Immune System Sensing and Pattern Recognition

Vocabulary flashcards on innate immune sensing, pattern recognition receptors (TLRs, CLRs, NLRs, RLRs), PAMPs, DAMPs, and key historical hypotheses.

Frank Macfarlane Burnet

Immunologist who re-published 'The Production of Antibodies' in 1949 and hypothesized that the immune system must learn what 'self' is and avoid attacking it.

Janeway-Medzhitov Hypothesis

A 1989 hypothesis proposed by Charles Janeway and Ruslan Medzhitov stating that the immune system looks for pathogens based on evolutionarily conserved 'patterns' (PAMPs) using pattern recognition receptors (PRRs) to discriminate between infectious non-self and non-infectious self.

Pathogen Associated Molecular Patterns (PAMPs)

Evolutionarily conserved molecular structures (such as cell wall components and flagella) shared among broad classes of pathogens that are difficult for organisms to change and are absent from self tissues.

Pattern Recognition Receptors (PRRs)

Fixed, germline-encoded receptors expressed by immune and non-immune cells that sense evolutionarily conserved PAMPs or DAMPs to induce immediate cellular responses.

Toll-like Receptors (TLRs)

A family of PRRs consisting of 10 receptors in humans and 13 in mice that target conserved bacterial and viral products located outside the cell or inside endosomes.

C-type Lectin Receptors (CLRs)

A family of PRRs that bind unique carbohydrates (such as $\beta$-glucan and $\alpha$-mannan) especially important for detecting fungal pathogens, driving both NF-$\kappa$B-mediated inflammation and strong phagocytosis.

NOD-like Receptors (NLRs)

A family of roughly 22 cytosolic PRRs that detect bacterial products (such as peptidoglycan) in the cytoplasm, including products shed by bacteria like Shigella.

RIG-I-like Receptors (RLRs)

A family of cytosolic PRRs (including RIG-I, MDA5, and LGP2) that act as sensors for viral nucleic acids, specifically detecting uncapped 5'-triphosphate viral RNA.

Danger Hypothesis

A hypothesis proposed by Polly Matzinger in 1994 stating that the immune system does not have receptors for every pathogen, but constantly searches for evidence of damage or danger and responds only when danger is occurring.

MyD88 and TRIF

The primary signaling adaptors for Toll-like Receptors (TLRs) that drive proinflammatory and interferon response pathways.

NF-$\kappa$B

A transcription factor activated downstream of PRRs that drives the expression of proinflammatory genes, including cytokines and chemokines.

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

Cytokines driven by IRF transcription factors (such as IRF3 and IRF7) downstream of viral sensing PRRs that signal cells to stop synthesizing proteins.

Damage Associated Molecular Patterns (DAMPs)

Endogenous molecules recognized by PRRs when present in abnormal locations or altered states due to cellular stress, tissue destruction, or matrix degradation (such as HMGB1 and extracellular matrix degradation products).

NLRP3 Inflammasome

A cytosolic multiprotein complex activated by cellular disturbances (such as calcium efflux, reactive oxygen species, and mitochondrial DNA) that converts inactive pro-IL-1$\beta$ into highly active IL-1$\beta$.

Pyroptosis

A form of programmed inflammatory cell death triggered by Gasdermin D pore formation following inflammasome activation, releasing cytokines to recruit immune cells.

Jules Hoffmann

Immunologist who discovered the essential role of the 'Toll' molecule in fly (Drosophila) innate immunity.

Bruce Beutler

Immunologist who discovered the ligand for TLR4, sharing the 2011 Nobel Prize for discoveries concerning the activation of innate immunity.