5: Hypersensitivity

Question 1

Types of hypersensitivity

Answer 1

Type :
I - IgE mediated, anaphylactic/immediate
II - antibody mediated
III - immune complex mediated
IV - delayed or T-cell mediated

Question 2

In hypersensitivity reactions, the immune system

Answer 2

reacts in a way that damages the body rather than protecting it

Question 3

Exaggerated immune reactions can lead to

Answer 3

Sepsis
Hypercytokinaemia (cytokine storm)
Organ dysfunction
Fatal tissue damage

Question 4

Type I hypersensitivity

Answer 4

Mediated by IgE antibodies against environmental allergies
Immediate hypersensitivity - within mins
Targeted to multivalent environmental agents - allergens

Tested for by skin prick test - wheal and flare reaction to specific known allergens

Question 5

Test for Type I hypersensitivity

Answer 5

Skin prick test, looking for wheal and flare reaction to specific allergens

two phases :
1. sensitisation phase
2. re-exposure leading to anaphylaxis

Question 6

Sensitisation phase

Answer 6

Complex - mechanism not exactly understood, influenced by genetics, environment and age

Th2-cells and follicular Th cells produce IL-4 and IL-3
B cell class switching from IgM to IgE production
Th2 cells recruit eosinophils

IgE by B cells not found in circulation, loaded onto Fc receptors of mast cells and basophils

Allergen encountered again, cross-linking of two IgE bound on membrane of mast cell and basophils, leading to rapid immune reaction - sensitisation

Question 7

Crosslinking causes

Answer 7

rapid degranulation, release of inflammatory mediators
- occurs at lower antigen concentrations than normal immune reactions

Question 8

Phases of T1 hypersensitivity

Answer 8

3 phases :
Early phase- degranulation of mast cells, within minutes
Later response - within a few hours, recruitment of neutrophils
Late response - 3/4 days, eosinophils recruited, Th2 cells present

Question 9

Anaphylaxis is a

Answer 9

medical emergency

Question 10

Anaphylaxis can be treated by

Answer 10

• adrenaline injection ; counteracting vasodilation, EpiPen
• antihistamines
• feet up to maintain brain perfusion
• Monitor for biphasic anaphylaxis

Question 11

Biphasic anaphylaxis

Answer 11

Unknown anaphylactic shock following first anaphylactic shock

Question 12

Type II hypersensitivity

Answer 12

IgG or IgM mediated cytotoxicity reactions
Self-antibodies produced by self-reactive B cells (escaped tolerance)

Secrete self-reactive IgM or IgG when activated by self-reactive T cells

Question 13

By which mechanisms can hypersensitivity II result in disease

Answer 13

Anti-receptor activity; blocking or activating its function
Antibody dependent cell-mediated cytotoxicity (ADCC)
Classical activation of complement cascade

Question 14

Cytotoxic mechanisms of Type II hypersensitivity

Answer 14

Complement neutrophil activation
Membrane Attack Complex
Antibody opsonisation and phagocytosis
Natural Killer cells against antibodies

Question 15

Receptor binding in Type II hypersensitivity

Answer 15

Blocking receptors e.g Myasthenia gravis
Activating receptors e.g. Graves’ disease

Question 16

Type III hypersensitivity

Answer 16

Small soluble antigens make immune complexes less immunogenic, not removed by spleen
Self reactive B cells switched from IgM to IgG Production

immune complexes become deposited in blood vessel walls

Question 17

In type 3 hypersensitivity, immune complex deposition in blood vessel walls can lead to:

Answer 17

Activation of complement system
Activation of neutrophil degranulation
leads to tissue damage at site of deposition

Question 18

Example of Type 3 hypersensitivity

Answer 18

Systemic Lupus Erythematosus

Question 19

Systemic Lupus Erythematosus

Answer 19

Auto-antibodies against DNA and nuclear proteins
Complement activated by immune complexes, leading to :
damage by MAC formation
oedema by anaphylatoxins
neutrophil recruitment

Question 20

In Lupus (T3 hypersensitivity) immune complexes are deposited in

Answer 20

kidneys (blood filtration)
joints (synovial fluid, filtered from blood vessel walls)

Question 21

Compare Complement in Type 2 and Type 3 hypersensitivity

Answer 21

T2: Complement used in small amounts- because damage is localised
T3: Complement used in large amounts (C3 & C4 can be used as diagnostic markers)

Question 22

Compare Antigens in Type 2 and Type 3 hypersensitivity

Answer 22

T2: antigens cell-surface bound
self-antigens / foreign antigens e.g drugs

T3: antigens soluble
mostly self-antigens (except serum sickness)

Question 23

Compare damage in Type 2 and Type 3 hypersensitivity

Answer 23

T2: damage where immune complexes are formed (tissue specific)

T3: Damage where immune complexes are deposited (not tissue specific)

Question 24

Type IV hypersensitivity

Answer 24

T-cell mediated
Delayed-type hypersensitivity; T cell recruitment takes time
NOT antibody mediated
damage occurs through both CD4+ Th cell or CD8+ cytotoxic T cell

Question 25

Reactions of type 4 hypersensitivity

Answer 25

Sensitisation phase
Re-exposure and immune response

Question 26

Use of T4 hypersensitivity in testing

Answer 26

Can be used in Mantoux skin test for TB
(poison ivy)

Question 27

Haptens

Answer 27

small proteins functioning as antigens when bound to proteins

Question 28

Sensitisation phase of T4 hypersensitivity

Answer 28

Exposure leads to dendritic cell uptake
DC present to specific naive T cells in lymph node
T cells differentiate into mature Th1-cells –> form memory cells

Question 29

Re-exposure in T4 hypersensitivity

Answer 29

Specific memory T cells respond, induce inflammation in tissue
leads to Th1-cell expansion

leads to Macrophage activation - incr. vascular permeability, causing swelling (oedema) and redness

Question 30

Involvement of T cells in T4 hypersensitivity

Answer 30

Dependant on signals T cells receive from phagocytes

• differentiation to Th17 cells; IL-17 secretion that recruits neutrophils
  -CD8+ self-specific cytotoxic T cells directly kill cells within antigens