chapter 4 Flashcards
Should those barriers be breached, innate immune system receptors recognize the threat via:
pathogen-associated molecular patterns (PAMPs) found on
microbes
Aging, dead, or damaged self-structures can also be recognized via:
Damage-associated molecular patterns (DAMPs
recognize PAMPs and DAMPs and target
them for clearance
Pattern recognition receptors (PRRs)
Specific for molecules and molecular patterns
associated with pathogens and molecules produced by
dead/damaged cells
innate
Highly specific; discriminates between even minor differences
in molecular structure of microbial or nonmicrobial molecules
adaptive
A limited number of conserved, germ line–encoded receptors
innate
Highly diverse; a very large number of receptors arising from
genetic recombination of receptor genes in each individual
adaptive
Some memory (observed in invertebrate innate responses and mouse/human NK cells)
innate
Persistent memory, with faster response of greater magnitude
on subsequent exposure
adaptive
Very good self/nonself discrimination; no microbe-specific self/nonself patterns in host
innate
Very good self/nonself discrimination; occasional failures of discrimination result in autoimmune disease
adaptive
Soluble components of blood: Many antimicrobial peptides, proteins, and other mediators, including cytokines
innate
Soluble components of blood: antibodies and cytokines
adaptive
major cell types: phagocytes, NK cells, leukocytes, epithelial and endothelial cells
innate
major cell types: T cells, B cells, antigen-presenting cells
adaptive
What are the PAMP ligands recognized by innate PRRs?
- Toll-like receptors (TLRs)
- C-type lectin receptor (CLR)
- AIM2-like receptors (ALR)
- RIG-I-like receptor (RLR)
- NOD-like receptors (NLRs)
-recognize many types of pathogen molecules
-homologous to fruit fly receptor
-dimers with extracellular leucine-rich (LRR) domains that bind PAMPs and DAMPs
-membrane bound
Toll-like receptors (TLRs)
what helps determine what each TLR will bind?
location
What ligand and microbe is recognized by TLR3?
double-stranded RNA and viruses
What ligand and microbe is recognized by TLR4?
LPS and gram-negative bacteria
What ligand and microbe is recognized by TLR5?
flagellin and bacteria
What ligand and microbe is recognized by TLR7?
single stranded RNA and viruses
What ligand and microbe is recognized by TLR8?
viruses
What ligand and microbe is recognized by TLR9?
CpG unmethylated dinucleotides and bacterial DNA/ some herpesviruses
Different TLRs recruit different adapter proteins to the_______________
Toll/IL-1R domain
Different TLRs recruit different adapter proteins to the
Toll/IL-1R domain
WHat are the TLR binding pathways activated by binding of PAMPs?
- NF-κB transcription factor activation
- Interferon regulating factor (IRF) pathways
- MAP kinase pathway downstream transcription factors such as AP-1
- activate innate and inflammatory responses
- generally recognize carbohydrate components of fungi, viruses, mycobacteria, parasites, allergens
-trigger signaling pathways leading to transcription
-Transcription factors induce expression of proinflammatory cytokines, IL-1β, TNF, and IL-23
C-type lectin receptors (CLRs)
cytosolic receptors that bind bacterial and viral double-stranded DNA
AIM2-like receptors (ALRs)
Binding of multiple _________________ via pyrin domains yields long filaments that together with other cellular proteins form inflammasomes
ALRs to dsDNA
multiprotein complex that promotes inflammation by processing precursor forms of pro-inflammatory cytokines, such as IL-1 and IL-18
infalmmasome
- (RIG-I and MDA5 ) recognize viral double-stranded RNAs
- RNA bound by ____ helicase domain
-Function as cytosolic PRRs
RIG-I-like receptors (RLRs)
What activates cGAS and STING?
cytosolic DNA and dinucleotides
RLRs trigger signaling pathways that activate:
-IRFs to trigger antiviral interferon responses
- NF-κB transcription factor
bind PAMPs, diaminopimelic acid and muramyl peptides, of bacterial cell walls
NOD1 and NOD2
-activated by PAMPs and DAMPs
-Induce expression of genes encoding antimicrobial
proteins and peptides
-Initiate autophagy by forming autophagosomes
that fuse with lysosomes to then kill bacteria
Nucleotide oligomerization domain
(NOD)-like receptor receptors (NLR)
limination of intracellular pathogens and organelles by envelopment by intracellular membranes
and fusion of resulting autophagosomes with lysosomes.
Autophagy
PRR signaling pathways activate expression of a large
variety of genes (innate):
- Antimicrobial peptides
- Type I interferons (potent antiviral activity)
- Cytokines (inflammatory IL-1, TNF-α, and IL-6)
- Chemokines
- Enzymes: iNOS and COX2
What is the definition of phagocytosis?
Defined as engulfment and
internalization of materials
such as microbes for their
clearance and destruction
What are the steps of phagocytosis?
- bacterium binds to PRRs on membrane evaginations called pseudopodia
- bacterium is ingested, forming phagosome
- phagosome fuses with lysosome
- bacterium is killed and then digested by low pH-activated lysosomal enzymes
- digestion products are released from cell
How does destruction occur through phagocytosis?
enzyme degradation, antimicrobial proteins, and toxic effects of reactive oxygen and reactive nitrogen species (ROS and RNS)
Proinflammatory ___________________triggered
by innate responses to infection, damage, or harmful
substances
cytokines and chemokines
Early components of inflammation include:
-Increased vascular permeability
-Recruitment of neutrophils and other leukocytes from the blood to the site of damage/infection
Why is regulation and control of inflammatory responses important?
-Defects in PRRs and signaling pathways increase susceptibility to infections
-Defects that allow the systems to remain abnormally “turned on” contribute to inflammatory disorders
some lymphocytes express TLRs but use them as _____________
costimulatory receptors
-a key bridge between innate and adaptive
-They bring antigens from the site of infection and present them to T cells in lymph nodes
-This activates the T cells, allowing them to differentiate into
particular pathogen-specific subsets for the best antigen clearance
dendritic cells
