Hypersensitivity Flashcards
Hypersensitivity reactions are excessive immune responses to different types of antigens that cause damage. What are some examples of antigens that provoke these reactions? (3)
- Infectious agents
- Environmental substances
- Self antigens - autoimmunity
What are the 4 types of hypersensitivity reactions?
- Type 1 - immediate
- Type 2 - cell-bound antigen
- Type 3 - immune complex
- Type 4 - delayed
Main difference between them is their onset
Give an example of an infectious agent that can cause hypersensitivity reactions
Influenza virus
- It damages epithelial cells in the respiratory tract
- It can sometimes elicit an exaggerated immune response - trigger high levels of cytokine secretion (cytokine storm) which attract leukocytes to the lungs and trigger vascular changes that lead to hypotension and coagulation.
- In severe influenza, inflammatory cytokines also spill out into the systemic circulation, causing ill effects in remote parts of the body, such as the brain
Are all infections capable of causing hypersensitivity reactions?
No and the infections that do elicit hypersensitivity do not do so in every case
Give an example of an environmental substance that can trigger hypersensitivity reactions?
Dust triggers responses because it is able to enter the lower extremities of the respiratory tract, an area rich in adaptive immune response cells.
- Dust can mimic parasites and may stimulate an antibody response.
- If the dominant antibody is IgE, it may subsequently trigger immediate hypersensitivity, which manifests as allergy symptoms such as asthma or rhinitis.
- If the dust stimulates IgG antibodies, it may trigger a different kind of hypersensitivity, such as farmer’s lung.
What is a hapten?
- Smaller molecules sometimes diffuse into the skin and may act as haptens, triggering a delayed hypersensitivity reaction.
- Haptens are small molecule irritants that bind to proteins and elicit an immune response
Examples:
- Contact dermatitis caused by nickel
- Drugs administered orally, by injection or onto the surface of the body can elicit hypersensitivity reactions mediated by IgE or IgG antibodies or by T cells.
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Summary
What is a Type 1 hypersensitivity reaction like?
Type 1 hypersensitivity / atopy / allergy: is the immediate hypersensitivity reaction to environmental antigens mediated by IgE. It is mediated through the degranulation (release of granules) of mast cells and eosinophils and the effects are felt within minutes of exposure.
- Atopy genes (increased risk of developing allergy) or environmental factors result in polarisation of T-cells into Th2 cells. B-cells are then stimulated with IL-4 (secreted by CD4+TH2 cells) to produce IgE antibodies specific to the allergen/antigen.
- The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity, the antibody is IgE instead of IgA, IgG, or IgM.
- Mast cells and basophils coated by IgE antibodies are “sensitised” and later exposure to the same causes degranulation of these cells which results in an allergic response
What is the difference between allergy and atopy?
Atopy is an exaggerated IgE-mediated immune response; all atopic disorders are type I hypersensitivity disorders.
Allergy is any exaggerated immune response to a foreign antigen regardless of mechanism.
Examples of type 1 hypersensitivity / atopy responses i.e what allergic symptoms do you get from these reactions?
- Anaphylaxis - low blood pressure, angioedema and airway obstruction - can be fatal
- Rhinitis - discharge, sneezing, nasal obstruction
- Asthma - reversible airway obstruction occurs in the bronchi
- Dermatitis
- Eczema - chronic, itchy inflammation of the skin occurs
- Urticaria - hives
How do allergens access the body?
Through inhalation, ingestion, contact or administered drugs
What are the 2 key allergens associated with peanut allergies?
- Ara h2
- Ara h8
How are mast cells and eosinophils involved in type 1 hypersensitivity/atopy?
- Mast cells initiate allergic symptoms after allergen and IgE interact. They do this by process of ‘degranulation’ i.e releasing mediators that cause allergic symptoms such as histmaine, prostaglandin and cytokines (chemokines and TNF)
- Mast cells have receptors for IgE and FCER1 receptors (high affinity IgE receptor) and they are resident in many tissues.
- Eosinophils migrate to tissues where type I hypersensitivity reaction is
Describe the genetics behind allergies
Allergies are the result of multifactorial genetic predisposition - affects many genes. 2 examples are:
- Fillagrin - expressed by keratinocytes and involved in maintaining epithelial barriers, moisturising surfaces and controlling pH - polymorphisms in the gene encoding this is found in 50% of severe eczema.
- Lipopolysaccharide
Exposure to environmental factors on top of these genetic predispositions adds the risk of developing allergies. Timing of interaction between genetic and environmental factors is important.
How does anaphylaxis come about?
- Mast cell degranulation releases mediators that produce prostaglandins and leukotrienes
- The result is vasodilation and increased vascular permeability
- Shift of fluids from the vascular to the extra-vascular space resulting in a fall in vascular tone => Severe drop in blood pressure.
- IN the skin, mast cells release histamine further contributing to swelling and fluid shift.
What is a type 2 hypersensitivity reaction?
Interaction between IgG or IgM antibodies and antigens present on the surface of cells (such as circulating RBCs) or extracellular material (such as basement membrane)
This subsequently leads to cell lysis (RBCs), tissue damage or loss of function through mechanisms such as:
- Complement activation via the classical complement pathway
- Antibody dependent cell-mediated cytotoxicity - active cell lysis of target cell
- Antibody-receptor activity - Fc receptor on macrophages
This process takes several hours but if there is enough antibody within the system, it could take seconds.
What are some good examples of a type 2 hypersensitivity reaction?
- Reactions between different blood groups - immune mediated haemolysis:
- Blood transfusion reactions - ABO incompatible blood
- Rhesus D - transmission of incompatible maternal antibodies to fetal red blood cells causing hemolytic anemia in the fetus
- Auto-immune haemolysis could also be induced by drugs or infections
- Goodpasture’s syndrome - IgG autoantibodies bind to glycoprotein in the basement membrane of the lung and glomeruli in the kidney. Anti–basement membrane antibody activates complement, which can trigger an inflammatory response.
What is type 3 hypersensitivity?
An abnormal immune response to an antigen, mediated by the formation of antigen-antibody aggregates called “immune complexes’’.
- These are either cleared by the complement system or cause immune complex disease.
- Damage due to the immune complexes is either localised (i.e farmer’s lung, glomerulonephritis) or systemic (i.e SLE or glomerulonephritis)
- Immune complexes take some time to form and to initiate tissue damage.
