What is hypersensitivity?
Hypersensitivity is an inappropriate or exaggerated immune response against antigens or allergens. This includes both allergy and auto immunity
It is a consequence of:
- Reaction against self antigen
- Inappropriate reactions against microbes
- Reactions against environmental antigens
Once a hypersensitivity reaction starts it is difficult to control or terminate it.
General characteristics of hypersensitivity reactions
There are 4 types of hypersensitivity:
- Immediate type (allergy)
- Antibody mediated hypersensitivity
- Immune complex
- Cell-mediated hypersensitivity
Types i-iii are antibody-mediated Type iv is cell-mediated
It doesn’t occur on first exposure as the immune system needs to be sensetised,
Hypersensitivity vs Autoimmunity
Hypersensitivity describes the mechanisms of how the body reacts to certain stimuli and most of these mechanisms are involved in autoimmune disorders. Hypersensitivity types ii-iv are involved in autoimmune disorders, not so much type i though.
Features of autoimmune diseases are breakdown of tolerance of body, presence of autoantibodies and leukocyte infiltration. They may be systemic and effect lots of tissues throughout the body or localised to specific sites. There is female biases as well as there is a higher likelihood of you getting one if someone in your family has once. There are associated between HLA (human leukocyte antigen) complexes and antibodies.
Additonally often lesions can be classified by the type of hypersensitivity which has caused itf
Type 1: Allergy
Rapid, antibody mediated, degranulation of mast cells/basophils, occurs within minutes
This is reaction to an allergen to degranulate mast cells and basophils. Local anaphylaxis can occur.
Allergens can include:
- small soluble proteins
- dust mite faeces
- food components
- insect salive
- plant excretions
- chemicals
- drugs
How does it work
B cells make IgE antibodies which stick to mast cells and basophils. when secondary exposure occurs binding to the antibodies cause mast cells to degranulate. B cells need to be activated by Th2 cells and then class switch to make IgE which will then attach to mast cells.
Atopy is the genetic tendency to develop allergic diseases you could:
- have more IgE molecules and mast cells
- higher affinity Fc domain receptors on mast cells and basophils
- IgE levels higher than 1 µg/mL
- genetic predisposition
Hygiene hypothesis
Type 2: Antibody (cytotoxic)
Initiated by binding of antibody to a cell membrane or extracellular matrix, occurs within a day
The antibodies are directed against target antigens on the surface of cells or tissue components.
The mechanisms of tissue injury include:
- Opsonisation and phagocytosis
- Complement and Fc-mediated inflammation (neutrophil activation)
- Antibody mediated cellular dysfunction (antibody binding to receptors disabiling them)
Type 3 Immune complex
Antibody binds to soluble molecules to form immune complexes, occurs within 1-2 days
This usually occurs when there is high antigen and antibody concentrations at the same time. Complexes form. This can damage vascular wall and glomerulus. 2 phases, first phase is complexes form second phase is adherence of complex to a vascular wall (or glomerulus). the immune complexes will the activate complement, neutrophils etc
Type 4: Cell-mediated
Attack by immune cells in absence of antibodies, Occurs in around 3 days
There are 2 main mechanisms for this:
- Delayed type hypersensitivity CD4 T cells produce cytokines - mediate inflammation. CD8 T cells also contribute to cytokines
- Direct cell cytotoxicity CD8 cell mediated - they directly kill cells
Granulomas are a type of type iv sensitivity