L11: Overview of Innate Immunity

Question 1

What activates the innate response?

Answer 1

PAMP receptors on innate immune cells

Question 2

How do defensins work?

Answer 2

Amphipathic helical structures (polarized based on hydrophobic molecules). Can use electrical potential of bacterium to insert into membranes and create a pore.

Question 3

What makes defensins?

Answer 3

neutrophils and macrophages. Gastrointestinal and repiratory tract cells.
some effector cells.

Question 4

What does C5 initiate?

Answer 4

MAC (membrane attack complex)

Question 5

What will recognition of a PAMP cause to change on the cell surface of an APC?

Answer 5

Initiate phagocytosis, inflammatory cytokine response and on the surface, expression of B7 on APCs

Question 6

What will activation of a mannose receptor do?

Answer 6

promote phagocytosis by phagocyte without relaying an intracellular signal

Question 7

What is a signaling PRR? What are the two main types?

Answer 7

membrane receptor that when activated will tell cell it has encountered a pathogen.
Two main types are Toll-like and NOD-like

Question 8

What are Toll-like receptors?

Answer 8

membrane proteins that recognize microbial constituents and mediate signalling that initiates cytokine production

Question 9

What are NOD-like receptors?

Answer 9

cytoplasmic proteins recognize microbial products and initiate signaling that results in production of inflammatory cytokines

Question 10

What is TLR4 and what does it do?

Answer 10

It is a Toll-like receptor that recognizes gram negative bacteria and initiates cytokine production

Question 11

What do TLR2 and TLR6 do?

Answer 11

It is a Toll-like receptor that recognizes gram positive bacteria and initiates cytokine production

Question 12

What are secreted PRRs?

Answer 12

pattern recognition receptors that are secreted from host cells. (Ex: complement receptors, collectins, serum amyloid, CRP, mannose binding protein)
Most common are CRP and mannose-binding protein, which are both produced during the acute-phase response and can initiate complement activation

Question 13

What does mannose-binding protein initiate?

Answer 13

lectin pathway

Question 14

What does CRP initiate?

Answer 14

classical pathway in a nonspecific manner

Question 15

What do C4 and C2 initiate?

Answer 15

classical pathway

Question 16

What does C1 binding to CRP do?

Answer 16

initiate binding and cleavage of C4, which will produce a C4b that will bind to microbial membrane and initiate classical pathway

Question 17

What does CRP bind to on microbial membranes?

Answer 17

phoshocholine

Question 18

What cytokines will macrophages release during the innate response? What do they do?

Answer 18

IL-6, TNF-alpha, IL-1beta.
They initiate fever response.
TNF-alpha and IL1beta cause inflammation.
They also release IL-12 which activates NK cells.

Question 19

How to IL-1, IL-6 and TNF-alpha released from macrophages affect liver?

Answer 19

promote production of acute phase proteins (CRP, mannose binding lectin), which will activate complement opsonization

Question 20

How to IL-1, IL-6 and TNF-alpha released from macrophages affect bone marrow?

Answer 20

promotes neutrophil mobilization, which will promote phagocytosis

Question 21

How to IL-1, IL-6 and TNF-alpha released from macrophages affect hypothalamus?

Answer 21

cause fever response

Question 22

How to IL-1, IL-6 and TNF-alpha released from macrophages affect fat, muscle?

Answer 22

upregulates metabolism and activity to increase body temperature

Question 23

What does TNF-alpha do?

Answer 23

contricts capillaries. (prevents dissemination of pathogens)
This can be problematic in sepsis because it will constrict blood vessels everywhere and potentially shut down organs

Question 24

What are B1 B cells?

Answer 24

subset of B cells that respond to TI-2 antigens. They have a very limited Ig receptor repertoire, but specialize in recognizing carbs in bacterial pathogens

Question 25

Could a 3 year old react to a TI-2 antigen?

Answer 25

No. The B1 B cell innate response system is not produced until about 5 years of age

Question 26

What will a virus infected cell start secreting? What is the purpose?

Answer 26

``` IFN-alpha and beta. These make neighboring cells more resistant to infection. It also increases expression of ligands for receptors on NK cells. Also upregulates MHC class I and inhibitory ligand on neighboring cell surfaces. ```

Question 27

What cell is the primary control of virus infected cell in an innate way?

Answer 27

NK cells that react to TNF-alpha and beta

Question 28

What does an NK cell look for before killing a cell?

Answer 28

MHC class I. In virus infected cells it is not produced as much.

Question 29

Can NK cells ever clear an infection?

Answer 29

No. They rely on MHC class I levels dropping, which doesnt occur until cell is already infected.

Question 30

What is a MIC protein?

Answer 30

an activator on cell surfaces that will promote NK cell assassination

Question 31

What does factor P do?

Answer 31

Properdin (protects). it binds to C3b in complement cascades and prevents factor H from marking it for degradation by factor I.

Question 32

What would a mannorse or glucan PRR cause?

Answer 32

these are endocytic pattern recognition receptors and would promote endocytosis by phagocytes.

Question 33

Which Toll-like receptor is important for binding flagellated pathogens?

Answer 33

TLR-5

Question 34

What type of PRR is MBL?

Answer 34

Mannin-binding lectin is a secreted PRR. Will bind to variety of bacteria, viruses, fungi and protozoa. After binding, MASPs bind to it and become activated (they then cleave C2 and C4 to carry on lectin pathway.)

Question 35

What does TNF-alpha do to capillaries near sites of infection?

Answer 35

it constricts them and causes clotting, preventing the pathogen from entering the blood stream and forcing it to enter the lymphatic system.

Question 36

Which cytokines are associated with the acute-phase response?

Answer 36

IL-1, IL-6, TNF-alpha

Question 37

Do B1 B cells undergo affinity maturation?

Answer 37

No. There is no memory response either.

Question 38

Which of these are Type I interferons: IFN-alpha, IFN-beta, IFN-gamma?

Answer 38

IFN-alpha and beta. | Gamma is a beast of its own