Chapter 4

Question 1

What is the major signal transduction pathway that TLR engage to activate cells?

Answer 1

NF-kB

Question 2

Receptors of innate immune system are encoded by () genes whereas receptors of adaptive immunity are generated by () genes.

Answer 2

Germline gene

Somatic gene

Question 3

Name the structures recognised by innate immune system.

1) molecules produced by microbial pathogens
2) endogenous molecules produced by damaged cells

Answer 3

1) PAMP (pathogen-associated molecular patterns)

2) DAMP (damage-associated molecular patterns)

Question 4

List the entities under PAMP & DAMP.

Answer 4

PAMP (nucleic acids, proteins, cell wall lipids, carbohydrates)

DAMP (stress-induced proteins, crystals, proteolytically cleaved ECM, mitochondria, nuclear proteins)

Question 5

List the entities under cell-associated & soluble pattern recognition receptors.

Answer 5

Cell-associated PRP

• membrane (TLR, CLR, scavenger receptors, N-Formyl met-leu-phe receptors)
• cytosolic (NLR, RLR, CDS)

Soluble PRP
- pentraxins, collectins, ficolins, complement

Question 6

What is the signalling structure for TLR?

This structure is also found in () & ().

Answer 6

Toll/IL-1 receptor (TIR) domain in cytoplasmic tails

*TIR is also found in IL-1 & IL-8.

Question 7

TLR also recognises endogenous molecules whose expression or location indicate cell damage. What are these molecules?

Answer 7

HSP (heat shock proteins)

HMGB1 (for transcription & DNA repair)

Question 8

() & () bind to lipid A of LPS, forming a complex that interacts with TLR4 & initiates signalling.

Answer 8

MD2 (myeloid differentiation protein 2)

CD14 (for efficient LPS-induced signalling)

Question 9

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?

Answer 9

UNC-93B

Herpes simplex encephalitis

Question 10

All TLRs signal through MyD88 except ().

The above TLR signals through ().

Answer 10

TLR3

TRIF

Question 11

Which TLR signals through MyD88 & TRIF?

Answer 11

TLR4

Question 12

These TLR are most highly expressed in plasmacytoid DC, signal through MyD88-dependent, TRIF-independent pathway that activates NF-kB & IRF.

Answer 12

Endosomal TLR7 & TLR8

Question 13

Name 3 major transcription factors activated by TLR.

Answer 13

Nuclear factor kB (NF-kB)
Activation protein (AP-1)
Interferon response factor (IRF3 & IRF7)

Question 14

Name the surface TLR(s) that recognise

1) bacterial polypeptide
2) bacterial peptidoglycan
3) lipopolysaccharide
4) bacterial flagellin

Answer 14

1) TLR1:TLR2 & TLR2:TLR6
2) TLR2
3) TLR4
4) TLR5

Question 15

Name the endosomal TLR(s) that recognise

1) dsRNA
2) ssRNA
3) CpG DNA

Answer 15

1) TLR3
2) TLR7 & TLR8
3) TLR9

Question 16

Name 4 cytosolic receptors for PAMP & DAMP.

Answer 16

NOD-like receptors (NLR)
Cytosolic DNA sensors (CDS) & STING pathway
RIG-like receptors (RLR)
Inflammasomes

Question 17

Name 3 NLR subfamilies & their respective effector domain that serve innate immunity.

Answer 17

NLRB uses BIR
NLRC uses CARD (NOD1 & NOD2)
NLRP uses Pyrin

Question 18

Defect in Pyrin domain of NLRP causes which disease?

And what’s the gene involved?

Answer 18

Familial Mediterranean fever in MEFV gene mutation

Question 19

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 ().

Answer 19

Paneth cells
MDP (muramyl dipeptide)
Defensins
Blau syndrome

Question 20

NOD1 recognises () derived mainly from gram-negative bacterial peptidoglycan.

Answer 20

DAP (diaminopimelic acid)

Question 21

Function of NLRB.

Answer 21

Detect flagellin to control Legionella pneumophila infection.

Question 22

Function of NLRP.

Answer 22

Caspase 1 activation

Question 23

CDS detects () in cytosol & induces () pathway which is ()-induced activation of () responses.

Answer 23

microbial dsDNA
STING (stimulator of IFN genes)
dsDNA
Type 1 IFN

Question 24

Name 2 CDS that work through STING independent pathway.

Answer 24

RNA polymerase 3 activates RIG-1 pathway.

AIM2 forms inflammasome, generates IL-1b.

Question 25

() is the cytosolic sensor of viral RNA (dsRNA & RNA-DNA) that respond by inducing production of antiviral type 1 interferons.

Answer 25

RIG-like receptors (RLR)

Question 26

Give 2 examples of RLR.

Answer 26

RIG-1 (retinoid-inducible gene 1) | MDA5 (melanoma differentiation-associated gene 5)

Question 27

RLR are recruited to outer mitochondrial membranes by () which activates (), () & () to induce type 1 interferon production.

Answer 27

MAVS (mitochondrial antiviral-signalling) protein | IRF3, IRF7 & NF-kB

Question 28

Functions of inflammasomes.

Answer 28

To generate active form of IL-1b & IL-18 (caspase-1)

Question 29

Inflammasome activation causes () characterised by apoptosis of macrophage & DC but not neutrophils & others.

Answer 29

Pyroptosis

Question 30

() recognise microbial surface carbohydrates to facilitate microbe phagocytosis & chemokine secretion.

Answer 30

C-type lectin receptors

Question 31

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

Answer 31

1) mannose receptors, langerin 2) mannose receptors, Dectin-1, Dectin-2 & Mincle 3) Dectin-1 & Dectin-2 4) Dectin-2 & Mincle 5) DC-Sign

Question 32

Scavenger receptors mediate uptake of () into cells via expression of () & () on macrophage.

Answer 32

Oxidised lipoproteins | SR-A & CD36

Question 33

() expressed in leukocytes, recognises bacterial peptides containing N-formylmethionyl residues & stimulates directed cell movement.

Answer 33

Formyl-peptide receptor 1 (FPR1)

Question 34

() 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.

Answer 34

alpha-defensins (crypticidin) | Paneth cell

Question 35

() produced by neutrophils & mucosal epithelium protect against infections by direct toxicity & leukocyte activation.

Answer 35

Cathelicidin

Question 36

C-terminal fragment of cathelicidin named () can bind & neutralise LPS that is recognised by TLR4.

Answer 36

LL-37

Question 37

() is the major source of antiviral cytokines type 1 IFN due to abundant expression of ().

Answer 37

``` Plasmacytoid DC endosomal TLR (3, 7, 8, 9) ```

Question 38

Name the cytokines responsible for 1) defense against viruses 2) defense against helminths & allergic inflammation 3) intestinal barrier function & lymphoid organogenesis

Answer 38

1) IFN-gamma 2) IL-5 & IL-13 3) IL-17 & IL-22

Question 39

Which cytokines are responsible for innate lymphoid cells (ILC) development?

Answer 39

IL-7 (for ILC1, ILC2 & ILC3) | IL-15 (for ILC1)

Question 40

NK cells are identified by expression of () and () & absence of ().

Answer 40

CD56 & CD16 | CD3

Question 41

Name 2 NK cells granules. | Name cytokines responsible for NK cell expansion & activation.

Answer 41

Perforin & granzyme | IL-12, IL-15, IL-18 & type 1 IFN

Question 42

Activating receptors of NK cells transmit signals via (). | Entities include...

Answer 42

ITAM (immunoreceptor tyrosine-based activation motifs) | KIR, NKG2D & CD16

Question 43

Inhibitory receptors of NK cells recognise () & transmit signals via (). Entities include...

Answer 43

Class 1 MHC ITIM (immunoreceptor tyrosine-based inhibition motif) KIR & lectins

Question 44

Name 4 entities of soluble effector molecules of innate immunity.

Answer 44

Complement system Pentraxins Collectins Ficolins

Question 45

() activate complement by binding C1q & initiating classical pathway.

Answer 45

Pentraxins

Question 46

Name 4 entities of pentraxins.

Answer 46

Short pentraxins C-reactive proteins (CRP) Serum amyloid P (SAP) Long pentraxins PTX3

Question 47

CRP synthesis in liver is induced by () & ().

Answer 47

IL-1 & IL-6

Question 48

() provides protection against microbes including Aspergillus fumigatus & influenza virus.

Answer 48

Long pentraxin PTX3

Question 49

Name 2 members of collectin.

Answer 49

Mannose-binding lectin (MBL) | Pulmonary surfactant proteins SP-A & SP-D

Question 50

() has fibrinogen-type carbohydrate recognition domain which functions to opsonise bacteria & activate complement like MBL.

Answer 50

Ficolins

Question 51

Name the 2 molecular ligands of ficolins.

Answer 51

N-acetylglucosamine | Lipoteichoic acid

Question 52

2 cytokines that induce Th17 differentiation.

Answer 52

IL-1 & IL-6

Question 53

Which cytokine induces Th1 differentiation.

Answer 53

IL-12 | IL-27

Question 54

Name the type 1 interferons that is produced by 1) macrophage & plasmacytoid DC 2) fibroblast

Answer 54

1) IFN-alpha | 2) IFN-beta

Question 55

This cytokine inhibits expression of IL-12.

Answer 55

IL-10

Question 56

This cytokine induces proliferation of memory CD8+ T cells.

Answer 56

IL-15

Question 57

This cytokine maintains IL-17-producing T cells.

Answer 57

IL-23

Question 58

This cytokine induces Th1 differentiation & Th17 inhibition.

Answer 58

IL-27

Question 59

Which TNF receptor activates caspase & apoptosis?

Answer 59

Type 1 TNF receptor (TNF-RI)

Question 60

Septic shock is largely mediated by which cytokine?

Answer 60

TNF

Question 61

Name 1 mediator of acute inflammatory response with many similar actions with TNF & its entities.

Answer 61

IL-1 (IL-1a & IL-1b)

Question 62

() cleaves gasdermin D for non-canonical inflammasome signalling in pyroptosis.

Answer 62

Caspase-11

Question 63

() cleaves pro-IL-1b to IL-1b.

Answer 63

Caspase-1

Question 64

() which contains gp130 that activates STAT3, is a major contributor to rheumatoid arthritis.

Answer 64

IL-6

Question 65

() is caused by HHV-8 that encodes IL-6 homolog.

Answer 65

Castleman’s disease

Question 66

TNF & IL-1 induce postcapillary venule endothelial cell to express () & stimulate () and () secretion which bind to receptors of neutrophils & monocytes respectively.

Answer 66

E-selectin | CXCL8 & CCL2

Question 67

() is produced by phagocyte oxidase in respiratory burst in which its deficiency leads to ().

Answer 67

Reactive oxygen species (ROS) | Chronic granulomatous disease

Question 68

Intracellular destruction of microbes in phagolysosome involves () & ().

Answer 68

ROS & NO

Question 69

Nitric oxide is produced by () in macrophage.

Answer 69

Inducible nitric oxide synthase (iNOS)

Question 70

Name 2 enzymes of neutrophils & their respective functions.

Answer 70

``` Elastase (broad-spectrum serine protease to kill bacteria) Cathepsin G (phagocytosis) ```

Question 71

Neutrophil extracellular traps (NETs) formation in NETosis requires histone citrullination by 4 enzymes.

Answer 71

Peptidylarginine deiminase (PAD4) Elastase Myeloperoxidase (MPO) Phagocyte oxidase

Question 72

This cytokine is responsible for intravascular thrombosis & cachexia.

Answer 72

TNF

Question 73

Cytokine for septic shock outcome prediction.

Answer 73

TNF

Question 74

Cytokines in autoimmune diseases.

Answer 74

TNF IL-1 IL-6 IL-12

Question 75

Name 4 mechanisms in limiting innate immune response.

Answer 75

IL-10 IL-1RA Autophagy genes Negative regulatory signalling pathway

Question 76

() are inhibitors of JAK-STAT signalling pathways linked to cytokine receptors.

Answer 76

Suppressors of cytokine signalling (SOCS) proteins

Question 77

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

Answer 77

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