Autoimmunity Flashcards
What are the 4 gene regions that are expressed to form the heavy chains variable region of an antibody?
V segments (40 segments)
D segments (24 segments)
J segments (6 segments)
Contant region (Mu, delta, gamma, alpha and epsilon segments)
What are the 3 gene regions that are expressed to form the light chains variable region of an antibody?
V segments (45 segments)
J segments (5 segments)
Contant region (Kappa or lambda segments)
How are antibody variable regions expressed?
Segments are chosen at random, 1 from each of the segment types, VJD and constant
What are the 3 outcomes of antigen receptors for a progenitor T or B cell?
Unsuccessful antigen receptor
Successful antigen receptor
Self-reactive antigen receptor
How are autoreactive immune cells destroyed or inactivated?
using tolerance mechanisms
Central tolerance - Deletion of lymphocytes in the primary lymphoid tissue
Peripheral tolerance - Deletion of lymphocytes that escape the primary lymphoid tissue, by T regulatory cells
What is the function of a regulatory T cell?
They are crucial for suppression of hyper-reactive and auto-reactive T cells via the production of anti-inflammatory cytokines
What does IPEX stand for?
Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritance Syndrome
What are the symptoms of IPEX syndrome?
Severe infection
Intractable diarrhoea
Eczema
Onset Type I diabetes
Autoimmune manifestation
What causes IPEX syndrome?
Mutation of the FOXP3 gene
Prevents the production of regulatory T cells
What are the 2 types of genetic factors that can cause auto immunity
Single gene mutations - e.g. IPEX syndrome
Complex gene mutations - e.g. MHC genes
How many MHC-I molecules does each cell have?
6:
2x HLA-A
2x HLA-B
2x HLA-C
How many MHC-II molecules do APCs express?
6:
2x HLA-DR
2x HLA-DQ
2x HLA-DP
What are some examples of environmental factors that can increase risk of autoimmunity?
Infection
Smoking
Hormone levels
Tissue damage
What are some examples of autoimmune mechanisms?
Molecular mimicry
Alterations to self-antigens
Antigen sequestration
Bacterial superantigens
How does acute rheumatic fever occur?
It occurs after a Group A Streptococcal infection
Strep. M5 proteins are similar in structure to cardiac tissue proteins, so when an immune response is triggered against the pathogen, the cardiac tissue is also attacked and damaged
How does Drug-induced haemolytic anaemia occur?
Antibodies become directed against RBCs as a result of a drug
What is antigen sequestration?
The hiding of antigens behind anatomical structures
How can antigen sequestration lead to an autoimmune response?
Sequestered self antigens can be released during infection, leading to an autoimmune response
What is an example of an autoimmune disease caused by antigen sequestration?
Post-traumatic autoimmune uveitis
How do bacterial super antigens cause autoimmunity?
Super antigens can activate all lymphocytes when they interact with an antigen presenting cell, even if there is no peptide antigen present
What is Goodpasture’s syndrome?
An autoimmune disease that affects the lungs and kidneys, causing pulmonary alveolar haemorrhage and glomerulonephritis
What causes Goodpasture’s syndrome?
the presence of auto reactive antibodies to the alpha 3 chain of type IV collagen, found in the basement membrane of the alveoli and glomeruli
What are the treatment options for Goodpasture’s syndrome?
Immunosuppressive drugs
Anti-inflammatory drugs
Plasmapheresis
Smoking cessation
What are some examples of autoimmune diseases caused by type III hypersensitivity reactions?
Systemic Lupus erythematosus
Rheumatoid arthritis
Glomerulonephritis
What occurs in SLE?
Increase apoptosis of cells combined with defective clearance of apoptotic clearance, as well and dysregulation of neutrophil NETs
What are examples of autoimmune diseases driven by type IV hypersensitivity reactions?
Heart - Autoimmune myocarditis
Pancreas - Diabetes mellitus type I
Thyroid - Hashimoto’ thyroiditis
Nervous system - Multiple Sclerosis
Musculoskeletal system - Rheumatoid arthritis
