Innate Immunity: The Early Defense Against Infections

Comprehensive vocabulary flashcards covering Chapter 2: Innate Immunity, including cellular receptors, components, inflammatory responses, leukocyte recruitment, complement, antiviral defense, and microbial evasion mechanisms.

Innate Immunity

The early line of host defense present and ready to act immediately against microbes and dead cells, blocking infection at epithelial barriers and clearing dead tissue without requiring clonal expansion.

Pathogen-Associated Molecular Patterns (PAMPs)

Conserved molecular structures shared across classes of microbes, such as bacterial lipopolysaccharide (LPS), peptidoglycan, flagellin, and viral double-stranded RNA (dsRNA).

Damage-Associated Molecular Patterns (DAMPs)

Endogenous molecules released from stressed, damaged, or necrotic host cells following sterile injury (e.g., tissue infarction, hypoxia) that trigger innate inflammation.

Pattern-Recognition Receptors (PRRs)

Germline-encoded cellular receptors of the innate immune system with limited diversity that recognize microbial PAMPs and host DAMPs.

Toll-Like Receptors (TLRs)

A major family of innate pattern-recognition receptors located on the cell surface and in endosomes that recruit adaptor proteins to trigger inflammatory and antiviral transcription factors.

TLR-4

A cell surface Toll-like receptor that specifically recognizes bacterial lipopolysaccharide (LPS, also known as endotoxin).

TLR-2

A cell surface Toll-like receptor that recognizes bacterial peptidoglycan and forms heterodimers with TLR-1 or TLR-6 to recognize bacterial lipopeptides.

TLR-5

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

Endosomal TLRs (TLR-3, TLR-7, TLR-8, TLR-9)

Intracellular Toll-like receptors that detect ingested microbial nucleic acids: TLR-3 binds dsRNA, TLR-7 and TLR-8 bind ssRNA, and TLR-9 binds unmethylated CpG DNA.

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

A transcription factor activated downstream of TLR and NLR signaling that increases the expression of inflammatory cytokines, endothelial adhesion molecules, and costimulators.

Interferon Regulatory Factors (IRFs)

Transcription factors activated downstream of TLR signaling that stimulate the production of type I interferons ($\text{IFN-}\alpha$, $\text{IFN-}\beta$) to induce an antiviral state.

NOD-Like Receptors (NLRs)

A family of cytosolic pattern-recognition receptors; NOD-1 and NOD-2 recognize bacterial peptidoglycan-derived structures and activate NF-$\kappa$B.

NLRP-3 Inflammasome

A cytosolic multi-protein complex composed of the sensor NLRP-3, an adaptor, and inactive caspase-1; assembled in response to stress signals (ATP, urate crystals, altered $\text{K}^+$) to cleave pro–IL-1$\beta$ into active IL-1$\beta$.

RIG-Like Receptors (RLRs)

Cytosolic receptors that detect viral RNA within the host cytoplasm and trigger the production of type I interferons.

Cytosolic DNA Sensors (CDSs)

Cytosolic pattern-recognition receptors that detect viral or microbial DNA in the cytoplasm and initiate type I interferon production.

C-Type Lectin Receptors

Membrane-bound receptors that recognize fungal glycans (dectins) and microbial terminal mannose residues to promote phagocytosis and defense.

N-Formylmethionine Receptor

A cellular receptor that binds bacterial protein peptides containing N-formylmethionine, stimulating phagocyte migration and antimicrobial functions.

Defensins and Cathelicidins

Locally produced antimicrobial peptides secreted by epithelial cells and phagocytes that destroy microbial cell membranes at portals of entry.

Intraepithelial Lymphocytes

T lymphocytes embedded in epithelial layers with limited antigen receptor diversity that recognize and kill microbes and infected cells.

Morphology of Blood Neutrophils and Monocytes

Microscopic appearance of the two major phagocytes: (A) blood neutrophil displaying a multilobed nucleus and lysosomes, and (B) blood monocyte displaying a typical horseshoe-shaped nucleus.

Neutrophils (Polymorphonuclear Leukocytes)

The most abundant circulating white blood cells ($\sim 4{,}000\text{--}10{,}000/\mu\text{L}$) that act as first responders in acute inflammation, have a short lifespan of hours in tissue, and rapidly clear bacteria and fungi.

Monocytes

Circulating leukocytes ($\sim 500\text{--}1{,}000/\mu\text{L}$) with horseshoe-shaped nuclei that are recruited to inflamed tissues, where they mature into long-lived macrophages.

Tissue-Resident Macrophages

Long-lived macrophages arising from early embryonic precursors (yolk sac, fetal liver) that persist in homeostatic tissues, including microglial cells, Kupffer cells, and alveolar macrophages.

Classically Activated Macrophages (M1)

Macrophages activated by microbial products (via TLRs) and IFN-$\gamma$ that produce ROS, NO, and inflammatory cytokines to destroy phagocytosed microbes.

Alternatively Activated Macrophages (M2)

Macrophages induced by IL-4 and IL-13 that mediate tissue repair, extracellular matrix synthesis, and the termination of inflammation.

Dendritic Cells

Tissue sentinel cells that process microbial antigens, produce inflammatory cytokines, and display costimulatory ligands to link innate immunity with naive T-cell activation.

Mast Cells

Bone-marrow-derived cells in skin and mucosal barriers that rapidly release histamine, proteolytic enzymes, prostaglandins, and cytokines upon microbial or antibody stimulation.

Innate Lymphoid Cells (ILCs)

Lymphoid cells that lack rearranged T-cell antigen receptors and are classified into three major groups corresponding functionally to Th1, Th2, and Th17 subsets of CD4+ T cells.

Natural Killer (NK) Cells

Lymphoid cells comprising $\sim 10\%$ of circulating lymphocytes that destroy stressed or infected cells and secrete IFN-$\gamma$ in response to macrophage-derived IL-12.

NK-Cell Inhibitory Receptors

Receptors on NK cells that bind self class I MHC-self peptide complexes on healthy host cells, delivering inhibitory signals that prevent cell lysis.

Antibody-Dependent Cellular Cytotoxicity (ADCC)

The lysis of antibody-coated target cells mediated by the low-affinity Fc receptor CD16 expressed on NK cells.

$\gamma\delta$ T Cells

A subset of T cells found primarily in epithelial linings that express antigen receptors with limited diversity to provide rapid innate-like defense.

NK-T Cells

A specialized lymphocyte subset with limited T-cell receptor diversity that recognizes microbial lipids presented by the non-polymorphic class I-like molecule CD1.

B-1 Cells

A non-traditional B-cell population found primarily in peritoneal and mucosal tissues that produces natural IgM antibodies against bacterial carbohydrates.

Marginal-Zone B Cells

B cells located at the margins of splenic follicles that mount rapid antibody responses against blood-borne, polysaccharide-rich microbes.

Complement System

A proteolytic cascade of circulating and membrane proteins that can be activated by the alternative, classical, or lectin pathways to promote opsonization, inflammation, and microbial lysis.

C3b

The key complement cleavage fragment deposited on microbial surfaces that functions as an opsonin for phagocyte uptake and forms downstream C5 convertase.

C3a and C5a

Soluble complement fragments released during cascade activation that act as chemoattractants and inflammatory mediators to recruit leukocytes.

Membrane Attack Complex (MAC)

A terminal complement pore assembled by components C6, C7, C8, and C9 that integrates into microbial membranes to cause osmotic lysis.

Mannose-Binding Lectin (MBL)

A plasma collectin that recognizes microbial carbohydrate surface patterns, opsonizing microbes and initiating the lectin complement pathway.

C-Reactive Protein (CRP)

A liver-derived acute-phase protein that binds phosphorylcholine on microbes, functioning as an opsonin and activating the classical complement pathway.

Tumor Necrosis Factor (TNF)

A principal pro-inflammatory cytokine produced by macrophages, mast cells, and T cells that promotes endothelial activation, neutrophil recruitment, fever, acute-phase synthesis, and cachexia.

Interleukin-1 (IL-1)

A pro-inflammatory cytokine produced by macrophages, dendritic cells, and endothelial cells that causes endothelial activation, fever, liver acute-phase synthesis, and Th17 differentiation.

Interleukin-12 (IL-12)

A cytokine produced by dendritic cells and macrophages that activates NK cells and T cells to produce IFN-$\gamma$ and promotes Th1 differentiation.

Interferon-$\gamma$ (IFN-$\gamma$)

A cytokine secreted by NK cells and T cells that potently activates macrophages to destroy ingested microbes and enhances adaptive immunity.

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

Antiviral cytokines produced by plasmacytoid dendritic cells and virus-infected cells that inhibit viral replication, induce viral RNA degradation, and increase class I MHC expression.

Interleukin-10 (IL-10)

An anti-inflammatory cytokine secreted by macrophages, dendritic cells, and T cells that inhibits cytokine production and reduces costimulator and class II MHC expression.

Selectins

Endothelial adhesion molecules induced by TNF and IL-1 that bind leukocyte selectin ligands to mediate low-affinity tethering and leukocyte rolling along venular endothelium.

Integrins

Heterodimeric leukocyte adhesion molecules that shift from low-affinity to high-affinity states in response to chemokines, binding ICAM-1 and VCAM-1 to cause firm adhesion.

Leukocyte Adhesion Deficiencies (LADs)

Inherited disorders characterized by genetic mutations in integrins or selectin ligands, leading to defective leukocyte extravasation and recurrent bacterial infections.

Phagolysosome

The digestive cytoplasmic vesicle formed when an ingested phagosome fuses with a lysosome, bringing toxic metabolites and enzymes in contact with the microbe.

Phagocyte Oxidase

The multi-protein enzyme complex that converts molecular oxygen into reactive oxygen species (ROS) within phagolysosomes to kill internalized microbes.

Inducible Nitric Oxide Synthase (iNOS)

A cytosolic enzyme induced in activated macrophages that converts arginine into nitric oxide (NO) and citrulline to mediate microbial killing.

Neutrophil Extracellular Traps (NETs)

Extracellular structures composed of nuclear chromatin and antimicrobial granule proteins released by dying neutrophils to trap and kill extracellular microbes.

Chronic Granulomatous Disease (CGD)

An inherited primary immunodeficiency caused by a deficiency in phagocyte oxidase, resulting in impaired intracellular killing, recurrent infections, and granuloma formation.

Costimulators

Molecules induced on dendritic cells during innate immune responses to microbes that deliver Signal 2 to naive T cells alongside antigen recognition (Signal 1).

C3d

A complement cleavage product deposited on blood-borne microbes that binds complement receptor 2 (CR2) on B cells, delivering the second signal for B-cell activation.

Capsular Polysaccharide (Pneumococcal Evasion)

A protective carbohydrate capsule produced by pneumococci that inhibits phagocytosis by preventing direct phagocyte contact.

Catalase (Staphylococcal Evasion)

An enzyme produced by staphylococci that breaks down reactive oxygen intermediates, allowing survival within phagocytes.

Sialic Acid Expression (Neisseria meningitidis Evasion)

A surface modification by Neisseria meningitidis that inhibits the assembly and activity of alternative pathway C3 and C5 convertases.

M Protein (Streptococcal Evasion)

A virulence protein expressed by streptococci that blocks C3 binding to the bacterium and inhibits C3b binding to phagocyte complement receptors.

Modified LPS (Pseudomonas Evasion)

A lipid modification in the outer membrane of Pseudomonas that confers resistance against host antimicrobial peptide antibiotics.