innate immune defences and inflammation

Question 1

What is innate immunity

Answer 1

• The first line of defence against infection
• present at birth and passed down genetically
• occurs within min of pathogen recognition

Question 2

What are some innate barriers to infection

Answer 2

Physical: skin, resp tract, GI tract

soluble: complement, defensins and collectins
induced: innate immune cells, PRR’s, interferon

Question 3

What is the role of defensins

Answer 3

They insert themselves into membranes and form pores

Question 4

List some soluble innate immune molecules

Answer 4

lysozymes: most effective against Gram+ bac

antimicrobial peptides: disrupt microbial membranes

collectins, ficolins and pentraxins: bind to pathogens and targets them for phagocytosis and activate complement

complement components: lyse bac, opsonise bac and induce inflammation

Question 5

List 3 antimicrobial peptides and their functions

Answer 5

Histatins: produced in oral cavity and fight against pathogenic fungi

cathelicidins: broad spec anti bac properties

defensins, 2 classes, alpha and beta

Question 6

What are collectins

Answer 6

innate immune molecules that have globular lectin heads that bind to bac cell surface sugars

Question 7

What are ficolins

Answer 7

innante immune molecules, monosaccharides found in bac cell- walls

Question 8

What are pentraxins

Answer 8

innate immune molecules, cyclic multimeric proteins in the plasma e.g. CRP, which is used as a clinical measure of inflammation

Question 9

What are the 3 complement pathways and where do they all converge

Answer 9

Classical pathway, lectin pathway and alternative pathway, they all converge onto c3 convertase which causes downstream events

Question 10

What is the complement system

Answer 10

A series of 30 proteins that are constantly circulating in blood and in fluids, when they detect foreign material they initiate a cascade of reactions that amplify the signal, they work to generate inflammation and rapidly remove the pathogen.

these proteins are made in the liver but also by monocytes, epithelial cells of the intestine and urinary tract etc.

Question 11

outline the complement components

Answer 11

They circulate as an inactive form in the blood
they have proteolytic enzymatic activity,
they split into small and large fragments when activated and “a” is usually the small fragment

Question 12

What induces the classical/ lectin and alternative pathways

Answer 12

Antigen-antibody complexes or CRP, collectins and ficolins, activated by microbial surfaces, you will always converge onto C3 convertase

Question 13

What is the result of converging onto C3 convertase

Answer 13

C3 convertase splits C3 into its small and large fragments which come together with C3b to make C5 convertase which then splits C5 which comes together with terminal complement components to make MAC (membrane attack complex)

Question 14

What does the MAC (membrane attack complex do)

Answer 14

It can lyse infected cells and other complement components can opsonization (label infected cells), cause extravasation to move infected cells from the blood into tissues.

Question 15

Outline the classical pathway

Answer 15

Initiated by C1 activation, (c1 is a complex of c1q,r,s), when C1 binds to CRP or a antigen-antibody complex

C1 must then bind to at least 2 Fc domains, IgM is the most efficient at activating complement as It has 5 Fc domains

Question 16

Why doesnt Serum IgM activate complement

Answer 16

Because it is in a planar (inactive form), the shape changes on binding antigen to reveal binding sites for C1q

Question 17

How is the classical pathway amplified

Answer 17

once C1q has binded to IgM, C1r has a conformational change which causes C1s to cleave into C2 and C4 thich split into their large and small fragments and come together to create C3 convertase

Question 18

Outline the lectin pathway

Answer 18

activated by ficolins and lectins (MBL), MBL binds to carbs and GP’s on bac and some viruses which causes similar downstream mech as classical pathway

Question 19

Outline the alt pathway

Answer 19

C3 spontaneously splits into its large n small fragments,
the large fragment binds to the plasma membrane of bac which makes C3b more susceptible to cleavage by factor D into C3b,Bb which in turn can hydrolyse more C3 to amplify the signal.

Question 20

Outline complement deficiency in SLE

Answer 20

90% of people deficient for C4 have SLE, less C4 means less C3b