Autoimmune and Autoinflammatory Disease 1 Flashcards
What triggers a) fevers/malaise seen in primary EBV and b) abscess formation and what is the immune response?
Pathogens
Adaptive immune response: Cytokines
Innate immune response: Neutrophils
What triggers a) sacroiliac joint inflammation in an individual with axial spondyloarthritis and b) anaemia due to red cell haemolysis secondary to anti-red cell antibodies?
No obvious pathogen
a) Innate immune response: Cytokines
b) Adaptive immune response: Antibodies
In the absence of a pathogen, what immunopathology do the following cause?
a) Innate immune response
b) Mixed Innate/Adaptive
c) Adaptive immune response
a) Auto-inflammatory
b) Mixed
c) Auto-immune
What is the pathophysiology of auto-inflammatory diseases?
Local factors at sites predisposed to disease lead to activation of innate immune cells such as macrophages and neutrophils, with resulting tissue damage.
What is the pathophysiology of auto-immune disease?
Aberrant T cell and B cell responses in primary and secondary lymphoid organs lead to breaking of tolerance with development of immune reactivity towards self-antigens.
Organ-specific antibodies may predate clinical disease by years.
Adaptive immune response plays the predominant role in clinical expression of disease.
Are the following polygenic or monogenic?
a) Innate immune response
b) Mixed Innate/Adaptive
c) Adaptive immune response
a) Polygenic and monogenic
b) Polygenic
c) Polygenic and monogenic
What is a germline mutation affecting DNA synthesis?
Alteration in DNA that occurs in germ cells (sperm and ova and progenitors) and will be passed on to offspring.
What is a somatic mutation affecting DNA synthesis?
Alteration in DNA that occurs in a single body cell after conception, does not affect germ cells and so is not inherited.
What are epigenetics?
(Heritable) Change in gene expression e.g. via DNA methylation.
What is microRNA (miRNA)?
Small, non-coding, single stranded RNA.
Targets mRNA and regulate protein production.
What are rare monogenic auto-inflammatory diseases?
Familial mediterranean fever
TRAPS
What are polygenic auto-inflammatory diseases?
Crohn’s disease
Ulcerative colitis
Osteoarthritis
Giant cell arteritis
Takayasu’s arteritis
What are mixed pattern diseases?
Axial spondyloarthritis
Psoriatic arthritis
Behcet’s syndrome
What are polygenic auto-immune diseases?
Rheumatoid arthritis
Systemic lupus erythematosus
Myaesthenia Gravis
Primary biliary cirrhosis
Pernicious anaemia
ANCA associated vasculitis
Graves disease
Goodpasture disease
What are the rare monogenic auto-immune diseases?
APS-1, APECED
ALPS
IPEX
What is the pathophysiology of monogenic auto-inflammatory disease?
Mutations in a gene encoding a protein involved in a pathway associated with innate immune cell function.
Abnormal signalling via key cytokine pathways involving TNF-alpha and/or IL-1 is common.
What are signs and symptoms of monogenic auto-inflammatory disease?
Periodic fevers
Skin/joint/serosal/CNS inflammation
High CRP