Chapter 4 Flashcards
What is the major signal transduction pathway that TLR engage to activate cells?
NF-kB
Receptors of innate immune system are encoded by () genes whereas receptors of adaptive immunity are generated by () genes.
Germline gene
Somatic gene
Name the structures recognised by innate immune system.
1) molecules produced by microbial pathogens
2) endogenous molecules produced by damaged cells
1) PAMP (pathogen-associated molecular patterns)
2) DAMP (damage-associated molecular patterns)
List the entities under PAMP & DAMP.
PAMP (nucleic acids, proteins, cell wall lipids, carbohydrates)
DAMP (stress-induced proteins, crystals, proteolytically cleaved ECM, mitochondria, nuclear proteins)
List the entities under cell-associated & soluble pattern recognition receptors.
Cell-associated PRP
- membrane (TLR, CLR, scavenger receptors, N-Formyl met-leu-phe receptors)
- cytosolic (NLR, RLR, CDS)
Soluble PRP
- pentraxins, collectins, ficolins, complement
What is the signalling structure for TLR?
This structure is also found in () & ().
Toll/IL-1 receptor (TIR) domain in cytoplasmic tails
*TIR is also found in IL-1 & IL-8.
TLR also recognises endogenous molecules whose expression or location indicate cell damage. What are these molecules?
HSP (heat shock proteins)
HMGB1 (for transcription & DNA repair)
() & () bind to lipid A of LPS, forming a complex that interacts with TLR4 & initiates signalling.
MD2 (myeloid differentiation protein 2)
CD14 (for efficient LPS-induced signalling)
Which protein in ER is required for endosomal localisation & proper function of TLR3, 7, 8 & 9?
Genetic deficiency of this protein leads to susceptibility of which infection?
UNC-93B
Herpes simplex encephalitis
All TLRs signal through MyD88 except ().
The above TLR signals through ().
TLR3
TRIF
Which TLR signals through MyD88 & TRIF?
TLR4
These TLR are most highly expressed in plasmacytoid DC, signal through MyD88-dependent, TRIF-independent pathway that activates NF-kB & IRF.
Endosomal TLR7 & TLR8
Name 3 major transcription factors activated by TLR.
Nuclear factor kB (NF-kB)
Activation protein (AP-1)
Interferon response factor (IRF3 & IRF7)
Name the surface TLR(s) that recognise
1) bacterial polypeptide
2) bacterial peptidoglycan
3) lipopolysaccharide
4) bacterial flagellin
1) TLR1:TLR2 & TLR2:TLR6
2) TLR2
3) TLR4
4) TLR5
Name the endosomal TLR(s) that recognise
1) dsRNA
2) ssRNA
3) CpG DNA
1) TLR3
2) TLR7 & TLR8
3) TLR9
Name 4 cytosolic receptors for PAMP & DAMP.
NOD-like receptors (NLR)
Cytosolic DNA sensors (CDS) & STING pathway
RIG-like receptors (RLR)
Inflammasomes
Name 3 NLR subfamilies & their respective effector domain that serve innate immunity.
NLRB uses BIR
NLRC uses CARD (NOD1 & NOD2)
NLRP uses Pyrin
Defect in Pyrin domain of NLRP causes which disease?
And what’s the gene involved?
Familial Mediterranean fever in MEFV gene mutation
NOD2 is produced by () which recognises () to stimulate expression of (). Gain-of-function mutation of NOD2 causes increased NOD signalling & NF-kB activation leading to ().
Paneth cells
MDP (muramyl dipeptide)
Defensins
Blau syndrome
NOD1 recognises () derived mainly from gram-negative bacterial peptidoglycan.
DAP (diaminopimelic acid)
Function of NLRB.
Detect flagellin to control Legionella pneumophila infection.
Function of NLRP.
Caspase 1 activation
CDS detects () in cytosol & induces () pathway which is ()-induced activation of () responses.
microbial dsDNA
STING (stimulator of IFN genes)
dsDNA
Type 1 IFN
Name 2 CDS that work through STING independent pathway.
RNA polymerase 3 activates RIG-1 pathway.
AIM2 forms inflammasome, generates IL-1b.
() is the cytosolic sensor of viral RNA (dsRNA & RNA-DNA) that respond by inducing production of antiviral type 1 interferons.
RIG-like receptors (RLR)
Give 2 examples of RLR.
RIG-1 (retinoid-inducible gene 1)
MDA5 (melanoma differentiation-associated gene 5)
RLR are recruited to outer mitochondrial membranes by () which activates (), () & () to induce type 1 interferon production.
MAVS (mitochondrial antiviral-signalling) protein
IRF3, IRF7 & NF-kB
Functions of inflammasomes.
To generate active form of IL-1b & IL-18 (caspase-1)
Inflammasome activation causes () characterised by apoptosis of macrophage & DC but not neutrophils & others.
Pyroptosis
() recognise microbial surface carbohydrates to facilitate microbe phagocytosis & chemokine secretion.
C-type lectin receptors
Name the C-type lectin receptor involved in
1) phagocytosis
2) antifungal immunity
3) Th17 differentiation
4) mycobacterium immunity
5) hepatitis C virus & HIV-1 infection
1) mannose receptors, langerin
2) mannose receptors, Dectin-1, Dectin-2 & Mincle
3) Dectin-1 & Dectin-2
4) Dectin-2 & Mincle
5) DC-Sign
Scavenger receptors mediate uptake of () into cells via expression of () & () on macrophage.
Oxidised lipoproteins
SR-A & CD36
() expressed in leukocytes, recognises bacterial peptides containing N-formylmethionyl residues & stimulates directed cell movement.
Formyl-peptide receptor 1 (FPR1)
() is mainly produced by () in small bowel to limit the amount of luminal microbes in which they kill microbes by disrupting function of microbial membranes.
alpha-defensins (crypticidin)
Paneth cell
() produced by neutrophils & mucosal epithelium protect against infections by direct toxicity & leukocyte activation.
Cathelicidin
C-terminal fragment of cathelicidin named () can bind & neutralise LPS that is recognised by TLR4.
LL-37
() is the major source of antiviral cytokines type 1 IFN due to abundant expression of ().
Plasmacytoid DC endosomal TLR (3, 7, 8, 9)
Name the cytokines responsible for
1) defense against viruses
2) defense against helminths & allergic inflammation
3) intestinal barrier function & lymphoid organogenesis
1) IFN-gamma
2) IL-5 & IL-13
3) IL-17 & IL-22
Which cytokines are responsible for innate lymphoid cells (ILC) development?
IL-7 (for ILC1, ILC2 & ILC3)
IL-15 (for ILC1)
NK cells are identified by expression of () and () & absence of ().
CD56 & CD16
CD3
Name 2 NK cells granules.
Name cytokines responsible for NK cell expansion & activation.
Perforin & granzyme
IL-12, IL-15, IL-18 & type 1 IFN
Activating receptors of NK cells transmit signals via ().
Entities include…
ITAM (immunoreceptor tyrosine-based activation motifs)
KIR, NKG2D & CD16
Inhibitory receptors of NK cells recognise () & transmit signals via (). Entities include…
Class 1 MHC
ITIM (immunoreceptor tyrosine-based inhibition motif)
KIR & lectins
Name 4 entities of soluble effector molecules of innate immunity.
Complement system
Pentraxins
Collectins
Ficolins
() activate complement by binding C1q & initiating classical pathway.
Pentraxins
Name 4 entities of pentraxins.
Short pentraxins
C-reactive proteins (CRP)
Serum amyloid P (SAP)
Long pentraxins PTX3
CRP synthesis in liver is induced by () & ().
IL-1 & IL-6
() provides protection against microbes including Aspergillus fumigatus & influenza virus.
Long pentraxin PTX3
Name 2 members of collectin.
Mannose-binding lectin (MBL)
Pulmonary surfactant proteins SP-A & SP-D
() has fibrinogen-type carbohydrate recognition domain which functions to opsonise bacteria & activate complement like MBL.
Ficolins
Name the 2 molecular ligands of ficolins.
N-acetylglucosamine
Lipoteichoic acid
2 cytokines that induce Th17 differentiation.
IL-1 & IL-6
Which cytokine induces Th1 differentiation.
IL-12
IL-27
Name the type 1 interferons that is produced by
1) macrophage & plasmacytoid DC
2) fibroblast
1) IFN-alpha
2) IFN-beta
This cytokine inhibits expression of IL-12.
IL-10
This cytokine induces proliferation of memory CD8+ T cells.
IL-15
This cytokine maintains IL-17-producing T cells.
IL-23
This cytokine induces Th1 differentiation & Th17 inhibition.
IL-27
Which TNF receptor activates caspase & apoptosis?
Type 1 TNF receptor (TNF-RI)
Septic shock is largely mediated by which cytokine?
TNF
Name 1 mediator of acute inflammatory response with many similar actions with TNF & its entities.
IL-1 (IL-1a & IL-1b)
() cleaves gasdermin D for non-canonical inflammasome signalling in pyroptosis.
Caspase-11
() cleaves pro-IL-1b to IL-1b.
Caspase-1
() which contains gp130 that activates STAT3, is a major contributor to rheumatoid arthritis.
IL-6
() is caused by HHV-8 that encodes IL-6 homolog.
Castleman’s disease
TNF & IL-1 induce postcapillary venule endothelial cell to express () & stimulate () and () secretion which bind to receptors of neutrophils & monocytes respectively.
E-selectin
CXCL8 & CCL2
() is produced by phagocyte oxidase in respiratory burst in which its deficiency leads to ().
Reactive oxygen species (ROS)
Chronic granulomatous disease
Intracellular destruction of microbes in phagolysosome involves () & ().
ROS & NO
Nitric oxide is produced by () in macrophage.
Inducible nitric oxide synthase (iNOS)
Name 2 enzymes of neutrophils & their respective functions.
Elastase (broad-spectrum serine protease to kill bacteria) Cathepsin G (phagocytosis)
Neutrophil extracellular traps (NETs) formation in NETosis requires histone citrullination by 4 enzymes.
Peptidylarginine deiminase (PAD4)
Elastase
Myeloperoxidase (MPO)
Phagocyte oxidase
This cytokine is responsible for intravascular thrombosis & cachexia.
TNF
Cytokine for septic shock outcome prediction.
TNF
Cytokines in autoimmune diseases.
TNF
IL-1
IL-6
IL-12
Name 4 mechanisms in limiting innate immune response.
IL-10
IL-1RA
Autophagy genes
Negative regulatory signalling pathway
() are inhibitors of JAK-STAT signalling pathways linked to cytokine receptors.
Suppressors of cytokine signalling (SOCS) proteins
List the inducer cytokines & T cells responsible for the following situations.
1) defense against intracellular pathogens
2) defense in allergy & asthma
3) anti-tumour & prevent autoimmunity
4) immune regulation
5) defense against extracellular bacteria
6) defense against autoimmunity
7) defense against viral infection
1) IL-12 & Th1
2) IL-4 & Th2
3) IL-4/TGF-b & Th9
4) IL-2/TGF-b & Treg
5) IL-6/TGF-b & Th17
6) IL-6/IL-21 & Tfh
7) IL-15 & NKT cell
