivity usually develop?

Answer 7

5-12 hrs

Question 8

Which antibodies do type II hypersensitivity reactions involve?

Answer 8

IgG or IgM

Question 9

Which antigens do type II hypersensitivity reactions target?

Answer 9

Cell bound antigens

• exogenous: blood group antigens, Rhesus D antigens
• endogenous: self antigens

Question 10

What are the 2 different outcomes induced in type II hypersensitivity reactions?

Answer 10

Tissue/cell damage

Physiological change

Question 11

Describe the mechanisms of type II hypersensitivity causing tissue/cell damage

Answer 11

Complement activation - cell lysis, neutrophil recruitment/activation, opsonisation
Antibody-dependent cell cytotoxicity

Question 12

Give examples of the complement activation mechanism in type II hypersensitivity

Answer 12

Haemolytic disease of the newborn (HDN)

Transfusion reactions

Question 13

Give examples of antibody-dependent cell cytotoxicity mechanism in type II hypersensitivity

Answer 13

Autoimmune haemolytic anaemia
Immune thrombocytopenic purpura
Goodpastures syndrome

Question 14

Give 2 examples of disease caused by type II hypersensitivity (IgM)

Answer 14

Haemolytic transfusion reactions

Immune mechanism - ABO or Rhesus D antigens

Question 15

Give an example of disease caused by type II hypersensitivity (IgG)

Answer 15

Haemolytic disease of the newborn

Question 16

What are the mechanisms of type II hypersensitivity causing physiological change?

Answer 16

Receptor stimulation (Graves’ disease)
Receptor blockade (myasthenia gravis)

Question 17

What are the therapeutic approaches to type II hypersensitivity causing tissue/cell damage?

Answer 17

Anti-inflammatory drugs
Plasmapheresis
Splenectomy
Intravenous immunoglobulin

Question 18

Which diseases is plasmapheresis therapy used in?

Answer 18

Myasthenia gravis
Goodpastures syndrome
Graves’ disease

Question 19

How long after initial exposure does type II hypersensitivity develop?

Answer 19

3-8 hrs

Question 20

Which immune complexes are involved in type III hypersensitivity?

Answer 20

Immune complexes between IgG or IgM and antigens

Question 21

What does type III hypersensitivity target?

Answer 21

Soluble antigens - foreign (infection), endogenous (self antigens)

Question 22

What is tissue damage caused by in type III hypersensitivity?

Answer 22

Caused by the deposition of immune complexes in host tissues

Question 23

What are the key factors that affect immune complex pathogenesis in type III hypersensitivity?

Answer 23

Complex size
Host response
Local tissue factors

Question 24

What are the immune mechanisms in type III hypersensitivity?

Answer 24

1. Intermediate-sized immune complexes deposited in the tissue
2. Complement activated
3. Neutrophil chemotaxis
4. Neutrophil adherence and degranulation

Question 25

Give examples of diseases caused by type III hypersensitivity reactions

Answer 25

Rheumatoid arthritis - develop antibodies against Fc portion of IgG Glomerulonephritis Systemic lupus erythematosus

Question 26

How long after initial exposure does type IV hypersensitivity develop?

Answer 26

24-72hrs

Question 27

Which cells does type IV hypersensitivity involve?

Answer 27

Lymphocytes and macrophages

Question 28

What are the subtypes of type IV hypersensitivity?

Answer 28

Contact hypersensitivity Tuberculin hypersensitivity Granulomatous hypersensitivity

Question 29

Which cells are present in the effector phase of type IV hypersensitivity?

Answer 29

TH1 | Macrophages

Question 30

Give examples of diseases caused by type IV hypersensitivity to exogenous antigens

Answer 30

Contact hypersensitivity - epidermal reaction e.g. nickel, poison ivy, organic chemicals Granulomatous hypersensitivity - tissue damage e.g. TB, leprosy, schistosomiasis, sarcoidosis

Question 31

Give examples of diseases caused by type IV hypersensitivity to endogenous antigens

Answer 31

Pancreatic islet cells - DM Thyroid gland - Hashimoto’s thyroiditis Fc portion of IgG - rheumatoid arthritis

Question 32

What is the therapy for type III and IV hypersensitivity?

Answer 32

Anti-inflammatory drugs - NSAIDs, corticosteroids, steroid-sparing agents Monoclonal antibodies

Question 33

What are the mechanisms of type I hypersensitivity?

Answer 33

Abnormal adaptive immune response against the allergens - T helper 2 response against exposure, causes IgE production IgE causes mast cell activation

Question 34

Name the important mast cell mediators

Answer 34

Tryptase Histamine IL-4, IL-13, IL-5 Leukotrienes C4, D4, E4

Question 35

What is urticaria caused by?

Answer 35

Mast cell activation within the epidermis | Mediators are histamine and leukotrienes/cytokines

Question 36

What is angioedema caused by?

Answer 36

Mast cell activation in deep dermis | Mediators are histamine and bradykinin

Question 37

What are the systemic manifestations of allergic reactions (anaphylaxis)?

Answer 37

Systemic activation of mast cells leads to: - hypotension - cardiovascular collapse - generalised urticaria - angioedema - breathing problems

Question 38

What is the action of IM adrenaline in anaphylactic shock?

Answer 38

Reverses peripheral vasodilation and reduces oedema and alleviates hypotension Reverses airway obstruction/bronchospasm Increases the force of myocardial contraction Inhibits mast cell activation

Question 39

What is the therapy for type I hypersensitivity?

Answer 39

Oral immunotherapy - allergen desensitisation Omalizumab - anti-IgE monoclonal antibody Mepolizumab - anti-IL5 monoclonal antibody Anti-histamine Leukotriene receptor antagonists Corticosteroids