Innate Immunity + NK Cells Flashcards
T/F: Innate immunity is natural immunity present from birth designed to protect the body without prior contact with the infectious agent
- true
What are routes of infection for pathogens?
- airway, GI tract, reproductive tract, external surface, wounds, insect bites
T/F: Innate immunity is a late response (>96 hours)
- false, immediate (0-96 hours)
What are methods of protection against infection?
1st line defenses such as phagocytosis, complement, interferon, inflammation,and fever are part of innate immunity
- false, these are 2nd line defenses
- 1st line defenses are skin, mucous membranes, chemicals
What are the kinds of physical barriers of innate immunity?
- 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
What are the kinds of humoral barriers of innate immunity?
- 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
What are the kinds of cellular barriers of innate immunity?
- neutrophils: phagocytose microorganisms
- macrophages: ingest and kill microorganisms/infected cells, function as APC, wound healing
- NK cells: kill infected/tumor cells
- eosinophils: eliminate parasites
What are the two cells of the phagocytic system?
- neutrophils and macrophages
T/F: macrophages circulate the bloodstream looking for foreign objects to ingest and degrade
- false; neutrophils
- monocytes also circulate blood before entering tissue to replenish macrophage populations
What cell is identified by expression of CD66?
- Neutrophils
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?
- 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
What cells are identified by expression of C14, CD11b, or F4/80?
- macrophages
T/F: macrophages have both granules and lysosomes
- false, just lysosomes that contain factors for intercellular killing mechanisms
T/F: neutrophils react to danger signals generated at sites of pathogen entry that induce chemotaxis towards the site
- false; macrophages
- N-formyl-methionine: secreted by bacteria
- peptides of coagulative system
- complement system components
- cytokines secreted by tissue macrophages
What are the receptors phagocytes use to bind to microorganisms?
- complement receptors
- scavenger receptor
- Fc receptors
- toll-like receptors
Phagocytes possess receptors for ___ complement component. ____ binds the antigen and then later binds to its receptor on the phagocyte. What does this trigger?
- C3b
- activation of phagocytosis
SRA, CD68, Lox-1, and C36 are all ___________ receptors that directly bind to _______ found on bacterial surfaces to initiate phagocytosis
- scavenger receptors
- polyamines
T/F: Fc receptors are only applicable using recurrent infections
- 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
What phagocyte receptor recognizes PAMPs?
- 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
What is the purpose of phagocytosis?
- 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
What is the process of phagocytosis?
- 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
What are the two established killing pathways in neutrophils, monocytes, and macrophages?
- oxidative pathways: generation of ROS and RNS
- non-oxidative pathway: lysosomal toxic substances
Respiratory burst is the several-fold increase in the use of _________ and __________ during phagocytosis
- oxygen + glucose
The oxygen dependent intracellular killing pathway refers to the respiratory burst which leads to formation of _______ which are toxic to microorganisms
- reactive oxygen species
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-)
- Pentose-phosphate
- cytochrome
- superoxide anion (*O2-) x2
Myeloperoxidase is released during the fusion of azurophilic granules with phagosome.
Myeloperoxidase uses ________ and Cl- to produce ______________
- H2O2
- hypochlorous acid
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
- superoxide anion
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.
- TNFa
- iNOS (inducible nitric oxide sythetase)
- NO
- IFNy also induces iNOS
What are ROS? RNS?
- ROS: superoxide anion, hydroxyl radical, hydrogen peroxide, hypochlorite anion
- RNS: nitric oxide, nitrogen dioxide, peroxynitrite
The main mechanism of the non-oxidative intracellular killing pathway is dependent on ___________
- 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
What are the sentinel cells? What do they do?
- macrophages, dendritic cells, mast cells
- use PRRs (pattern recognition receptors) to sense PAMPs and DAMPs
T/F: DAMPs are exogenous molecules released from damaged cells
- false, ENDOGENOUS
- damage-associated molecular patterns
What are PAMPs?
- pathogen-associated molecular patterns
- repetitive common types of molecules broadly expressed by pathogens NOT found in host tissues
- eX: peptidoglycan, lipopolysaccharide, lipoteichoic acids, mannan
What are the 5 classes of PRRs?
- Toll-like receptors
- NOD-like receptors
- RIG-Ike receptors
- C-type lectin receptors
- Peptidoglycan-recognition receptors
Major PRRs located on host cell membranes or within that signal the presence of invaders are?
- toll-like receptors
- know internal compartment
All TLRs signal through _______, except for TLR3 which signals through ______.
The result of signaling is the production of __________
- MyD88
- TRIF
- proinflammatory cytokines
_______ are found inside cells and detect pathogens in cytoplasm, generally intracellular bacteria
- NOD-like receptors (nucleotide-binding oligomerization domain-like receptor)
T/F; NOD1 detects bacterial peptidoglycan, NOD2 detects muramyl dipeptides
- true
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 __________.
- NFkB
- type I interferons (IFNs)
- NLRs can also be activated by DAMPs
__________ are expressed in the cytoplasm, detect viral RNA, and induce production of IFNs and inflammatory cytokines
- RIG-like receptors (retinoic acid inducible gene-like receptor)
___________ 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
- C-type lectin receptors (CLRs)
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 _________
- antimicrobial peptides, ex: defensin
- skin, bone marrow, and intestines
- can also bind LPS and lipoteichoic acid
Natural killer cells originate from __________ , are found in _________, and live for ______
- bone marrow
- blood, spleen, liver
- approx. a week
T/F: NK cells are always found in tissues
- false, only migrate to tissues in large numbers when inflammatory reaction is underway
T/F: NK cells do not possess receptors generated through gene segment rearrangement
- true
T/F: NK cells contain granules
- true; they are called large granular lymphocytes (LGL)
In humans and mouse NK cells, identification is via expression of ________________
- CD56, CD16, and lack of CD3
T/F: there is no exclusive NK cell marker in pigs, but CD2+, C8+, CD3-, and NKp46 is used
- true;
- cattle use CD335 (NKp46) as well
What are the roles of NK cells in innate immunity?
- 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
T/F: stressed cells express major histocompatibility complex class I (MHC I) on their surface, signaling to NK cells that they should be killed
- false, normal cells have MHC I
- stressed cells have suppressed expression, or failure of expression
Proteins like ___________ are highly expressed on stressed cells
- MICA (MHC I chain-related A), MICB, Rae-1, H60
T/F; the inhibitory receptor signals of NK cells block activating signals, preventing killing of normal cells
- true
NK receptors differ between species
Humans, cattle, cats, dogs, and pigs have ________________, white mice, rats and horses have ____________
- KIRs (killer cell immunoglobulin-like receptors) or CD158
- KLRs (killer cell lectin-like receptors
KIRs are ______________ that are highly polymorphic, including _______ and ________
- 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
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.
- NKG2D receptor
What are some important activating receptors on NK cells? Inhibitory?
- NKp46, CD16, NKG2D (also reduction/lack of MHC1 expression)
- CD94/NKG2A
