L2 Cells of Innate Immunity

Question 1

what are the cells involved in innate immunity?

Answer 1

• phagocytes
• mast cells and basophils
• eosinophils
• NK cells

Question 2

What cells types make up phagocytes?

Answer 2

• neutrophils

- macrophages

Question 3

what are the macrophages called in the brain?

Answer 3

microglial cells

Question 4

what are the macrophages called in the lung?

Answer 4

alveolar macrophages

Question 5

what are the macrophages called in the liver?

Answer 5

Kupffer cells

Question 6

what are the macrophages called in the spleen?

Answer 6

macrophages

Question 7

what are the macrophages called in the kidney

Answer 7

mesangial phagocytes

Question 8

what are the macrophages called in the joint?

Answer 8

synovial A cells (synoviocytes)

Question 9

when do monocytes become macrophages?

Answer 9

once they enter the cell

Question 10

what type of macrophages are found in the lymph node?

Answer 10

resident and recirculating macrophages (monocytes?)

Question 11

how is a phagolysosome formed?

Answer 11

PAMPs on bacterium binds to PRRs on macrophage

macrophage engulfs bacterium by phagocytosis and a lysosome joins the phagosome= phagolysosome

Question 12

how is direct recognition carried out?

Answer 12

PAMPs (pattern activation molecule patterns) on pathogen binds to PRR (pattern recognition receptors) on phagocyte

Question 13

what is the role of TLRs?

Answer 13

a group of membrane bound receptors that exists on cytosolic vesicles and external cell membranes

there are about 10 different ones - each recognize different molecular patterns and signaling leads to different signaling cascades

Question 14

How are opsonins produced?

Answer 14

1. B cells secreting IgG antibodies
2. macrophages generate IL-6 – target hepatocytes to secrete CRP
3. Complement release C3b

Question 15

define opsonins

Answer 15

molecules that have attached to the pathogen

Question 16

an interaction of any of the 3 pathogen-bound opsonins triggers what?

Answer 16

phagocytosis

Question 17

how are receptors on the phagocyte and opsonins paired?

Answer 17

on phagocyte —- on pathogen

FcYR — FcY (IgG)
CRP-BP —- CRP
CR-1 —– C3b

*These are not PRR (pattern recognition receptors), they are specific receptors

Question 18

what are the armamentariums contained within the phagosome?

Answer 18

1. Lysosomes (4)
2. NADPH oxidase (ROIs, ROSs) (4)
3. iNOS - inducible nitric oxide synthase (NO and other RNI)

Question 19

define phagosome?

Answer 19

recognition and binding of pathogen is followed by ingestion of a portion of the plasma membrane which extends outward and surrounds the microbe forming a phagocytic vacuole.

vesicle that contains the engulfed pathogen

Question 20

when the lysosomes fuses with the phagosome, what are the 4 lysosomal products that are released?

Answer 20

1. defensins
2. lysozyme
3. lactoferrin
4. myeloperoxidase

*cytotoxic to microorganisms

Question 21

what is the role of lactoferrin?

Answer 21

binds to iron - removes an essential ingredient for microbial growth

Question 22

what is the role of lysozyme?

Answer 22

destroys muramic acid in bacterial cell walls

Question 23

what is the role of defensins?

Answer 23

permeabilize bacterial and fungal membranes

Question 24

what is the role of myeloperoxidase?

Answer 24

released from lysosomal granules

enzyme requires to generate hypochlorite

Question 25

what is the role of hypoclorite?

Answer 25

potent antimicrobial agent that mediates its function by halogenating bacteria` cell walls.

Question 26

what is required for the function of the NADPH oxidation complex?

Answer 26

glucose - from pentose phosphate pathway

Question 27

what activates NADPH oxidase?

Answer 27

the respiratory burst from phagocytosis

Question 28

NADPH uses oxygen in the presence of cytosolic NADPH to generate?

Answer 28

superoxide anion

Question 29

what is a superoxide anion?

Answer 29

reactive oxygen species (ROS) aka reactive oxygen intermediate (ROI)

Question 30

what is the initiating step for the other ROSs/ROIs?

Answer 30

the generation of the superoxide anion

Question 31

what are the products that result from the activation of NADPH oxidase?

Answer 31

1. superoxide 2. hydroxyl radical 3. hydroxyl ion 4. hydrogen peroxide * hypochlorite is formed when myeloperoxidase is available - it is a catalyst

Question 32

what enhances the activation of NADPH oxidase?

Answer 32

interferon gamma and tumor necrosis factor (IFNY and TNF)

Question 33

what is formed when nitric oxide reactions with ROI?

Answer 33

reactive nitrogen intermediates (RNIs)

Question 34

why are Nitric oxide and other RNIs important?

Answer 34

elimination of intracellular organisms that are resistance to ROIs and lysosomal enzymes in phagolysosomes

Question 35

what are the molecular targets of NO?

Answer 35

iron sulfur proteins in the ETC -- inhibit respiratory cycle

Question 36

what does the synthesis of NO require?

Answer 36

nitric oxide synthase

Question 37

what is nitric oxide synthase?

Answer 37

L-arginine + oxygen ----[iNOS]---> L-citruiline +NO

Question 38

what cytokines activate iNOS

Answer 38

TNF | IFNY

Question 39

what cytokines do the down regulation of iNOS?

Answer 39

IL-4 TGF Beta (transforming growth factor) - most effective IL-10

Question 40

what are the cytokines secreted by activated macrophages?

Answer 40

``` IL-1 IL-6 IL-12 IL-18 TNF IL-15 ```

Question 41

which cytokines play a role in inflammation?

Answer 41

TNF | IL-1

Question 42

what are the chemokines secreted by activated macrophages?

Answer 42

IL-8 (CXCL8) | MCP-1 (CCL2)

Question 43

describe the role of TLR 2 and TLR 4 in generation of pro IL-1

Answer 43

signaling of TLR 2 and 4 --> activation of NFkB (transcription factor required for transcription of pro-IL-1) = inflammatory cytokine secrete by activated macrophages

Question 44

how is caspase 1 generates from procapase 1?

Answer 44

the NALP3 inflammasome complex converts proenzyme to its active form -- then that activates IL-1 and IL-18

Question 45

how do PAMPs and DAMPs activate the inflammasome

Answer 45

PAMPs and DAMPs are responsible for binding the damaged molecules of microbial products once those are bound = inflammasome!

Question 46

what are 5 examples of DAMPs

Answer 46

- MSU - monosodium urate monohydrate -uric acid crystal - gout - cholesterol crystals - skin irritants - sunburn! - glucose derived ROS - Type II DM - free fatty acids - asbestos

Question 47

what are the receptors on macrophages that play a role in immune response

Answer 47

- for cytokines - for chemokines - for PRRs - for FcyR - for CRP-R - for CR-1

Question 48

identify the tissue distribution of CD200R

Answer 48

cells of myeloid lineage

Question 49

what is the role of CD200?

Answer 49

suppresses immunity activity | expression on tumor cells suppresses anti-tumor cytotoxic immune responses

Question 50

what cells is CD 200 expressed on

Answer 50

T cells B cells dendritic cells