Lecture 2

Question 1

What are the general principles of innate immunity

Answer 1

• It’s the oldest form of immunity
  -It’s always available (no memory)
• It’s a major form of immunity in young children
  -It’s crucial in initiating and directing adaptive immune responses

Question 2

What are barriers and what do they consist of

Answer 2

Barriers are the initial defence in innate immunity.
They are part of the bodies interface with the environment.
Tight junctions link epithelial cells to mucosal surfaces and prevent bacteria from entering

Question 3

What are the advantages of keratinized skin

Answer 3

It is generally impermeable, it covers the outer surface of our body and is a good barrier to infection (unless it becomes compromised)

Question 4

What do keratinocytes produce

Answer 4

They produce keratin which isn’t degraded by microbial enzymes

Question 5

What do secretory glands do and example

Answer 5

They secrete sebum which contains fatty acids, defensins (antimicrobial peptides such as cathelicidin and LL-37) which disrupt membrane integrity.

Question 6

How do commensals protect against pathogens

Answer 6

The microbiome helps protect the body against infection using pathogens.

Question 7

How does mucous membrane protect against pathogens

Answer 7

Mucous is secreted from stratified squamous cells and coat mucosal surfaces to trap microbes. Cilia then waft away the mucous

Question 8

How big is the mucous membrane

Answer 8

It’s the largest interface with the environment (200-300 square metres) and is semi/selectively permeable.

Question 9

How do pre-formed mediators protect against pathogens

Answer 9

They can induce inflammation or recruit innate immune cells.

Question 10

What does lysozyme do

Answer 10

Lysozyme present in secretions such as tears acts by cleaving a bond in peptidoglycan

Question 11

Structure of antimicrobial peptides

Answer 11

B-sheet core structure stabilized by 3 conserved intramolecular disulphide bonds
Alpha forms are preforms/ Beta forms are synthesised de novo

Question 12

How do antimicrobial peptides help defend against pathogens

Answer 12

They’re cationic and disrupt lipid layers in bacteria, fungi and enveloped viruses

Question 13

Structure of defensins

Answer 13

Defensins range in length from 29-47 amino acids.

Question 14

What is complement

Answer 14

An ancient defence mechanism, discovered as a heat-sensitive substance that complemented antibodies in killing bacteria.

Question 15

Where is complement present

Answer 15

Present in serum

Question 16

What does complement consist of

Answer 16

> 20 soluble proteins found in blood and other body fluids

Question 17

What’s the order of the classical pathway

Answer 17

C1, C4, C2, C3, 5, 6, 7, 8, 9

Question 18

What is the central event of complement activation

Answer 18

C3 -> C3b + C3a

Cleavage of C3 exposes a reactive thioester in c3b which can bind covalently to adjacent proteins/ carbohydrates

Question 19

What are the 3 pathways of complement activation to generate c3 convertase

Answer 19

Classical pathway (antibody binding)

Mannose-binding lectin pathway (MBL binding to mannose)

Alternative binding

Question 20

Whats the C3 convertase in classical and MBL pathway

Answer 20

C4bC2a

Question 21

What’s the C3 convertase in the alternative pathway

Answer 21

C3bBb

Question 22

What happens in the alternative pathway

Answer 22

C3 is cleaved into C3a and C3b. C3b is either rapidly degraded, however, in the presence of LPS, it binds to it and becomes stable.
It then binds to factor B which is cleaved by factor D resulting in c3bBb
This is then converted into C5 convertase by properdin.
C5 is then cleaved to C5a and C5b.
C6 and C7 then bind to form C5bC6C7.
C8 and C9 then bind to form MAC

Question 23

What does C3a do

Answer 23

Triggers Ca2+ influx which facilitates extraversion acute phase reactants which circulate in the blood stream

Question 24

What is MAC (membrane attack complex)

Answer 24

MAC is a destructive pore in the membrane that allows lysosomes to enter

Question 25

What can C5a do

Answer 25

Recruits phagocytes and induces inflammation aka, chemoattractants “anaphylatoxins”.
C5a/c3a can also act on local blood vessels, increasing blood flow, permeability and phagocyte adhesion

Question 26

What does C3b do

Answer 26

Promotes opsonisation
Pathogens coated with C3b are recognised by phagocytes with C3b receptors facilitating binding and phagocytosis.

On it’s own it can promote phagocytosis of bacteria or fungi

Question 27

What does C5b-C9 do and the disadvantage

Answer 27

Forms the membrane attack complex leading to lysis.
Not as effective against gram positive (complement components can’t penetrate)

Question 28

What does carboxypeptidase N inactivate

Answer 28

C3A and C5A

Question 29

What does factor H inhibit

Answer 29

Alternative pathway

Question 30

What does C1 inhibitor inactivate

Answer 30

C1