Flashcards in autoimmune disease and hypersensitivity Deck (38)
what is hypersensitivity?
a group of disorders in which the normally beneficial components of the immune response act in an exaggerated or innappropriate fashion to environmental antigens which do not normally cause tissue damage
what is the difference between types I,II and III hypersensitivity and type IV sensitivity?
types I-III are mediated by antibodies, while type IV is caused by the innapropriate action of Th1 cells
what is responsible for damage caused to tissues in cases of hypersensitivity?
the exaggerated immune response rather than the antigen itself
how does type I hypersensitivity arise?
through inappropriate synthesis of IgE by the immune system.
what is the difference between allergy and atopy?
atopy is the presence of innapropriate IgE with no clinical symptoms, in allergy the patient will display some form of clinical problem
what is the IgE directed against in type I hypersensitivity?
how can environmental antigens be encountered?
what happens in type I sensitivity after exposure to the environmental antigen?
mast cells and allergen specific IgE produced
release of inflammatory mediators
what are some examples of inflammatory mediators ?
histamine (pre formed)
prostaglandins (newly synthesised)
what are some of the effects of inflammatory mediators produced in type I hypersensitivity?
smooth muscle contraction
what is type II hypersensitivity mediated by?
IgG or IgM antibodies
what are the antibodies produced in type II hypersensitivity directed against?
antigens found on the surface of cells or fixed within certain tissues
how are tissues damaged in type II hypersensitivity?
antibody binds to antigen
fc binding of immunoglobulin and stimulation of phagocytes
antibody dependent cellular cytotoxicity (ADCC)
what effects does type II hypersensitivity have on target cell function?
inhibition of function
where can the antigens come from in type II hypersensitivity?
external (exogenous) or self derived
what do the clinical presentations of type III hypersensitivity arise from?
abnormal deposition of formed antigen (Ag) and antibody(Ab) complexes/immune complexes
what happens in pathological immune complex formation?
abnormal immune complex formation causes the complexes to precipitate into tissues and cause inflammation
what two forms of inflammation typically present in type III hypersensitivity?
serum sickness - systemic illness where immune complexes are deposited throughout many tissues
arthus reaction - localised disorder where complexes form locally in tissues
what do the immune responses in type IV sensitivity occur as a result of?
contact with inert environmental substances or as a reaction to infection with certain micro-organisms
what is the name for a low molecular weight environmental agent in a type IV hypersensitivity reaction?
what is the name for the host protein that the environmental agent binds to?
why do environmental agents have to bind to host proteins in order to produce an immune response?
their molecular weight is too low individually to evoke an immune response
how long does it take for clinical effects to present in type IV hypersensitivity?
typically 48-72 hours from antigen exposure
what happens in type IV hypersensitivity reactions after the antigen has been presented?
cytokines are produced (overactivity/dysregulation), which leads to inflammation
what is autoimmune disease?
group of clinical disorders characterised by tissue or organ damage mediated through aberrant cellular and/or humoral immunological mechanisms which are directed against autoantigens (self antigens)
what is non-organ specific autoimmunity?
when specific autoantigens are present in a ubiquitous way throughout many tissues
what is organ specific autoimmunity?
when the autoantigens causing the immune response are localised to specific tissues or organs
what is tolerance with regard to autoimmune disease?
the process whereby the immune system avoids producing damaging reactions against self antigens
what two types of tolerance are there?
central tolerance and peripheral tolerance
what is central tolerance?
deletion of autoreactive T and B cells during cell maturation
what is peripheral tolerance?
inhibiting the activity of autoreactive cells which escape the central tolerance process
is immune recognition of self antigens always damaging?
give an example of physiological (normal) immunity
when T cells recognise antigens which is complexed with self molecules
when antibodies recognise and bind portions of other antibodies, regulating their production and activity
what is the aetiology of autoimmune disease?
immune regulatory factors
"other" factors such as age, trauma and malignant disease
what are the effector mechanisms involved in autoimmune disease?
identical to those in normal immune response:
cellular (T cell) or antibody (B cell) activity
antibody activation of complement mediated inflammation
immune complex formation
recruitment of innate immune components (phagocytes, cytokines)
what is thought to be the cause of tolerance to an autoantigen being broken?
combination of one or more environmental factors combined with one or more genetic factors
what are the consequences of tolerance to an autoantigen being broken?
allows for a potential or actual autoimmune response to occur against the autoantigen