Theme 3 Neutralizing Threats

Question 1

What are complement proteins?

Answer 1

a group of serum proteins circulating in the body in an inactive form.

Question 2

What are the outcomes of complement system?

Answer 2

• Target cell membrane lysis
• Chemotaxis movement of immune cells in response to a chemical stimulus.
• Opsonization to enhance phagocytosis
• Inflammation

Question 3

What are the three activation pathways of complement?

Answer 3

• Classical: Antigen - Antibody
• Lectin: PAMP - lectins
• Alternative: Spontaneous hydrolysis (C3 is always being made but unless it binds to the membrane of a target cell it quickly degrades)

Question 4

what are the two C3 convertases?
What are the two C5 convertases?

Answer 4

C3bBb and C4b2a
C3bBb3b and C4b2a3b

Question 5

Which complement pathway is most likely to be activated by a bacterial or fungal wall component?

Answer 5

the lectin pathway

Question 6

CR1
Function?

Answer 6

it binds C1 immune complexes to RBCs which then take them to the liver so that macrophages, which also have CR1 can strip them and phagocytose them. The CR1 on the macrophage also allows them to better consume free floating complement coated bacteria.

Question 7

CR2
Function?

Answer 7

CR2 binds to C3b on opsonized bacteria/ antigens and signals B cells through their BCRs

Question 8

C3aR/C5aR
Function?

Answer 8

C3aR/ C5aR binding causes the release of proinflammatory cytokines from basophils, eosinophils and neutrophils.

Question 9

How are complement proteins regulated?

Answer 9

• C1 inhibitor, dissociated the C1 complex
• Decay accelerating factors for C3 convertases
• Factor I degrades C3b and C4b
• Protectin inhibits the Membrane Attack complex

Question 10

If C3b can’t opsonize, what type of pathogen will be a more common infection?

Answer 10

encapsulated bacterial infection will be more common as they are mainly cleared by opsonization + phagocytosis.

Question 11

What could a reduction in CR1 cause?

Answer 11

Immune complex disorders due to a low clearance rate.

Question 12

How do pathogens evade the complement system?

Answer 12

• interfere with the initial antibody mediated activation
• microbial proteins bind to and inactivate complement proteins
• microbial proteases bind to and destroy complement proteins
• Some microbial proteins are non-functional analogs of complement proteins.

Question 13

What are the five stages of phagocytosis?

Answer 13

1) bacterium binds to PRRs or opsonin proteins
2) bacterium is ingested forming phagosomes
3) lyzosome and phagosomes fuse
4) Bacterium is killed and then digested by low pH- activated lysosomal enzymes, antimicrobial proteins, and ROS/RNSs.
5) Digested products are released from cell.

Question 14

How are pathogens killed in the lysosome?

Answer 14

• enzyme degradation
• antimicrobial proteins
• toxic effects
• reactive oxygen and nitrogen species.

Question 15

What percentage of WBCs circulating lymphocytes are NK cells?

Answer 15

5-10%
They secrete cytokines

Question 16

How are Natural killer cells unique from T and B cells?

Answer 16

• They do not undergo receptor gene rearrangement.

Question 17

What are the two functions of activated NK cells?

Answer 17

• They either kill the altered self-cell by releasing perforin and granzymes to induce apoptosis
• They release cytokines to induce adaptive responses against the altered self cell.

Question 18

How does the body prevent NK/ILC-1 cells from killing healthy self cells?

Answer 18

NK cells need to be licensed to kill by having a prior interaction with a healthy cell through the MHC I inhibitor receptor.

Question 19

Distinguish between ADD and ADCC

Answer 19

ADD (antibody dependent degranulation)
- used in the context of killing foreign material.
- mediated by neutrophils, basophils, mast cells, eosinophils and macrophages.

ADCC (antibody dependent cell cytotoxicity)
- used in the context of killing host cells.
- mediated by NK cells.

Question 20

Explain NETs (neutrophil extracellular trap).
- What?

• How?
• Why?

Answer 20

• networks of extracellular fibres consisting of strands of chromatin and proteins formed in the final stages of active neutrophil death.
• DNA strands are decorated with antimicrobial proteins
• NETs bind, neutralize, and kill pathogens at a site of inflammation.
• NET formation can be stimulated by DAMPS, PAMPs, and cytokines like IL-8.

Question 21

Besides neutrophils, what other leukocyte has been recently shown to have the ability to produce extracellular traps?

Answer 21

Eosinophils in the context of work infection.(EETs)