Lecture 2 Flashcards
What are the general principles of innate immunity
- 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
What are barriers and what do they consist of
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
What are the advantages of keratinized skin
It is generally impermeable, it covers the outer surface of our body and is a good barrier to infection (unless it becomes compromised)
What do keratinocytes produce
They produce keratin which isn’t degraded by microbial enzymes
What do secretory glands do and example
They secrete sebum which contains fatty acids, defensins (antimicrobial peptides such as cathelicidin and LL-37) which disrupt membrane integrity.
How do commensals protect against pathogens
The microbiome helps protect the body against infection using pathogens.
How does mucous membrane protect against pathogens
Mucous is secreted from stratified squamous cells and coat mucosal surfaces to trap microbes. Cilia then waft away the mucous
How big is the mucous membrane
It’s the largest interface with the environment (200-300 square metres) and is semi/selectively permeable.
How do pre-formed mediators protect against pathogens
They can induce inflammation or recruit innate immune cells.
What does lysozyme do
Lysozyme present in secretions such as tears acts by cleaving a bond in peptidoglycan
Structure of antimicrobial peptides
B-sheet core structure stabilized by 3 conserved intramolecular disulphide bonds
Alpha forms are preforms/ Beta forms are synthesised de novo
How do antimicrobial peptides help defend against pathogens
They’re cationic and disrupt lipid layers in bacteria, fungi and enveloped viruses
Structure of defensins
Defensins range in length from 29-47 amino acids.
What is complement
An ancient defence mechanism, discovered as a heat-sensitive substance that complemented antibodies in killing bacteria.
Where is complement present
Present in serum
What does complement consist of
> 20 soluble proteins found in blood and other body fluids
What’s the order of the classical pathway
C1, C4, C2, C3, 5, 6, 7, 8, 9
What is the central event of complement activation
C3 -> C3b + C3a
Cleavage of C3 exposes a reactive thioester in c3b which can bind covalently to adjacent proteins/ carbohydrates
What are the 3 pathways of complement activation to generate c3 convertase
Classical pathway (antibody binding)
Mannose-binding lectin pathway (MBL binding to mannose)
Alternative binding
Whats the C3 convertase in classical and MBL pathway
C4bC2a
What’s the C3 convertase in the alternative pathway
C3bBb
What happens in the alternative pathway
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
What does C3a do
Triggers Ca2+ influx which facilitates extraversion acute phase reactants which circulate in the blood stream
What is MAC (membrane attack complex)
MAC is a destructive pore in the membrane that allows lysosomes to enter
What can C5a do
Recruits phagocytes and induces inflammation aka, chemoattractants “anaphylatoxins”.
C5a/c3a can also act on local blood vessels, increasing blood flow, permeability and phagocyte adhesion
What does C3b do
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
What does C5b-C9 do and the disadvantage
Forms the membrane attack complex leading to lysis.
Not as effective against gram positive (complement components can’t penetrate)
What does carboxypeptidase N inactivate
C3A and C5A
What does factor H inhibit
Alternative pathway
What does C1 inhibitor inactivate
C1
