Innate immunity (L6)

Question 1

What are the main differences between adaptive and innate immunity?

Answer 1

Adaptive- generates large numbers of different antibodies, each of which has a very high affinity to very specific targets identified by a previous contact with the pathogen
Innate- no memory

Question 2

What is recognised by c-type lectins?

Answer 2

Two adjacent C-OH groups

Question 3

What is recognised by CRP?

Answer 3

The phosphocholine head-group of membrane phospholipids

Question 4

What is the complement?

Answer 4

A protein cascade that is major defence and clearance system in the bloodstream. Composed of a cascade of sequentially activated, distinct plasma proteins. Highly evolved

Question 5

What are C-type lectins?

Answer 5

Include MBL and lung surfactant proteins A and D which recognise carbohydrate on the surface of invading pathogens

Question 6

What are C-reactive proteins?

Answer 6

The prototypic acute-phase reactant whith huge increases in serum concentration following tissue infection or injury. Recognition includes phospholipids on pathogens and damaged self cells

Question 7

What are the pathways of compliment activation?

Answer 7

Classical, alternative and lectin

Question 8

How is the classical pathway activated?

Answer 8

Activated by C1 binding to immune complexes including antibodies and C-reactive protein.

Question 9

How is the alternative pathway activated?

Answer 9

Triggered by susceptible foreign surfaces such as bacteria and yeast cell walls. Involved binding of C3

Question 10

How is the lectin pathway activated?

Answer 10

Initiated by lectin binding to carbohydrate on microbial surfaces

Question 11

What is the structure of the C1 complex?

Answer 11

Composed of C1q and the serine proteases C1r and C1s

Question 12

What is the structure of C1q?

Answer 12

Six subunits, each containing 3 polypeptide chains of 226 amino acids
Three chains form a collagen-like triple helix at the amino terminus and a globular C-terminal region

Question 13

What are the binding properties of C1q?

Answer 13

Recognises and binds opsonins
Binding site found in the globular head regions
Non-immune activators of the classical pathway usually bind to and activate via collagen-like tail
CRP binding site on C1q reported to be in the collagen-like region

Question 14

What is the crystal structure of ACRP30 fragment?

Answer 14

Homotrimer of beta-sandwich protomers each of which has a 10-strand jelly-roll folding topology

Question 15

What is the crystal structure of collagen X NC1 domain trimer?

Answer 15

Homotrimer of beta-sandwich protomers each of which has a 10-strand jelly-roll folding topology
Intersubunit contacts almost entirely hydrophobic near base of trimer and become progressively more hydrophillic towards top of trimer, forming a pronounced solvent-filled central channel

Question 16

What is the crystal structure of C1q trimer?

Answer 16

Smae overall fold as ACRP30 and collagen X NC1 domain trimer

C1q composed of 3 distinct chains

Question 17

What is the significance of the calcium ion in the C1q trimer?

Answer 17

The calcium ion is asymmetric relative to the trimer which involves chains A and B but not C
Coordinated by 6 oxygen ligands- AspB172, GlnA177, GlnB179, main chain carbonyl of TyrB173 and 2 waters

Question 18

What are the recognition properties of C1q?

Answer 18

Overlay of subunits-strong conservation of beta strands, significant variability in loops
Different charged and hydrophobic residues on surface

Question 19

What is the proposed interaction between C1q and IgG?

Answer 19

Possible interaction with the B subunit of C1q and suggests C1q binds not only to Fc region but also Fab arm
IgG b12 structure shows extreme interdomain flexibility so Fab binding interactions may be variable and may not apply to all IgG subtypes