Immunological tollerance Flashcards
What is an antigen?
Substance capable of generating an immune response
What is immunological tolerance?
Unresponsiveness of the immune system to an antigen
(Not only self antigens, but also fetus, gut flora, plant pollens etc.)
What is autoimmunity?
An immune response to self antigens
Due to a failure of immunological tolerance
Usually due to a combination of genetic and environmental factors
Leads to immune-mediated damage of specific tissues
How can autoimmunity occur?
The immune system can respond to an “infinite” number of threats.
It is pre-programmed to recognise all threats by genetic recombination with T and B cells, producing an infinite variety of receptors, hence and infinite number of antigens can be responded to by specific T and B cells.
On stimulation, by a specific antigen, the T/B cell will replicate massively to provide a specific response.
How can autoimmunity go wrong?
Pre-programmed T and B cells can also recognise our own self antigens.
This needs to be tightly regulated else our immunological response can attack our own tissue. This regulation is called immunological tolerance
What is central tolerance?
“Central tolerance” develops in thymus and bone marrow
Main role is to prevent immune responses to self antigens
Most active in fetus & declines after birth
How does Central tolerance work?
Immature lymphocytes that recognise self antigens → “clonal deletion” (by apoptosis) or “clonal anergy” (by regulatory T lymphocytes)
What is peripheral tolerance?
“Peripheral tolerance” develops in other peripheral lymphoid tissues
Also prevents immune responses to fetus, gut flora, plant pollens etc.
Active throughout life
How does peripheral tolerance work?
Mature lymphocytes that recognise self or benign antigens → “clonal suppression” (by regulatory T lymphocytes)
Why do we need to understand immunological tolerance?
A better understanding of tolerance should improve our understanding, diagnosis and treatment of :
- Autoimmune diseases
- Recurrent miscarriages
- Hypersensitivity disorders
- Chronic infections that evade clearance
- Malignancies that seem to induce tolerance
- Rejection of organ transplants & graft-versus-host disease
What causes a loss of immunological tolerance
Almost all loss of tolerance seems to be B cell mediated rather than T cell
It is usually due to a combination of genetic and environmental factors
Give examples of immunological diseases that affect the following systems:
CNS
Cardiovascular
Respiritory
Endocrine
Gastrointestinal
Dermatological
Rheumatological
Multiple sclerosis (MS), myasthenia gravis (MG), Guillain–Barré syndrome (GBS)
Dressler’s syndrome, rheumatic fever, temporal arteritis
Idiopathic pulmonary fibrosis
Graves’ disease, Hashimoto’s thyroiditis, diabetes mellitus (type 1)
Pernicious anaemia, coeliac disease, Crohn’s disease, ulcerative colitis (UC)
Psoriasis, vitiligo, alopecia
Rheumatoid arthritis (RA), lupus
Name some immunological pathophysiology’s that occur due to environmental factors
Possibly due to “molecular mimicry” of self-antigens by …
Infections :
Streptococcal infection → rheumatic fever urethritis or gastroenteritis → reactive arthritis
Campylobacter gastroenteritis → Guillain–Barré synd.
Chemicals :
anti-convulsants or antibiotics → drug-induced lupus halothane (general anaesthetic) → liver necrosis
Trauma :
exposure of self-antigens in protected sites (eg. eye, testes)
Name some immunological pathophysiology’s that occur due to environmental factors
Possibly due to “molecular mimicry” of self-antigens by … Mostly B cell mediated
Infections :
Streptococcal infection → rheumatic fever urethritis or gastroenteritis → reactive arthritis
Campylobacter gastroenteritis → Guillain–Barré synd.
Chemicals :
anti-convulsants or antibiotics → drug-induced lupus halothane (general anaesthetic) → liver necrosis
Trauma :
exposure of self-antigens in protected sites (eg. eye, testes)
What specific antibodies would you want to detect to confirm the following diseases?
- Graves disease
- Rheumatoid arthritis
- Hashimoto’s thyroidtis
- TSH receptor
- RhF
- Thyroid Peroxidase
Can also do HLA testing for most autoimmune diseases
