L2 Cells of Innate Immunity Flashcards

1
Q

what are the cells involved in innate immunity?

A
  • phagocytes
  • mast cells and basophils
  • eosinophils
  • NK cells
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2
Q

What cells types make up phagocytes?

A
  • neutrophils

- macrophages

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3
Q

what are the macrophages called in the brain?

A

microglial cells

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4
Q

what are the macrophages called in the lung?

A

alveolar macrophages

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5
Q

what are the macrophages called in the liver?

A

Kupffer cells

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6
Q

what are the macrophages called in the spleen?

A

macrophages

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7
Q

what are the macrophages called in the kidney

A

mesangial phagocytes

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8
Q

what are the macrophages called in the joint?

A

synovial A cells (synoviocytes)

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9
Q

when do monocytes become macrophages?

A

once they enter the cell

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10
Q

what type of macrophages are found in the lymph node?

A

resident and recirculating macrophages (monocytes?)

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11
Q

how is a phagolysosome formed?

A

PAMPs on bacterium binds to PRRs on macrophage

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

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12
Q

how is direct recognition carried out?

A

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

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13
Q

what is the role of TLRs?

A

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

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14
Q

How are opsonins produced?

A
  1. B cells secreting IgG antibodies
  2. macrophages generate IL-6 – target hepatocytes to secrete CRP
  3. Complement release C3b
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15
Q

define opsonins

A

molecules that have attached to the pathogen

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16
Q

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

A

phagocytosis

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17
Q

how are receptors on the phagocyte and opsonins paired?

A

on phagocyte —- on pathogen

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

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

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18
Q

what are the armamentariums contained within the phagosome?

A
  1. Lysosomes (4)
  2. NADPH oxidase (ROIs, ROSs) (4)
  3. iNOS - inducible nitric oxide synthase (NO and other RNI)
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19
Q

define phagosome?

A

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

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20
Q

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

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

*cytotoxic to microorganisms

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21
Q

what is the role of lactoferrin?

A

binds to iron - removes an essential ingredient for microbial growth

22
Q

what is the role of lysozyme?

A

destroys muramic acid in bacterial cell walls

23
Q

what is the role of defensins?

A

permeabilize bacterial and fungal membranes

24
Q

what is the role of myeloperoxidase?

A

released from lysosomal granules

enzyme requires to generate hypochlorite

25
Q

what is the role of hypoclorite?

A

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

26
Q

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

A

glucose - from pentose phosphate pathway

27
Q

what activates NADPH oxidase?

A

the respiratory burst from phagocytosis

28
Q

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

A

superoxide anion

29
Q

what is a superoxide anion?

A

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

30
Q

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

A

the generation of the superoxide anion

31
Q

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

A
  1. superoxide
  2. hydroxyl radical
  3. hydroxyl ion
  4. hydrogen peroxide
    * hypochlorite is formed when myeloperoxidase is available - it is a catalyst
32
Q

what enhances the activation of NADPH oxidase?

A

interferon gamma and tumor necrosis factor (IFNY and TNF)

33
Q

what is formed when nitric oxide reactions with ROI?

A

reactive nitrogen intermediates (RNIs)

34
Q

why are Nitric oxide and other RNIs important?

A

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

35
Q

what are the molecular targets of NO?

A

iron sulfur proteins in the ETC – inhibit respiratory cycle

36
Q

what does the synthesis of NO require?

A

nitric oxide synthase

37
Q

what is nitric oxide synthase?

A

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

38
Q

what cytokines activate iNOS

A

TNF

IFNY

39
Q

what cytokines do the down regulation of iNOS?

A

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

40
Q

what are the cytokines secreted by activated macrophages?

A
IL-1
IL-6
IL-12
IL-18
TNF
IL-15
41
Q

which cytokines play a role in inflammation?

A

TNF

IL-1

42
Q

what are the chemokines secreted by activated macrophages?

A

IL-8 (CXCL8)

MCP-1 (CCL2)

43
Q

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

A

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

44
Q

how is caspase 1 generates from procapase 1?

A

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

45
Q

how do PAMPs and DAMPs activate the inflammasome

A

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

46
Q

what are 5 examples of DAMPs

A
  • MSU - monosodium urate monohydrate -uric acid crystal - gout
  • cholesterol crystals
  • skin irritants - sunburn!
  • glucose derived ROS - Type II DM
  • free fatty acids
  • asbestos
47
Q

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

A
  • for cytokines
  • for chemokines
  • for PRRs
  • for FcyR
  • for CRP-R
  • for CR-1
48
Q

identify the tissue distribution of CD200R

A

cells of myeloid lineage

49
Q

what is the role of CD200?

A

suppresses immunity activity

expression on tumor cells suppresses anti-tumor cytotoxic immune responses

50
Q

what cells is CD 200 expressed on

A

T cells
B cells
dendritic cells