Hypersensitivity Flashcards
Define ‘hypersensitivity’
A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign agent.
What type of hypersensitivity reaction is an allergy?
Hypersensitivity reaction type I
What is an allergen?
Give examples.
An allergen is an antigen that causes an allergic reaction.
Examples include proteins and haptens
What are the 4 types of hypersensitivity reactions?
Type I = IgE-mediated hypersensitivity
Type II = IgG-mediated cytotoxic hypersensitivity (or IgM mediated)
Type III = immune complex-mediated hypersensitivity
Type IV = cell-mediated hypersensitivity
Which is the most common type of hypersensitivity reaction?
Type I (allergy - IgE-mediated)
What is Type I hypersensitivity also known as?
Immediate hypersensitivity (onset is rapid) or IgE mediated hypersensitivity
What is the term used to describe individuals who have a genetic predisposition for allergy?
Atopy
What is anaphylaxis?
An acute serious allergic response
What is a hapten?
A hapten is any small molecule that can be recognised by a specific antibody but cannot elicit an immune response by itself. A hapten must be chemically linked to a protein molecule to elicit an immune response.
Discuss the mechanisms of Type I hypersensitivity.
- During first exposure, IgE producing B-cells are activated (sensitisation)
- IgE binds to Fc receptor on mast cells and CD63 on basophils
- IgE recognises allergen and upon next exposure binds rapidly and causes immediate degranulation (elicitation). Mast cells release histamine.
Describe the stages of a Type I hypersensitivity reaction detailing the role of APC cells and T cells.
- Upon first exposure to antigen, APC cell processes antigen and presents it to TH2 cell.
- TH2 cell releases IL-2 and IL-4 which activates B-cell.
- B cells proliferate and differentiate into plasma cells that synthesise and secrete IgE antibody.
- IgE binds to mast cell receptor by Fc region, sensitising the mast cells.
- Upon subsequent exposure to allergen, mast cells with IgE bind to antigen and release inflammatory molecules, resulting in allergy symptoms.
Histamine is released by mast cells and basophils upon degranulation. What are the main roles of histamine?
Immune cell recruitment, neurotransmitter, vasodilator, endothelial constriction, bronchoconstrictor
Name 3 types of cutaneous atopy.
Allergic rhinitis (hay fever) Atopic dermatitis (allergic eczema) Asthma (lower respiratory tract)
What is systemic anaphylaxis?
Anaphylactic shock throughout the whole body
Arises from mast cell degranulation
Anaphylatoxins produced by the complement cascade can also cause systemic anaphylaxis
What happens during systemic anaphylaxis?
Oedema of the larynx - blocks breathing
Bronchiole constriction
Discuss different types of allergy tests.
Skin prickle and patch test (for a skin reaction)
Blood test - measure IgE levels in blood
Food challenge - diagnose food allergy
What is an anti-histamine?
An anti-allergy drug. Anti-histamines compete with histamine for the receptor binding site. Block histamine action.
Anti-histamines can be inverse agonists or antagonists.
What does hydrocortisone do?
Blocks histamine synthesis.
What effect does epinephrine have as an anti-allergy drug?
Best immediate treatment for anaphylactic shock. Reverses effects of granules (vasoconstriction, relaxes muscles)
- increases peripheral vascular resistance
- improves blood pressure
- causes bronchodilation
- reduces inflammatory mediator release
What does hypo- or de-sensitisation involve?
Repeat injections of allergen
Describe a Type II hypersensitivity reaction
IgG-mediated cytotoxic hypersensitivity
Involves activation of complement by IgG or IgM binding to an anti-genie cell
Cell is lysed by membrane attack complex formation and antibody-dependent cell-mediated cytotoxicity (NK cells, CD8+ T cells)
Name a common example of when a Type II hypersensitivity reaction might occur.
Transfusion of mismatched blood type/autoimmune haemolytic anaemia
Describe a Type III hypersensitivity reaction
Immune complex-mediated hypersensitivity
Involves reactions against soluble antigens circulating in the serum
Antibody-antigen immune complexes are deposited in organs which leads to: complement activation, neutrophil recruitment and inflammation-mediated damage.
Give some examples of a Type III hypersensitivity reaction.
- Rheumatoid arthritis
- Arthus reaction
- Serum sickness
- Oral erythema multiforme (EM)
Describe the condition ‘Arthus reaction’
A Type III hypersensitivity reaction
Antibody-antigen complexes are localised e.g. blood vessel walls
Can arise from injected particles (e.g. booster vaccinations) but can also arise from inhaled or ingested allergens (e.g. coeliac disease)
Describe ‘serum sickness’
Type III hypersensitivity reaction
A systemic form of Arthus reaction
Antibody-antigen complexes circulate and lodge in many different tissues.
Describe ‘Oral Erythema Multiforme (EM)’
Type III hypersensitivity reaction
Crusty blistering of oral mucosa
Deposition of immune complexes in the microvasculature of the oral mucous membrane
Can follow virus infections e.g. HSV
Can be caused by drugs e.g. trimethoprimsulfamethoxazole to treat U.T.Is.
Describe a Type IV hypersensitivity reaction
Cell mediated
T-cell mediated hypersensitivity (no antibodies)
Delayed hypersensitivity - takes time to recruit T cells
Localised T cell reaction at site of exposure (e.g. contact dermatitis)
Involves CD4+ cells and CD8+ cells
Name some examples of Type IV hypersensitivity reactions
Contact dermatitis Diabetes Type I Multiple Sclerosis Tissue graft rejection Orofacial granulomatosis - possibly?
