Autoimmunty Flashcards
What cell type can override Treg cells?
Th17 by releasing IL-17
What’s the difference between an autoimmune reaction and an autoimmune disease?
A disease is pathological and cause harm to tissues/organs
A reaction can be part of the normal bodily processes, attacking cells that are damaged, in the wrong place or neoplastic
Autoimmune diseases can be split into 2 categories?
Organ specific with a single tissue specific Ab e.g. Anti-GAD
Non-Organ Specific with non-specific Abs e.g. ANA
Give some examples of organ specific autoimmune diseases?
Graves Hashimotos Myasthenia Gravis Pernicious Anaemia Type 1 DM
Give some examples of non-organ specific autoimmune disorders?
SLE
RA
Systemic Sclerosis
Systemic Vasculitis
Try to list 5 different mechanisms of autoimmune disease?
1) Cell Mediated Autoimmunity
2) Antibody Mediated (Type 2 hypersensitivity)
3) Immune complex mediated (Type 3 hypersensitivity)
4) Innate Recruitment
5) Molecular Mimicry
What conditions operate by cell mediated autoimmunity/
Type 1 DM
Psoriasis
Coeliac disease
T &NK cells are involved
What major conditions operate by antibody mediated autoimmunity?
Goodpasture’s Syndrome
Myasthenia Gravis
What happens in good pastures syndrome?
Anti-GBM Abs react to type 4 collagen in the basement membrane –> lung haemorrhage & glomerulonephritis
What happens in Myasthenia GRavis?
Auto-reactive T cells & Anti-Ach receptor Abs attach to receptors at NMJ –> Muscle weakness & fatigueability
It’s primarily an Ab disorder but T cells are involved hence why we look for and resect thymomas
Give an example of an Immune Complex mediated autoimmune disorder?
SLE
How does molecular mimicry work?
Pathogen or other molecule (e.g. penicillin) mimics your own cell’s antigen
–> Body attacks that antigen and then your own one too
Example of a condition that works by molecular mimicry?
Rheumatic Fever
Strep carries an antigen very similar to that found on muscle cells –> Myocardial damage and myositis
How can we treat autoimmune disorders?
Suppression of the damaging immune response
- Anti-inflammatories
- Steroids
- Immunosuppresants e.g. MTX
- Plasmapheresis
Replacement of the function of the damaged organ :
- Stem cell/marrow transplant
- Replacing lost physiological factors
- Organ/tissue graft
What is a newer treatment available for autoimmune disease?
T-reg cll therapies n
Epidemiology of autoimmune disease?
- 3% of the population
- Affects women more than men
- Affects those between 15-65 (excretion of DM1)
what are environmental factors which can lead to autoimmune disease?
- Infections
- drugs
- UV radiation
what are genetic components which can lead to autoimmune disease?
- Clusters in families
- common polymorphisms in the MHC complex
- Mutation to the AIRE gene
what is the AIRE gene?
- Transcriptional factors expressed by the medullary epithelial cells in the thymus
- Involved in the regulation of the expression of tissue- restricted antigens
- In the absence of AIRE- self-reactive T cells are not eliminated
How does central tolerance develop?
-Developing T cells in the thymus
• If they do not recognise MHC are not selected
• If they recognise self peptide + MHC are negatively selected and killed by apoptosis
How does peripheral tolerance develop?
- Anergy: T cells in the body which recognise antigen on MHC become anergic/ non-responsive
- T-regulatory cells: inhibit neighbouring T cells by killing them by apoptosis
What happens once tolerance has been broken down?
The resulting inflammation may allow presentation of further peptides.
•The immune response broadens and local tissue damage accelerates (epitope spreading).
•This implies that, once the barrier of tolerance is broken down, autoimmune responses may be easier to sustain.
How can peripheral tolerance be overcome?
- Inappropriate presentation of self-antigens
- Inappropriate or increased local expression of co-stimulatory molecules
- Alterations in the way in which self-molecules are presented to the immune system
