7. Autoinflammatory and Autoimmune Diseases 1 Flashcards
What is immunopathology?
Damage to the host caused by the immune response. Quite often the problems that occur after infection will actually be a result of the immune response rather than the pathogen itself (e.g. abscesses)
What are fevers / malaise seen in primary EBV caused by? And what is the immune response?
Pathogen. Adaptive immune response - cytokine
What are abscess formations caused by and what is the immune response?
Pathogen. Innate immune response - neutrophils
What is sacroiliac joint inflammation in an individual with ankylosing spondylitis caused by and what is the immune response?
No obvious pathogen. Innate immune response - cytokines
What is anaemia due to red cell haemolysis secondary to anti-red cell antibodies caused by and what is the immune response?
No obvious pathogen. Adaptive immune response - antibodies
What does auto-inflammatory or autoimmune disease refer to?
Immunopathology in the absence of infection
If the disease is driven by components of the innate immune system, what is it described as being?
Auto-inflammatory
If the disease is driven by abnormalities in components of the adaptive immune response, what is it described as being?
Autoimmune
If the diseases is driven by mixed innate/adaptive system, what is it described as being?
Mixed (auto-inflammatory and autoimmune)
What occurs in auto-inflammatory diseases?
Local factors at sites predisposed to disease lead to activation of innate immune cells such as macrophages and neutrophils, which result in tissue damage.
What occurs in autoimmune disease?
Aberrant T and B cell responses in primary and secondary lymphoid organs leads to breaking of tolerance with the development of immune-reactivity towards self-antigens. The adaptive immune response plays the predominant role in the clinical expression of disease. Organ-specific antibodies may be present for a long time before the diseases manifest.
How does the spectrum of immunological disease vary?
This ranges from the monogenic auto-inflammatory diseases to the monogenic autoimmune diseases
Which immunological diseases are more common, monogenic or polygenic?
Most polygenic diseases are pretty common
What are examples of rare monogenic auto-inflammatory diseases?
Familial mediterranean fever, TRAPS
What are examples of polygenic auto-inflammatory disease?
Crohns disease, UC, osteoarthritis, giant cell arteritis, Takayasu’s arteritis
What are examples of mixed pattern diseases?
Ankylosing spondylitis, psoriatic arthritis, Behcet’s syndrome
What are examples of polygenic auto-immune diseases?
Rheumatoid arthritis, Myasthenia Gravis, pernicious anaemia, Graves disease, systemic lupus erythematosus, primary biliary cirrhosis, ANCA associated vasculitis, Goodpasture disease
What are examples of rare monogenic auto-immune diseases?
APS-1, APECED, ALPS, IPEX
What causes monogenic auto-inflammatory disease?
Mutations in gene encoding a protein involved in a pathway associated with innate immune cell function. This often leads to abnormal signalling via key cytokine pathways involving TNF-alpha and/or IL1
Which monogenic auto-inflammatory diseases are autosomal dominant?
Muckle Wells syndrome, familial cold auto-inflammatory syndrome, chronic infantile neurological cutaneous articular syndrome, TNF receptor associated periodic syndrome
Which monogenic autoinflammatory diseases are autosomal recessive?
Hyper IgD with periodic fever syndrome and familial mediterranean fever
What gene and protein is involved in Muckle Wells Syndrome?
Gene: NLRP3 gain of function. Protein: NALP3, cryopyrin
What gene and protein is involved in familial cold auto-inflammatory syndrome?
Gene: NLRP3 gain of function. Protein: NALP3, cryopyrin
What gene and protein is involved in chronic infantile neurological cutaneous articular syndrome?
Gene: NLRP3 gain of function. Protein: NALP3, cryopyrin