Innate immunity L4

Question 1

PAMPS

Answer 1

pathogen associated molecular patterns
highly conserved and common across species - not present on human cells
examples
- mannose
peptidoglycan
viral DNA
LPS in gram -ve bacteria
liptoteichoic acid - gram +ve bacteria
unmethylated CpQ DNA - base genetic material in bacteria
dsRNA - virus
glucans - fungi

Question 2

DAMPS

Answer 2

damage by pathogen to host cells, indication tissue damage or tissue, or can be released by dying tissues

Question 3

PRRs

Answer 3

pattern recognition receptors that recognise PAMPs and DAMPS, found on all innate cells and can be either intracellular or extracellular.

• detect danger and amplification for immune response

Question 4

complement system

Answer 4

proteins in the blood that complement the immune system to help recognise danger/pathogens and link adaptive and innate
- 3 pathways

Question 5

classical pathway

Answer 5

adaptive - responds to antigen/antibody complex causing C3 cleavage

Question 6

lectin pathway

Answer 6

innate
responds to carbohydrates on pathogens like mannose

Question 7

alternative pathway

Answer 7

spontaneous hydrolysis of C3

Question 8

c3b

Answer 8

binds to amino acids and hydroxyls only found on pathogen - not host
- self amplification loop
- labels pathogens for phagocytosis - opsonisation
- causes cleavage of C5

Question 9

c3a + c5a

Answer 9

circulates blood and recruits neutrophils and monocytes to infection site causing inflammation

Question 10

c5b

Answer 10

cleaved by c3b, causes membrane attack pores forming to cause lysis

Question 11

phagocytosis

Answer 11

occurs after detection used as a killing mechanism to digest and break down cells by lysosomes, can then become APC

• SAMPLES THE ENVIRONMENT FOR MICROBES

macrophages, neutrophils = innate
Dendritic cells = adaptive

Question 12

macrophages

Answer 12

dont move from infection site
killing pathogens and become APC to activate T cells at infection site

when resting, mop up debris and surveys environment, and found in all barrier tissues, scan for danger via PRRs

Question 13

dendritic cell

Answer 13

migrate from infection site to LN to activate T cells at LN, does not kill cells though.

Question 14

first danger signal = tissue damage

Answer 14

DAMPS secreted from stressed/damaged or dead host cells, indicate that there is a potential break in barriers, detected via PRRs

cause macrophage activation

Question 15

2nd danger signal - PAMPs

Answer 15

these are detected also by PRRs causing activation of innate system

Question 16

examples of PAMPS

Answer 16

conserved molecules
- gram -ve = LPS in wall
- lipoteichoic acid in gram +ve
- flagellin - flagella
- unmethylated CpG DNA - genetic bacterial material
- dsRNA = virus
gluons / chitin = fungi

Question 17

avoid pathogen recognition by PRRs

Answer 17

change or modify their PAMPS
- salmonella change LPS to reduce ability to active PRRs

ebola virus inhibits PRR signalling pathway

Question 18

macrophage red alert characteristics

Answer 18

increased size
enhanced phagocytosis
releasing toxic material
better killer
releasing pro-inflammatory cytokines - TNF-alpha

Question 19

resting state - surveillance mode

Answer 19

macrophage clearing debris, low presence of DAMPS/PAMPS and low cytokines and no T cell activation

Question 20

yellow alert - early activation and recognising danger

Answer 20

macrophages recognise DAMPS/PAMPS as increase via PRRs, increasing activity
releasing cytokines to amplify inflammatory respond
becoming PAC to activate T cells and await to see if this is a pathogenre

Question 21

red alert - full activation

Answer 21

fully activated macrophages - pathogen clearance and immune signalling
DAMPS/PAMPs high level
lots of cytokines released to recruit cells
T cells activated and adaptive response triggers

Question 22

pro-inflammatory cytokine - TNF-ALPHA

Answer 22

secreted by macrophage in red alert to recruit immune cells like neutrophils and NK from blood to infection site and activate cells for fighting infection
- stimulates production of acute phase proteins - CRP

Question 23

signs of inflammation

Answer 23

tissue redness and swelling - immune cell infiltration and increased blood flow

heat and fever, increased metabolic activity and immune response

Question 24

neutrophils

Answer 24

recruited from blood to infection site driven by TNF-A

phagocytosis, released cytokines and ROS to kill and form pus

very short lived

Question 25

NK

Answer 25

recruited from blood to infection site via TNF-A release cytokine like IFN-Y to activate macrophages and enhance them and kills cells either apoptoses or revert back to resting

Question 26

getting rid of inflammation

Answer 26

as pathogens are killed, decrease in DAMPS/PAMPs so less activation of macrophages by PRRSs, less TNF-A cytokine, less recruitment of cells to infection, less IFN-Y produced, less activation whole feedback loop to slow down and resolve inflammation - if this doesn't then septic shock can occur

Question 27

advantages of innate

Answer 27

rapid response and always present/on one cell has multiple PRRs so can respond to multiple pathogens simultaneously all innate cells have PRRS, so lots of cells to respond to infection detecting evolutionary conserved regions PAMPs so hard for pathogens to evade this can identify the type of microbe it is from virus to bacteria etc due to PAMPS

Question 28

disadvantages of innate

Answer 28

lack of specificity and general response non-adaptive as receptors encoded in germ-line, cannot adapt to novel pathogens no immune memory