Innate Immunity: Recognition of Pathogens and Effector Mechanisms

Comprehensive vocabulary flashcards covering the recognition of pathogens, pattern recognition receptor families, soluble opsonins, TLR/NLR/RLR signaling pathways, antiviral interferon-stimulated genes, and phagocytic effector mechanisms in innate immunity.

Self/Non-Self Recognition Model

The immunological model proposed by Charles Janeway positing that the immune system discriminates between foreign entities (such as pathogens or transplants) and host tissue, mounting defenses against non-self structures.

Danger Model

The immunological model proposed by Polly Matzinger stating that the immune system does not primarily distinguish between self and non-self, but rather discriminates between entities that cause cell damage or danger and those that do not.

Pattern Recognition Receptors (PRRs)

Host innate immune sensors—which can be membrane-bound, cytosolic, or soluble—that detect conserved structural motifs characteristic of microbes or tissue damage.

Pathogen-Associated Molecular Patterns (PAMPs)

Evolutionarily conserved molecular structures present on or within pathogens but absent from host cells, serving as invariant identifying markers for innate immune recognition.

Danger-Associated Molecular Patterns (DAMPs)

Endogenous host-derived molecules typically sequestered inside intact cells (such as HMGB1 or ATP) that are released during non-physiological cell death or tissue stress to alert PRRs.

Lipopolysaccharide (LPS)

A major glycolipid component of the outer membrane of Gram-negative bacteria that acts as a prototypical PAMP recognized by host innate receptors like TLR4.

$N$-formylmethionine (fMet)

A specialized amino acid residue that initiates protein synthesis in bacteria but is absent from host cytosolic translation, allowing innate sensors to identify bacterial proteins as non-self.

Unmethylated CpG Dinucleotides

Regions of DNA containing unmethylated cytosine-phosphate-guanine motifs commonly found in bacterial and viral genomes, which trigger innate responses via endosomal TLR9.

Opsonization

The process of tagging or coating a pathogen with host-derived soluble proteins (such as collectins, pentraxins, antibodies, or complement) to facilitate binding and ingestion by phagocytic receptors.

Collectins

A family of soluble C-type lectin PRRs characterized by a collagen-like triple helix stalk, a neck region, and trimeric carbohydrate recognition domains (CRDs) that bind microbial surface sugars.

Mannan-Binding Lectin (MBL)

A soluble liver-derived acute phase collectin with six CRD clusters that binds repeating mannan/sugar motifs on diverse pathogens and initiates the lectin pathway of complement.

Surfactant Protein A (SP-A)

A soluble collectin secreted by alveolar epithelial cells that binds repeating carbohydrate arrays on pulmonary pathogens (e.g., Pneumocystis carinii and Haemophilus influenzae) to promote phagocytic clearance in the lungs.

Pentraxins

A superfamily of plasma proteins characterized by a cyclic pentameric disc-like structure that binds microbial and damaged-host ligands in a $\text{Ca}^{2+}$-dependent manner.

C-Reactive Protein (CRP)

An acute phase pentraxin synthesized by hepatocytes in response to $\text{IL-6}$ that binds microbial phosphocholine and damaged cell polycations to activate complement and facilitate phagocytosis; serves as a major clinical marker of systemic inflammation.

Serum Amyloid P Component (SAP)

A hepatocyte-derived pentraxin that binds phosphoethanolamine, microbial sugars (including LPS), polyanions, and apoptotic or necrotic cells to mediate opsonization and phagocytic removal.

Pentraxin 3 (PTX3)

A locally produced pentraxin synthesized by macrophages, dendritic cells, neutrophils, and endothelial cells in response to $\text{IL-1}$ and $\text{TNF-}\alpha$ that acts as a local inflammatory mediator rather than a marker of systemic inflammation.

Macrophage Mannose Receptor (MR / CD206)

A cell-surface endocytic PRR containing $8$ carbohydrate recognition domains (CRDs) that achieve high-affinity binding through multi-point attachment to repeating mannose patterns on pathogens.

Toll-like Receptors (TLRs)

A class of evolutionary conserved type I transmembrane PRRs expressed on the plasma membrane or endosomal membranes that sense distinct pathogen components to trigger inflammatory and antiviral transcription programs.

Leucine-Rich Repeat (LRR) Domain

The curved, solenoid-shaped extracellular or luminal motif of TLRs and NLRs directly responsible for binding microbial ligand patterns.

TIR Domain (Toll/IL-1 Receptor Domain)

The conserved intracellular cytoplasmic domain of TLRs and IL-1 receptors that mediates downstream signaling by recruiting adapter proteins such as MyD88 or TRIF.

High Mobility Group Box 1 (HMGB1)

A nuclear DNA-binding architectural protein that functions as a DAMP when passively released from necrotic cells, interacting with TLR4 to stimulate $\text{NF-}\kappa\text{B}$ and pro-inflammatory cytokine expression.

NOD-like Receptors (NLRs)

A family of $23$ cytosolic PRRs in humans containing nucleotide-binding oligomerization domains and leucine-rich repeats that recognize intracellular PAMPs and DAMPs.

NOD1

A cytosolic NLR homodimer that senses diaminopimelic acid (DAP)—a bacterial peptidoglycan fragment—and recruits RIP2 to induce $\text{NF-}\kappa\text{B}$, AP-1, and type I interferon production.

Inflammasome

A high-molecular-weight cytosolic protein complex (such as NLRP3 assembled with ASC) that activates caspase-1 to proteolytically cleave pro-$\text{IL-1}\beta$ and pro-$\text{IL-18}$ into their active, secreted forms.

Pyroptosis

A rapid, caspase-1-dependent programmed inflammatory cell death pathway that results in cell membrane rupture, destroying intracellular pathogen niches and releasing pro-inflammatory cytokines and DAMPs.

RIG-I-like Receptors (RLRs)

A family of cytosolic RNA helicases (including RIG-I) that recognize uncapped viral double- or single-stranded RNA and interact with the mitochondrial adapter MAVS to trigger type I interferon gene transcription.

Protein Kinase R (PKR)

An interferon-stimulated cytosolic enzyme that binds viral dsRNA, auto-phosphorylates, and phosphorylates the translation initiation factor $\text{eIF2}\alpha$ to arrest host and viral protein synthesis.

$2',5'$-Oligoadenylate Synthetase (OAS)

An interferon-stimulated cytosolic enzyme activated by viral dsRNA that synthesizes $2',5'$-oligoadenylate chains to activate latent RNase L, which degrades viral and cellular single-stranded RNA.

Myxovirus Resistance (Mx) Proteins

Interferon-induced dynamin-like GTPases that oligomerize into rings around viral nucleocapsid components, preventing viral transcription, genome replication, and capsid assembly.

Cardinal Signs of Inflammation

The five classical physiological manifestations of acute local inflammation: heat (calor), redness (rubor), swelling (tumor), pain (dolor), and loss of function (functio laesa).

Acute Phase Response

A systemic reaction triggered by inflammatory cytokines ($\text{IL-1}\beta$, $\text{IL-6}$, $\text{TNF-}\alpha$) acting on the hypothalamus to induce fever, the bone marrow to stimulate leukopoiesis, and hepatocytes to synthesize acute phase proteins.

Fibrosis

The excessive accumulation of extracellular matrix proteins and collagen driven by persistent fibroblast proliferation during chronic, unresolved inflammation, leading to architectural destruction of tissue.

Neutrophil Extracellular Traps (NETs)

Extracellular web-like structures composed of extruded decondensed nuclear chromatin and antimicrobial granule proteins released by activated neutrophils to snare and kill microbes.

Phagolysosome

A digestive intracellular vesicle formed by the fusion of an internalized phagosome with a lysosome, characterized by an acidic pH ($4.5-5.0$) that activates acid hydrolases, antimicrobial peptides, and degradative enzymes.

Respiratory Burst

The rapid uptake of molecular oxygen by activated phagocytes via membrane-associated NADPH oxidase, generating superoxide anion radicals ($\cdot\text{O}_2^-$) and downstream reactive oxygen species (ROS) to destroy ingested pathogens.