Lecture 4 Flashcards
(25 cards)
What are two functions of T cells?
- help other immune cells become more responsive or effective
- kill cells
What are CD4+ cells?
T-helper cells, recognize MHC Class II
What are CD8+ cells?
cytotoxic T-cells, recognize MHC Class I
How does the adaptive immune system get activated?
dendritic cells activate T cells: T-cell receptor recognizes MHC molecule with a peptide antigen
How does MHC-peptide loading work?
phagocytic dendritic cells degrade pathogen components, load antigens onto MHC molecules
What are some PRRs for bacteria?
mannose receptor, LPS receptor (CD14), TLR-4, TLR-2, scavenger receptor, glucan receptor
What are some PRRs for fungi?
Dectin-1 receptor recognizes carbohydrates (beta-glucan) on fungi
How do TLR1 and TLR2 work together?
Their convex surfaces have binding sites for lipid side chains of triacyl lipopeptides, binding of each TLR to same lipopeptide induces dimerization which brings their cytoplasmic TIR domains into proximity
Which TLR(s) form a homodimeric complex? Heterodimeric?
TLR4 = homodimeric
TLR1 / TLR2 = heterodimeric
How does TLR4 recognize a ligand?
5 acyl chains of LPS bind to a pocket within MD-2 on TLR4. The free acyl chain binds to the outer convex surface of another TLR4, inducing a dimer. An LPS bound to the second TLR4/MD2 stabilizes the dimer.
Describe the TLR signaling pathway
- Dimerized TLRs recruit IRAK1 and IRAK4, activating ubiquitin ligase TRAF-6
- TRAF-6 is polyubiquinated, creating scaffold for activation of TAK1
- TAK1 associates with IKK and phosphorylates IKKbeta, which phosphorylates Ikbeta
- Ikbeta is degraded, releasing NFkB into the nucleus to induce expression of cytokine genes
How can viruses be characterized?
Enveloped or non-enveloped, genome can be +/-, single stranded, double stranded, RNA, or DNA
How are non-enveloped viruses detected?
Receptor mediated endocytosis –> endocytosis –> endosomal fusion –> genomic content leaks out to endosome and is detected
How do TLRs signal via endosomes?
TLR3 in endosome binds dsRNA and signals via TRIF to induce IFN gene expression
TLR7 in endosome binds ssRNA and signals via MyD88 to induce IFN gene expression
How are enveloped viruses detected?
binding –> fusion –> release of genomic content –> detection –> activation of anti-viral response
What are RLRs?
retionic acid inducible genes
What is the purpose of RIG-I and MDA-5? How do they differ?
Detect cytosolic viral RNAs
Host RNAs are capped
RIG-I recognizes uncapped ssRNAs, MDA-5 recognizes dsRNA
cGAS-STING pathway
dsRNA from viruses activates cGAS to produce cGAMP from ATP and GTP
cGAMP or other cyclic dinucleotides bind to STING dimer present on ER membrane, activate its signaling
STING activates kinase TBK1 to phosphorylate IRF3, which enters nucleus and induces expression of type I interferon genes
Examples of extracellular PRRs
TLR –> bacterial cell wall lipid
Lectin –> fungal polysaccharide
Examples of cytosolic PRRs
NLR –> bacterial peptidoglycans
RLR –> viral RNA
Examples of endosomal recognition
TLR recognizes nucleic acids of ingested microbes
What are NLRs?
NOD-like Receptors that recognize cellular damage
What is NOD1?
PRR that recognizes a breakdown product of peptidoglycan: gamma-glutamyl-diaminopimelic acid
What is NOD2?
PRR that recognizes a breakdown product of peptidoglycan: muramyl dipeptide
