Allergy And Hypersensitivities

Question 1

Outline the types of hypersensitivity

Answer 1

• Type I- mast cells with FCεRI on surface respond to allergen antigens IgE-> degranulation
• Type II- Antibodies bound to target cell result in killing of cell by K cell/macrophage/phagocytosis
• Type III- Antibodies and antigens form large immune complexes which immune cells respond to- macrophage/neutrophil
• Type IV- delayed type hypersensitivity- T cells activated by peptide-MHC
• Type V- antibody stimulates a response it shouldn’t- eg hormone release
• Innate- PRRs respond to PAMP

Question 2

Outline Type I hypersensitivity

Answer 2

IgE mediated mast cell degranulation:
E.g. respiratory tract- hay fever, skin- eczema, mouth/throat- food
• IgE- present at low level in serum and short half life. Class switching to IgE promoted by IL-4 and IL-13 and inhibited by INFγ
• Elevated in:
- certain parasitic diseases
- hyper-IgE syndrome- defective IFNγ so Increased IL-4
- allergy

• IgE mechanism- FcεRI on mast cells detect allergen antigens- there are many receptors which leads to cross-linking-> signalling within cells to release granules and mediator synthesis

• people without allergies have fewer FcεRI on surface- no signalling
• degranulation- histamine and serotonin stored in granules are released
• inflammatory mediator synthesis- TNFα, prostaglandins, leukotrienes

• Th2/Thf must be activated to produce IL4 and IL13

• > these act on B cells to make them switch to IgE and become mast cells
• > endothelial cell activation by histamine

Question 3

Why are some people more allergic than others?

Answer 3

• Genes- FcRε, HLA-DQ, IL-2Rβ, IL4R
• Environment- fewer infections as children means less Th1 produced therefore more Th2?
• Dietary conundrums- small regular exposure

Question 4

What pharmacotherapy allergy treatments are common?

Answer 4

• Corticosteroids- suppress transcription of pro inflammatory genes
• sodium chromoglycate- blocks mediator release from mast cells
• Montelukast- leukotriene receptor antagonist

Question 5

Outline type II hypersensitivity

Answer 5

Antibody mediated killing- cytotoxic hypersensitivity:
• Antibody is bound to host target cell. Fc region then activated NK/macrophages
• E.g.
- transplantation- transfusion rejection
- haemolytic disease of newborn (HDN) due to Rhesus factor incompatibility
- Many autoimmune diseases

• HDN:

• sensitisation- RhD- mother forms antibodies against RhD+ baby blood during first pregnancy
• must protect second pregnancy from antibodies which can cross placenta and cause killing of RBCs

• Autoimmune disease- Ab mediated cell dysfunction

• blocking antibody against cell surface receptors
• e.g. Myasthenia gravis- Antibodies to acetylcholine receptors

Question 6

Outline type V hypersensitivity

Answer 6

Stimulatory antibody against cell surface receptors

E.g. Graves’ disease (antagonistic anti-TSHR)- activates thyroid gland

Question 7

Outline Type III hypersensitivity

Answer 7

Immune complex mediated:
• Large antibody-antigen complexes form and are deposited where blood flow is slowed (skin, kidney, lungs) on vascular endothelium
-> activation of macrophages etc, but complex is too large to be phagocytosed- frustrated phagocytosis (causing tissue damage)
-> clotting and inflammation

• E.g.

• allergies- farmers lung from fungus
• infections- post-streptococcal glomerular nephritis
• some autoimmune diseases- systemic lupus erythematosus (SLE)

Question 8

Outline Type IV hypersensitivity

Answer 8

Delayed type hypersensitivity (DTH)- T cell mediated
• Peptide-MHC presents to TCR on T cell-> cytokines activate macrophages
• E.g.
- allergies- allergic contact dermatitis
- Tuberculin skin reactions to mycobacterial antigens- Mantoux test
• Chronic local DTH reaction- continuous activation of T cells causes accumulation of large number of macrophages which join up
-> Epitheloid cells/giant cells
-> Lung granuloma (closed off area of T cells and giant cells)

Question 9

Outline innate hypersensitivity

Answer 9

• Acute inflammation- sepsis/toxic shock syndrome (super antigen is binding to T cells- doesn’t have to bind at specific binding site so huge T cell activation)
• Over activation of the macrophage has also been associated with many major chronic diseases- Atherosclerosis, Alzheimer’s, Type II diabetes