encounter with innate and adaptive immunity

Question 1

complement

Answer 1

proteins mainly produced by the liver (also by immune cells)
- consists fo a series of inactive precursor proteins
- activated by cleavage which then activates the next protein in the series
- products generated cause a range of effects

constitutively present in blood and tissue
- low concentrations of complement in CSF

Question 2

what pathways is complement activated by

Answer 2

classical
alternative
lectin

Question 3

anti-microbial roles of complement - lysis

Answer 3

the first is that it can cause lysis of bacteria
- and this involves complement proteins C5 to C9 and they join together to form the membrane attack complex or Mac.
- And that basically punches holes in bacterial membranes and that results in bacterial lysis
-and that’s due to water being able to flow into the cells, ions go out, you get osmotic Shock and It causes lysis.

Question 4

antimicrobial roles of complement - opsonisation

Answer 4

○ the key complement factor involved there is c3b.
○ it coats the surface of microbes and that basically tags them for recognition by phagocytes.
○ phagocytes have a complement receptor on the surface - so microbes that are coated in c3b are easily recognized by phagocytes and they get phagocytosed and destroyed.

Question 5

antimicrobial roles of complement - activation of the inflammatory response.

Answer 5

○ neutrophils need to leave the bloodstream and travel to the site of infection and that requires vasodilation for them to be able to escape from the blood stream Crossing endothelial wall.
○ And also they need to follow a chemotactic response to get to the site of infection
§ and that is a role of complements.
- So it’s important for the vasodilation and allowing the cells to leave the bloodstream.
-But also they provide the chemotactic factors and the signal for them to move to the site infection.

Question 6

lectin activaition pathway of complement

Answer 6

MBL binds mannose on bacterial surface -> C4, C2 -> C3 convertase formation

Question 7

classical activation pathway of complement

Answer 7

Antigen: antibody complexes -> C1, C4, C2 -> C3 convertase formation

Question 8

alternative activation pathway of complement

Answer 8

C3b binds bacterial surface -> C3, factors B, D -> C3 convertase

Question 9

after formation of C3 convertase, what leads to recruitment of inflammatory cells

Answer 9

cleavage of C3 exposes a highly reactive bond which mediates covalent binding to target surfaces
-> C4a, C3a, C5a -> recruitment of inflammatory cells

Question 10

after formation of C3 convertase, what leads to opsonisation

Answer 10

cleavage of C3 exposes a highly reactive bond which mediates covalent binding to target surfaces
-> C3b - binds to complement receptors on phagocytes -> opsonisation

Question 11

after the formation of C3 convertase, what leads to membrane attack complex lysis of bacteria

Answer 11

cleavage of C3 exposes a highly reactive bond which mediates covalent binding to target surfaces -> C3b -> Terminal complement components C5b, C6, C7, C8, C9
-> membrane attack complex lysis of bacteria

Question 12

key components of the complement pathway - C3b

Answer 12

binds to microbial PAMPs -> opsonisation
- monocytes, macrophages and neutrophils have C3b receptors
- individuals that lack C3 suffer recurrent infections

Question 13

key components of the complement pathway - C5a, C3a and C4a

Answer 13

inflammatory mediators
- C5a, C3a, C4a can act as anaphylatoxins (activate mast cells)
- chemotaxis (C5a particularly important)
- cause vascular permeability

Question 14

key components of the complement pathway -membrane attack complex (components C5b - C9)

Answer 14

inserts into the bacterial cell membrane forming transmembrane channels which leads to osmotic lysis of gram negative bacteria

Question 15

specific/ adaptive defence system

Answer 15

due to T lymphocytes and B lymphocytes

recognise pathogens using variable antigen-specific - cell surface receptors
- almost infinite number of different versions:
- each has a unique binding site for a different ligand
- generated by gene rearrangement

only those lymphocytes that are specific for components of infecting pathogen are selected
-> divide, proliferate and differentiate into effector lymphocytes
-> some proliferate into memory lymphocytes

Question 16

T cells

Answer 16

2 main types - CD8 or CD4 glycoprotein markers
T cel receptors recognise peptide antigens ‘presented’ on the surface of cells - antigen needs to be presented bound to MHC cells

Question 17

what are the 2 classes of MHC molecule that present peptide antigens to the 2 main types of T cells

Answer 17

MHC class I:
- present antigens of cytoplasmic origin to CD8 T cells
- cytotoxic cells (cell-mediated immunity)

MHC class II:
- present phagocytosed antigens of extracellular origin to CD4 T cells
-> differentiate into effector T helper cells
-> help B cells become antibody-producing plasma cells
-> hekp CD8 T cells to become cytotoxic T cells
-> activate macrophages

antigen characteristics determine whether presented on MHC-I or MHC-II

Question 18

what do helper T lymphocytes do - pathway

Answer 18

• CD4 + helper T lymphocyte + APC with microbial antigen presented on MHC class II
  leads to - cytokines
  leads to -> activation of macrophages, inflammation, activation of T and B lymphocytes

Question 19

cell-mediated immunity: cytotoxic T lymphocytes - pathway

Answer 19

CD8 + cytotoxic T lymphocyte + infected APC expressing microbial antigen on MHC class I
-> killing of infected cell

Question 20

antibody-mediated immunity: B lymphocytes and antibodies

Answer 20

B cell + antibody > effector b lymphocytes , neutralisation of microbe phagocytosis, complement activation, neutralisation by agglutination

Question 21

antibody-mediated immunity: B lymphocytes and antibodies - antibacterial roles

Answer 21

• neutralisation by agglutination:
  
  • cause pathogen or protein such as a toxin to aggregate and thereby block binding to target/ action
• facilitate phagocytosis
• activation of complement
• block attachment (e.g. binds ligands essential for binding to host cell receptor)

Question 22

what do bacteria need to evade in innate and adaptive immunity

Answer 22

• phagocytosis and killing by phagocytes
• antimicrobial activity of complement
• recognition and killing by antibodies and T cells

Question 23

strategies for evading phagocyte recognition - contact with phagocyte prevented by a capsule

Answer 23

expression of a capsule prevents contact with the phagocyte
capsule can prevent C3b receptors on phagocytes from binding to C3b attached to bacterial cell wall

e.g. streptococcus, pneumoniae

Question 24

evasion of phagocyte recognition (and complement activation and antibody binding)

Answer 24

possess capsules:
- loose, relatively unstructured, polymer coat
- mainly composed of polysaccharides
- protect form phagocyte recognition (shields PAMPs)
- prevent complement recognition/ activation (alternate pathway)
- prevent antibody binding by shielding antigens or resembling host polysaccharides ( will also prevent complement activation by classical pathway)

Question 25

strategies for evading phagocyte recognition - opsonisation prevented by producing protein that binds antibodies

Answer 25

organisms produce proteins which prevent interaction between opsonising antibody and phagocyte
- block phagocytic process

Question 26

strategies for evading phagocyte recognition - avoidance of phagocytic killing

Answer 26

• organism releases toxins e.g. staphylococci streptococci
• phagocyte killed by toxin
• organism may induce macrophage apoptosis

Question 27

strategies for evading phagocyte recognition - resistance to killing

Answer 27

organisms resist killing by producing antioxidants e.g. catalase, superoxide dismutase, raise pH (urease), adaptation to low Fe and low Mg

Question 28

resistance to phagocytic killing

Answer 28

• resistance to nitric oxide and reactive oxygen species: cell surface polysaccharides interact with/ detoxify reactive oxygen species
  - avoid induction/reduce strenght of oxidative burst
• resistance to defensins
• tough cell walls: refractory to lysosomal proteases and lysozyme
• resistant to low pH: urease and H+ transporters
• nutrient acquisition mechanisms

Question 29

strategies for evading phagocyte recognition - phagolysosome fusion/ acidification inhibited

Answer 29

e.g. mycobacterium tuberculosis, salmonella

• organism escapes from phagosome/ phagolysosome and lives in the cytoplasmic compartment of the cell e.g. shigella sp. Listeria monocytogenes

Question 30

surviving phagocytosis

Answer 30

• prevent phagocytosis - prevent contact, block phagocytosis, avoid opsonisation
• toxin productions
• escape phagosome before fuses with lysosome
• prevent phagosome-lysosome fusion/ acidification
• raise pH of phagosome
• reduce effectiveness of toxic compounds

Question 31

surviving phagocytosis - reduce effectiveness of toxic compounds

Answer 31

• resistance to defensins
• production of catalase, SOD, flavohaemoglobin
• cell surface polysaccharides that intwract with/ detoxify oxygen radicals
• reduce strength of oxidative burst
• tough cell walls
• NO resistance
• resistance to low pH
• nutrient acquisition mechanisms

Question 32

how do bacteria evade complement - prevention of complement opsonisation and killing by alternative pathway

Answer 32

sialic acid capsules: E coli K1, neisseria meningitidis

sialylation of LPS: N. meningitidis, N. gonorrhoea

silaylation of pili: N. meningitidis, N. gonorrhoea

Question 33

how do bacteria evade complement - prevention of MAC mediated lysis

Answer 33

O- antigen mioety of lipopolysaccharide
- high affinity for C5b

MAC deposited away from cell membrane

Question 34

how do bacteria evade complement - produce surface protein that prevents opsonisation

Answer 34

• M protein of streptococci acts as a receptor for factor H
• potentiates c3bBb dissociation

Question 35

how do bacteria evade complement - -REVENT ANTIBODY RECOGNITION

Answer 35

• prevent activation of classical pathway

Question 36

how do bacteria evade complement - produce a protease to destroy complement

Answer 36

reduces inflammatory signalling
- Group A streptococci secrete a C5a protease
-yersinisa: C3b and C5a proteases

neisseria meningitidis: alternative cleavage of C3 by NalP

Question 37

how do bacteria evade complement - shedding of outer membrane vesicles

Answer 37

• blebbing
• prevent complement activation near bacteria

Question 38

how do bacteria avoid the antibody response

Answer 38

• SlgA protease
• molecular mimicry: express antigen similar to host structues
• coating with host proteins: e.g. binding fibronectin, lactoferrin, transferrin, IgG
• antigenic variation
• phase variation

Question 39

antigenic variation

Answer 39

changes in gene sequence leading to changes in the amino acid sequence of an antigen

Question 40

phase variation

Answer 40

reversible on/ off switch resulting in variation in the level of expression of one or more antigens