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Module 2 > Innate Immunity and Bacterial Infection > Flashcards

Innate Immunity and Bacterial Infection Flashcards

1
Q

What is the modulat design of the innate immune system?

A

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

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2
Q

What are teh 2 functions of hte innate immune response?

A

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

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3
Q

What are the 3 main features of PAMPs?

A

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

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4
Q

What is the structure of the gram positive cell wall?

A

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

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5
Q

what is the structure of the gram negative cell wall?

A

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

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6
Q

What is the function of NOD1?

A

responds to peptidoglycan with modified aa mesoDAP

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7
Q

What type of bacteria does NOD1 generally recognise?

A

gram neg

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8
Q

What type of bacteria does NOD2 generally recognise?

A

both gram neg and gram positive

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9
Q

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

A

staphylococcus; streptococcus

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10
Q

What are the protections against extracellular bacteria at epithelial surfaces
‘

A

antimicrobial peptides; antibodies esp. IgA

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11
Q

How can intracellular pathogens be categoriesd?

A

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

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12
Q

What are exotoxins?

A

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

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13
Q

What are endotoxins?

A

nonsecreted constituents of bacterial structure taht triggers phagocytes to release cytokines

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14
Q

give an example of an important endotoxin?

A

LPS

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15
Q

What are the chemical barriers of epithleium in the skin?

A

beta-defensins; lamellar bodies; cathelicidin; fatty acids

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16
Q

What are the chemical barriers of epithelium in the gut?

A

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

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17
Q

What are the chemical barriers of lung epithelium?

A

pulmonary surfactant; alpha-defensins; cathelicidin

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18
Q

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

A

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

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19
Q

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

A

keratinocytes of hte stratum spinosum

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20
Q

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

A

lamellar bodies

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21
Q

What happens to the lamellar bodies in the skin?

A

secreted into the intercellular space to form a waterproof lipid layer

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22
Q

Which cells in the lung produce and secerete antimicrobial defensins?

A

type II pneumocytes

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23
Q

What cells in the intestine produce alpha defensins and RegIII?

A

paneth cells in the epithelial crypts

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24
Q

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

A

sitmulate the epithelial cells to produce antimicrobial peptides

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25
Q

What is mucin production in the gut related to?

A

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

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26
Q

How do antimicrobial peptides attack bacteria?

A

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

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27
Q

Describe the peptidoglycan polymer?

A

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

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28
Q

What is the function of teichoic acid and lipoteichoic acid?

A

links the pepptidoglycan layer to bacterial cell membrane

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29
Q

What is the structure of LPS?

A

lipid A which is attached to a polysaccharide cire

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30
Q

What is the function of lysozyme?

A

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

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31
Q

What type of bacteria is lysozyme more effective against?

A

gam positive (greater accessibility to peptidoglycan)

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32
Q

What is the function of secretory phospholipase A2?

A

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

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33
Q

Give examples of antimicrobial enzymes?

A

lysozyme and secretory phosspholipase A2

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34
Q

What are the main classes of antimicrobial peptide?

A

defensins; cathelicidins; histatins

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35
Q

What is an amphipathic structure?

A

positively charged region separated from a hydrophobic region

36
Q

What is the structure of defensins?

A

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

37
Q

What is the mechanism of action of defensins?

A

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

38
Q

Which chromosome encodes most defesins?

A

8

39
Q

What are the 3 subfamilies of defensin?

A

a; b and theta

40
Q

How are the subfamilies of defensin differentiated?

A

basis of amino acid sequence

41
Q

What are the a-defensins produced by paneth cells?

A

cryptdins

42
Q

What cells constitutively produce cathelicidins?

A

neutrophils and macrophages

43
Q

How are all the antimicrobial peptides generated?

A

proteolytic processing from inactive propeptides

44
Q

What are defensins stored in in neutrophils?

A

primary granules

45
Q

what are cathelicidins in neutrophils stored in?

A

secondary granules

46
Q

What cleaves cathelicidins in neutrophils?

A

neutrophil elastase from primary granules in phagosomes

47
Q

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

A

C-type lectins require calcium

48
Q

What is the function of RegIII?

A

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

49
Q

what cytokine induces the synthesis of acute phase proteins?

A

IL-6

50
Q

What is the function of CRP released by the liver?

A

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

51
Q

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

A

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

52
Q

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

A

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

53
Q

What is the function of the acute phase response?

A

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
Q

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

A

multicellular parasites

55
Q

What is the defense strategy against multicellular parasites?

A

preventing entry and promoting expulsion

56
Q

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

A

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

57
Q

What happens upon PRR stimulation of DCs?

A

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

58
Q

What is tthe function of Th1 cells?

A

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

59
Q

What is the function of Th2 cells?

A

helminiths; allergic inflammation

60
Q

What is hte function of th9 cells?

A

mucous production and tissue inflammation

61
Q

What is the function of Th17 cells?

A

extracellular pathogens

62
Q

What is the function of Th22 cells?

A

tissue inflammation

63
Q

What is the differentation cyyokine of Th1 cells?

A

IL-12

64
Q

What is the differentiation cytokine of Th2 cells?

A

IL-4

65
Q

What is the differentiation cytokine of Th9 cells?

A

IL-4 and TGF-beta

66
Q

What is the differentiation cytokine of TH17 cells?

A

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

67
Q

What is the differentiation cytokine of Th22 cells ?

A

TNFa and IL-6

68
Q

What are the effector cytokines of Th1 cells?

A

IFNy

69
Q

What are the effector cytokines of Th2 cells?

A

IL4; IL5; IL13; IL25; IL31 and IL33

70
Q

What are the effector cytokines of Th9 cells

A

IL9

71
Q

What are the effector cytokines of Th17 cells?

A

IL6; IL8; IL17; IL22; IL26

72
Q

What are the effector cytokines of Th22 cells?

A

IL22

73
Q

What cells do Th17 cells stimualte?

A

neutrophils

74
Q

What cells do Th1 cells stimualte?

A

macrophages

75
Q

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

A

colonization of hte epithelium

76
Q

What is the transmission of pneumococcal infection?

A

airborne droplets

77
Q

Where does pneumococcus colonise?

A

nasopharyngeal

78
Q

What happens when there is local spread of pneumococcus ?

A

otitis media/ sinusitis

79
Q

What happens when there is aspiration of pneumococcus ?

A

penumonia

80
Q

What happens when there is epithelial translocation of pneumococcus ?

A

septicaemia

81
Q

What happens when there is endothelial translocation of pneumococcus ?

A

meningitis

82
Q

What chemokines recruit neutrophils?

A

CXCL1/CXCL2

83
Q

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

A

downregulation of tight junctions to allow effector cells into lumen

84
Q

What happens if bacteria breach teh epithelium?

A

tissue resident cells kill bacteria

85
Q

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

A

Th17

86
Q

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

A

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

Module 2 (38 decks)

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