Block A Lecture 1 (pattern recognition) Flashcards
(40 cards)
What are the two arms of the immune system?
Innate or natural (non-adaptive) immunity
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Acquired or specific (adaptive) immunity
What are the key characteristics of innate immunity?
- The early phase of the host response
- Present in all individuals at all times
- Does not increase with repeated exposure
- Discriminates between groups of pathogens
- Predates separation of animal and plant lineages
What are the three phases of the initial infection response?
innate phase
Early induced innate response phase
Adaptive immune response
How does the innate immune system recognise pathogens?
Through pathogen-associated molecular patterns (PAMPs) by germline-encoded receptors of the innate immune system – pathogen recognition receptors (PRRs)
Name three soluble mediators of innate immunity and their functions.
Mucins: May prevent adhesion to epithelium by microorganisms.
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Lysozyme: Glycosidase that attacks peptidoglycan in the bacterial cell wall.
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Defensins: Disrupt cell membranes of bacteria and fungi via pore formation.
Give two examples of complement activation molecules and what they recognise.
Mannose-binding lectin: Recognises sugars, e.g. mannose, fucose.
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Ficolin: Recognises oligosaccharides containing acetylated sugars.
What are the main families of Pathogen Recognition Receptors (PRRs)?
C-type lectin family
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Scavenger receptors
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Complement and Fc receptors
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Toll-like receptors (TLRs)
What do Toll-like receptors (TLRs) recognise?
Molecular patterns not found in healthy vertebrate cells.
What was the key discovery about Toll receptors that led to a Nobel Prize in 2011?
The receptor protein Toll was first discovered in the fruit fly – Drosophila melanogaster.
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Flies deficient in the Toll receptor are dramatically more susceptible to fungal infection.
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Later it was found that humans and other mammals use these receptors to detect infections, kick-starting the innate immune response.
What is the key intracellular signalling domain in both TLRs and IL-1R, and what is its function?
Toll/IL-1 Receptor (TIR) domain
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Critical for downstream signalling in innate immune responses
What are the cellular locations of mammalian TLRs
Extracellular
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Intracellular
How do TLRs dimerise?
Heterodimers: E.g., TLR-1 and -2 located on cell surfaces can directly recognise bacterial triacyl lipoproteins. Dimerization brings their cytoplasmic Toll–IL-1 receptor (TIR) domains together to initiate cell signalling.
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Homodimers: E.g., TLR-4 recognises LPS in association with the accessory protein MD-2. Stabilisation leads to signal transduction.
Card 13
Describe the two main TLR4 signalling pathways.
MyD88-dependent (proinflammatory cytokines): Primarily leads to the production of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β. Uses the adaptor proteins MyD88 and TIRAP.
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TRIF-dependent (Type 1 interferons): Leads to the production of type I interferons (IFN-α and IFN-β) and late-phase NF-κB activation. Uses the adaptor proteins TRIF and TRAM.
What are the key outcomes of TLR4 signalling?
Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) via NF-κB activation.
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Type I interferons (IFN-α, IFN-β) through the activation of IRF3 in the TRIF-dependent pathway.
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Activation of MAPK pathways (ERK, JNK, and p38), which contribute to inflammation, cell survival, and apoptosis.
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Antimicrobial defence by promoting phagocytosis and recruitment of immune cells like macrophages and neutrophils to the site of infection.
What are NOD-like receptors (NLRs)?
Cytoplasmic receptor proteins that act as intracellular sensors of bacterial invasion and cellular damage.
What domains are present in NLRs and what are their functions?
Nucleotide-binding oligomerization domain (NOD): Central domain for oligomerization.
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Variable domains: Detect microbial products or cellular damage.
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Caspase recruitment domain (CARD) (in the NOD subfamily): Structurally related to the TIR death domain in MyD88 and can dimerize with CARD domains on other proteins to induce signalling.
Give examples of NLRs and the molecules they sense.
NOD1: Senses γ-glutamyl diaminopimelic acid (iE-DAP), a breakdown product of peptidoglycans of Gram-negative bacteria.
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NOD2: Recognises muramyl dipeptide (MDP), which is present in the peptidoglycans of most bacteria.
What are inflammasomes?
Multiprotein complexes formed by pyrin-containing NOD-like receptors (NLRP family), such as NLRP1 and NLRP3. They drive pro-inflammatory cytokine production and induce cell death.
Describe the NLRP3 inflammasome activation process.
NLRP3 is activated.
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NLRP3 forms an inflammasome complex with the adaptor protein ASC.
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ASC recruits and activates caspase-1.
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Caspase-1 processes inactive cytokines like IL-1β and IL-18 into their active forms.
What is the importance of PRRs in immune surveillance and inflammation?
Act as the first line of defence, enabling rapid detection and elimination of pathogens before adaptive immunity kicks in.
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Play a crucial role in the balance between health and disease, as proper regulation is essential to prevent overactive immune responses.
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Targeting PRR pathways holds therapeutic potential for treating autoimmune disorders, infectious diseases, and designing vaccine adjuvants.
What does the C-type lectin family recognise?
β-1,3-linked glucans, common components of fungal cell walls. The mannose receptor may recognise mannose-containing structures on pathogens but also plays a role in the clearance of host protein
What do scavenger receptors recognise?
Scavenger receptors are structurally heterogenous; they recognise various anionic polymers and acetylated low-density lipoproteins. They may bind pathogens (e.g., bacterial cell wall) or host products.
What do complement and Fc receptors recognise?
omplement and Fc receptors recognise Complement-coated and antibody-coated organisms
What signalling cascades do TLRs and IL-1R activate?
Both TLRs and IL-1R activate similar signalling cascades – MAPK and NFκB.
