27 - Hypersensitivity

What is hypersensitivity?

Altered immunologic response to an antigen that results in disease or damage to the host

What are the 4 hypersensitivity reactions?

- Type I: IgE mediated

- Type II: Antibody mediated

- Type III: Immune complex mediated

- Type IV: Cell mediated

What cells are involved in type 1 hypersensitivity reactions?

- Mast cells

- Basophils

What are the clinical features of type 1 hypersensitivity?

- Onset 15-30mins

- Weal and flare

What is the mechanism of Type 1 hypersensitivity?

1) Allergen binds to IgE on mast cell

2) IgE cross linking triggers degranulation

3) Histamines are released causing vasodilation and smooth muscle contraction

What are some examples of type 1 hypersensitivity reactions?

- Eczema

- Asthma

- Hay fever

- Anaphylaxis

Give 6 physiological effects of histamine:

1) Vasodilatiom

2) Permeability of capillaries increases

3) Tachycardia

4) Bronchoconstriction

5) Swelling and inflammation

6) Adrenaline levels increase

What is uriticaria?

Hives

What is rhinitis?

Inflammation of the nose

Give 8 symptoms of anaphylaxis:

1) Angioedema

2) Severe abdominal pain

3) Hypotension

4) Shortness of breath

5) Wheezing

6) Dizziness

7) Cyanosis

8) Respiratory arrest

Describe the dual allergen exposure hypothesis:

Early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitisation whereas early oral exposure to food increases tolerance

What is desensitisation therapy?

Exposing child to an allergen to build immunity

What are 3 diagnostic methods for allergies?

1) Specific IgE blood tests

2) Skin prick test

3) Oral challenge test

What is the atopic triad?

1) Asthma

2) Rhinitis

3) Eczema

What are 2 treatments for rhinitis?

1) Nasal steroids

2) Anti-histamines

What causes rhinitis?

- Dust mite

- Animal hair

- Pollen

What are 3 characteristics of eczema?

1) Itching

2) Skin blister

3) Cracking skin

What are 2 treatments for eczema?

1) Topical steroids

2) Moisturisers

What is the mechanism for Type 2 hypersensitivity?

1) APC binds to antigen triggering presentation of antibodies to B cells:

- cytotoxic T cells bind to antigen releasing perforin/granzymes causing apoptosis

- activation of the complement cascade

- antibody blocks antigen altering function

What antibodies are involved in type 2 hypersensitivity?

IgG and IgM

What drug is a common triggering antigen for Type 2 hypersensitivity?

Penicillin

What are some examples of Type 2 hypersensitivity?

- Blood transfusion

- Grave's disease

- Goodpasture's nephritis

What is the mechanism for Type 3 hypersensitivity?

1) Antibodies are produced in response to antigen and enter the blood

2) Antibody binds to antigen forming an immune complex

3) Immune complexes become lodged in vessels

4) Complement cascade is activated:

- increased vascular permeability (oedema)

- cytokines released attracting neutrophils

What are some examples of Type 3 hypersensitivity?

- SLE (lupus)

- Rheumatoid arthritis

What are the 2 stages in the mechanism for Type 4 hypersensitivity?

Sensitisation and sensitised

What is the mechanism for sensitisation of Type 4 hypersensitivity?

1) APC is exposed to antigen and engulfed

2) APC presents antigen to a naive CD4 T cell

3) Naive cell matures to a T helper cell

What is the mechanism sensitised of Type 4 hypersensitivity?

1) Repeat exposure to antigen and sensitised T helper cell binds

2) Cytokines are released and activate:

- macrophages which release histamines

- cytotoxic T cells which directly damage cells

What are some examples of Type 4 hypersensitivity?

- Coeliac disease

- Type 1 diabetes

What common antigens cause Type 4 hypersensitivity?

- Metals (e.g nickel)

- Poison ivy