Hypersensitivity

Question 1

Hypersensitivity

Answer 1

Inappropriate stimulation of the adaptive immune system, resulting in tissue damage from inflammatory reactions, and even death.

Types I-V mechanisms:
types I, II, III, V – antibody mediated
type IV – T-cell mediated

Question 2

Immediate hypersensitivity

Answer 2

• initiated in a sensitised recipient (from previous contact with Ag) within minutes of further exposure to Ag
• Ab-mediated eg Type

Question 3

Delayed hypersensitivity

Answer 3

appears only after some days (48-72hr)

T-cell mediated – Type IV

Question 4

Types of hypersensitivity

Answer 4

1. immediate hypersensitivity IgE
2. antibody mediated IgM, IgG
3. immune complex mediated
4. T cell mediated

Question 5

Genetic susceptibility to immediate hypersensitivity

Answer 5

Polymorphs in genes (chr.5q31) IL-4, IL-5, IL-13

Question 6

Hygiene hypothesis

Answer 6

Related to decrease in infections in early life

pre-natal/childhood infections train immune system => less likely to respond to environmental allergens
(Fewer allergies in children brought up on farms than city children)

Question 7

Allergic response- sensitisation phase

Answer 7

Question 8

Allergic response- effector phase

Answer 8

Mast cell degranulation
Mast cells release inflammatory mediators

Trigger mechanisms

• allergen cross-linking
• IgE on surface
• FceRI receptors

Question 9

Mast cell activation causes…

Answer 9

Question 10

Late reaction (immediate hypersensitivity)

Answer 10

Question 11

Eosinophils

Answer 11

Question 12

Immediate hypersensitivity stages

Answer 12

Question 13

Mast cells and non-atopic allergy

Answer 13

triggered by temperature extremes & exercise
IgE and Th2 not involved
mast cells hypersensitive to activation
~20%-30% of immediate hypersensitivity

Question 14

Direct triggers of mast cell degranulation

Answer 14

Opiates, contrast media, vancomycin

C5a, C3a anaphylatoxins

Question 15

Anaphylaxis

Answer 15

Systemic exposure to allergen (even small doses)

• injections (drugs eg, penicillin)
• insect bites (eg bee venom)
• absorption across epithelia
  - - mucosa gut (peanut, shellfish; skin

Clinical manifestations

• drop in blood pressure (vascular shock)
• difficulty in breathing (airway constriction)
• widespread oedema
• Vomiting, abdominal cramps, diarrhoea

Question 16

Allergy treatment

Answer 16

Antihistamines
Mast cell stabilisers (stop histamine release)
Decongestants (shrink swollen membrane sin nose)

Corticosteroids
Epipen (adrenaline)
Anti IL-4 Omalizumab

Question 17

type 2: cytotoxic

Answer 17

Antibody formed against antigen on cell surfaces → cell lysis by:
1) activation of the classical complement pathway IgG, IgM Abs

2) ADCC – antibody-dependent cell-mediated cytotoxicity by NK cells binding IgG Ab via their Fc receptors

3) phagocytosis of RBCs, platelets – mediated by
Fc receptors on macrophages and C3b
(from complement activation)

Question 18

Type 2: Haemolytic disease of newborn

Answer 18

Ab response to RhD on foetal rbc, when mother RhD-ve

Sensitisation -> no sensitisation (anti-D) -> haemolytic disease (rhesus prophylaxis introduced)

Question 19

What type of hypersensitivity is Grave’s?

Answer 19

Type 2/V

hyperthyroidism

Question 20

Type 3 immune complex mediated hypersensitivity

Answer 20

Ag/Ab (IgG, IgM) complexes form in excess and deposit on (or near) blood vessel walls in tissues causing local inflammation and tissue damage (immune complex disease)

Streptococcus      			 
Staphylococcus 			 
Malaria
Leprosy
Viruses

Inhaled antigens – Pigeon fancier’s lung (pigeon antigens
Farmer’s lung (fungi in mouldy hay)
Hep B

autoimmune- RA, SLE

Question 21

Goodpasture’s syndrome vs systemic lupus

Answer 21

Goodpastures- type 2

Lupus- 3

Question 22

Mechanism of inflammation

Answer 22

complement activation →
      C5a, C3a 
   → release of mediators from
        mast cells,macrophages
   → attract neutrophils etc
       (C5a)
  neutrophils → FcRs, C3bR
   → enzymes, ROI, NO

basophil, platelet binding by FcgR
→ further release of vasoactive amines
platelets → microthrombi

Question 23

Type 4 cell mediated , delayed

Answer 23

T cell mediated eg TB, Listeria, herpes, measles

Question 24

Mechanism of type IV hypersensitivity

Answer 24

Question 25

What type of cells mediate type IV?

Answer 25

CD4+ Th1 cells

Question 26

Granuloma formation

Answer 26

1. Mycobacterial, TH1-type granulomas Mycobacterium tuberculosis, M leprae infections eg TB – bacteria persist in alveolar macrophages ``` Ag presented on MHCII to CD4+ TH1 cells macrophages activated (IFNg) ``` influx of monocytes to infection site differentiate to macrophages, activated, retained form granuloma (healed tubercule) to ‘seal off’ infected macrophage The process is cytokine driven: Th1 cell -> RANTES (chemokine for monocytes) -> MIF (retention of macrophages) macrophage -> MCP-1 (chemokine for monocytes) -> TNF-alpha, IL1 (= ↑ adhesions for extravasation)

Question 27

Granuloma structure

Answer 27

persistent Ag in centre macrophages – necrosis macrophages (from blood monocytes) form concentric rings of ‘epithelioid’ cells other cell types – eosinophils, T-cells giant cells – multinucleate fibrous connective tissue (fibrosis) calcification CD8+ T cells: possible source of cytokines lyse bacterial-infected macrophages produce granulysin – bactericidal gamma-d-T cells: cytokine producing; cytotoxic

Question 28

Tuberculin reaction

Answer 28

skin test for memory TH1 cells against mycobacterial Ag purified protein derivative (PPD) from culture filtrate → skin presented on dendritic cells → firm red swelling at 48-72hr; T cells, macrophages

Question 29

Type V - stimulatory

Answer 29

modification of type 2 Persistent activation of target cell membrane receptor by autoAb, normally responding to hormone -> TSH (thyroid stimulating hormone) receptor by auto Ab in thyrotoxicosis (Graves’ Disease) → continuous thyroxine release