Flashcards in Autoimmune disease Deck (29)
What are the features of MHC I?
- Encoded by genes in HLA-A, HLA-B, HLA-C
- On all nucleated cells
- Presents antigen to CD8+ T cells
What are the features of MHC II
- Encoded by genes in HLA-DP, HLA-DQ, HLA-DR
- On dedicated APCs
- Presents antigen to CD4+ T cells
Where does central tolerance take place?
Thymus for T cells
Bone marrow for B cells
What are the features of peripheral tolerance?
Regulatory T cells (express FOXP3)
What are the common risk factors for autoimmune disease?
- Sex (hormonal influence)
- women >> men
- autoimmunity more common in elderly
- Sequestered Antigents
- May be recognised as foreign by the immune system (e.g. cell nucleus, eye, testis)
- Environmental triggers
- Trauma-tissue damage
What is the relevance of molecular mimicry in autoimmune disease?
In rheumatic fever antibodies against M protein of Streptococcus also react against the glycoproteins of the heart
How might changes in amount or nature or autoantigens cause autoimmunity?
- Citrullination of proteins make them more immunogenic (rheumatoid arthritis)
- Tissue transglutamase alters gluten to help it bind to HLA-DQ (coeliac disease)
- Failure to clear apoptotic debris increases availability of sequestered antigens inside the cell (systemic lupus erythamatosus)
What is the potential pathophysiology of autoimmune disease?
- Autorective B cells and autoantibodies
- Directly cytotoxic
- Activation of complement
- Interfere with normal physiological function
- Autoreactive T cells
- Directly cytotoxic
- Inflammatory cytokine production
- General inflammation and end-organ damage
What is thought to be the aetiology of SLE?
Defects in apoptosis?
What causes the malar rash?
Sunlight - Anti-nuclear antibodies bind to skin cells that have been damaged by UV light and form immune complexes with their antigen.
How does lupus become systemic?
Immune complex deposition in other organs.
How might T cells contribute to autoimmunity?
Cause inflammation by inflammatory cytokines or by helping B cells make autoantibodies
What is the pathophysiology of Hashimoto's Thyroiditis?
- Destruction of thyroid follicles by autoimmune process
- Associated with autoantibodies to thyroglobulin and to thyroid peroxidase
- Leads to hypothyrodism
What is the pathophysiology of Grave's disease?
- Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
- Leads to hyperthyrodism
What is the pathphysiology of myasthenia gravis
Autoantibodies block the muscarinic ACh receptor and target it for destruction.
What is the pathophysiology of pernicious anaemia?
anti-IF or anti-IF receptor autoantibodies block the uptake of B12 from the gut.
What kind of autoantibodies are formed in SLE?
Which part of the immune system is involved in autoinflammation?
Which part of the immune system is involved in autoimmunity?
Are autoantibodies usually present during autoinflammation?
What are the clinical features of autoinflammation?
Recurrent and unpredictable attacks
What are the clinical features of autoimmunity?
What is the conceptual understanding of autoinflammation?
Tissue-specific factors/danger signals
What is the conceptual understanding of autoimmunity?
Breaking of self-tolerance
Where is the main genetic susceptibility for autoinflammation?
Cytokine and bacterial sensing pathways
Where is the main genetic susceptibility for autoimmunity?
MHC II, adaptive response genes, anti B and T cell
Give examples of autoinflammation.
Monogenic hereditery periodic fevers, polygenic Crohn’s disease, spondylarthropathies
Give examples of autoimmunity.
RA, SLE, IPEX