Innate immunity 2 Flashcards
Cryopyrin-Associated periodic syndromes (CAPS)
NLRP3 gene mutation
- Gain in function
- exon 3
XS production of IL-1
- Fever
- Joint pains
Includes
- Muckle wells syndrome
- Familial cold autoinflammatory syndrome
Treated with IL-1 receptor antagonist (IL-1RA, anakinra)
Muckle wells syndrome
A type of CAPS
- NLRP3 gain in function
Triggered by
- Cold, heat, fatigue, many stresses
Can also occur spontaneously.
Symptoms
- Fever
- Joint pain
- Rash
- Conjunctivitis/ Uveitis
- Potentially threatening amyloidosis
Familial cold autoinflammatory syndrome
- Cause
- Trigger
- Symptoms
- Prevalence
Type of CAPS
- NLRP3 gain in function
Triggered by cold exposure
Symptoms
- Fever
- Headache
- Joint pain
- Hives
- Sometimes conjuctivitis
Prevalence
- 1:1 million
RIG-1-like receptors (RLRs)
Senses cytoplasmic RNA
- Signal produces pro-inflammatory cytokines, IFN
Includes:
RIG-1
MDA5
RIG-1
Receptor that binds to ssRNA with 5’triphosphate
Recognises
- Flavivirus–> Hep C
- Orthomyxovirus-> Flu
MDA5
Rig-1-like receptor
- Recognises long dsRNA
Picornavirus detection
- Mutation = IFN related disease
STING
Stimulator of interferon gene
- Protein coded by gene TMEM173
Produces IFN type 1
- IFN protects infected cells and local cells from local infection via autocrine/ paracrine signalling
Activated by cGMP from viral DNA or GMP/AMP from bactrria
SAVI
STING- associated vasculopathy with onset in infancy.
- Gain of function for STING gene (TMEM173)
Symptoms
- Inflammation of skin, BVs and lungs
Acute phase response
The release of acute-phase proteins in response to cytokines during infection and inflammation
- TNF
- IL-6
- IL-1
Effects
- Opsonisation
- Phagocytosis
- Activation of complement pathway
Acute phase proteins
MBL
Fibrinogen
C-reactive protein
Serum amyloid protein
SP-A,D.
Clinical detectors of acute phase response
Raised levels of certain acute phase proteins:
Erythrocyte sedimentation rate (ESR)
C-reactive protein.
Phagocyte recruitment
Chemokines attract phagocytes to site of infection
- Phagocyte rolls across endothelium due to weak bonds formed to receptors.
- Receptors are unregulated on endothelium [ICAM-1/2]
- Adhesion of phagocyte to endothelium receptors via integrins.
- Phagocyte migrate through endothelial gaps Tissue
Describe the process of phagocytosis.
- Phagocyte receptors (Scavenger, MBL) recognise and binds to receptors on the pathogen.
- Microbe internalised via endocytosis into phagosome.
- Phagosome containing pathogen fuses with lysosome to Phagolysosome.
- Pathogen degraded in phagolysosome by multiple mechanisms
Mechanism of degradation in phagocytosis
Acidification
Toxic oxygen-derived products/ Nitrogen oxides.
Antimicrobial peptides
Antimicrobial enzymes
Competitors: lactoferrin, Vit-B12 binding protein.
NETs (Neutrophil Extracellular Traps)
Release of nuclear chromatin from neutrophils undergoing cell death (NETosis)
- Traps microbes for phagocytosis.
