First Aid, Chapter 1 Immune Mechanisms, Innate Immunity and Toll-Like Receptors

Question 1

What are the innate mechanisms used on extracellular bacteria?

Answer 1

Complement activation Phagocytosis: Recognition by pattern recognition receptors (PRR)

Question 2

What are the innate mechanisms used on intracellular bacteria?

Answer 2

Nucleotide binding oligomerization domain-like receptors (NLRs)

Question 3

What are the innate mechanisms used on fungi?

Answer 3

Neutrophil phagocytosis Complement activation

Question 4

What are the innate mechanisms used on viruses?

Answer 4

Phagocytosis: Toll-like receptors (TLRs) and NK cells

Question 5

What are the innate mechanisms used on parasites?

Answer 5

Phagocytosis; Complement (alternative pathway)

Question 6

What is the difference in the genetics of innate immunity vs. adaptive immunity?

Answer 6

Innate immunity: Response encoded in host germ line DNA

Adaptive immunity: somatic gene rearrangement

Question 7

What does the innate immune system recognize in pathogens?

Answer 7

Recognize conserved sequences such as pathogen-associated molecular patterns (PAMPs)

Question 8

What does the adaptive immune system recognize in pathogens?

Answer 8

Recognize unique antigenic determinants: TCR and (MHC restricted-) Ig receptors

Question 9

What are the components of the innate immune system?

Answer 9

Complement Pattern recognition receptors (PRRs) on immune cells Phagocytes Mast cell or basophils NK cells

Question 10

What are the components of the adaptive immune system?

Answer 10

T lymphocytes, B lymphocytes, and complement

Question 11

What are antimicrobial peptides (AMPs)? What are they produced by?

Answer 11

AMP are ubiquitous cationic proteins that play a role in innate immunity. They provide defense against bacteria and fungi viruses. Produced by keratinocytes.

Question 12

What are the families of AMPs in humans?

Answer 12

Two families in humans:
o Human β defensins: HBD1, 2, 3
o Human cathelicidins: LL37 o Lactoferrins: hLF1-11
o Histatins

Question 13

How do AMPs work?

Answer 13

Interact with phospholipids of microbial membranes, enter cell and mediate antiproliferative effects

Question 14

Why are atopic dermatitis patients susceptible to staph aureas infections?

Answer 14

AMPs are decreased in a Th2 environment. Atopic dermatitis patients are susceptible to Staphylococcus aureus infection due to a decrease in AMP.

Question 15

What environment are AMPs decreased in?

Answer 15

Th2 environment.

Question 16

What is the function of neutrophils?

Answer 16

Phagocytosis and oxidative burst or free radical production

Question 17

What is the function of monocytes or macrophages?

Answer 17

Phagocytosis and secretion of proinflammatory cytokines

Question 18

What are two types of dendritic cells?

Answer 18

APCs (conventional) and antiviral (plasmacytoid)

Question 19

What are the functions of eosinophils?

Answer 19

Antihelminthic, antibacterial, and secretion of proinflammatory mediators or free radicals

Question 20

What are the functions of mast cells?

Answer 20

Antibacterial, antiviral, and secretion of proinflammatory cytokines

Question 21

What are the functions of basophils?

Answer 21

Antibacterial, antiviral, and secretion of proinflammatory cytokines

Question 22

What are the functions of NK cells?

Answer 22

Eliminates virus-infected cells and tumor cells (missing “self” hypothesis), and secretion of cytokines

Question 23

What are the function of intraepithelial lymphocytes?

Answer 23

Secretion of proinflammatory cytokines (phagocyte activation and killing of infected cells)

Question 24

What is the function of B-1 B lymphocytes?

Answer 24

Produce natural serum antibodies.

Question 25

What are PAMPs?

Answer 25

Pathogen associated molecular patterns (PAMPs) are conserved microbial sequences found on microorganims. Their strucutres are consistent and conserved.

Question 26

What are examples of PAMPs?

Answer 26

LPS on gran-negative bacteria on teichoic acid on gram on gram positive bacteria

Question 27

What are PRRs? Where are they found? What do they recognize?

Answer 27

Pattern recognition receptors on APCs (conventional dendritic cells, B lymphocytes, and macrophages). -PRRs identify PAMPs on microorganisms to detect infection.

Question 28

Name some pattern recognition receptors?

Answer 28

- fMLP (N-formyl met-leu-phe receptors) - CARD (Caspase activation and recruitment domains eg retinoic acid inducible gene-I-like receptors) - CLR C-type lectin receptors: mannose-binding lectin and macrophage mannose receptor) - NLR (Nucleotide-binding oligomerization domains NODs) - NACT-LRR and pyrin domain-containing proteins (NALPS) - TLR (toll-like receptors)

Question 29

Where are fMLP (N0formyl Met-Leu-Phe) receptors found? What class are they? What is their structure? What is their function?

Answer 29

- cell surface - signalling - G protein-coupled 7-transmembrane domain receptor - antibacterial

Question 30

Where are CARD (Caspase activation and recruitment domains eg retinoic acid inducible gene-l-like receptors) found? What class are they? What is their structure? What is their function?

Answer 30

-cytoplasm -signalling RNA helicase and caspase recruitment domains, component of inflammasome -cytoplasmic virus detection and to induce type 1 IFN production

Question 31

Where are CLRs (C-type lectin receptors mannose binding lectin and macrophage mannose receptors) found? What class are they? What is their structure? What is their function?

Answer 31

- Cell surface - secreted or endocytic - calcium-dependent carbohydrate binding domain - antifungal immunity

Question 32

Where are NLR or NACT-LRRs found? What class are they? What is their structure? What is their function?

Answer 32

- cytoplasm - signalling - c-terminal leucine-rich repeat and nucleotide-binding domain, central proteins of inflammasome - IL-1B and IL-18 secretion

Question 33

``` Where are TLRs found? What class are they? What is their function? ```

Answer 33

- cell surface and cytoplasm (TLR3) - signalling - antibacterial, antifungal, and antiviral immunity

Question 34

What is the inflammasome? What cytokines does it cause secretion of? What provides a platform for adaptor proteins SC and caspases to bind?

Answer 34

The inflammasome is multiprotein complex located in the cytoplasm that activates caspases 1 and 5, leading to production and secretion of IL-1 and IL-18. NALPs provide a platform to which the adaptor protein ASC and caspases bind

Question 35

What diseases are activating mutations in cold-induced autoinflammatory syndrome 1 (CIAS1) seen in?

Answer 35

Activating mutations in cold-induced autoinflammatory syndrome 1(CIAS1) is seen in Muckle-Wells syndrome (MWS), familial cold urticaria, and chronic infantile neurologic, cutaneous, and articular autoinflammatory disease (CINCA).

Question 36

Where are TLRs found?

Answer 36

TLRs are found on the cell surface or intracellularly. | -TLR 3, 7, 8, and 9 are found in the intracellular compartment and detect nucleic acids.

Question 37

What adapter protein plays a role in TLR signalling?

Answer 37

MyD88

Question 38

What is the ligand for TLR1? What is the source?

Answer 38

Ligand: lipoarabinomannan Source: mycobacteria

Question 39

What is the ligand for TLR2? What is the source?

Answer 39

Ligand: Zymosan Source: Fungi

Question 40

What is the ligand for TLR3? What is the source?

Answer 40

Ligand: dsRNA Source: Virus

Question 41

What is the ligand for TLR4? What is the source?

Answer 41

Ligand: Lipopolysaccharide, peptidoglycan, RSV fusion protein, and HSP (heat shock protein) 70 and HSP 90 Source: Gram-negative bacteria, gram-positive bacteria, RSV, and endogenous acute phase proteins

Question 42

What is the ligand for TLR5? What is the source?

Answer 42

Ligand: Flagellin Source: Flagellated bacteria

Question 43

What is the ligand for TLR6? What is the source?

Answer 43

Ligand: Diacyl lipopeptides Source: Mycoplasma

Question 44

What is the ligand for TLR7? What is the source?

Answer 44

Ligand: Imidazolquinolones Source: Synthetic

Question 45

What is the ligand for TLR8? What is the source?

Answer 45

Ligand: ssRNA Source: Virus

Question 46

What is the ligand for TLR9? What is the source?

Answer 46

Ligand: Unmethylated CpG (cytosine-phosphate-guanosine) motifs Source: Bacteria and DNA viruses

Question 47

What is the ligand for TLR10? What is the source?

Answer 47

Ligand and source: unknown

Question 48

What is the ligand for TLR11? What is the source?

Answer 48

Ligand: Profilin Source: Toxoplasma gondii

Question 49

What is signalling through MyD88 dependent pathways similar to?

Answer 49

Similar to signalling through IL-1.

Question 50

What TLR-signalling pathways are MyD88 involved in?

Answer 50

All except TLR3

Question 51

What is TLR3 signaling mediated through?

Answer 51

TLR3 signaling is mediated by the Toll-interleukin-1-receptor domain containing adapter-inducing interferon β (TRIF) and is MyD88 independent.

Question 52

What signaling pathways does TLR4 signal thorugh?

Answer 52

TLR4 can signal through both MyD88-dependent and -independent pathways (Figure 1-18).TLR 4 binds to lipopolysaccharide (LPS) via lipopolysaccharide-binding protein (LBP), MD2 (lymphocyte antigen 96), and CD14.

Question 53

What are TLR agonists 7 and 8 agonists? What are they used for?

Answer 53

TLR agonists, such as imiquimod (TLR 7) and resiquimod (TLR 7 and 8), are used topically for its antiviral and antitumor effects.

Question 54

What TLR mutations are associated with HSV1 encephalitis?

Answer 54

TLR 3, 7, 8, and 9

Question 55

What TLR mutations are associated with aspergillosis?

Answer 55

TLR4

Question 56

What TLR mutations are associated with adrenal insufficiency?

Answer 56

TLR 2, 4

Question 57

What innate signalling pathway mutations are associated with Crohn's disease or Blau's syndrome?

Answer 57

NOD2 (nucleotide oligomerization domain)

Question 58

What TLR mutation is associated with leprosy and TB?

Answer 58

TLR2

Question 59

What does IRAK4 or MyD88 deficieny cause?

Answer 59

Recurrent infections with pyogenic bacteria

Question 60

What does mutations in NEMO (NFkB essential modifier) cause?

Answer 60

Primary immune deficiency with infectious and mycobacterial susceptibilities

Question 61

Which TLR binds lipopolysaccharide (LPS) on gram-negative bacteria?

Answer 61

TLR4

Question 62

Which TLRs are present in the intracellular compartment and implicated in HSV1 encephalitis?

Answer 62

TLR 3, 7, 8, 9