Innate Immunity (Exam 1) Flashcards
_______ are part of microbes that are recognized by our innate immune system _________.
PAMPs
PRRs
What do PAMPs stand for vs. DAMPs?
PAMPs: pathogen-associated molecular patterns
DAMPs: damage-associated molecular patterns
What are DAMPs?
endogenous molecules made by damaged/necrotic cells that are recognized by the innate immune system
What are TLRs?
toll-like receptors (type of PRR)
Where are TLRs located? What do they recognize?
cell surface, sometimes endosomes
recognize degraded parts of microbes
Signaling protein that is a type of cytokine released when a virus is present
Type I Interferons
What do Type I Interferons induce?
antiviral state (response against virus)
What is NF-kB?
transcription factor
What does NF-kB (transcription factor) activate?
inflammatory genes
What is an IRF?
interferon responsive gene
Function of IRF
expresses Type I interferons
What are 3 families of PRRs that recognize various PAMPs of microbes?
- RIG-I-like receptor (RLR)
- NOD-like receptor (NLR)
- Toll-like receptor (TLR)
What do RIG-I-like receptors (RLR) recognize?
RNA in cytosol (when microbes get into cell)
What do NOD-like receptors recognize?
peptidoglycan (of microbe cell wall) and other things in cytosol
What do TLRs recognize?
degraded parts of microbes
What do TLR1 + TLR2 recognize on microbes?
bacterial lipopeptides
What does TLR2 by itself recognize?
bacterial peptidoglycan
What do TLR2 + TLR6 recognize?
bacterial lipopeptides
What does TLR4 recognize?
LPS (on cell surface of gram-neg bacteria)
What does TLR5 recognize?
flagellated bacteria
What does TLR3 recognize?
doubled-stranded RNA
What do TLR7 + TLR8 recognize?
single-stranded RNA
What does TLR9 recognize?
microbe DNA
What does CLR recognize?
carbohydrates on microbes
What do cytosolic DNA sensors (CDS) recognize?
microbial DNA
Epithelial barriers prevent infection by killing microbes locally by __________.
antimicrobial peptides (AMPs)
What are 2 examples of anti-microbial peptides (AMPs)?
defensins
cathelicidins
Defensins are small, cationic peptides that are (directly/indirectly) toxic to microbes and activate ________.
directly
inflammatory cells
Cathelicidins are AMPs in the epithelial barrier that can bind and neutralize _______.
LPS
How does the epithelial barrier kill microbes directly?
cytokine-producing innate lymphoid cells
What are the 3 subsets of innate lymphoid cells of epithelial barrier (ILCs)?
ILC1
ILC2
ILC3
Match the ILC subset to which transcription factor it activates and product it produces:
- ILC1
- ILC2
- ILC3
- TF: T-BET, Product: IFN-y
- TF: GATA3, Product: IL-5, IL-13
- TF: RORyt, Product: IL-17, IL-22
What response occurs when IFN-y is produced from ILC1 of the epithelial barrier?
viral defense
What response occurs when IL-5 & IL-13 are produced from ILC2 of the epithelial barrier?
helminth defense
allergy inflammation
What response occurs when IL-17 & IL-22 are produced from ILC3 of the epithelial barrier?
intestinal barrier
lymphoid organogenesis
What are opsonins?
soluble molecules secreted in bloodstream that bind to microbe surface for uptake by phagocyte cells
What are 4 examples of opsonins?
- antibody
- complement
- C-reactive protein
- mannose-binding lectin
What 2 ways do neutrophils use to harm ingested microbes?
- neutrophil net (extrude DNA)
- antimicrobial compounds
Macrophages (primarily) ingest and destroy microbes via _________.
phagocytosis
Once phagocytized, macrophages can destroy microbes in what 3 ways?
- enzyme degradation
- antimicrobial proteins
- reactive oxygen & nitrogen species
_______ is an example of a reactive nitrogen species used by macrophages to kill microbes.
nitric oxide
How is nitric oxide made to kill microbes?
iNOS in the cell uses arginine to make NO
Macrophages uses ROS (reactive oxygen species) to kill microbes by using ________ to convert oxygen –> ROS.
phagocyte oxidase
What two receptors do NK cells have which allows them to recognize infected cells? Which is always present on normal cells? Which is not activated with an infected cell?
activating receptor & inhibiting receptor
activating
inhibiting
What does the inhibitory receptor on NK cells do when bound? What is it bound to?
inhibits NK cell from killing
binds to MHC (major histocompatibility complex)
Which MHC is expressed on all cells? What is the exception?
MHC class I
exception: when virus infects cell and downregulates expression so evade immune system
When a virus downregulates MHC class I expression to evade the immune system, how is it still detected?
detected by NK cells
MHC molecule is not bound to inhibitory receptor on NK cell –> kills infected cell
What makes IL-12? What effect does IL-12 have on NK cells?
macrophages
activates NK cells to make IFNy
How does IFNy (produced by NK cells) effect macrophages?
makes them a better “killer” of microbes
What is complement?
plasma proteins that work to rid of microbes
List the 3 complement pathways.
- classical pathway
- mannose-binding lectin pathway
- alternative pathway
When is complement activated in the classical pathway?
when antibody binds to microbe
_____ is a soluble pentamer that will bind to a microbe and “fix” complement in the classical complement pathway.
IgM
What occurs for complement to be activated in the mannose-binding lectin complement pathway?
lectin molecule binds to pathogen surface
How is the alternative complement pathway activated?
starts on its own without outside activation
_______ is made by sentinel cells in the liver in response to IL-6 production.
C-reactive protein (CRP)
What is the function of C-Reactive Protein?
activates complement cascade
acts as opsonin to help clear microbes
What are the 3 main functions of complement?
- opsonize microbes
- recruit phagocytes to infection sites
- directly kill microbes (sometimes)
What are the 2 subsets of macrophages?
- M2 resolving
- M1 inflammatory
M2 resolving macrophages are driven to clear _______ cells and do what to tissue?
apoptotic
heal tissue
M1 inflammatory macrophages drive response by making ______ and use ____ to clear pathogens.
cytokines
NO
Term for accumulation of leukocytes, plasma proteins, and fluid from blood at the tissue site of infection or injury.
inflammation
List the 5 cardinal signs of inflammation.
- heat
- redness
- swelling
- pain
- loss of function
What are the 5 important innate cytokines?
- IL-1B
- TNF-a
- IL-6
- CXCL8
- IL-12
Which innate cytokine can cause shock in high amounts?
TNF-a
Match the innate cytokine to its functions:
- activate NK cells, adaptive immune response
- activate adaptive immune response, fever, acute-phase protein production
- chemotactic factor, recruit neutrophils, basophils, T cells to infection site, upregulate high-affinity receptor
- activates vascular endothelium, lymphocytes, fever, production of IL-6
- activates vascular endothelium & permeability, fever, compound mobilization
- IL-12
- IL-6
- CXCL8
- IL-1B
- TNF-a
What is a neutrophil net?
neutrophils extrude DNA to form extracellular traps
sticky DNA binds to keep microbes in the area
Term for normal process of cell turnover when a neutrophil becomes an apoptotic cell and is engulfed by macrophages.
efferocytosis
Macrophages engulfing apoptotic neutrophil cells will stimulate a _______ response and (upregulate/downregulate) the inflammatory response.
healing
downregulate
(T/F) Once antigen is recognized by a lymphocyte, the adaptive immune response will begin.
False - need TWO signals!
What are the 2 signals needed for the adaptive immune response to begin?
Signal 1: antigen recognition by lymphocyte
Signal 2: innate immune component
What 3 things in the innate immune response drive adaptive immunity?
- costimulators (B7)
- cytokines
- complement breakdown products
