1. Basics: Innate Immunity

Question 1

what is innate immunity

Answer 1

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

Question 2

describe the specificity of the innate immune system

Answer 2

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

Question 3

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

Answer 3

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

Question 4

list 5 cells involved in innate immunity

Answer 4

neutrophil
macrophage
dendritic cell
eosinophil
natural killer cell

Question 5

when does the innate immune reaction begin

Answer 5

hours following invasion

Question 6

describe the anatomical barrier

Answer 6

the epithelial layer that lines skin, mucosal and glandular tissue

Question 7

name 2 mucosal tissues

Answer 7

respiratory and gastrointestinal tract

Question 8

name 2 glandular tissues

Answer 8

salivary and mammary glands

Question 9

what is the purpose of tight junctions

Answer 9

prevent pathogens penetrating the barrier between cells

Question 10

what are mucins

Answer 10

a glycoprotein that prevents pathogen adherence to epithelial cells

Question 11

name 2 purposes of mucus

Answer 11

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

Question 12

describe the composition of vaginal secretions

Answer 12

acidic pH mucus that provides protection against fungal and bacterial infections

Question 13

what maintains the acidic pH of the vagina

Answer 13

lactic acid released from commensal lactobacteria

Question 14

which layer of the skin forms the physical barrier

Answer 14

keratinocytes at the top layer

Question 15

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

Answer 15

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.

Question 16

name 2 antimicrobial proteins

Answer 16

lysozyme
lactoferrin

Question 17

where is lysozyme and lactoferrin found

Answer 17

in mucosal and glandular secretions

Question 18

how does lysozyme act

Answer 18

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

Question 19

how does lactoferrin act

Answer 19

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

Question 20

name 2 antimicrobial peptides

Answer 20

defensins
dermicidin

Question 21

where are defensins found

Answer 21

skin, mucosal epithelia

Question 22

how do defensins work

Answer 22

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

Question 23

where is dermicidin found

Answer 23

skin (from sweat glands)

Question 24

how does dermicidin work

Answer 24

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

Question 25

how does the microbiome layer protect the host from pathogens

Answer 25

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

Question 26

define phagocytosis

Answer 26

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

Question 27

name 3 types of phagocytes

Answer 27

neutrophils macrophages dendritic cells

Question 28

how are neutrophils different from macrophages

Answer 28

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

Question 29

name 3 roles of phagocytes

Answer 29

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

Question 30

where are PRRs found

Answer 30

on the surface, in the cytosol and on the endosome

Question 31

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

Answer 31

interferons cytokines chemokines

Question 32

what are interferons used in

Answer 32

viral infection

Question 33

what is the role of chemokines

Answer 33

recruit cells to the site of infection

Question 34

list 3 DAMPs

Answer 34

heat shock proteins DNA beta amyloid

Question 35

what does DAMPs stand for

Answer 35

damage-associated molecular patterns

Question 36

name the 2 membrane associated PRRs

Answer 36

toll-like receptors c type lectin receptors

Question 37

name 2 cytosolic receptors

Answer 37

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

Question 38

what is the ligand of TLR4

Answer 38

lipopolysaccharide (Gram -ve bacteria)

Question 39

which TLR detects gram +ve bacteria

Answer 39

TLR2 detects peptidoglycan in Gram +ve membranes

Question 40

which TLR detects ss viral RNA

Answer 40

TLR7

Question 41

what is the outcome of TLR signalling

Answer 41

NF-kB activation

Question 42

what is NF-kB

Answer 42

a transcription factor that drives production of cytokines

Question 43

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

Answer 43

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

Question 44

what type of ligands to CLRs recognise

Answer 44

carbohydrate ligands

Question 45

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

Answer 45

kinase SYK and CARD9 = result in the production of pro-inflammatory cytokines and ROS

Question 46

where are CLRs typically expressed

Answer 46

on macrophages or DCs

Question 47

what are NLRs most highly expressed by

Answer 47

macrophages

Question 48

what do NLRs require

Answer 48

inflammasome activity

Question 49

name 4 proinflammatory cytokines

Answer 49

IL-1 beta TNF- alpha IL-6 CXCL8

Question 50

how does TNF-alpha act

Answer 50

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

Question 51

what is the role of IL-6

Answer 51

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

Question 52

what is the role of CXCl8

Answer 52

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

Question 53

how does IL-12 act

Answer 53

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

Question 54

what does RLR signalling lead to

Answer 54

type 1 interferon production

Question 55

what does the cGAS-STING pathway sense

Answer 55

cytosolic DNA

Question 56

what are the two types of interferon signalling

Answer 56

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

Question 57

name 3 actions induced by IFNs

Answer 57

increase MHC class 1 expression and APC in all cells activate dendritic cells and macrophages activate NK cells to kill-virus infected cells

Question 58

what 2 types of gremline encoded receptors does NK cells possess

Answer 58

inhibitory receptors activating receptors

Question 59

what molecules do inhibitory receptors detect

Answer 59

self molecules, e.g. MHC 1 - When MHC I is down-regulated by viruses, this is detected as “missing self”.

Question 60

what molecules do activating receptors detect

Answer 60

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

Question 61

once activated what do NK cells release

Answer 61

granules containing performs and granzymes which kill the target cell

Question 62

what is the role of langerhans cells

Answer 62

resident phagocytes in the skin

Question 63

what causes autoinflammation

Answer 63

over-production of pro-inflammatory cytokines

Question 64

what causes interferonopathies

Answer 64

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