Innate Immunity + NK Cells Flashcards

1
Q

T/F: Innate immunity is natural immunity present from birth designed to protect the body without prior contact with the infectious agent

A
  • true
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2
Q

What are routes of infection for pathogens?

A
  • airway, GI tract, reproductive tract, external surface, wounds, insect bites
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3
Q

T/F: Innate immunity is a late response (>96 hours)

A
  • false, immediate (0-96 hours)
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4
Q

What are methods of protection against infection?

A
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5
Q

1st line defenses such as phagocytosis, complement, interferon, inflammation,and fever are part of innate immunity

A
  • false, these are 2nd line defenses
  • 1st line defenses are skin, mucous membranes, chemicals
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6
Q

What are the kinds of physical barriers of innate immunity?

A
  • mechanical: skin, ciliary movement, peristaltic movement, washing via tears/saliva, mucous layer
  • chemical: fatty acids in sweat, lysozyme and phospholipids, low pH, surfactants
  • microbiological factors: normal skin biota
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7
Q

What are the kinds of humoral barriers of innate immunity?

A
  • complement system: proteins that work together to prevent infection
  • coagulative system: chemotactic factors, beta-lysine produced by platelets is G+ bactericidal
  • lactoferrin/transferrin: sequester iron
  • lysozyme: digest cell wall
  • interferons: type 1 interferons inhibit infection and viral replication
  • interleukin 1: increase T in inflammation and induce bactericidal acute phase proteins
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8
Q

What are the kinds of cellular barriers of innate immunity?

A
  • neutrophils: phagocytose microorganisms
  • macrophages: ingest and kill microorganisms/infected cells, function as APC, wound healing
  • NK cells: kill infected/tumor cells
  • eosinophils: eliminate parasites
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9
Q

What are the two cells of the phagocytic system?

A
  • neutrophils and macrophages
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10
Q

T/F: macrophages circulate the bloodstream looking for foreign objects to ingest and degrade

A
  • false; neutrophils
  • monocytes also circulate blood before entering tissue to replenish macrophage populations
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11
Q

What cell is identified by expression of CD66?

A
  • Neutrophils
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12
Q

Mature neutrophils contain two types of granules, azurophilic granules and seconday granules. Which granules contain myeloperoxidase and proteolytic enzymes such as elastase and cathepsin G?

A
  • azurophilic, they contain:
    • defensins: kill bacteria
    • proteolytic enzymes: degrade bacterial proteins
    • lysozyme: degrade bacterial cell wall
    • myeloperoxidase: generation of bactericidal substances
  • seconday granules
    • lysozyme
    • lactoferrin
    • NADPH oxidase: production of toxic radicals
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13
Q

What cells are identified by expression of C14, CD11b, or F4/80?

A
  • macrophages
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14
Q

T/F: macrophages have both granules and lysosomes

A
  • false, just lysosomes that contain factors for intercellular killing mechanisms
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15
Q

T/F: neutrophils react to danger signals generated at sites of pathogen entry that induce chemotaxis towards the site

A
  • false; macrophages
    • N-formyl-methionine: secreted by bacteria
    • peptides of coagulative system
    • complement system components
    • cytokines secreted by tissue macrophages
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16
Q

What are the receptors phagocytes use to bind to microorganisms?

A
  • complement receptors
  • scavenger receptor
  • Fc receptors
  • toll-like receptors
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17
Q

Phagocytes possess receptors for ___ complement component. ____ binds the antigen and then later binds to its receptor on the phagocyte. What does this trigger?

A
  • C3b
  • activation of phagocytosis
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18
Q

SRA, CD68, Lox-1, and C36 are all ___________ receptors that directly bind to _______ found on bacterial surfaces to initiate phagocytosis

A
  • scavenger receptors
  • polyamines
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19
Q

T/F: Fc receptors are only applicable using recurrent infections

A
  • true, only when antibodies are available
  • antibodies bound to antigens expose Fc region, which bind to Fc receptors on phagocytes, enhancing the activity of the phagocyte
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20
Q

What phagocyte receptor recognizes PAMPs?

A
  • toll-like receptors
  • when macrophages bind antigens via TLR they activate and secrete cytokines (IL-1, TNF, IL-6) in preparation for a inflammatory reaction
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21
Q

What is the purpose of phagocytosis?

A
  • detect and destroy microorganisms, remove damaged cells and foreign objects, induce production of cytokines, process and present antigens to induce an immune response by lymphocytes
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22
Q

What is the process of phagocytosis?

A
  • chemotaxis
  • detect and bind via receptors
  • surround w/ pseudopodia and engulf via endocytosis
  • enclose in phagosome
  • fuse with lysosome (phagolysosome)
  • release lysosome enzymes (proteases +O2 radicals)
  • digestion + release of waste
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23
Q

What are the two established killing pathways in neutrophils, monocytes, and macrophages?

A
  • oxidative pathways: generation of ROS and RNS
  • non-oxidative pathway: lysosomal toxic substances
24
Q

Respiratory burst is the several-fold increase in the use of _________ and __________ during phagocytosis

A
  • oxygen + glucose
25
Q

The oxygen dependent intracellular killing pathway refers to the respiratory burst which leads to formation of _______ which are toxic to microorganisms

A
  • reactive oxygen species
26
Q

Describe the generation of ROS:
- Glucose is metabolized through the ___________ pathway producing NADPH
- ___________ activates NADPH
- activated NADPH uses O2 producing ____________
- the ________ may be reduced to H2O2 and 1O2 by superoxide dismutase OR
- may react with H2O2 producing hydroxyl radicals (*OH) and ions (OH-)

A
  • Pentose-phosphate
  • cytochrome
  • superoxide anion (*O2-) x2
27
Q

Myeloperoxidase is released during the fusion of azurophilic granules with phagosome.
Myeloperoxidase uses ________ and Cl- to produce ______________

A
  • H2O2
  • hypochlorous acid
28
Q

The _______________ can react with a reactive nitrogen species NO (NITRIC OXIDE) to produce peroxynitrite, another RNS.

NO can also undergo oxidation to generate RNS nitrogen dioxide

A
  • superoxide anion
29
Q

When phagocytes bind bacteria though TLR, _______ is secreted which induces expression of __________.

This oxidizes L-arginine to yield L-citruline and _______, which is highly toxic to microorganisms.

A
  • TNFa
  • iNOS (inducible nitric oxide sythetase)
  • NO
  • IFNy also induces iNOS
30
Q

What are ROS? RNS?

A
  • ROS: superoxide anion, hydroxyl radical, hydrogen peroxide, hypochlorite anion
  • RNS: nitric oxide, nitrogen dioxide, peroxynitrite
31
Q

The main mechanism of the non-oxidative intracellular killing pathway is dependent on ___________

A
  • action of toxic substances in lysosomes:
    • cationic proteins: damage bacterial cell wall
    • lysozyme: damage mucopeptides in cell wall
    • lactoferrin: sequester iron
    • proteolytic and hydrolysis enzymes: digest killed bacteria
32
Q

What are the sentinel cells? What do they do?

A
  • macrophages, dendritic cells, mast cells
  • use PRRs (pattern recognition receptors) to sense PAMPs and DAMPs
33
Q

T/F: DAMPs are exogenous molecules released from damaged cells

A
  • false, ENDOGENOUS
  • damage-associated molecular patterns
34
Q

What are PAMPs?

A
  • pathogen-associated molecular patterns
  • repetitive common types of molecules broadly expressed by pathogens NOT found in host tissues
  • eX: peptidoglycan, lipopolysaccharide, lipoteichoic acids, mannan
35
Q

What are the 5 classes of PRRs?

A
  • Toll-like receptors
  • NOD-like receptors
  • RIG-Ike receptors
  • C-type lectin receptors
  • Peptidoglycan-recognition receptors
36
Q

Major PRRs located on host cell membranes or within that signal the presence of invaders are?

A
  • toll-like receptors
  • know internal compartment
37
Q

All TLRs signal through _______, except for TLR3 which signals through ______.

The result of signaling is the production of __________

A
  • MyD88
  • TRIF
  • proinflammatory cytokines
38
Q

_______ are found inside cells and detect pathogens in cytoplasm, generally intracellular bacteria

A
  • NOD-like receptors (nucleotide-binding oligomerization domain-like receptor)
39
Q

T/F; NOD1 detects bacterial peptidoglycan, NOD2 detects muramyl dipeptides

A
  • true
40
Q

Detection of PAMPs by NLRs leads to activation of ________ which leads to transcription of geneses responsible for expression of pro-inflammatory cytokines.

NLRs also signal through IRF3/7 leading to production of __________.

A
  • NFkB
  • type I interferons (IFNs)
  • NLRs can also be activated by DAMPs
41
Q

__________ are expressed in the cytoplasm, detect viral RNA, and induce production of IFNs and inflammatory cytokines

A
  • RIG-like receptors (retinoic acid inducible gene-like receptor)
42
Q

___________ are receptors that bind to carbohydrates in Ca-dependent manner, are involved in fungal recognition, modulation of the innate immune response and are expressed by most cell types including macrophages and DCs

A
  • C-type lectin receptors (CLRs)
43
Q

PGRPs (peptidoglycan recognition proteins) localized in large granules of neutrophils help detect G- and G+ bacteria, inducing production of ______________.

In pigs, PGRPs are expressed in _________

A
  • antimicrobial peptides, ex: defensin
  • skin, bone marrow, and intestines
  • can also bind LPS and lipoteichoic acid
44
Q

Natural killer cells originate from __________ , are found in _________, and live for ______

A
  • bone marrow
  • blood, spleen, liver
  • approx. a week
45
Q

T/F: NK cells are always found in tissues

A
  • false, only migrate to tissues in large numbers when inflammatory reaction is underway
46
Q

T/F: NK cells do not possess receptors generated through gene segment rearrangement

A
  • true
47
Q

T/F: NK cells contain granules

A
  • true; they are called large granular lymphocytes (LGL)
48
Q

In humans and mouse NK cells, identification is via expression of ________________

A
  • CD56, CD16, and lack of CD3
49
Q

T/F: there is no exclusive NK cell marker in pigs, but CD2+, C8+, CD3-, and NKp46 is used

A
  • true;
  • cattle use CD335 (NKp46) as well
50
Q

What are the roles of NK cells in innate immunity?

A
  • kill virus-infected, stressed, and tumor cells
    - in vitro activation with IL-2 and IFNy, they become lymphokine activated killer cells (LAK)
  • cytokine and chemokine production
    • IFNy, TNFa, IL-17, IL-22, MIP-1a, MIP-1b
51
Q

T/F: stressed cells express major histocompatibility complex class I (MHC I) on their surface, signaling to NK cells that they should be killed

A
  • false, normal cells have MHC I
  • stressed cells have suppressed expression, or failure of expression
52
Q

Proteins like ___________ are highly expressed on stressed cells

A
  • MICA (MHC I chain-related A), MICB, Rae-1, H60
53
Q

T/F; the inhibitory receptor signals of NK cells block activating signals, preventing killing of normal cells

A
  • true
54
Q

NK receptors differ between species

Humans, cattle, cats, dogs, and pigs have ________________, white mice, rats and horses have ____________

A
  • KIRs (killer cell immunoglobulin-like receptors) or CD158
  • KLRs (killer cell lectin-like receptors
55
Q

KIRs are ______________ that are highly polymorphic, including _______ and ________

A
  • type I transmembrane proteins
  • LILRs (leukocyte immunoglobulin-like receptors) and NKp46
  • KIRs, LILRs, and NKp56 expressed on NK cells
  • KIRs also expressed on subsets of lymphocytes
  • LILRs also expressed on leukocytes
56
Q

KLRs, like __________, recognize stress proteins such as MICA, MICB, ULBP (humans); Rae-1, MULT1, and H60 (mice). High expression of stress proteins allows binding of _______ which overrides the inhibitory signals and permits NK cell cytotoxicity.

A
  • NKG2D receptor
57
Q

What are some important activating receptors on NK cells? Inhibitory?

A
  • NKp46, CD16, NKG2D (also reduction/lack of MHC1 expression)
  • CD94/NKG2A