Physiology: hypersensitivities

Question 1

Hypersensitivity reactions

Answer 1

Question 2

TYPE I HYPERSENSITIVITY REACTIONS
Examples of some common conditions which are type I hypersensitivity reactions

Answer 2

Your classic allergic diseases - asthma, food allergies, anaphylaxis, allergic rhinitis (hay fever)

Question 3

TYPE I HYPERSENSITIVITY REACTIONS
With the pathophysiology of type I hypersensitivity reactions, what are the two steps?

Answer 3

Sensitisation and mast cell degranulation

Question 4

TYPE I HYPERSENSITIVITY REACTIONS
Describe the sensitisation step

Answer 4

• Exposure to allergen
• Dendritic cells phagocytose and express allergen antigens on its surface, then present this to Th2 cells
• Th2 cells then secrete IL-4, which drives B cells to switch isotype to secrete IgE
• IgE binds to Fc receptors on the surface of mast cells

Question 5

TYPE I HYPERSENSITIVITY REACTIONS
Describe the IgE threshold
Why do some people suddenly react to an allergen, after being fine with it for a long time?

Answer 5

Sensitisation will occur with repeated exposure.
IgE levels on mast cells will reach a threshold, which will trigger mast cell degranulation.

Due to the above reason

Question 6

TYPE I HYPERSENSITIVITY REACTIONS
Mast cell degranulation
- Allergen will bind to IgE (via Fc receptors) on mast cells
- Describe the pathways following this binding (pictured)
- Vasoactive amines include:

Answer 6

Histamine

Question 7

TYPE I HYPERSENSITIVITY REACTIONS
Th2 cells secrete with three interleukins?

Answer 7

IL-4, IL-5, IL-13

Question 8

TYPE I HYPERSENSITIVITY REACTIONS
Th2 cells - each interleukin is involved in which process?

Answer 8

Question 9

TYPE I HYPERSENSITIVITY REACTIONS
- The weep (mucus secretion) and sweep (peristalsis) response involves which interleukins?
- Is it aberrant in type I hypersensitivity reactions (and asthma)?

Answer 9

IL-4 and IL-13
Yes

Question 10

TYPE I HYPERSENSITIVITY REACTIONS
- What happens when there is low Th1 : high Th2?
High Th1 to low Th2?
- Do developing countries have a lower incidence of type I hypersensitivty reactions?

Answer 10

Low Th1/high Th2: prone to allergic diseases; not susceptible to worm infections
High Th1/low Th2: not susceptible to allergic diseases; prone to worm infections

Yes - they have a lower incidence

Question 11

TYPE I HYPERSENSITIVITY REACTIONS
What are some non allergen specific pharmacotherpies?

Answer 11

Antihistamines
B2 agonists (to reduce SMC contraction)
Corticosteroids

Question 12

TYPE I HYPERSENSITIVITY REACTIONS
Treatments
- Describe the process of aeroallergen immunotherapy
- What might this help with in terms of T cell responses?

Answer 12

Usually involves incremental subcutaneous administration of increasing amounts of allergen extract to induce immunological and physiological tolerance

May work by switching from Th response to a Treg response - to turn down/off type I hypersensitivty reaction

Question 13

TYPE I HYPERSENSITIVITY REACTIONS
Immunotherapies
- 2 side effects?
- 1 additional limitation?

Answer 13

Local skin reactions
Anaphylaxis (risk limits use in asthmatics)

Alternative strategies are required for potent allergens eg. latex, peanut

Question 14

TYPE 2 HYPERSENSITIVITY REACTIONS
Describe the mechanism

Answer 14

IgG and IgM antibodies bind to antigens on the cell surfcae, forming an antibody-antigen immune complex.
- Activates the classical pathway of the complement cascade (inflammation, opsonisation, microbe lysis)
- Complement independent leukocyte recruitment (where Fc receptors on leukocytes bind to immune complexes

Question 15

TYPE 2 HYPERSENSITIVITY REACTIONS
Examples of diseases?

Answer 15

Graves disease
Myasthenia gravis
Vasculitis
Autoimmune hemolytic anaemia

Question 16

TYPE 3 HYPERSENSITIVITY REACTIONS
How is it different from type 2?
Examples of diseases?

Answer 16

The immune complexes are formed between IgG/IgM and CIRCULATING, SOLUBLE ANTIGENS
Otherwise, involves the same mechanisms

Drug allergies (eg. to antibiotics)
Serum sickness
SLE
Glomerulonephritis

Question 17

TYPE 2/3 HYPERSENSITIVITY REACTIONS
- Can autoantibodies cross the placenta?
- Implications for baby? How to treat?

Answer 17

Yes
Babies may suffer from these diseases for their first months of life - but fades away as the baby’s own immune system develops
Plasmaphoresis can remove maternal autoantibodies

Question 18

TYPE IV HYPERSENSITIVITY REACTIONS
Pathophysiology - the two steps?

Answer 18

Sensitisation and elicitation

Question 19

TYPE IV HYPERSENSITIVITY REACTIONS
Sensitation - describe

Answer 19

• Dendritic cells at the site of antigen exposure process and present the antigen on MHC
• The dendritic cells migrate to the lymph nodes
• Th1 and cytotoxic T cells are generated (including memory cells - important for re-exposure)

Question 20

TYPE IV HYPERSENSITIVITY REACTIONS
Elicitation - describe

Answer 20

Th1 and cytotoxic T cells migrate from the lymph notes back to the original site

Cytotoxic T cells will lyse the affected cells - causing tissue damage

Th1 cells will release pro inflammatory cytokines
- Including IFN-y - which will lead to the recruitment of macrophages, which will further secrete pro inflammatory cytokines

Question 21

TYPE IV HYPERSENSITIVITY REACTIONS
- Treatment?

Answer 21

Antiinflammatories and steroids
Antihistamines won’t work

Question 22

TYPE IV HYPERSENSITIVITY REACTIONS
- Examples?

Answer 22

Contact sensitivity - eg. poison ivy, metal allergies
Mantoux test - used to diagnose TB
Type I diabetes
Multiple sclerosis