1. Basics: Innate Immunity Flashcards

1
Q

what is innate immunity

A

the primary response to pathogen invasion, components include both anatomical barriers as well as cellular responses

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2
Q

describe the specificity of the innate immune system

A

rather than recognise a specific pathogen - the innate immune system recognises classes of organisms

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3
Q

how are innate immune receptors encoded, what does this mean?

A

germline ended - means they are highly conserved and do not undergo random recombination unlike adaptive immunity receptors

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4
Q

list 5 cells involved in innate immunity

A

neutrophil
macrophage
dendritic cell
eosinophil
natural killer cell

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5
Q

when does the innate immune reaction begin

A

hours following invasion

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6
Q

describe the anatomical barrier

A

the epithelial layer that lines skin, mucosal and glandular tissue

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7
Q

name 2 mucosal tissues

A

respiratory and gastrointestinal tract

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8
Q

name 2 glandular tissues

A

salivary and mammary glands

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9
Q

what is the purpose of tight junctions

A

prevent pathogens penetrating the barrier between cells

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10
Q

what are mucins

A

a glycoprotein that prevents pathogen adherence to epithelial cells

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11
Q

name 2 purposes of mucus

A

chemical barrier containing natural antimicrobials
offers false binding sites for bacteria and viruses

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12
Q

describe the composition of vaginal secretions

A

acidic pH mucus that provides protection against fungal and bacterial infections

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13
Q

what maintains the acidic pH of the vagina

A

lactic acid released from commensal lactobacteria

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14
Q

which layer of the skin forms the physical barrier

A

keratinocytes at the top layer

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15
Q

describe an example of evolutionary resistance to epithelial barriers that has emerged in some pathogens

A

influenza A firmly attaches its surface glycoprotein (haemagglutinin A) to sialic acid expressed on the epithelial surface sialic acid receptor. This prevents it being swept out the respiratory tract by ciliated epithelial cells.

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16
Q

name 2 antimicrobial proteins

A

lysozyme
lactoferrin

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17
Q

where is lysozyme and lactoferrin found

A

in mucosal and glandular secretions

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18
Q

how does lysozyme act

A

cleaves glycosidic bonds of peptidoglycan in cell walls of bacteria = lysis

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19
Q

how does lactoferrin act

A

binds and sequesters iron = this limits the growth of bacteria and fungi

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20
Q

name 2 antimicrobial peptides

A

defensins
dermicidin

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21
Q

where are defensins found

A

skin, mucosal epithelia

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22
Q

how do defensins work

A

use electrostatic attraction to insert itself into the lipid bilayer where is can disrupt the membrane and act intraceullarly to kill cells and disable viruses

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23
Q

where is dermicidin found

A

skin (from sweat glands)

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24
Q

how does dermicidin work

A

produces channels in membranes that disrupt iron gradients = antibacterial & antifungal

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25
Q

how does the microbiome layer protect the host from pathogens

A

competition for space - commensal microbiota colonise a niche thus preventing pathogenic bacteria from gaining a foothold and producing toxins

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26
Q

define phagocytosis

A

the uptake of particulate materials (e.g. pathogens, dead cells) by a cell

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27
Q

name 3 types of phagocytes

A

neutrophils
macrophages
dendritic cells

28
Q

how are neutrophils different from macrophages

A

after phagocytosing neutrophils undergo cell death
macrophages and dendritic cells act as APCs after engulfing

29
Q

name 3 roles of phagocytes

A

kill pathogens and take up cell debris
detect PAMPs and secrete cytokines
act as APCs to activate B and T cells

30
Q

where are PRRs found

A

on the surface, in the cytosol and on the endosome

31
Q

PRRs activate signalling cascades, this leads to the production of what (3 things)

A

interferons
cytokines
chemokines

32
Q

what are interferons used in

A

viral infection

33
Q

what is the role of chemokines

A

recruit cells to the site of infection

34
Q

list 3 DAMPs

A

heat shock proteins
DNA
beta amyloid

35
Q

what does DAMPs stand for

A

damage-associated molecular patterns

36
Q

name the 2 membrane associated PRRs

A

toll-like receptors
c type lectin receptors

37
Q

name 2 cytosolic receptors

A

nucleotide-binding doman and leucine-rich repeat receptor (NOD-like receptor)

RIG-I like recetors

38
Q

what is the ligand of TLR4

A

lipopolysaccharide (Gram -ve bacteria)

39
Q

which TLR detects gram +ve bacteria

A

TLR2 detects peptidoglycan in Gram +ve membranes

40
Q

which TLR detects ss viral RNA

A

TLR7

41
Q

what is the outcome of TLR signalling

A

NF-kB activation

42
Q

what is NF-kB

A

a transcription factor that drives production of cytokines

43
Q

in response to viral protein TLR4 is activated, what does this in turn result in the production of

A

phosphorylation of IRF-3 or IRF-7 = result in the transcription of type 1 interferons

44
Q

what type of ligands to CLRs recognise

A

carbohydrate ligands

45
Q

once a CLR is activated, what kinase do they signal through? and what is the result?

A

kinase SYK and CARD9

= result in the production of pro-inflammatory cytokines and ROS

46
Q

where are CLRs typically expressed

A

on macrophages or DCs

47
Q

what are NLRs most highly expressed by

A

macrophages

48
Q

what do NLRs require

A

inflammasome activity

49
Q

name 4 proinflammatory cytokines

A

IL-1 beta
TNF- alpha
IL-6
CXCL8

50
Q

how does TNF-alpha act

A

induces blood vessels to become more permeable - allowing effector cells to enter infected tissue

51
Q

what is the role of IL-6

A

induces fat and muscle cells to metabolise = creates heat and raises the temp of the infected tissue

52
Q

what is the role of CXCl8

A

recruits neutrophils from the blood guiding them to the site of infection

53
Q

how does IL-12 act

A

recruits and activates NK cells
- these cells further produce cytokines to enhance the macrophages response to infection

54
Q

what does RLR signalling lead to

A

type 1 interferon production

55
Q

what does the cGAS-STING pathway sense

A

cytosolic DNA

56
Q

what are the two types of interferon signalling

A

autocrine (acting on the same cell)
paracrine (neighbouring cell)

57
Q

name 3 actions induced by IFNs

A

increase MHC class 1 expression and APC in all cells

activate dendritic cells and macrophages

activate NK cells to kill-virus infected cells

58
Q

what 2 types of gremline encoded receptors does NK cells possess

A

inhibitory receptors

activating receptors

59
Q

what molecules do inhibitory receptors detect

A

self molecules, e.g. MHC 1

  • When MHC I is down-regulated by viruses, this is detected as “missing self”.
60
Q

what molecules do activating receptors detect

A

detect MIC-A and MIC-B expressed on epithelial cells that have detected a virus , “altered self”

61
Q

once activated what do NK cells release

A

granules containing performs and granzymes which kill the target cell

62
Q

what is the role of langerhans cells

A

resident phagocytes in the skin

63
Q

what causes autoinflammation

A

over-production of pro-inflammatory cytokines

64
Q

what causes interferonopathies

A

over-production of type 1 interferons by the innate immune system

65
Q
A