chapter 4 immunology - Overview, barriers, TLRs, and TLR signaling

What does a PAMP represent?

A conserved structure associated with a pathogen.

What does a DAMP represent?

A molecule associated with cell or tissue damage.

What receptors recognize PAMPs and DAMPs in innate immunity?

Pattern-recognition receptors (PRRs).

What are the five major PRR families emphasized in this chapter?

TLRs, CLRs, RLRs, NLRs, and ALRs.

What are the major soluble effectors of innate immunity emphasized in this chapter?

Cytokines (including interferons) and complement.

What are the major cellular effectors of innate immunity emphasized in this chapter?

Epithelial barriers, phagocytes, and innate lymphocytes such as NK cells.

Which cell is emphasized as a bridge between innate and adaptive immunity?

Dendritic cells.

What types of pathogen structures commonly serve as bacterial PAMPs?

Cell-wall components and flagellin.

What pathogen structures are especially important PAMPs for viruses?

Nucleic acids.

What innate defenses protect the skin?

Antimicrobial peptides/proteins and fatty acids in sebum.

What major physical mechanism protects the airways and lungs?

Cilia sweep mucus outward; coughing and sneezing expel it.

What innate cell protects the alveoli of the lungs?

Macrophages.

What innate mechanisms protect the urogenital tract?

Flushing by urine/mucus, low pH, and antimicrobial peptides/proteins.

What helps protect the small intestine from pathogens?

Digestive enzymes, antimicrobial peptides/proteins, commensal microbes, and fluid flow.

What are basic barrier mechanisms and biochemical defenses considered?

The first line of immunological defense.

What do Toll-like receptors (TLRs) recognize?

PAMPs and DAMPs.

What extracellular domain of TLRs binds PAMPs and DAMPs?

Leucine-rich repeat (LRR) domain.

What cytoplasmic signaling domain do TLRs contain?

TIR (Toll/IL-1 receptor) domain.

What are the three major structural features of a TLR?

Extracellular LRR domain, transmembrane domain, and cytoplasmic TIR domain.

Where can TLRs be located?

On the cell surface or on endosomal/lysosomal membranes.

Why is TLR location important?

It determines which ligands/PAMPs the TLR encounters.

Which TLR is found on both the cell surface and endosomal membrane?

TLR4.

Most TLRs form what type of dimer?

Homodimers.

Which TLR is emphasized as an exception to the usual TLR homodimer pattern?

TLR2.

An endosomal TLR would be especially likely to recognize what type of viral material?

Viral nucleic acid.

Which endosomal TLR recognizes dsRNA?

TLR3.

Which endosomal TLRs recognize viral ssRNA?

TLR7 and TLR8.

Which endosomal TLR recognizes DNA/CpG-type nucleic acid?

TLR9.

Which TLR recognizes LPS from Gram-negative bacteria?

TLR4.

Which TLR recognizes bacterial flagellin?

TLR5.

What adaptor protein is recruited by most TLRs?

MyD88.

Where does MyD88 bind on a TLR?

The TIR domain.

What transcription factor does MyD88 signaling activate to produce inflammatory cytokines?

NF-κB.

What is the major result of NF-κB activation in TLR signaling?

Production of proinflammatory cytokines.

MyD88 signaling activates AP-1 through what pathway?

The MAP kinase pathway.

What cellular outcomes are associated with AP-1 activation in this chapter?

Cell differentiation, proliferation, and apoptosis.

Which endosomal TLRs use MyD88 to activate IRF7?

TLR7, TLR8, and TLR9.

What does IRF7 activation downstream of TLR7/8/9 produce?

Type I interferons IFN-α and IFN-β.

Which TLR recruits TRIF?

TLR3.

Where is TLR3 located?

Endosomal membrane.

Which transcription factors does TRIF-dependent TLR3 signaling activate to produce type I IFNs?

IRF3 and IRF7.

What type of interferons are produced downstream of IRF3/IRF7?

Type I interferons: IFN-α and IFN-β.

Besides IRFs, which two major transcriptional pathways can TLR3/TRIF activate?

NF-κB and AP-1.

What is the simplest distinction between MyD88 and TRIF?

Most TLRs use MyD88; TLR3 uses TRIF.

What effector molecules can TLR signaling induce?

Antimicrobial peptides, type I IFNs, inflammatory cytokines/chemokines, iNOS, and COX-2.