Hypersensitivity & 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 is bystander damage?
The exaggerated immune response associated with hypersensitivity is what causes the tissue damage, rather than the antigen
What mediates types 1,2 and 3 hypersensitivity?
Antibodies
What causes type 4 hypersensitivity?
Inappropriate actions of Th1 cells
What is another name for type 1 hypersensitivity?
Allergy
How does type 1 hypersensitivity arise?
Through the inappropriate synthesis of IgE by the immune system acting against environmental antigens (allergens)
In what ways can environmental antigens/allergens be encountered?
Airborne
Ingested
Injected
Skin contact
What other factors give rise to allergic problems?
interacting genetic factors
environmental influences
hormonal and neurological influences
immune regulatory factors.
Explain the difference between allergy and atopy?
Allergy = the presence of IgE in association with clinical symptoms
Atopy = the presence of IgE with no related symptoms
Explain the pathogenesis of type 1 hypersensitivity
- allergen exposure causes mast cells to release granule contents and plasma cells to produce IgE specific to the allergen
- causes the release of inflammatory mediators (newly formed e.g. prostaglandins and pre-formed e.g. histamine)
- allergic response (mucosal secretion/vasodilation/oedema/capillary leakage/smooth muscle contraction)
What is type 2 hypersensitivity?
- Inappropriate production of IgG or IgM antibodies which are directed against antigens found on the surface of cells or fixed within certain tissues
- Antigens can be external or self
Describe the mechanism of the tissue damamge that occurs in type 2 hypersensitivity
- antibody binds to the relevant antigen
- complement is activated
- Fc binding of immunoglobulin and stimulation of phagocytes
- ADCC (antibody dependent cellular cytotoxicity)
- inhibition or stimulation of target cell function
What is type 3 hypersensitivity?
clinical conditions which arise as a result of abnormal deposition of formed antigen/antibody complexes (immune complexes) in tissues
Describe the physiological immune complex process
- once formed they gain access to the bloodstream
- kept soluble in the blood and transported on RBCs to the spleen/liver
- phagocytes take them up and destroy them
Describe the pathological immune complex process
- complexes precipitate out into tissues, causing inflammation
What forms can the inflammation caused by immune complex precipitation taje?
Systemic illness with deposition in many tissues (serum sickness)
Localised disorder with deposition locally in tissues (arthus reaction)
What is type 4 hypersensitivity?
Inappropriate production/action of Th1 cells and cytokine products in response to contact with inert environmental substances or in reaction to infection with certain micro-organisms
Why do the reactions associated with type 4 hypersensitivity occur?
the body’s immune system finds it difficult to destroy agents due to their function, structure or ability to evade, confound or counteract immune responses
Why is it difficult for non-infectious environmental agents to produce a substantial immune response in themselves?
They are of too low a molecular weight
They need to bind to host proteins to produce an antigenic stimulus of sufficient size to incite a response
What is a hapten?
A non-infectious environmental agent with too low a molecular weight to produce a substantial response in itself
What is a carrier in relation to type 4 hypersensitivity?
The host protein that a hapten binds to to produce an antigenic stimulus of sufficient size to incite a response
What is another name given to type 4 hypersensitivity and why?
‘Delayed-type hypersensitivity’
There is a delay of 48-72 hours between antigen exposure and any clinical effect
Describe the pathogenesis of type 4 hypersensitivity
- hapten and carrier bind
- antigen uptake and presentation
- Th1 antigen recognition and cytokine production (overactivity / dysregulation)
- inflammation
What is an autoimmune disease?
A group of clinical disorders characterised by tissue or organ damage mediated through aberrant cellular and / or humoral immunological mechanisms which are directed against autoantigens
What is tolerance in association with autoimmunity?
The process whereby the immune system avoids producing damaging reactions against self antigens
Breakdown is a requirement for the development of autoimmune disease
How does tolerance arise?
Through deletion of autoreactive T and B cells during maturation (central tolerance)
Through inhibiting activity of of autoreactive cells which escape central tolerance (peripheral tolerance)
What factors give rise to autoimmunity?
Genetic factors Immune regulatory factors Hormonal factors Environmental factors Other factors (age/trauma/malignant disease)
Describe the effector mechanisms involved in autoimmune disease?
*Identical to those which operate in normal immune responses:
- T/B cell activity
- antibody activation of complement-mediated inflammation
- immune complex formation
- recruitment of innate immune components (phagocytes etc.)
What are two major contributors to autoimmunity ?
- environmental factors
- inheritance of particular HLA alleles (susceptibility)
- lead to a breakdown of tolerance
Describe the spectrum of clinical autoimmune disorders
From;
organ specific disorders (autoimmune endocrine disorders)
to
non-organ specific disorders (connective tissue disorders)
