Innate Immunity

Question 1

What cells belong to myeloid lineage?

Answer 1

• neutrophils
• basophils
• macrophages
• eosinophils

Question 2

What cells belong to lymphoid lineage?

Answer 2

• B cells
• T cells

Question 3

Activated macrophages secrete a range of…

Answer 3

Cytokines

Question 4

Which cytokines are responsible for fever?

Answer 4

IL-6, TNF-α, IL-1

Question 5

Which type of cell is most important in the innate immune response?

Answer 5

Neutrophils

Question 6

What are the functions of the innate immune system?

Answer 6

Phagocytes, complement, cytokines and NK cells:

1) Promote clearance of pathogens and other debris
2) Recruit immune cells to the site of infection
3) Activate adaptive immunity via antigen presentation

Question 7

What are the three functions of complement?

Answer 7

1) Opsonization of bacteria
2) Formation of the Membrane Attack Complex
3) Recruitment of phagocytic cells

Question 8

Describe the process of the MBL pathway.

Answer 8

1) MBL binds to pathogen
2) C4 and C2 complement proteins are cleaved into C4a, C4b and C2a, C2b
3) C2a and C4b join together to form C3 convertase
4) C3 convertase cleaves C3 to C3a and C3b
5) C3b acts as a powerful opsonin and helps with MAC formation
6) C3a recruits more phagocytes

Question 9

How does the classical pathway differ from the MBL pathway?

Answer 9

Very similar, except it is C1 that binds to the pathogen - either directly or to antibodies on its surface.

Question 10

How is C5 convertase created and what is its function?

Answer 10

• Formed from C3b when C3b joins C3 convertase
• Cleaves C5 to form C5a and C5b
• C5a is soluble; recruits immune cells/promotes inflammation
• C5b initiates formation of MAC

Question 11

Which complement proteins are most important for formation of MAC?

Answer 11

C5-C9

Question 12

Lacking C5-C9 (and thus the MAC defense mechanism) makes one more susceptible to…

Answer 12

Neisseria infections

Question 13

What are the major players in the INDUCED innate response?

Answer 13

Neutrophils

Question 14

How do dendritic cells differ from macrophages?

Answer 14

Both cells are professional APCs, but dendritic cells are not very good at killing

Question 15

How do APCs tell the difference between pathogen and host cells?

Answer 15

APCs have PRRs (pattern recognition receptors) that recognize PAMPs (found on various pathogens) and DAMPs

Question 16

What are the four types of PRRs?

Answer 16

1) Free receptors in serum (ex. MBL)
2) Membrane-bound phagocytic receptors
3) Membrane-bound signalling receptors (ex. TLRs, fMLP)
4) Cytoplasmic signalling receptors (NLRs)

Question 17

What does NFkB do and how is it activated?

Answer 17

Activated via toll-like receptors and nod-like receptors, NFkB induces expression of proinflammatory cytokines and antimicrobial peptides

Question 18

Which cytokine is most important for recruiting neutrophils/inducing chemotaxis?

Answer 18

IL-8 (aka CXCL8)

Question 19

What are cytokines produced by?

Answer 19

Activated macrophages (after complement cascade)

Question 20

In COVID-19, ____ could lead to excessive inflammation and tissue damage.

Answer 20

Complement activity and cytokines

Question 21

After IL-8 (CXCL8) binds to neutrophils, ___ (adhesion molecule) allows neutrophils to squeeze through tight junctions and into tissue via diapedesis.

Answer 21

LFA-1

Question 22

What does the F-Met-Leu-Phe receptor do?

Answer 22

• Example of a membrane-bound PRR
• Activate intracellular signalling pathways
• Induce production of ROS in the phagolysosome
• How neutrophils cells can kill

Question 23

How do neutrophils kill?

Answer 23

• Engulf and kill microbes to which they bind
• Contain cytoplasmic granules that hold antimicrobial peptides and granules
• Bacterial peptides such as fMLP will bind fMLP receptors and initiate signalling via Rac2, inducing production of NADPH oxidase
• NADPH oxidase creates superoxide ions and free radicals
• Superoxide dismutase converts superoxide ions to hydrogen peroxide, killing the pathogen

Question 24

Which cytokines activate NK cells?

Answer 24

IL-12, IFN-α, IFN-β

Question 25

What is the importance of NK cells?

Answer 25

Kill virus-infection host cells by releasing cytotoxic granules