Lecture 4: Innate Immunity (part I) Flashcards
What is opsonization
The process by which a pathogen is marked for elimination
functions of C-reactive protein (pentraxin)
- Opsonization of microbes, activation of complement
Circulating effector proteins of innate immunity
- Complement
- Mannose-binding lectin (collectin)
- C-reactive protein (pentraxin)
Cell receptors that recognize pathogen-associated molecular patterns (PAMPs) are termed
Pattern Recognition Receptors (PRRs)
Formyl peptide receptor-1 (FPR1) and all other chemoattractant receptors belong to the ____ superfamily
seven-transmembrane, guanosine triphosphate (GTP)-binding (G) protein-coupled receptor (GPCR) superfamily
What TLRs recognize extracellular pathogens
- TLR-1
- TLR-2
- TLR-4
- TLR-5
- TLR-6
What TLRs recognize intracellular pathogens
- TLR-3
- TLR-7
- TLR- 8
- TLR-9
What TLR(s) recognize Bacterial lipopeptides
- TLR-1:TLR-2
- TLR-6:TLR-2
What TLR(s) recognize bacterial peptidoglycan
TLR-2
What TLR(s) recognize LPS
- TLR-4
What TLR(s) recognize bacterial flagellin
- TLR-5
Which TLR(s) recognize dsRNA
- TLR-3
Which TLR(s) recognize ssRNA
- TLR-7
- TLR-8
Which TLR(s) recognize CpG DNA
- TLR-9
What are the major transcription factors activated by TLR signaling pathways are
- Nuclear factor kB (NF-kB)
- Activation protein (AP-1)
- Interferon response factor 3 (IRF3)
- Interferon response factor 7(IRF7)
Which TLR(s) use the adaptor protein MyD88 to activate the transcription factors NF-kB and AP-1
- TLRs that only use MyD88 to activate transcription factors NF-kB and AP-1
- TLR-1
- TLR-2
- TLR-5
- TLR-6
- TLR that can use MyD88 to activate transcription factors NF-kB and AP-1 but can also use TRIF to activate interferon transcription factors IRF3 and IRF7
- TLR-4
- TLRs that can use both MyD88 to activate NF-kB and IRF7
- TLR-7
- TLR-9
Which TLRs can induce both inflammatory and antiviral responses
- TLR-7
- TLR-9
- TLR-4
All TLRs except ____ signal through MyD88 and are therefore capable of activating NF-kB and inducing an inflammatory response
- TLR-3
Which TLR(s) use adaptor protein TRIF
- only use adaptor protein TRIF
- TLR-3
- is able to use both TRIF and MyD88
- TLR4
Which TLRs activate IRF transcription factors
- Use adaptor protein TRIF only to activate transcription IRF transcription factors
- TLR3
- TLR4 (is able to use adaptor protein MyD88 to activate NF-kB pathway)
- Use adaptor protein MyD88 to activate IRFs and NF-kB
- TLR7
- TLR9
What cells have TLR1:TLR2, TLR2:TLR6
- Monocytes
- Denritic cells
- eosinophils
- Basophils
- mast cells
TLR3 Is found on what cells
NK cells
TLR4 are found on what cells
- Macrophages
- Dendritic cells
- Mast cells
- Eosinophils
TLR5 is found on what cells
- Intestinal epithelium
What cells is TLR7 found on
- Plasmacytoid dendritic cells
- NK cells
- Eosinophils
- B cells
TLR8 is found on what cells
NK cells
TLR9 is found on what cells
- Plasmacytoid dendritic cells
- B cells
- eosinophils
- basophils
What TLRs are expressed on many innate cells as well as on B cells
TLR7 and TLR9
Explain TLR4 LPS signaling in Macrophages
- A complex of TLR4, MD2, CD14 and LPS is assembled at the macrophage surface
- MyD88 binds TLR4 and activates IRAK4 to phosphorylate TRAF6, which leads to the posphorylation and activation of IKK
- IKK phosphorylates IkB, leading to its degradation and the release of NFkB, which enters the nucleus
- NFkB activates transcription of genes for inflammatory cytokines, which are synthesized in the cytoplasm and secreted via the ER
When do macrophages arrive at inflammatory site
16-48 hrs
IL-12 (IL-12R) is a heterodimer composed of beta1 and beta2 subunits, both of which are members of the type ____ cytokine receptor family
Type I cytokine receptor family
_______ is a protein that is passively released during necrosis and uses the RAGE receptor to activate NF-kB pathway
High mobility group box (HMGB1)
HMGB1, HSPs, and Uric acid are all examples of ____ thst can acivate NF-kB pathway
DAMPs
NOD-like receptors (NLRs) act as ____ proteins that assemble signaling platforms that trigger NF-kB and mitogen-activated protein kinase signaling pathways. They also control the activation of the inflammatory ____
- Scaffolding proteins
- Inflammatory caspases
NLRs respod ot cytosolic PAMPs and DAMPs by binding other proteins and forming signaling complexes called ______. By recruitment to the complex, ________ activate the enzyme caspase-1 (a protease with cystein residue in the active site), which main function is
- inflammasome
- inflammasomes
- Caspase-1 main function is to cleave the inactive cytoplasmic precursor forms of two homologous cyokines called IL-1ß and IL-18 (proinflammatory cytokines)
Scavenger receptors comprise a structurally and functionally diverse collection of cell surface proteins that were originally grouped on the basis of the common characteristic of
mediating the uptake of oxidized lipoproteins into cells.
Scavenger receptors (SRs) are trimeric complexes of
type II transmembrane polypeptides
The scavenger receptor (SR) family consists fo
- Scavenger receptor class A type I
- Scavenger receptor class A type II
- MARCO
What are 3 distince extracellular structural domains in SRs
- SR cystein rich (SRCR) domain (absent in SR-A II)
- The collagen-like domain, which is implicated in the binding of polyanionic ligands
- The alpha-helical coiled-coil domain (absent in MARCO)
SRs bind various bacterial constituents based on ___ charges of bacterial LPS, Lipoteichoic acid, nucleic acids, ß-glucan, and proteins
negative
Lectin family receptors contain a conserved carbohydrate recognition domain for recognition of
microbial mannose, N-acetylglucosamine, and ß-glucans
Defensins are small cationic peptides that contain both
cationic and hydrophobic regions
Defensins are produced by epithelial cells of mucosal surfaces and by granule-containing luekocytes, including
neutrophils, NK cells, and CTLs
Defensins have direct toxicity to microbes, including
- bacteria
- fungi
- enveloped viruses
Defensins kill microbes by
inserting into and disrupting functions of the microbial membranes
Cathelicidins are antimicrobial peptides produced by
neutrophils and barrier epithlial cells in the skin, GI tract, and respiratory tract
Cathelicidins have multiple anitmicrobial mechanisms including
- Direct toxicity to microorganisms and the activation of leukocytes
- Some bind and neutralize LPS
- Some play an anti-inflammatory role by binding to DNA and blocking inflammasome activation