Immunology 3: Autoimmunity Flashcards
define autoimmunity
immune response against a self-antigen or antigens
define autoimmune disease
Tissue damage or disturbed physiological dysfunction due to an autoimmune response.
what does rheumatoid factor (RF) test for?
- Autoantibodies, usually of the IgM class, directed against the Fc portion of IgG.
- Around 5% of healthy normal people have a positive test but do not have autoimmune disease (i.e. RA).
Features of organ specific autoimmune disease.
- affect single organs
- autoimmune response against multiple antigens within that organ
- antigen: both cell surface or intracellular molecules
Features of non-organ specific autoimmune disease.
- Affects multiple organs.
- Autoimmune response against self-antigens widely distributed in the body.
- Antigen: typically intracellular.
list some organ-specific autoimmune diseases
- Hashimoto’s thyroiditis
- myasthenia gravis
- pernicious anaemia
- Addison’s disease
- type 1 diabetes
list some non-organ specific autoimmune diseases
- dermatomyositis
- SLE
- scleroderma
- rheumatoid arthritis
autoimmune disease epidemiology
- 3-5% of population
- peak age of onset 15-65 years (except type 1 diabetes)
- clustering withing families
- almost all more common in women except for ankylosing spondylitis.
what is tolerance?
non-responsiveness of the immune system to an antigen
describe self-tolerance
- Tolerance to self antigens is a fundamental property of the normal immune system,
- Failure of self-tolerance results in immune reactions against self antigens.
- Autoimmunity could be considered in terms of a breakdown of immune self-tolerance
describe the mechanism of central tolerance
- Occurs during lymphocyte development in thymus.
- T and B lymphocytes that recognise self-antigens are eliminated before they differentiate into fully immunocompetent cells.
- Most active in fetal life but continues throughout life as immature lymphocytes are generated.
describe the mechanism of peripheral tolerance
Inevitably some autoreactive cells evade deletion and reach the peripheral tissues, where they are controlled by peripheral tolerance mechanisms.
- ignorance: self-antigen is effectively invisible to the immune system as it is sequestered in an avascular organ.
- deletion
- anergy
- regulation (‘suppression’)
Naive CD4+ T cells need two signals to become activated and initiate an immune response:
- Antigen-specific signal through the T-cell antigen receptor - SIGNAL 1
- Non-specific co-stimulatory signal, usually signalled by CD28 (on T cell) binding to one of the B7 family (CD80 or CD86) on the dendritic or specialised B cell - SIGNAL 2
If the T cell receives both signals, then it will become activated and proliferate and produce cytokines.
Describe the deletion/anergy mechanisms of peripheral tolerance.
Lack of co-stimulation
- stimulation through T-cell receptor alone (without co-stimulatory signal) leads to longstanding anerfy or death of the T cell by apoptosis.
Describe the Regulation (‘Suppression’) mechanism of peripheral tolerance.
- Active suppression of self-reactive T cells by regulatory populations of T cell (Tregs).
- Generally defined by the markers CD4, CD25 and FoxP3.
- Exert their regulatory effects either through secretion of immunosuppressive cytokines such as IL-10 and TGF-beta or though cell contact dependent mechanisms, such as CTLA-4 expression.
autoimmune disease aetiology
- genetic: polygenic, strongest genetic associations is linkage to MHC (HLA in humans)
- female except for Ankylosing Spondylitis
- UV exposure
- cigarette smoking
- dietary factors: coeliac disease and gliadin
- certain drugs e.g. D-penicillamine
- infections
what self-antigen changes can cause failure of peripheral tolerance?
- De novo expression of self-antigen epitope that the immune system has not become tolerant to.
- Alterations in the way which self-molecules are presented to the immune system. (post-translational modifications)
what is HLA-B27 a risk factor for?
Ankylosing spondylitis
