Auto - Inflammtory Diseases Flashcards
(76 cards)
What is the difference between innate and adaptive immune system?
- innate immunity - body immediate, general defence against pathogens π¦
- adaptive immunity - specialised, targeted response that developed over time
What is the difference between ** auto inflammation π₯ ** and ** auto - immunity **?
β auto inflammation -> where the body will mistakenly trigger inflammation without an external threat.
β Autoimmunity β> when the body attacks its own tissues and cells
What sets the boundaries for auto immunity?
- mutations associated with cells and molecules invoved in the adaptive immune system (ie specific + targeted).
What sets the boundaries for auto - inflammation?
- mutations in cells associated with innate immunity at disease prone sites (rmb innate immunity associated with inflammation)
What are familial monogenic diseases?
𧬠genetic disorders, that are caused by a single gene.
The disease is often inherited within a predictable pattern within families, and can result in specific health problems or conditions.
What are familial monogenic diseases caused by?
- mutations in a single gene (ie in CF, disease is caused due to mutations in the CFTR gene and thus non functional CFTR)
What are the general characteristics of monogenic auto - inflammatory diseases?
β
unprovoked attacks of inflammation (ie may not be due to infection etc there is no stimulus)
β
absence of high tier autoantibodies or antigenic specific T cells , ie the adaptive immune response - ie the inflammation seen is largely mediated by the cells and molecules of the innate system.
β
pre - existing errors of the innate immune system β ie significant boost predisposition.
Give a few examples of familial monogenic auto inflammatory disorders?
- π₯΅ familial Mediterranean fever
- π₯Ά CAPS (cyropyrin associated periodic syndromes).
- Blau syndrome
Which gene is mutated in Familial Mediterranean Fever and what are the clincal features / symptoms of FMF?
Gene : 𧬠MEFV protein
Clinical Features : periodic fevers lasting 3 0 7hrs), inflammation of serous tissue (ie lining the heart and inner abdomen) , arthritis.
Which gene is mutated in Cryopyrin - associated period syndromes (ie FCAS, MWS, and NOMID) and what are the clincal features / symptoms of CAPS?
- 𧬠NLRP3 gene
Clinical features : - π₯Ά cold induced autoinflammation
- π cochlear inflammation
- π₯΅ fevers
- π€§ sterile menigitis
- 𦴠Bone lesions.
Which gene is mutated Blau Syndrome and what are the clincal features / symptoms of Blau Syndrome ?
𧬠mutated gene : NOD2
Clinical features :
- π¬ granulomatous dermatitis
- uveitis (inflammation of the inner eye) n
- arthritis π΅
Are these diseases, FMF, CAPS and Blau syndrome, autosomal dominant or recessive?
FMF - AR
BS - AD
CAPS - AD
Give 3 examples of the cryopyrin associated periodic syndrome (CAPS) diseases?
- β familial cold autoinflammatory syndrome (FCAS)
- β Muckle - Wells syndrome (MWS)
- β NOMID/ CINCA
What is CAPS?
A spectrum of disease ranging from mildFCAS to severe NOMID/CINCA. They are rare and hereditary inflammatory diseases that each encompass their own 3 phenotypes.
CAPS
What is FCAS and and what are the symptoms?
Familial cold autoinflammatory syndrome.
- inflammation that occurs when weather is cold π₯Άand temperatures are low βοΈ
- symptoms : rash on the skin, arthralgia (joint pain), conjunctivitis (red eye)
Mild caps
CAPS :
What is MWS and what are the symptoms?
Muckle - Wells Syndrome
CAPS characterised by skin / urticaria rash ** and ** sensorineural deafness π π§π½ββοΈ
Between mild and severe CAPS
CAPS
What is NOMID/CINCA and what are the symptoms?
A more sporadic (ie occurs randomly) and severe CAPS disease.
Symptoms include : progressive chronic meningitis, visual ποΈ and intellectual π§ damage, and destructive arthritis π¦΄
Auto - immune diseases tend to have flares what are these?
β
periodic fever syndromes where the disease will amplify and worsen and then go back to normal state periodically and sporadically.
π there isnβt necessarily a particular target for most of these types of conditions
What is caspase 1?
A converting enzyme that cleaves other proteins such as ** precursors for inflammatory cytokines IL - 1B and IL - 18 **
What are NLR proteins?
Other wise known as βNucleotide - binding Oligomerization Domain - like receptors (NOD)β are a type of protein/ receptor that detect harmful pathogens π¦ in our cells.
When they recognise these threats, they triger a series of signals that will β activate our immune system to defend against the invading cells.
Give two examples of inflammatory cytokines?
- IL - 1B
- IL - 18.
What are inflammasomes
- π₯΅ receptors of the **innate immune system* (obvs, they are inflammatory) β> they are large protein receptor structures made out of NLR proteins.
- β they regulate the activation of capsase 1 and they can induce inflammation in response to infectious microbes and molecules deceived from host proteins.
Describe the structure of the NLRP3 inflammasomes?
They are composed of a N - terminal effector domain that comprise capsase recruitment domains (CARD) and pyrin domains.
What does activation fo the NLR lead to ?
Triggering of severe important immune processes such as inflammasomes formation (lots of NLR proteins conjugating to form multi protein complexes, that activate the release of pro - inflammatory cytokines IL -1 beta and IL -18).
Induction of antimicrobial responses and initiation of cell death (pyroptosis to avoid spread of pathogens by removing infected cells).
