CHAPTER 2 Innate Immunity: The Early Defense Against Infections

This set of vocabulary flashcards covers the fundamental components, mechanisms, and signaling pathways of the innate immune response, including phagocytes, PRRs, the complement system, and the link to adaptive immunity.

Innate Immunity

The body’s first line of defense providing rapid, non-specific protection against pathogens from birth, acting within hours through physical barriers, chemical secretions, and immune cells.

Inflammation

A complex reaction of vascularized tissue to infection or cell injury involving the accumulation and activation of leukocytes and plasma proteins to kill extracellular microbes and eliminate damaged tissue.

Natural Killer (NK) Cells

Innate immune cells that destroy virus-infected or physiologically stressed host cells (like tumor cells) using cytotoxic granules and the secretion of $IFN\gamma$.

Type I Interferons (IFNs)

Cytokines ($IFN\alpha$ and $IFN\beta$) that inhibit viral replication within host cells by inducing interferon-stimulated genes (ISGs) and activate other immune cells like NK cells.

Plasmacytoid Dendritic Cell (PDC)

A specialized type of cell that secretes large amounts of Type I IFN during viral infections.

Pathogen-associated molecular patterns (PAMPs)

Conserved molecular motifs shared by microbes but not present on mammalian cells, such as lipopolysaccharide (LPS) or flagellin, which are recognized by the innate immune system.

Damage-associated molecular patterns (DAMPs)

Also called 'alarmins,' these are endogenous molecules released by dying, damaged, or stressed host cells that trigger inflammation and tissue repair.

Pattern Recognition Receptors (PRRs)

Germline-encoded sensors present on plasma/endosomal membranes or in the cytosol that detect pathogens and tissue damage by recognizing conserved molecular signatures.

Toll-Like Receptors (TLRs)

A major family of PRRs containing leucine-rich motifs and a cytoplasmic signaling domain that sense structurally diverse microbial products.

TLR4

The specific Toll-like receptor responsible for the recognition of bacterial lipopolysaccharide (LPS), also known as endotoxin.

TLR3

A Toll-like receptor specific for double-stranded RNA ($dsRNA$).

TLR9

A Toll-like receptor specific for unmethylated CpG DNA, which is abundant in microbial genomes.

NFκB

A transcription factor activated by TLR signaling that promotes the expression of pro-inflammatory cytokines, adhesion molecules, and costimulators.

NOD-Like Receptors (NLRs)

A family of cytoplasmic receptors that sense PAMPs and DAMPs in the cytosol, initiating signaling for inflammation or assembling the inflammasome.

Inflammasome

A multiprotein cytoplasmic complex (such as NLRP3) that activates caspases to proteolytically generate active forms of cytokines $IL-1\beta$ and $IL-18$.

RIG-I-like Receptors (RLRs)

Cytosolic sensors that bind to viral RNA and induce the production of antiviral Type I IFNs via interaction with the MAVS protein.

Defensins

Antimicrobial peptides produced by epithelial cells that provide a chemical barrier by killing bacteria and some viruses through membrane disruption.

Intraepithelial Lymphocytes (IELs)

Lymphocytes within epithelia that often express a TCR made of gamma and delta chains and recognize microbial lipids.

Neutrophils

The most abundant blood leukocytes ($4,000-10,000$ per $\mu l$); they are short-lived, quick-acting phagocytes that are the dominant cells of acute inflammation.

M1-type Macrophage

Classically activated macrophages that promote inflammation and destroy microbes by secreting pro-inflammatory cytokines (like $IL-1$, $IL-6$, $TNF\alpha$) and oxygen/nitrogen radicals.

M2-type Macrophage

Alternatively activated macrophages that inhibit inflammation and promote tissue repair and angiogenesis by secreting $IL-10$ and $TGF-\beta$.

Mast Cells

Bone marrow-derived cells in skin and mucosal barriers that contain granules with histamine, proteolytic enzymes, and cytokines to initiate inflammation.

Complement System

A set of plasma proteins that act as a cascade to provide defense via three pathways: alternative (microbe surface), classical (CRP/antibody), and lectin (MBL).

Opsonization

The process of coating a microbe with molecules (like $C3b$ or antibodies) to facilitate recognition and ingestion by phagocytes.

Membrane-attack complex (MAC)

A polymeric protein complex formed by the complement system that inserts into the microbial membrane to cause osmotic lysis.

Acute Phase Response

The rapid increase of circulating plasma proteins like MBL, C-reactive protein (CRP), and fibrinogen following an infection.

Selectins

Adhesion molecules (E-selectin and P-selectin) on endothelial cells that mediate the weak tethering and rolling of leukocytes during recruitment.

Integrins

Leukocyte surface molecules that mediate firm adhesion to the vascular endothelium prior to transmigration.

Diapedesis

The process of adherent leukocytes 'squeezing' between endothelial cells to enter the tissue space.

NADPH Oxidase

Also called phagocyte oxidase, this enzyme rapidly assembles in the phagolysosomal membrane to convert oxygen into reactive oxygen species.

iNOS (Inducible Nitric Oxide Synthase)

An enzyme produced mainly in macrophages that catalyzes the conversion of arginine into nitric oxide ($NO$) to kill microbes.

Neutrophil Extracellular Traps (NETs)

DNA-chromatin structures released by dying neutrophils that trap and kill bacteria and fungi at inflammatory sites.

ADCC (Antibody-dependent cell-mediated cytotoxicity)

A mechanism where NK cells recognize antibody-coated target cells via the $CD16$ receptor and induce apoptosis.

Adjuvant

A substance used in vaccines to provide a necessary 'second signal' (danger signal) to stimulate costimulatory molecule expression on APCs.