Innate Immunity

Question 1

physical barriers

Answer 1

intact skin
internal epithelium is lined with mucous and cilia preventing microbe binding

Question 2

why does cystic fibrosis lead to frequent

Answer 2

defective gene causes thick, sticky mucous which traps pathogens and is hard to remove from the lung

Question 3

which antimicrobial enzymes act as a chemical barrier
what do they do

Answer 3

lysozyme - break down peptidoglycan
phospholipase A2 - break down cell membrane

Question 4

what is the (immunological) effect of surfactants in the lung

Answer 4

important to maintain function
bind pathogens and make their removal by immune cells easier

Question 5

antimicrobial peptides and their function

Answer 5

defensins - modulate inflammation
cathelicidins - damage microbial membrane, inhibit DNA and protein synthesis
histatins: antifungal activity

Question 6

explain the microbiological barrier and give an example of what happens when its disrupted

Answer 6

competitive exclusion prevents colonisation of harmful bacteria
clostridium difficile infection

Question 7

what are the type of pattern recognition receptors
how are they encoded in the genome

Answer 7

phagocytic receptors
toll-like receptors
NOD-like receptors
RIG-I-like receptors
germline encoded - do not require somatic recombination

Question 8

ligands of these toll-like receptors:
TLR-3, -4, -5, -7, -8, -9

Answer 8

3: dsDNA
4: LPS
5: flagellin
7: ssRNA
8: ssRNA
9: CpG-ODN

Question 9

structure of TLRs

Answer 9

horseshoe like leucine rich domain that recognises ligand
transmembrane signal transduction
cytoplasmic TIR domain

Question 10

localisation of TLRs depending on target

Answer 10

localised on the cell membrane to recognise extracellular pathogens: bacteria
localised on the inside of the cell (on endosomes) to recognise intracellular pathogens: viruses

Question 11

what happens upon TLR activation

Answer 11

two TLRs dimerise and TIR domains are brought together - activation of enzyme activity
adaptor proteins activate kinases which lead to activation of transcription factors
gene expression of IL-6, TNFα, INFβ

Question 12

where are NOD-like receptors expressed and what do they recognise

Answer 12

expressed in the cytoplasm
sensors for intracellular bacteria

Question 13

NOD-like receptor activation

Answer 13

dimerization leading to kinase activity leading to expression of inflammatory cytokines

Question 14

diseases associated with NODs

Answer 14

Crohn’s disease
Blau syndrome

Question 15

RIG–like receptors localisation and target ligand

Answer 15

expressed in cytoplasm
sensors for cytoplasmic viral RNAs

Question 16

under the influence of cytokines, endothelial cells increase expression of what molecules into blood vessel lumens

Answer 16

selectins and ICAMs

Question 17

what is the consequence of selectin expression

Answer 17

capture and tethering of neutrophils to the vessel wall
‘selection’ of passing neutrophils

Question 18

what type of expressed molecules induce rolling

Answer 18

selectins
L-selectins on leukocyte
E-selectins on endothelium

Question 19

what molecules mediate firm adhesion of leukocytes to blood vessel walls and stop rolling

Answer 19

ICAM - Integrin binding
ICAM on endothelium
integrin on leukocyte

Question 20

what causes migration of adhered leukocytes through blood vessel wall during inflammation (after adhesion)

Answer 20

chemokines

Question 21

what are the systemic protective effects of cytokines in inflammation
which cytokines cause them

Answer 21

brain induces fever: TNF, IL-1, and IL-6
liver produces acute phase proteins: IL-1, IL-6
bone marrow increases leukocyte production: TNF, IL-1, IL-6

Question 22

what are the systemic pathological effects of cytokines in inflammation
what cytokine causes them

Answer 22

septic shock:
low cardiac output
thrombus formation and increased permeability in blood vessels
insulin resistance in multiple tissues

TNF

Question 23

which immune cells are involved in innate immunity

Answer 23

macrophages
dendritic cells
neutrophils
NK cells

Question 24

what are the key receptors used by macrophages

Answer 24

toll like receptors

Question 25

what is the process of phagocytosis

Answer 25

chemotaxis and adherence
ingestion of microbe into phagosome
fusion of phagosome with a lysosome - phagolysosome
digestion of microbe by enzyme forming residual body
discharge of waste

Question 26

what are the leukocytes to move to site of infection

Answer 26

neutrophils

Question 27

what is the function of neutrophils

Answer 27

kill microbes by releasing granules of degrading enzymes and ROS

Question 28

what disease results from impaired development of neutrophils
what is the result

Answer 28

severe congenital neutropenia
recurrent bacterial infections in various organs

Question 29

where does production of reactive oxygen and nitrogen species
why does it result in a respiratory burst

Answer 29

in the phagosome
results in a transient increase in oxygen consumption

Question 30

what is the effect of chronic granulomatous disease

Answer 30

mutation in NADPH causing granuloma formation due to inability to kill phagocytosed bacteria
presence of cytokines and increased susceptibility to infection

Question 31

what causes maturation of dendritic cells

Answer 31

mature in response to cytokines (infection)

Question 32

what is the role of dendritic cells
where are they located

Answer 32

antigen presentation triggering Ag-specific lymphocyte response
located at body surface and in the T-cell area of lymphoid organs

Question 33

where are NK cells developed and from what

Answer 33

bone marrow
lymphoid progenitor

Question 34

which cytokines activate NK cells

Answer 34

IFNα/β
IL-12/18

Question 35

what features and role of NK cells

Answer 35

two types of surface receptor (activating and inhibitory)
pre-formed cytosolic granules
kill infected or malignantly transformed cells