Innate Immunity 2 Flashcards
Which are the innate lymphoid cells that are triggered without antigen presentation?
Gamma delta T cells Nk cells ILC1 ILC2 ILC3
Phagocyte recruitment happens in these steps?
Cytokines dilate blood vessels and chemokines attract monocytes and neutrophils to infection
Cell adhesion molecules ICAM 1 and VCAM1 are upregulated on endothelium, which bind to integrins of leukocytes
Rolling and extravasation?
- Rolling
- Activation
- Arrest/adhesion
- Transendothelial migration
Opsonins?
Complement component c3b
Collectins such as mbl
Antibodies
NETosis?
Nuclear chromatin is released of neutrophils to trap microorganisms to help phagocytosis
PRRs?
C type leptin Toll like NOD like Rig I like Cytosolic DNA sensors
C like receptors bind to?
Glycan structures
Toll genes important for?
Development
Immunity to the fungal and bacterial infections
D toll 18 wheeler
Toll like receptor structure?
Extracellular: leucine rich repeats
Cytosolic- TIR domain
Tlr10 responds to?
Double stranded RNA
Cell surface TLRs recognise in host
HSP70
Fibrinogen
Fibronectin
Adaptor molecules?
Trig/TRAM/ MyD88/Mal
MyD88 gain of function mutation causes?
Waldenstrom macroglobulinemia, 90% of patients, lymphoma cells proliferate in bone marrow, B cells make large amount of IgM which causes excess bleeding, vision problems and headaches
Lymphoma causes anaemia, thrombocytopenia, neutropenia
TLR 3 deficiency causes?
Herpes simplex encephalitis
It’s a double stranded DNA. Virus but when it replicates it produces DSRNA, which TLR3 binds to
TLR8?
HIV
TLR2 and 4 conditions?
Sepsis and tuberculosis
Atherosclerosis and Alzheimer’s
TLR 7 8 9 condition?
Systemic lupus erythematosus
Aldara is an agonist of what and for which condition?
TLR7 for genital warts
TLR7 for melanoma
TLR antagonist 7 8 and 9 for?
Autoimmunity
TLR4 antagonist for?
Sepsis
NLRs receptor types?
NLRCs and NLRPs
C- caspase recruitment domain CARD
P- pyrin domain
NLRCs bind to?
Peptidoglycan
NOD1 binds to?
IE-DAP- only gram -ve
NOD 2 bind to?
Muramyl dipeptide present in both positive and negative bacteria
NOD2 gain of function linked to?
Sarcoidosis, granulomas develop in the organs of the body
NOD2 loss of function?
Susceptibility to Crohn’s disease
NLRP3 activated by?
Cellular stress, K efflux ATP ROS and lysosomal damage,
Inflammasome
Inflammasome activation is essential for?
IL1 and IL18
How is inflammasome activated?
Uric acid crystals- gout Asbestos Silica Amyloid beta Islet amyloid polypeptide Hemozoin
NLRP3 gain of function?
Cryopyrin associated periodic syndrome (CAPS)
Over production of IL1
How can you stop IL1 for people with Muckle wells syndrome, and familial cold auto inflammatory syndrome?
Anakinra IL-1RA
RIG I like receptors bind to?
Cytoplasmic 5’RNA and the signal to produce pro-inflammatory cytokines and IFN
MDA5 recognises?
Long double stranded RNA
C-GAS STING recognises?
Double stranded DNA of viruses. Converts ATP/GTP to cGAMP, recognised by STING. STING signals to make interferon.
STING gain of function?
Too much type 1 IFN, causing inflammation
Causes STING associated vasculopathy with onset in infancy SAVI
Characteristic of acute phase response?
Raised erythrocytes sedimentation rate ESR and CRP
Phagocytosis is performed by?
Neutrophils
Dendritic cells
Macrophages
Antimicrobial mechanisms of phagocytes?
Acidification Toxic oxygen products Toxic nitrogen products Antimicrobial peptides Enzymes Competitors like lactoferrin
Pattern recognition receptors?
C type leptin Toll like Nod like Rig 1 like Cytosolic dna sensors
DAMPS?
Damage associated molecular patterns, molecules released from necrotic cells
C type lectin receptors cause?
Assist with phagocytosis and induce inflammatory cytokines production
E.g mbl
In drosophila toll like receptor family had?
Dtoll and 18 wheeler
Cell surface ligand bacterial?
Lipopolysaccharide
Flagellin
Lipoteichoic acid
Endosomal ligands, for viral products and host?
DsRNA
SsRNA
DNA
TLR signalling induces genes for?
Pro inflammatory and anti inflammatory cytokines
MHC and co stimulatory molecules
Antimicrobial peptides and complement components
What are the adaptor proteins?
trif/TRAM
MyD88/Mal
What do NK cells use to create holes?
Granzyme
Perforin
Cells that are dying how are they detected?
By scavenger receptors on phagocytosis, noticing phospholipid changes
Phagocyte mechanisms for the phagolysosomes?
Acidification less than 4
Toxic oxygen derived products Toxic nitrogen products Antimicrobial peptides Lysozyme Lactoferrin- sequesters iron needed for bacterial growth
To signal TLRs have to?
Bring TIR domains together
TLR2 binds to either?
TLR 6 for diacyl lipopeptides
TLR 1 for triacy lipopeptides
TLR5 recognises?
Flagellin
TLR4 recognises?
LPS
TLR3 only uses which adaptor molecule?
TRIF, which gives rise to IFN
MYD88 deficiency caused?
Life threatening, recurrent progenitor bacterial infections
For allergy which TLR do you need to activate?
9
Inflammasome caspases does what?
Cleaves pro-IL1 form
What is Muckle well syndrome caused by?
Cold
MDA5 mutations related with?
Lupus and Aicardi goutieres disease
Acute phase response is induced by?
IL1 and Il 6 and TNF, produced by liver
Signs of mucked wells syndrome?
Can occur spontaneously or be triggered by cold, heat, fatigue, or other stresses.
Symptoms of fever, rash, arthralgia, conjunctivitis, uveitis, sensorineural deafness, and potentially life-threatening amyloidosis
Familial cold autoinflammatory syndrome signs?
fever urticarial rash with headache, arthralgia, and sometimes conjunctivitis
