Hypersensitivity and Autoimmunity Flashcards
What is hypersensitivity?
A group of disorders in which the normally beneficial components of the immune response act in an exaggerated or inappropriate fashion to environmental antigens which do not normally cause tissue damage.
What types of hypersensitivity are mediated via antibodies?
types I, II, III
What is type IV caused by?
the inappropriate actions of Th1 cells.
How does type I arise?
through the inappropriate synthesis of IgE by the immune system which is directed against environmental antigens
How can the body interact with allergens?
- airborne
- ingested
- injected
- skin contact
What is atopy?
a state of sub-clinical immune sensitisation
What is the pathogenesis of allergy?
- allergen exposure
- mast cell+ allergen specific IgE
- release of inflammatory mediators
- mucosal oedema, capillary leakage, secretions, smooth muscle contraction, vasodilation
What is type II mediated via?
IgG or IgM which are directed against antigens found on the surface of cells or fixed with certain tissues
Why can the distinction in type II be blurred between hypersensitivity and autoimmune?
The antigens can be exogenous (external) or they can be derived from self
Once the antibody has bound to the relevant antigen, damage to the tissue arises through…
- complement activation
- Fc binding of immunoglobulin and stimulation of phagocytes
- antibody dependent cellular cytotoxicity (ADCC)
- effects on target cell function (inhibits/stimulates)
How do the clinical conditions arise in type III?
as a result of abnormal deposition of formed antigen/ antibody complexes in tissues
In what way are type II and type III reactions similar?
-Both may arise as a result of an antibody reaction occurring against an exogenous or self-antigen
What usually happen to immune complexes?
-once formed they usually gain acces to the bloodstream and are kept soluble in the blood and transported attached to RBC to the liver and spleen where fixed phagocytes such as Kupffer cells take up and destroy complexes.
Immune complexes can be…
- physiological
- pathological
Why do clinical signs occur in pathological immune complex formation?
as a result of predisposing factors in either the antigen involved or in the immune response to that antigen
What is the end result of abnormal immune complex formation?
- the complexes precipitate out into tissues and cause inflammation.
- the inflammation can lead to serum sickness or arthus reaction
What cytokine products are involved in type IV?
interleukin-2 and y-interferon
Why do these inappropriate responses occur?
in response to contact with inert environmental substance or as a reaction to infection with certain micro-organisms
What must non-infections environmental agents do to cause a type IV response?
-bind to a host proteins to produce an antigenic stimulus of sufficient size to incite a response
What is a low molecular weight agent termed?
hapten
Why is type IV frequently called delayed type hypersensitivity?
It can take between 48-72 hours for a response to occur
What is the pathogenesis of type IV reactions?
- hapten and carrier or micro-organism cause antigen uptake and presentation
- Th1 antigen recognition/cytokine production
- inflammation
Autoimmune disease
A group of clinical disorders characterised by tissue or organ damage mediated through abhorrent cellular and or humoral immunological mechanisms which are directed against autoantigens.
Tolerance
The process whereby the immune system avoids producing damaging reactions against self antigens.
How does tolerance arise?
through deletions of autoreactive T and B cells during cell mutation or by inhibiting the activity of autoreactive cells which escape the central tolerance process
What is the aetiology of autoimmunity?
- genetic factors
- immune regulatory factors
- hormonal factors
- environmental factors
- other factors
What are the effector mechanisms involved in autoimmunity?
- cellular (T cells) or antibody (B cell) activity
- autoantibody activation of complement-mediated inflammation
- immune complex formation
- recruitment of innate immune components
What are important contributants to autoimmunity?
environmental factors and inheritance of particular HLA alleles
