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Flashcards in L3 - Innate immunity 2 Deck (27)
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i) name one role of neutrophils and two things that they produce? 

ii) name four things macrophages produce? what can this activate?

iii) which cell can antigen present? (2)

iv) what is the main role of NK cells? what two molecules does it release to do this? which other cells can they activate?

v) name two cell types that have both adaptive and innate qualities 

vi) what are the two types of dendritic cell? what does each one produce/do?

i) ROS, antimicrobial peptides 
- do phagocytosis

ii) macrophages produces inflam mediators, ROS, cytokines, complement proteins > activates complement cascade

iii) dendritic cells (myeloid) and macrophages can APC

iv) NK cells lyse viral infected cells 
- release granzyme and perforin 
- can also activate macrophages 

v) adaptive and innate = GD T cells and NK cells (express PRRs)

vi) plasmacytoid dendritic > lymphoid and produces IFN
myeloid dendritic > APC and prod pro inflam cytokines 



i) name two things phagocytes release 

ii) what action do cytokines have on local blood vessels? what two cell types do chemokines attract to site of infection?

iii) name two cell adhesion molecules that are upregulated on the endothelium? what do these bind? 

iv) what are the four stages of phagocytes getting to site of infection?

i) release cyto and chemokines

ii) cytokines cause bv to dilate
- chemokines attract monocytes and neutrophils to infection

iii) ICAM1 and VCAM1 are upreg on the endothelium and bind integrins on leucocytes in the blood 

iv) phagocyte rolls > activates >
arrest/adhesion > transendothelial migration 



i) name three cells it is performed by?

ii) what is it?

iii) what do opsonins do? name three things that opsonise? 

iv) name four phagocytic receptors and what they bind to

v) what do scavenger receptors bind to? what do they recognise? (3)


i) neutrophils, dendritic cells, macrophages

ii) capture and digestion of a foreign particle

iii) opsonins highlight molecules to be phagocytosed and engage with receptors on phagocytic cells 
- complement components (C3b), collectins (MBL), antibodies 

iv) phago receptors = complement receptors, Fc receptors (for antibodies), mannose R (for MBL), scavenger receptors

v) scavenger receptors bind to lipid 
- they recognise bacteria, viruses and apoptotic cells 



i) what do phagocytic receptors bind? 

ii) by what mechanism are pathogens internalised?

iii) once internalised - what forms? how does this degrade the microorganism?

i) phago receptors bind opsonins

ii) receptor mediated endocytosis

iii) once inside > phagolysosome (fusion of endosome and lysososome)
- bacteriocidal enviro inside the phagolyso causes MO to be degraded 



i) what pH are products from MPs/neutrophils?

ii) name three toxic oxygen derived products? what do these do?

iii) name two antimicrobial peptides produced by macrophages? and two produced by neutrophils?

iv) what role does lyosozyme play?

v) name two competitors that stop bacterial growth

i) pH 3.5-4

ii) superoxide, hydrogen perioxide, singlet oxygen
- these can break down pathogens 

iii) MP > cathelicidin, macrophage elastase derived peptide
NP > defensins, cathelicidin 

iv) lysozyme digest cells walls of some gram positive bacteria (peptidoglycan)

v) competitors > lactoferrin and vitamin B12 binding protein 



i) what is NETosis?

ii) what is released during NETosis? what does this do?

i) a special form of cell death that some neutrophils under go

ii) nuclear chromatin is released from cells 
- this traps MOs and aids phagocytosis 



i) where are C type lectin receptors found?

ii) name two places TLRs are found?

iii) name three PRRs that are found in the cytosol? which type of pathogens may these target

iv) what do these receptors recognise? what are these called?

i) C type lectin receptors are found on the cell surface

ii) TLRs found on cell surface and on the surface of the endosome

iii) PRRs in the cytosol - NOD like receptors (NLRs), Rig I like receptors (RLRs), cytosolic DNA sensors (CDS)
- may target viruses as they can get into cytosol 

iv) receptors recognise conserved structures = PAMPs
(pathogen associated molecular patterns)



i) what are they? can the pathogen exist without them?

ii) why must the innate immune system focus on PAMPs? give two examples of a PAMP

iii) what is a damage associated molecule pattern? 

iv) are PAMPs always on pathogenic bacteria?

v) what occurs in microbes thay plays a role in their ability to survive and adapt?

i) highly conserved elements that the pathogen cannot live without

ii) innate imm sys must focus on PAMPs as microbes evolve rapidly
- cell wall structures and nucleic acids

iii) DAMP = molecules released from necrotic cells 

iv) no - can be on gut bacteria etc (MAMPs)

v) random mutations 



i) where are they expressed? 

ii) what do they bind to? what does this depend on?

iii) what do type I CLRs assist with? what are type II CLRs involved in?

iv) name a soluble CLR - what does this bind on the pathogen?
- name two other things this receptor can do

i) by most cell types that phagocytose glycoprotein and microbes

ii) bind to carbohydrates in a calcium dependent mannor

iii) type I > antigen uptake by phagocytes
type II > fungal recogition 

iv) soluble CLR = MBL
- binds carbohydrate on pathogen surfaces 
- also activates complement and induces phago by acting as an opsonin 



i) which organism were these receptors discovered in? which two types of infections developed when the organism was deficient in these receptors?

ii) what domain does the extracellular part contain? what is this the site of?

iii) once activated - which domain is there a conformational change in? how many amino acids make up this domain?

i) drosophila
- developed bacterial and fungal infections when deficient 

ii) extracell domain = LRR (leucine rich repeats) which is the site of pathogen binding (engages PAMP, DAMP)

iii) activation > conform change in TIR intracell domain
- TIR domain = 200 amino acids conserved across all TLRs



i) what has to happen for the triggering of signal activity?

ii) which two type of dimers can be formed? what does this affect?

iii) what do TLRs bind to induce dimerisation? what is brought close when dimerisation occurs?

i) need TLR to come together in a pair and two TIR domains brought close 

ii) form homo (2 receptors of same subtype) or heterodimers
- affects downstream signalling and what ligands they bind 

iii) TLRs bind the lipid side change on a lipopeptide 
- two TLRs must bind the same lipopeptide to induce dimerisation and bring TIR domains close together 



i) how many TLRs are there in humans? 

ii) where are most TLRs found? where are some also found? what do they recognise here?

iii) what happens in the endosome? name three things that TLRs will recognise here?

iv) which TLR is TLR10 in competition with? why?

i) 10

ii) most are found on the cell surface (recog lipopeptidesm flagellin and LPS)
- some found on the endosome - recog nuc acid structures

iii) endosome = pathogen is broken down & gen mat exposed
- TLR can recog dsRNA, ss RNA and CpG DNA

iv) TLR10 is in competition with TLR 3 as they both recognise dsRNA



i) which TLRs are found on the cell surface? what do these mainly recognise?

ii) which TLRs are found on the endosomal surface? what do these mainly recognise?

iii) which host/DAMP molecules do cell surface TLRs recognise?

iv) which host/DAMP molecules do endosomal TLRs recognise?

v) what can complement deficiency result in? what does this cause in relation to TLRs? what molecule is released?

i) TLR 1,2,4,5,6
- recognise bacterial products eg LPS

ii) TLR 3,7,8,9,10
- mainly recognise viral products eg dsRNA

iii) cell surface TLRs recog protein/lipid from host eg HSP70

iv) endosomal TLRs recog host DNA/RNA

v) complement defic > autoantibodies that are not cleared and bound to own DNA and RNA 
- taken up by immune cells and trigger TLRs in the endosome to release IFN = classic of lupus 



i) which four adaptor proteins can be used ds of TLRs? which TLR uses all four?

ii) what adaptor protein do most TLRs engage with? which two pathways does this drive? what is ultimately produced?

iii) why type of cytokines does TLR signalling induce gene expression of?

iv) name two molecules that can be upregulated following TLR activation

v) name two things that can be released following TLR activation 

vi) which downstream pathway activates IFN? which pathway activates interleukins?


i) Trif, TRAM, MYD88, Mal
- TLR4 uses all of them 

ii) most TLRs engage with MyD88
- this drives NFKb and AP1 which ultimately activated interleukins

iii) TLRs induce expression of pro inflammatory cytokines

iv) upregulation of MHC and co-stimulatory molecules

v) release of antimicrobial peptides and complement components

vi) Trif pathway > IFN
MyD88 pway > interleukins 



i) what is waldenstrom macroglobulinemia?

ii) what % of these patients have a MyD88 mutation? what does this cause?

iii) which Ig do B cells make large amounts of? name three things this can cause

iv) name three things that lymphoma cells proliferating in the BM can cause?

i) a rare type of non hodgkins lymphoma

ii) 90% of patients have MyD88 mutation
- causes cell growth and survival 

iii) B cells make lots of IgM which causes excess bleeding, vision problems and headaches

iv) prolif lymphoma cells can cause anaemia, neutropenia and thrombocytopenia 



i) can you live without it?

ii) in a study - what did MyD88 defic children suffer from? how was their resistance to microbes?

iii) what did clinical status improve with? give a suggestion of the mechanism of this?

i) yes

ii) children had recurrent pyogenic bacterial infections (pneumonia/s.aureus infec) 
- normal resistance to microbes and otherwise well

iii) clinical status improved with age 
- compensatory effect of adaptive immunity (as this improves with age) 



i) deficiency in which TLR is the only one to be linked to immunodeficiency?

ii) which virus does deficiency in this TLR predispose to? what type of virus is this?

i) TLR3

ii) linked to herpes simplex encephalitis (HSE) 
- inflammation in the brain 
- dsDNA virus that prodces dsRNA during replication 



i) name four diseases that activate TLR2 and TLR4?

ii) name a TLR agonist that can be used for treatment of genital warts and melanoma? what TLR does it agonise?

iii) what environmental agent can be used to tolerise against an allergen? which TLR does it work on?

iv) in what situation would you want to antagonise TLR activity? (2) 

v) what three TLRs does SLE activate? where are these found?

i) alzheimers, atheroscleoris, sepsis, tb

ii) aldara > agonises TLR7

iii) ragweed pollen can tolerise against allergens and works on TLR9

iv) antagonise in autoimmunity and sepsis 

v) SLE > TLR 7,8,9 (endosomal) 



i) what repeats do they have in them? what do these interact with?

ii) where are they exclusively found? 

iii) what are the two main groups? 

i) leucine rich repeats that interact with PAMPs

ii) exclusively found in the cytoplasm

iii) NLRCs and NLRPs



i) give two examples of receptors in this family

ii) what does the C stand for?

iii) which amino acid is rich in the domain? what does this bind? 

iv) which domain is used to signal? what does this produce (2)

i) NOD1 and NOD2

ii) C = caspase recruitment domain 

iii) leucine rich domain that binds peptidoglycan in bacteria

iv) CARD domain used to signal > NFKb and cytokine prod




i) what do they detect?

ii) what does NOD1 bind? which type of bacteria is this found in?

iii) what does NOD2 bind? what type of bacteria is this found in?

iv) what is NOD2 GOF mutation linked to? what happens in this condition?

v) what is NOD2 LOF mutation associated with? 

i) similar yet distinct peptides of peptidoglycan 

ii) NOD1 binds iE DAP - mainly found in gram neg bacteria

iii) NO2 binds muramyl dipeptide - found in gram + and -

iv) NOD2 GOF linked to sarcoidosis (AI) > granulomas develop in organs of the body

v) NOD2 LOF > chrohns disease suceptibility 



i) which one is best characterised? what is this activated by? (give three examples)

ii) which two things does it come together with to form the inflammasome? 

iii) what is the inflammasome essential for? 

iv) what is formed in lots of conditions that activates the inflammasome? give four example of diseases 

i) NLRP3 > activated by cellular stress eg K+ efflux, ATP and ROS

ii) comes together with caspase 1 and ASC > inflammasome

iii) inflammasome is essential for IL-1 and IL-18 secretion 

iv) formation of crystals > activates IS
- gout, asbestos, silica, alz (amyloid beta), malaria (hemozoin crystals), type II diabetes 



i) what happens in frustrated phagocytosis? what gets activated? what does this cause?

ii) which two pro interleukins does the inflammasome cause cleavage of?

ii) which transcription factor drives transcription of IL-1b? what is this made as? which inflammosome proteins cleaves it?



i) macrophage tries to break something down and the MP gets stuck which activates the inflammasome
- this causes interleukin activation and increased inflammation 

ii) pro IL-1 and pro IL-18

iii) Nfkb drives transcription of IL-1b
- made as pro IL-1 and cleaved by caspase 1 from the inflammosome 




i) what happens when there is GOF in NLRP3?

ii) CAPS syndrome is caused by a rare mutation in which exon of NLRP3? what does this cause?

iii) what can trigger Muckle Well Syndrome? (3) give four symptoms

iv) what is familial cold autoinflam syndrome caused by? what does this trigger? give four symptoms 

v) what can both conditions be treated with? what does this drug do?

i) lots of production of IL-1

ii) CAPS syndrome caused by mutation in exon 3 of NLRP3
- causes over production of IL-1 

iii) muckle well - spontaneous, cold, heat, fatigue, other stress
- fever, rash, arthralgia, conjunctivitis, life threat amyloidosis

iv) familial cold autoinflam syndrome caused by exposure to cold > triggers NALP3 inflammosome > prod IL-1
- fever, uriticarial rash, headache, arthralgia 

v) both conditions can be treated with anakinra
- antagonises IL-1 



i) where are they found? what do they sense? why is this relevant?

ii) what do they signal to produce? (2)

iii) what does RIG I bind to? why does it not recognise self cells?

iv) what does MDA5 preferentially recognise? what is it critical for detection of?

v) what have mutations in MDA5 been associated with? (2) 

i) found in the cytosol and sense cytoplasmic RNA 
- RNA is an intermediate for viruses

ii) signal to produce pro inflammatory cytokines and IFN

iii) RIG I binds to ssRNA containing 5'triphos
- doesnt bind our cells as 5' RNA is capped so cant be recog

iv) MDA5 preferentially recog long dsRNA
- critical for detection of picornavirus

v) mutations in MDA5 have been assoc with IFN related disease such as SLE and aicardi goutier syndrome 



i) name two cytosolic DNA sensors

ii) what does viral dsDNA bind? what does this cause the production of?

iii) what is the ligand for STING? what happens when STING binds its ligand?

iv) what does a GOF mutation in sting cause? 

v) what type of disease is SAVI? what is it caused by? what do patients produce too much of? what does this cause?

vi) how may bacteria directly activate the STING pathway? what do they release?

i) cGAS and STING

ii) viral dsDNA binds cGAS which causes it to convert ATP and GTP to cGAMP > ligand for sting 

iii) cGAMP is ligand for STING
- binds and signals to produce IFN alpha and beta 

iv) GOF mutation in STING causes lots of IFN alpha to be produced

v) SAVI (stimulator of interferon genes assoc vasculopathy onset infancy) is an autoinflammatory disease caused by GOF mut in gene coding for STING
- patient produces too much type I IFN > abnormal inflammation through body (skin, bv and lungs) 

vi) bacteria can release cyclic dinucleos such as cdiGMP and CdiAMP that directly activate STING 



i) where are acute phase proteins mainly produced?

ii) name three things that APPs are induced by? what situations does this happen in? (2)

iii) what can APPs actvate? what does this induce? 

iv) name two parameters that are characteristic of an acute phase response? what are these used clinically to detect?

v) name four APPs

i) in the liver

ii) cytokines such as TNF, IL-6 and IL-1
- happens in infection and inflammation

iii) APPs can activate complement and induce opsonisation and phagocytosis

iv) CRP and raised erythrocyte sedimentation rate
- clinically detect inflammation 

v) serum amyloid protein, CRP, fibrinogen, MBL