Innate Immunity and Bacterial Infection Flashcards Preview

Module 2 > Innate Immunity and Bacterial Infection > Flashcards

Flashcards in Innate Immunity and Bacterial Infection Deck (86):
1

What is the modulat design of the innate immune system?

collection of mechanisms cobbled over time in response to a new mechanism of microbial virulence

2

What are teh 2 functions of hte innate immune response?

immediate, non-sepcific host defense; initiation of adaptive respose

3

What are the 3 main features of PAMPs?

invariant among microbes of a given class; products of pathways unique to microbes; essential roles in microbial physiology

4

What is the structure of the gram positive cell wall?

plasma membrane with thick layer of peptidoglycan with teichoic acid and lipoteichoic acid

5

what is the structure of the gram negative cell wall?

plasma membrane; thin layer of peptidoglycan; outer membrane with LPS

6

What is the function of NOD1?

responds to peptidoglycan with modified aa mesoDAP

7

What type of bacteria does NOD1 generally recognise?

gram neg

8

What type of bacteria does NOD2 generally recognise?

both gram neg and gram positive

9

What species of extracellular bacteria are protected by a polysaccharide capsule that resists engulfment?

staphylococcus; streptococcus

10

What are the protections against extracellular bacteria at epithelial surfaces
'

antimicrobial peptides; antibodies esp. IgA

11

How can intracellular pathogens be categoriesd?

those that replicate freely in the cell and those that replicate within intracellular vesicles

12

What are exotoxins?

secreted toxin released by extracellular bacterial pathogens that act at the surface of host cells

13

What are endotoxins?

nonsecreted constituents of bacterial structure taht triggers phagocytes to release cytokines

14

give an example of an important endotoxin?

LPS

15

What are the chemical barriers of epithleium in the skin?

beta-defensins; lamellar bodies; cathelicidin; fatty acids

16

What are the chemical barriers of epithelium in the gut?

low pH; enzymes eg pepsin; alpha-defensins (cryptdins); regIII(lecticidins); cathelicidin

17

What are the chemical barriers of lung epithelium?

pulmonary surfactant; alpha-defensins; cathelicidin

18

What are the chemical barriers of the eyes/nose/oral cavity epithelium?

enzymes in tears and saliva (lysoszyme); histatins; beta-defensins

19

Which cells in the skin produce beta-defensins and cathelicidin?

keratinocytes of hte stratum spinosum

20

What are beta-defensins and cathelicidins in the skin incorporated into?

lamellar bodies

21

What happens to the lamellar bodies in the skin?

secreted into the intercellular space to form a waterproof lipid layer

22

Which cells in the lung produce and secerete antimicrobial defensins?

type II pneumocytes

23

What cells in the intestine produce alpha defensins and RegIII?

paneth cells in the epithelial crypts

24

How do commensal microbes help strengthn the barrier functions of hte epithelia?

sitmulate the epithelial cells to produce antimicrobial peptides

25

What is mucin production in the gut related to?

microbial load e.g lots more microbes in colon than in stomach so colon has lots more mucin

26

How do antimicrobial peptides attack bacteria?

often positively charged and attracted to the plasma membrane of bacteria causing pore formation

27

Describe the peptidoglycan polymer?

alternating residues of beta (1,4) N-acetylglucosamine (GlcNAc); N-acetylmuramic acid (MurNAc) that are cross-linked by peptide bridges into a dense 3-D network

28

What is the function of teichoic acid and lipoteichoic acid?

links the pepptidoglycan layer to bacterial cell membrane

29

What is the structure of LPS?

lipid A which is attached to a polysaccharide cire

30

What is the function of lysozyme?

cleaves the beta (1,4) linkages creating a defect in the peptidoglycan layer and exposing the underlying cell membrane

31

What type of bacteria is lysozyme more effective against?

gam positive (greater accessibility to peptidoglycan)

32

What is the function of secretory phospholipase A2?

basic enzyme that enters the bacterial cell wall to hydrolyse phospholipids in the cell membraen

33

Give examples of antimicrobial enzymes?

lysozyme and secretory phosspholipase A2

34

What are the main classes of antimicrobial peptide?

defensins; cathelicidins; histatins

35

What is an amphipathic structure?

positively charged region separated from a hydrophobic region

36

What is the structure of defensins?

short cationic peptides that have 3 disulfide bonds stabilising a common amphipathic structre

37

What is the mechanism of action of defensins?

elecrostatic attraction of positive defensin to bilyaer then insertion of hydrophobic region into the membrnae bilayer and formation of a pore

38

Which chromosome encodes most defesins?

8

39

What are the 3 subfamilies of defensin?

a; b and theta

40

How are the subfamilies of defensin differentiated?

basis of amino acid sequence

41

What are the a-defensins produced by paneth cells?

cryptdins

42

What cells constitutively produce cathelicidins?

neutrophils and macrophages

43

How are all the antimicrobial peptides generated?

proteolytic processing from inactive propeptides

44

What are defensins stored in in neutrophils?

primary granules

45

what are cathelicidins in neutrophils stored in?

secondary granules

46

What cleaves cathelicidins in neutrophils?

neutrophil elastase from primary granules in phagosomes

47

What is the difference between lectins and C-type lectins?

C-type lectins require calcium

48

What is the function of RegIII?

produced by paneth cells and bind to peptidoglycan forming a pore (again, gram positive)

49

what cytokine induces the synthesis of acute phase proteins?

IL-6

50

What is the function of CRP released by the liver?

binds phophorylcholine on bacterial surfaces acting as an opsonin and activating complement

51

what is the function of mannon-binding lectin released by the liver?

binds mannose residues on bacterial surfaces, acting as an opsonin and activating complement

52

How do pulmonary surfactants A and D bind to pathogen surfaces?

through globular lectin-domains attached to a collagen-like stalk

53

What is the function of the acute phase response?

early in an infection provies the host proteins with many of hte functional properties of antibodies to bind and target for destruction, but without the specificity

54

What pathogens do mast cells and basophils play a role in host defense against?

multicellular parasites

55

What is the defense strategy against multicellular parasites?

preventing entry and promoting expulsion

56

What is hte function of histamine and prostaglandins b=produced by mast cell and basophils?

act on smooth muscle- coughing, sneezing and D&V; C-fibres- itch (expulsion of parasite)

57

What happens upon PRR stimulation of DCs?

upregulates costimulatory moelcules and stimulates cytokines that skew naive T cell differentation

58

What is tthe function of Th1 cells?

intracellular pathogens; apoptosis of tissue cells; activation-induced cell death

59

What is the function of Th2 cells?

helminiths; allergic inflammation

60

What is hte function of th9 cells?

mucous production and tissue inflammation

61

What is the function of Th17 cells?

extracellular pathogens

62

What is the function of Th22 cells?

tissue inflammation

63

What is the differentation cyyokine of Th1 cells?

IL-12

64

What is the differentiation cytokine of Th2 cells?

IL-4

65

What is the differentiation cytokine of Th9 cells?

IL-4 and TGF-beta

66

What is the differentiation cytokine of TH17 cells?

TGFb; IL-6; IL-21 and IL-23

67

What is the differentiation cytokine of Th22 cells ?

TNFa and IL-6

68

What are the effector cytokines of Th1 cells?

IFNy

69

What are the effector cytokines of Th2 cells?

IL4; IL5; IL13; IL25; IL31 and IL33

70

What are the effector cytokines of Th9 cells

IL9

71

What are the effector cytokines of Th17 cells?

IL6; IL8; IL17; IL22; IL26

72

What are the effector cytokines of Th22 cells?

IL22

73

What cells do Th17 cells stimualte?

neutrophils

74

What cells do Th1 cells stimualte?

macrophages

75

What is oten the first step in disease for pathogenic bacteria?

colonization of hte epithelium

76

What is the transmission of pneumococcal infection?

airborne droplets

77

Where does pneumococcus colonise?

nasopharyngeal

78

What happens when there is local spread of pneumococcus ?

otitis media/ sinusitis

79

What happens when there is aspiration of pneumococcus ?

penumonia

80

What happens when there is epithelial translocation of pneumococcus ?

septicaemia

81

What happens when there is endothelial translocation of pneumococcus ?

meningitis

82

What chemokines recruit neutrophils?

CXCL1/CXCL2

83

What effect does activation of DCs at the mucosal surface have on epithelial cells?

downregulation of tight junctions to allow effector cells into lumen

84

What happens if bacteria breach teh epithelium?

tissue resident cells kill bacteria

85

What T cells promote a more vigorous response at mucosal surfaces on re-encountering pathogen?

Th17

86

Why is there a suggestion that TLR signalling may be redundant in huamsn?

patients with homoxygous mutation in MyD88 or IRAK4 die only from infection of strep or staph in childhood, but no issues in adulthood