Lec 2 - Innate Immunity

Question 1

Describe the 3 ways in which phagocytes can recognise pathogens

Answer 1

• antibodies bound to pathogens & recognition of their Fc receptors - via complement (eg C3b) bound to pathogens - PRRs recognising PAMPs

Question 2

What are PAMPs? Give examples

Answer 2

• conserved and common to many microbes - allow immune system to recognise self and non self cells - are vital to the pathogen therefore can’t mutate to avoid the immune system - eg bacteria -> LPS (Gram -ve), flagellins, unmethylted CpG DNA, formylated proteins, viruses = dsRNA

Question 3

Describe the 3 results of PRRs binding to PAMPs

Answer 3

phagocytosis chemotaxis signalling

Question 4

What are the main PRRs involved in initiating phagocytosis?

Answer 4

• C type lectins (macrophage mannose receptors) - CD14/LPS receptors - scavenger receptors

Question 5

What is the job of chemotactic receptors on phagocytes?

Answer 5

• bind chemoattractants - move phagocyte to the site of infection by moving along a CA diffusion gradient

Question 6

What is the structure of chemotactic receptors?

Answer 6

have 7 transmembrane helical domains - GPCRs that bind G proteins (chemoattractants)

Question 7

Give an example of a chemoattractant and its receptor

Answer 7

C5a = CA and neutrophils have C5a receptor

Question 8

What happens when a chemoattractant binds to a GPCR?

Answer 8

• release of chemotaxis mediator - production of ROS and RNS

Question 9

Where are Toll Like Receptors and what are they?

Answer 9

found on either cell surfaces or endosomes they sense the presence of microbes - do not phagocytose them

Question 10

Draw the strucure of a TLR

Answer 10

Question 11

Dimerisation of the TLR induces the expression of _____ and ______

Answer 11

inflammatory cytokines AND interferons

Question 12

Describe the sequence of events during phagocytosis

Answer 12

Question 13

Give 5 examples of bacteriocidal agents that are released into the phagosome

Answer 13

• acidification (bacteriocidal)
• lysozymes (break down peptidoglycan)
• ROS (superoxide, hydroxyl radical)
• RNS
• antimicrobial compounds (defensins)

Question 14

Describe the process (including the names of the enzymes invovled) in producing ROS following respiratory burst after phagocytosis

Answer 14

• respiratory burst due to activation of the membrane bound NADPH oxidase (in phagolysosome membrane)
• O2 -> superoxide (O2-)
• superoxide dismutase then converts O2- to H2O2
• peroxidase (+ Fe) convert H2O2 to hydroxyl radicals and hypochlorite ions (OCl-)

Question 15

Describe how RNS are produced

Answer 15

• inducible NO synthase convert Arg + O2 (from respiratory burst) into NO + citrulline
• NO can kill pathogens but are also precursors for other RNS such as nitrite

Question 16

How have some bacteria (eg E. coli and Y. pestis) mutated so they can resist NO?

Answer 16

• have flavohaemoglobin so can convert NO to nitrates

Question 17

What are NETs that are made by neutrophils?

Answer 17

Neutrophil Extracellular Traps

• DNA (chromatin) that contain antimicrobials (defensins) that are thrown over pathogens following NETosis

Question 18

Draw a diagram that shows how NK cells recognise altered self cells (MHC-I etc)

Answer 18