Autoimmune Disease Flashcards
What is immunologically acted on in Graves’ disease?
TSH receptors in thyroid
What is immunologically acted on in type 1 diabetes?
Beta islet cells of the pancreas
What are some examples of autoimmune diseases of HLA B27-associated apondyloarthropathies?
Reactive arthritis
Psoriatic arthritis
Urethritis
Iritis
What is systemic lupus erythematosus characterised by?
Autoantibodies binding to nuclear antigens
What is autoimmunity?
Failure of regulatory controls to attacking host components
What is immune tolerance?
Knowing what to attack/what not to attack
What is central tolerance?
Destruction of self-reacting T or B cells before they enter circulation
What happens in central tolerance ?
Immature B cells in bone marrow encounters antigen in a form which can cross-link their IgM, triggering apoptosis
What is peripheral tolerance?
Destruction or control of any self-reactive T or B cell which do not enter circulation
What are the types of peripheral tolerance?
Ignorance
Anergy
Regulation
When does ignorant peripheral tolerance happen?
Antigen present in too low a concentration to reach the threshold for T cell receptor trigger
Immunologically privileged sites means there are T cells but they cant get to the sites
What causes anergic peripheral tolerance?
Naive T cell seeing its MHC without appropriate costimulatory protein
What is Anergy?
Naive T cells need costimulation to become activated
If they dont, they’re less likely to be stimulated in future even if costimulation is present
Which cells inhibit T cells?
Treg cells
Which disease has defective treg cells been observed in?
Multiple sclerosis
How does treg regulation happen?
Expresses transcription factor FOXP3
What conditions does a mutation in FOXP3 lead to?
Fatal autoimmune disorder
Immune disregulation
Polyendocrinopathy
Eneropathy X-linked syndrome
What does autoimmune regulator (AIRE) do?
A specialised transcription factor that allows thymic expression of genes that are expressed in peripheral tissues
How does AIRE promote self-tolerance?
Allowing the thymic expression of genes from other tissues
Which autoimmune conditions are more likely in females?
Lupus
MS
Which autoimmune conditions are more common in males?
Ankylosis spondylitis
Which autoimmune condition is equally common in women and men?
Diabetes
What is the hygiene hypothesis of autoimmune disease?
Exposure to different pathogens may lead to expression/non-expression of a disease
What might trigger a breakdown of self tolerance?
Loss of/problem with regulatory cells
Release of sequestered antigen
Modification of self
Molecular mimicry
How does modification of self take place?
Citrullination
What is citrulline?
An amino acid not coded by DNA
What may citrullination be increased by?
Inflammation
What is an example of molecular mimicry?
Rheumatic fever
What is rheumatic fever triggered by?
Infection with streptococcus pyrogen
How does Graves’ disease happen?
Autoantibodies bind TSH receptor and stimulate it, causing hyperthyroidism
How can Graves’ disease be transferred?
IgG antibodies
What causes myasthenia gravis?
Autoantibodies binding to ACh receptors that block the binding ability of ACh
How are immune complexes in SLE and vasculitis formed and what do they cause?
Autoantibodies to soluble antigens form immune complexes
Deposited in tissue
Can lead to activation of complement and phagocytic cells
Which autoimmune diseases can be transferred across the placenta?
IgG mediated ones
What is the autoimmune pathology of T cells?
Direct killing by CD8+ CTL
Self-destruction induced by cytokines such as TNFalpha
Recruitment and activation of macrophages leading to bystander tissue destruction
CD4 cells providing help for Ab and cytotoxicity
What do TH17 cells produce?
Cytokine IL-17
What do TH17 produce?
Cytokines involved in the recruitment, migration and activation of immune cells
What anti-inflammatories are used in autoimmune treatment?
NSAIDs and corticosteroids
What theraputic strategies are used to treat T and B cell depletion?
Anti-CD4
Anti-CD20
What are examples of theraputic antibodies?
Anti-TNF
Anti-VLA-4
