2. innate immunity: soluble effectors

Question 1

what is innate immunity?

Answer 1

1st line defence against infection
present at birth, passed form generation
occurs within minutes of pathogen recognition (rapid)

Question 2

innate immunity memory

Answer 2

present in plants, invertebrates, vertebrates

epigenetic modification

Question 3

epigenetic modification

Answer 3

innate immunity memory 
histone modification 
DNA methylation 
modification miRNA 
long-noncoding RNA expression

Question 4

physical innate barriers to infection

Answer 4

skin
respiratory tract
gastrointestinal tract

Question 5

soluble innate barriers to infection

Answer 5

complement
defensives
collectins

Question 6

induced innate barriers to infection

Answer 6

innate immune cells
pattern recognition receptors (PRRs)
interferon

Question 7

what happens when tissue is damaged?

Answer 7

causes release of vasoactive and chemotactic factors, triggering local increase in blood flow and capillary permeability
permeable capillaries allow an influx of fluid (exudate) and cells
phagocytes migrate to site of inflammation
phagocytes and antibacterial exudate destroy bacteria

Question 8

soluble innate immune molecules

Answer 8

enzymes (lysozymes)
antimicrobial peptides
collectins, ficolins, pentraxins
complement components

Question 9

lysozyme actions

Answer 9

secreted by phagocytes and paneth cells from small intestine
most effective against Gram+ bacteria
cleaves bond between alternating sugars making up peptidoglycan wall
leaves bacteria lipid bilayers exposed and vulnerable

Question 10

antimicrobial peptides

Answer 10

histacins
defensins
cathelicidins
cover epithelial surfaces
kill bacteria in minutes (disrupt membrane)
secreted by neutrophils, epithelial cells, paneth cells
inhibit DNA and RNA synthesis

Question 11

histatins

Answer 11

antimicrobial peptides
produced in oral cavity
active against pathogenic fungi, eg. candida albicans

Question 12

cathelicidins

Answer 12

antimicrobial peptides
LL-37
broad spectrum
against gram negative and positive bacteria

Question 13

defensins

Answer 13

2 classes: alpha and beta
35-40aa amphipathic peptides
stabilised by disulphide bonds
disrupt microbial membranes (not of host)

Question 14

collectins

Answer 14

globular lectin-like heads
bind bacterial cell surface sugars
sialic acid cleaves mannose antigens on host cells

Question 15

ficolins

Answer 15

recognises acylated compounds (COCH3)

eg n-acetylglucosamine, monosaccharide in bacterial cell walls

Question 16

pentraxins

Answer 16

cyclic multimeric proteins found in plasma

Question 17

c-reactive protein (CRP)

Answer 17

used as clinical measure of inflammation

Question 18

actions of collectins, ficolins and pentraxins

Answer 18

soluble pattern recognition receptors (PRRs)
act as opsonins that bind pathogens and infected cells
targets cells for phagocytosis
activate complement through classical pathway/lectin pathway

Question 19

complement system

Answer 19

series over 30 proteins - constantly circulate in blood and fluids and bathe body tissues
detect presence of foreign material - initiate cascade which amplify signal
cooperate with other host defence systems to generate inflammation and rapidly remove pathogen

Question 20

complement components

Answer 20

circulate as pro-form in blood
some have proteolytic activity
on activation, split into small and large fragments - triggers amplification cascade
normally ‘a’ is small fragment, except c2a

Question 21

classical pathway

Answer 21

initiated by c1 activation
antibody:antigen complex
c1 = complex of 3 proteins (c1q, c1r, c1s)

Question 22

classical pathway activation

Answer 22

triggered when c1 binds to Fc region of antibody-antigen complex
c1 must bind at least 2 Fc domains
IgM most effective (IgG1 and IgG3 also, when close together)

Question 23

why is IgM most efficient at activating complement?

Answer 23

has 5 Fc domains

Question 24

serum IgM

Answer 24

cannot bind c1
has planar conformation
shape changes on binding to antigen, reveals binding site for c1q

Question 25

classical pathway amplification

Answer 25

binding c1q with Fc domain causes conformational change in c1r
c1s is cleaved - can active ate c2 and c4 splitting into large/small fragment
c3 convertase can activate over 200 c3 molecules
c4b, c2a and c3b form c5 convertase to activate c5

Question 26

lectin pathway

Answer 26

antibody independent, activated by ficolins and mannose binding lectin (MBL)
MBL binds mannose residues
similar downstream mechanism to classical pathway
upon binding, MBL forms complex with MASP-1 and MASP-2
activate complex cleaves C2 and C4

Question 27

alternative pathway

Answer 27

c3 spontaneously hydrolyses
c3b binds to cell and factor B
susceptible to cleavage by factor D to Bb
C3bBb can hydrolyse more C3 to create more C3b

Question 28

membrane attack complex (MAC)

Answer 28

final product of complement cascade
forms a poor that inserts into membrane
allows diffusion or ions and small molecules
water moves into cell, killing it
human cells have soluble and cell surface associated proteins that prevent MAC formation