Lecture 11- effector responses against infectious agents

Question 1

briefly what is the innate immune response?

Answer 1

first, fast line of defense
tries to eliminate the pathogen quickly
majority of innat immune system are of the myeloid lineage

Question 2

What are many cells of the innate immune response activated by?

Answer 2

Pathogen Recognition Receptors (PRRs)- e.g. toll like receptors

Question 3

what cells are in the innate immune response?

Answer 3

macrophage
mast cells
eosinophils
neutrophills
dendritic cells
basophils

Question 4

What are the roles of the phagocytes?

Answer 4

macrophages and neutrophils kill pathogens.
dendritic cells phagocytose to present pathogen antigen to t cells
(macrophages can present too but later in the response)

Question 5

Macrophages

Where are they? how are they made>

Answer 5

reside in tissues
produced from:
monocytes that enter the tissues from circulation
or embryonic cells during development

Question 6

what’s a nickname for macrophages?

Answer 6

professional phagocyte

Question 7

neutophils

Answer 7

90% of circulating granulocytes
very readily activated
move to sites of inflammation
short life span-> die into pus
highly phagocytic
can move towards pathogen, chemotaxis

Question 8

how does phagocytosis kill the pathogen?

Answer 8

pathogen is internalized. phagosome fuses with lisosome. makes phagolysosome. acidic environment and enzymes kill pathogen
then granules with antimicrobial peptides and enzymes fuse too and kill them

Question 9

what do eosinophils and basophils do?

Answer 9

They’re bad at phagocytosis
instead they mediate effects by releasing toxic granules and chemical mediators.
Neutrophils can also do this as they are granulocytes

Question 10

How are eosinophils and basophils activated to degranulate?

Answer 10

By a number of mechanisms including complement, antibody and cytokines. Act on these cells during infection and cause it to release granules

Question 11

What are Mast cells?

Answer 11

Basophil-like but found int tissue not blood.

Question 12

What do mast cells do?

Answer 12

They bind IgE on cell surface with high affinity at rest
Mast cells activated when IgE binds antigen, cross linking of antibody, triggers signals inside mast cell-> degranulates.

Question 13

Natural killer cell

Answer 13

not myeloid origin

kills “altered” cells-> infected or tumour cells

Question 14

How does NK cell work?

Answer 14

NK cells express inhibitory and activating receptors. Most cells in our body express ligands for these receptors.
MHC class I= major ligand for inhibiotry receptors.
So if an NK cell scans body and comes across cell that’s normal, you get binding of activation receptor to activating ligand but also inhibitory binds too.
But when cell is altered- activation ligand binds but inhibitory ligand is downregulated so there is now just activating signal saying kill the cell.

Question 15

How does the innate immune response help to drive the adaptive immune response?

Answer 15

Cytokine production by the innate cells can help drive the more specific T and B cell responses= adaptive immune response

Question 16

How does the adaptive immune response regulate the innate response?

Answer 16

The T and B cells make cytokines and antibodies which can aid and regulate the more innate immune response.
cross talk

Question 17

What is complement?

Answer 17

• Major component of the innate immune system
• identified in 1890s as improving antibody=mediated killing of bacteria
• also provides important early antibody-independent killing of pathogens
• collection of over 30 different soluble proteins (not cellular)
• made in liver as inactive precursors, present in the blood and other body fluids in inactive form

Question 18

Where is complement made?

Answer 18

• collection of over 30 different soluble proteins (not cellular)
• made in liver as inactive precursors, present in the blood and other body fluids in inactive form

Question 19

What are most complement proteins?

How are they activated?

Answer 19

Most of the proteins are enzymes (inactivation)
Then cleavage into two parts activates it
cleavage into smaller part= mediators of inflammation
bigger part- contains binding site for next protein in cascade and an active enzymatic site (activated when this is cleaved)

Question 20

What are the 3 pathways of complement activation?

Answer 20

1. Classical
2. Alternative
3. Lectin

Question 21

What do all 3 pathways of complement activation do?

Answer 21

all pathways generate C3 convertase, which cleaves C3, leaving C3b bound to the microbial surface and releasing C3a

Question 22

Describe binding in 1. classical, 2. alternative and 3. lectin complement pathways

Answer 22

1. complement binds to antibody bound to pathogen surface
2. complement binds to pathogen surface
3. complement binds to mannose binding protein bound to pathogen surface

Question 23

classical pathway of complement activation

Answer 23

classical pathways involves the first component of complement- c1.
c1 made up of subunits- c1q, c1s, c1r
involves ANTIBODY
c1q binds to the IgM or IgG antibody bound to bacterial surface
binding of c1q to antibody, activates c1r which cleaves and activates c1s which is serine protease so cleaves serine residues.
c1s cleaves c4 to c4a and c4b, which binds to the microbial surface.
c4b binds to c2, which is cleaved by c1s, to c2a and c2b, forming c4b2a.(c4b and c2a bound together)
c4b2a is an active c3 convertase, cleaving c3 to c3a and c3b which binds to the microbial surface or to the convertase itself
one molecule of c4b2a can cleave up to 1000 molecules of c3 so amplification

Question 24

alternative pathways of complement activation

involves…?

Answer 24

• does not require antibody

- involves other complement factors B and D

Question 25

alternative pathway

Answer 25

1. c3 undergoes spontaneous hydrolyssis which allows it to bind to factor B, allowing B to be cleaved by factor D into Ba and Bb.
2. this complex of c3(H20)Bb is a C3 convertase, cleaving more C3 into C3a and c3b. C3b is rapidly inactivated unless it binds to cell surface
3. c3bBb complex is also a c3 convertase and deposits many molecules of c3b on the pathogen surface

Question 26

lectin pathway

Answer 26

-mannose binding lectin (MBL) is present in serum
-mannose is often on surface of pathogens
-once MBL has bound, MBL associated proteases (MASPs) bind to MBL
-MBL-MASP complex cleaves c4 and c2 in the same way as classical pathway.
so get c4b and c3 activation

Question 27

How does c3 cleavage lead to removal of pathogen? 4 main ways

Answer 27

1. Induction of cell lysis in infected cells
2. Opsonisation of pathogen
3. Induction of chemotaxis and inflammation
4. Immune complex clearance (small antibody-soluble antigen complexes, not enough antibody to mediate phagocytosis)