VET 402 Innate Immunity II (Lecture #11)

Vocabulary practice flashcards covering Pattern Recognition Receptors (TLRs, NLRs, RLRs, cGAS-STING), Inflammasomes, Cytokines and Chemokines, the Complement System cascades, the Acute Phase Response, and Antiviral Host Defenses involving Type I Interferons and Natural Killer (NK) cells from VET 402 Lecture 11.

Pattern Recognition Receptors (PRRs)

Host sensors that detect conserved exogenous microbial molecular structures (PAMPs/MAMPs) or endogenous tissue damage signals (DAMPs) to initiate innate immune responses.

Pathogen-Associated Molecular Patterns (PAMPs / MAMPs)

Conserved exogenous molecular structures found across classes of microbes—such as lipopolysaccharide (LPS), flagellin, peptidoglycan, viral dsRNA, and unmethylated CpG DNA—that are recognized by PRRs.

Damage-Associated Molecular Patterns (DAMPs)

Endogenous danger signals released by stressed, damaged, or necrotic host tissues following trauma, burns, cuts, or infection (e.g., extracellular ATP, heat-shock proteins, and extracellular DNA).

Mannose-Binding Lectin (MBL)

A soluble, liver-produced lectin-type PRR composed of carbohydrate-recognition domains, an $\alpha$-helical coiled coil, and a collagen helix that recognizes mannose and fucose residues on microbial surfaces to activate the complement system.

Toll-like Receptors (TLRs)

A phylogenetically conserved family of transmembrane PRRs (13 identified in humans and mice) located on the plasma membrane or in endosomes that sense extracellular or endocytosed microbial components.

TLR4

A plasma membrane Toll-like receptor that, together with MD-2, senses lipopolysaccharide (LPS) from Gram-negative bacteria.

TLR5

A cell-surface Toll-like receptor that specifically recognizes bacterial flagellin.

TLR3

An endosomal Toll-like receptor that detects viral double-stranded RNA (dsRNA) and signals via the TRIF adaptor pathway to induce Type I interferons through IRF3.

TLR7 and TLR8

Endosomal Toll-like receptors that recognize viral single-stranded RNA (ssRNA).

TLR9

An endosomal Toll-like receptor that detects unmethylated CpG DNA motifs present in bacteria, viruses, parasites, and fungi.

NOD1 and NOD2

NLR-family cytosolic sensors that detect intracellular bacterial peptidoglycan breakdown products (such as muramyl dipeptide) and signal through RICK (RIP2/RIPK2) to activate NF-$\kappa$B.

RIG-I

A CARD-family cytosolic RNA helicase sensor (RLR-family) that detects viral double-stranded RNA in the cytoplasm to stimulate antiviral responses.

cGAS-STING

A cytosolic pattern recognition pathway that senses cytoplasmic double-stranded DNA (dsDNA) to induce Type I interferons and pro-inflammatory signaling.

NF-$\kappa$B (Nuclear Factor Kappa B)

A primary transcription factor maintained in the cytoplasm by I$\kappa$B at rest; upon activation and I$\kappa$B phosphorylation by IKK, it rapidly translocates to the nucleus (peaking within ~$10\text{ minutes}$) to induce pro-inflammatory cytokines, chemokines, and adhesion molecules.

Inflammasome

A large cytoplasmic multiprotein complex (up to ~$1\,\mu\text{m}$ in diameter) containing an NLR sensor (e.g., NLRP3), the adaptor ASC, and pro-caspase-1; it cleaves pro-IL-1$\beta$ and pro-IL-18 into active cytokines and induces Gasdermin D pore formation.

Gasdermin D (GSDMD)

A pore-forming protein cleaved during inflammasome activation that inserts into the plasma membrane to facilitate cytokine release and trigger inflammatory cell death (pyroptosis).

Autocrine Signaling

A mode of cytokine signaling in which a secreted cytokine binds to receptors on and alters the function of the exact same cell that produced it.

Paracrine Signaling

A mode of cytokine signaling where released chemical messengers act locally on neighboring target cells in close proximity.

Endocrine Signaling

A mode of signaling in which cytokines enter the systemic circulation to act on distant organs and tissues (e.g., bone marrow, liver, and brain).

Tumor Necrosis Factor-alpha (TNF-$\alpha$)

A major pro-inflammatory cytokine secreted by macrophages and dendritic cells that increases vascular permeability, induces local endothelial activation, and triggers fever and shock when present systemically.

Interleukin-1$\beta$ (IL-1$\beta$)

A potent pro-inflammatory cytokine processed by caspase-1 that activates vascular endothelium and lymphocytes, causes local tissue destruction, and acts on the hypothalamus to produce fever.

Interleukin-6 (IL-6)

A pro-inflammatory cytokine that stimulates lymphocyte activation, promotes antibody production, and acts on hepatocytes to trigger the synthesis of acute-phase proteins.

CXCL8 (IL-8)

A chemotactic cytokine (chemokine) produced by activated macrophages and tissue cells that recruits neutrophils, basophils, and T cells to infection sites via its GPCR receptor.

Interleukin-12 (IL-12)

A pro-inflammatory cytokine produced by macrophages and dendritic cells that activates Natural Killer (NK) cells and drives naive CD4 T cells to differentiate into $T_H1$ cells.

Interleukin-10 (IL-10)

An anti-inflammatory cytokine that inhibits the macrophage production of pro-inflammatory cytokines such as TNF-$\alpha$, IL-1$\beta$, and IL-6 to prevent excessive inflammation.

Chemokines

Small chemotactic cytokines characterized by conserved cysteine motifs (classified into C, CC, CXC, and $CX_3C$ families) that guide leukocyte migration and extravasation.

Complement System

A proteolytic cascade of more than 30 circulating liver-derived plasma proteins that surveil body fluids and rapidly activate via three distinct pathways to destroy pathogens.

Classical Pathway

A complement activation pathway initiated when the C1 complex (specifically C1q) binds directly to pathogen surfaces or to antigen-bound antibodies (IgM or IgG).

Lectin Pathway

A complement activation pathway initiated by soluble pattern recognition proteins (such as MBL or ficolins) and MASP proteases binding microbial terminal carbohydrates.

Alternative Pathway

A complement pathway initiated by continuous, low-level spontaneous hydrolysis of C3 into $C3(H_2O)$, which recruits factor B and factor D to form a C3 convertase on microbial surfaces.

C3b

The large cleavage fragment of complement C3 that covalently binds to microbial surfaces to function as a potent opsonin and participate in downstream C5 convertase complexes.

Anaphylatoxins (C3a and C5a)

Small, soluble complement cleavage fragments that induce smooth muscle contraction, increase vascular permeability, drive mast cell degranulation, and recruit/activate phagocytes.

Complement Receptor 1 (CR1)

A cell-surface receptor on phagocytes and erythrocytes that binds C3b-opsonized microbes or immune complexes, mediating phagocytic uptake or delivery to the liver and spleen for disposal.

Two-Signal Complement Phagocytosis Requirement

The requirement that macrophages bind C3b-coated bacteria via CR1 (signal 1) and simultaneously detect C5a via the C5a receptor (signal 2) to trigger efficient phagocytosis.

Membrane Attack Complex (MAC)

A hollow transmembrane pore assembled from complement proteins C5b, C6, C7, C8, and multiple C9 units (outer diameter ~$16\text{ nm}$) that inserts into microbial lipid bilayers to cause osmotic lysis.

Acute Phase Response (APR)

A systemic innate reaction orchestrated by pro-inflammatory cytokines (IL-6, IL-1$\beta$, and TNF-$\alpha$) that alters liver protein production, mobilizes bone marrow neutrophils, and produces fever.

C-Reactive Protein (CRP)

An acute-phase pentraxin protein synthesized by the liver during inflammation that binds phosphocholine on bacterial surfaces to act as an opsonin and activate complement via C1q.

Type I Interferons (IFN-$\alpha$ and IFN-$\beta$)

Antiviral cytokines induced by viral detection pathways that signal through STAT1:STAT2 and IRF9 (forming ISGF3) to establish an antiviral state in host cells.

Plasmacytoid Dendritic Cells (pDCs)

Specialized circulating dendritic cells that express endosomal TLR7 and TLR9, secreting up to ~$1000\times$ more Type I interferons than standard cells in response to viral nucleic acids.

Protein Kinase R (PKR)

An interferon-stimulated, RNA-dependent protein kinase that phosphorylates translation initiation factor eIF-2, thereby arresting host and viral protein synthesis.

$2'\text{-}5'$ Oligoadenylate Synthetase

An interferon-inducible enzyme activated by viral dsRNA that synthesizes $2'\text{-}5'$-linked adenosine oligomers, which in turn activate RNase L to degrade viral and host RNA.

Mx Proteins

Interferon-induced nuclear and cytoplasmic dynamin-like GTPases that assemble into ring complexes around viral ribonucleoprotein complexes, trapping them and preventing viral replication.

Natural Killer (NK) Cells

Innate lymphoid cells (ILCs) lacking rearranged B or T cell antigen receptors that produce IFN-$\gamma$ and trigger target cell apoptosis via perforin and granzyme secretion.

Missing-Self Recognition

A mechanism by which NK cells kill target cells: engagement of inhibitory receptors by normal MHC class I delivers a negative signal blocking lysis, whereas cells with downregulated or absent MHC class I fail to deliver this inhibition and are killed.

Perforin and Granzymes

Cytotoxic granule proteins released by NK cells and CD8+ T cells; perforin polymerizes to form pores in the target cell membrane, facilitating entry of granzyme serine proteases that activate caspases to trigger apoptosis.