Immunology of Autoimmune disease Flashcards
Everone has low levels of autoantibodies or autoreactive T cells.
True or false?
True
In order for autoimmunity to occur, there must be a _________ susceptibility followed by an ___________ ________ or ___________
Genetic
Initiating event or trigger
What is IPEX syndrome?
Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome
An inherited condition which involves a mutation in the FOXP3 gene
This gene is responsible for regulatory T cells which means autoimmunity is abundant in IPEX syndrome
How can IPEX syndrome treated?
Haematopoeitic stem cell transplant
Use of immunosuppressive drugs
How are hugely diverse B and T cell populations obtained?
T cell receptor alpha and beta chain gene segments are randomly re-arranged creating a huge variety of B and T cells
However, this also means the likelyhood of autoreactivity increases
What are the two tolerance mechanisms which try to counteract autoreactivity?
- Central tolerance - the removal of self-reactive lymphocytes in primary lymphoid tissues
- Peripheral tolerance - inactivation of self-reactive lymphocytes that escape central tolerance (mediated by regulatory T cells)
How do regulatory T cells cause suppression?
Secretion of IL-10 and TGF beta
Which HLA gene is associated with ankylosing spondylitis?
HLA B27
Which HLA gene is associated with rheumatoid arthritis?
HLA DR4
Which HLA gene is associated with SLE?
HLA-DR3
Which HLA gene is associated with multiple sclerosis?
HLA-DR2
Which HLA gene is associated with idiopathic diabetes mellitus?
- HLA-DR3
- HLA-DR4
Which HLA gene is associated with myasthenia gravis?
HLA-DR3
What are the three forms of HLA class I?
- HLA - A
- HLA - B
- HLA - C
What are the three forms of HLA class II?
- HLA - DR
- HLA - DQ
- HLA - DP
Genes for HLA are encoded on which chromosome?
6
What is the significance of having such variety in a population in terms of HLA alleles?
Different alleles can bind different peptides
Hence, some alleles will be more protective or susceptible to certain genetic conditions
What is molecular mimicry?
This is when antibody produced to a foreign antigen can cross-react with self antigen.
This is due to the similar peptide structure of the foreign and self antigen
What are superantigens?
Antigens which can activate lymphocytes outwith the binding sites
What is antigen sequestration?
Release of antigen not normally available for recognition
SLE involves which type of hypersensitivity reaction?
III
Rheumatoid arthritis involves which type of hypersensitivity reaction?
IV
When immune complexes form in the body, why is complement binding useful?
It aids removal
In SLE, why is the clearance of apoptotic bodies and immune complexes delayed?
A C1Q mutation creating abnormal C2 and C4 which cannot aid in the removal process
A Mac1 mutation which hinders many processes including apoptosis
Anti-dsDNA is associated with which condition?
SLE
Anti-Sm is associated with which condition?
SLE
Anti-Ro (SSA) and Anti-La (SSB) are associated with which conditions?
Sjogren’s syndrome
(also subacute cutaneous SLE and neonatal lupus syndrome)
Anti-U3-RNP is associated with which condition?
Systemic sclerosis
Anti-centromere antibody is associated with which condition?
Systemic sclerosis
Anti Scl-70 antibody is associated with which condition?
Systemic sclerosis
Anti-Jo-1 antibody is associated with which condition?
Polymyositis
Why does rheumatoid arthritis occur?
Infiltration of the synovium by self reactive CD4+ T cells
Then
Secondary involvement of activated B cells and autoantibodies
What is the role of TNF alpha and IL-1 in the disease process of rheumatoid arthritis?
- Stimulates fibroblasts, osteoclasts and chrondrocytes
- Stimulates release of matrix metalloproteinases
What is a rheumatoid factor?
An autoantibody directed against the common (Fc) region of human IgG
Which antibodies are highly apecific for rheumatoid arthritis?
Anti-citrullinated peptide antibodies (ANPA)
These are highly specific to RA, but only postive in around 70% of cases
what is myasthenia gravis (MG)
autoimmune disorder characterised by severe muscle weakness and progressive fatigue
what is the pathogenesis of myasthenia gravis
The autoimmune attack occurs when auto IgG autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at neuromuscular junction of skeletal muscle - type II hypersensitivity
It is believed that the initial step triggering humoral immunity (CD4+ produces B cells) in MG takes place in thymic tissue and thymoma
what causes myasthenia gravis
90% has no known cause, thymic tumour causes 10%
genetic predisposing factor = HLA association
medicatios linked = antibiotics, B blockers, lithium, magnesium
factors which worsen exacerbation: warm weather, surgery, emotional stress, menstruation, pregnancy
what are symptoms of myasthenia gravis
facial droop, expressionless face, difficulty chewing and swallowing, drooling, episode of choking, nasal and low volume speech
less frequently = muscles of neck, shoulder girdle and hip flexors
in advanced stages = all muscles weak
how is myasthenia gravis treated
increase neurotransmission = anticholinesterase agents (pyridostrigmine)
- side effects = abdo cramps, diarrhoea, increased bronchial secretion, bradycardia, increased muscle cramps
reduce autoimmunity = immunosuppressants or corticosteroids, plasmapheresis (removes AChR antibodies), IVIg, eculizumab (inhibits cleavage of C5 preventing MAC)
surgery = thymectomy (eliminates source of continued antigenic stimulation)
