W4 Flashcards
(32 cards)
What are the two main types of intracellular (cytoplasmic) PRRs?
NOD-like receptors (NLRs) and NOD proteins (NOD1, NOD2).
What are the major components of innate antiviral defenses?
NK cells, Type I IFNs, and antiviral signaling pathways
What is the function of adaptor proteins in PRR signaling?
They help in domain binding and bridge signaling molecules.
Give two examples of adaptor proteins.
MyD88 and MAL
What do kinases do in PRR signaling?
They attach phosphate groups to activate signaling proteins
Name two kinases involved in PRR signaling.
IRAK1/IRAK4 and TAK1
What is the function of E3 ubiquitin ligases in PRR signaling?
They ligate together ubiquitin scaffolds
Name an example of an E3 ubiquitin ligase
TRAF6
What transcription factors are activated by TLR signaling?
NF-κB, AP-1, and IRF
What are three key pro-inflammatory cytokines induced by TLR activation?
IL-8, IL-6, and IL-1β
How does TLR4 recognize LPS?
Indirectly, with the help of accessory proteins MD-2 and CD14
What do NLRs detect?
Cellular damage, stress signals, and PAMPs
What are two major NOD proteins, and what do they recognize?
NOD1: Detects γ-DAP from Gram-negative bacteria.
NOD2: Detects muramyl dipeptide (MDP) from Gram-positive and Gram-negative bacteria.
In which cells is NOD2 specifically expressed, and what does it regulate?
Paneth cells in the gut, where it regulates α/β defensin expression
What happens when NODs sense bacterial peptidoglycan components?
They trigger a signaling cascade leading to NF-κB activation and cytokine gene transcription
Which kinase is recruited when NODs are activated?
RIP2 kinase
What are the general steps of NLR activation?
Pathogen detection
Oligomerization of NLR
Caspase-1 activation
Cleavage of IL-1β and IL-18
Gasdermin D formation
Pyroptosis
What happens in the resting state of NLRP3?
It is bound to chaperone proteins (e.g., HSP90), preventing dimerization
What triggers NLRP3 activation?
K+ ion efflux from injured cells
What is the function of caspase-1 in inflammasome activation?
It cleaves pro-IL-1β and pro-IL-18 into their active inflammatory forms
What is the function of Gasdermin D?
It forms pores in the cell membrane, leading to pyroptosis
What is the consequence of excessive NLRP3 activation?
Autoinflammatory syndromes due to excessive inflammation
What are cytokines?
Proteins that act on immune cell receptors to regulate activity and gene expression.
How do cytokines differ in their effects?
Some act locally (autocrine, paracrine), while others have systemic (endocrine) effects
