p.12
Cytosolic RNA and DNA Sensors
What is the function of cyclic GMP-AMP (cGAMP) in the STING pathway?
It binds to STING and initiates signaling for type I IFN gene expression.
p.11
NOD-Like Receptors (NLRs) and Inflammasomes
What is the NLRP3 inflammasome responsible for processing?
Pro-interleukin-1β (pro-IL-1β) to active IL-1.
p.12
Components of Innate Immunity
What additional function does STING have besides inducing type I IFN production?
It stimulates autophagy for degrading organelles and pathogens.
p.4
Cellular Receptors: Toll-Like Receptors (TLRs)
What types of receptors are found in innate immunity?
Innate immunity features various types of invariant receptors, such as Toll-like receptors and RIG-like receptors.
p.5
Inflammation and Immune Reactions
How does the innate immune system respond to DAMPs?
It serves to eliminate damaged cells and initiate tissue repair.
p.5
Cellular Receptors: Toll-Like Receptors (TLRs)
What is the role of innate immune receptors?
They are encoded by inherited genes and are identical across all cells expressing them.
p.6
Epithelial Barriers in Innate Immunity
How are most microbial infections acquired?
Through the epithelial barriers of the skin and gastrointestinal, respiratory, and genitourinary systems.
p.12
Cytosolic RNA and DNA Sensors
What molecule does cytosolic dsDNA bind to for signaling?
Cyclic guanosine monophosphate – adenosine monophosphate (cGAS).
p.12
Cytosolic RNA and DNA Sensors
What pathway do most innate cytosolic DNA sensors engage to induce type I IFN production?
The stimulator of IFN genes (STING) pathway.
p.7
Components of Innate Immunity
What are the five major families of cellular receptors in innate immunity?
TLRs, C-type lectin receptors (CLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), and cytosolic DNA sensors (CDSs).
p.1
Overview of Innate Immunity
What is the primary role of innate immunity?
To provide early defense against infections.
p.15
Cytokines and Signaling in Innate Immunity
What stimulates the production of neutrophils?
Cytokines known as colony-stimulating factors (CSFs).
p.4
Overview of Innate Immunity
How do microbes evade innate immunity compared to adaptive immunity?
Microbes cannot easily evade innate immunity by mutation, while they can evade adaptive immunity by mutating antigens, which are not essential for their survival.
p.7
Cytokines and Signaling in Innate Immunity
What is the role of transcription factors activated by TLR signals?
They stimulate expression of cytokines and proteins involved in inflammatory and antiviral responses.
p.11
Cytosolic RNA and DNA Sensors
What role do cytosolic DNA sensors (CDSs) play in the immune response?
They recognize microbial dsDNA and activate signaling pathways for antimicrobial responses.
p.7
Cellular Receptors: Toll-Like Receptors (TLRs)
What are TLRs and where are they located?
TLRs (Toll-Like Receptors) are located on cell surfaces and endosomes, recognizing microbial proteins, lipids, and polysaccharides.
p.9
NOD-Like Receptors (NLRs) and Inflammasomes
What do NLRs contain at their C-terminal?
A nucleotide oligomerization domain (NOD).
p.5
Recognition of Microbes and Damaged Cells
What is an example of a DAMP?
High mobility group box protein 1 (HMGB1) and extracellular adenosine triphosphate (ATP).
p.7
Overview of Innate Immunity
What can mutations affecting TLRs or their signaling molecules lead to?
Rare autosomal recessive diseases characterized by recurrent infections.
p.7
Overview of Innate Immunity
What infections are individuals with TLR-3 mutations particularly susceptible to?
Herpes simplex virus infections.
p.3
Inflammation and Immune Reactions
What is the role of leukocytes in inflammation?
They accumulate and activate at infection or tissue injury sites to kill extracellular microbes and eliminate damaged tissues.
p.9
NOD-Like Receptors (NLRs) and Inflammasomes
What inflammatory diseases are associated with polymorphisms of the NOD2 gene?
Inflammatory bowel disease.
p.5
Components of Innate Immunity
What is a key function of healthy cells in relation to innate immunity?
Healthy cells express molecules that block innate immune responses.
p.2
Overview of Innate Immunity
What are the questions focused on regarding innate immunity in this chapter?
How innate immunity recognizes microbes and damaged cells, how its components combat different microbes, and how it stimulates adaptive immune responses.
p.1
Components of Innate Immunity
What are innate lymphoid cells?
Cells that produce cytokines and help in the defense against infections.
p.13
Cellular Receptors: Toll-Like Receptors (TLRs)
What does the formyl peptide receptor 1 recognize?
Polypeptides with an N-terminal formylmethionine, a specific feature of bacterial proteins.
p.8
Cytokines and Signaling in Innate Immunity
What is the end result of TLR signaling?
Production of cytokines, adhesion molecules, and stimulation of adaptive immunity.
p.4
Recognition of Microbes and Damaged Cells
What is the role of pattern recognition receptors in innate immunity?
They recognize shared microbial structures, making innate immunity a highly effective defense mechanism against pathogens.
p.2
Overview of Innate Immunity
What is innate immunity?
A type of host defense that is always present and functional, ready to recognize and eliminate microbes and dead cells.
p.2
Overview of Innate Immunity
How does innate immunity differ from adaptive immunity?
Innate immunity provides immediate defense against infections, while adaptive immunity requires antigen stimulation and takes several days to develop.
p.1
NOD-Like Receptors (NLRs) and Inflammasomes
What is the function of inflammasomes?
To activate inflammatory responses in the presence of pathogens.
p.7
Cellular Receptors: Toll-Like Receptors (TLRs)
What do TLRs in endosomes recognize?
They recognize nucleic acids released from ingested microbes.
p.12
Cytokines and Signaling in Innate Immunity
Which kinases are recruited and activated by STING?
TBK1 (TANK-binding kinase 1).
p.14
Epithelial Barriers in Innate Immunity
What are defensins and cathelicidins?
Antimicrobial substances produced by epithelia.
p.14
Epithelial Barriers in Innate Immunity
What are the three steps depicting the functions of epithelia in innate immunity?
1) Physical barrier to infection, 2) Killing of microbes by antibiotics, 3) Killing of microbes by intraepithelial lymphocytes.
p.5
Overview of Innate Immunity
What distinguishes innate immunity from adaptive immunity?
Innate immunity has nonclonal receptors that recognize the same microbe, while adaptive immunity has diverse antigen receptors formed by gene rearrangement.
p.5
Overview of Innate Immunity
How does the adaptive immune system prevent autoimmunity?
By eliminating or inactivating self-reactive lymphocytes upon encounter with self antigens.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
What are tissue-resident macrophages?
Macrophages that are always present in most healthy organs and tissues.
p.1
Components of Innate Immunity
What is the function of mast cells in the immune response?
They release histamine and other mediators during allergic responses and inflammation.
p.1
Cytokines and Signaling in Innate Immunity
What is the role of cytokines in innate immunity?
They are signaling molecules that mediate and regulate immunity and inflammation.
p.13
Epithelial Barriers in Innate Immunity
How do keratin and mucus contribute to pathogen defense?
Keratin forms a physical barrier, while mucus provides a chemical barrier against infection.
p.4
Components of Innate Immunity
What is the estimated number of molecular patterns recognized by innate immunity?
About 1,000 molecular patterns.
p.14
Epithelial Barriers in Innate Immunity
What role do epithelia play in innate immunity?
They provide physical barriers and produce antimicrobial substances.
p.9
NOD-Like Receptors (NLRs) and Inflammasomes
What do NOD1 and NOD2 recognize?
Different dipeptides derived from bacterial cell wall peptidoglycan.
p.9
Cytokines and Signaling in Innate Immunity
What transcription factor do NOD1 and NOD2 activate?
NF-κB transcription factor.
p.9
NOD-Like Receptors (NLRs) and Inflammasomes
Where is NOD2 highly expressed?
In intestinal Paneth cells in the small bowel.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
How do neutrophils enhance phagocytosis?
By expressing receptors for complement activation products and antibodies that coat microbes.
p.1
Phagocytes: Neutrophils and Monocytes/Macrophages
What roles do phagocytes like Neutrophils and Macrophages play?
They are responsible for engulfing and destroying microbes.
p.3
Overview of Innate Immunity
How does the response of the innate immune system change with repeat encounters with a microbe?
The innate immune system responds in essentially the same way and does not remember prior encounters.
p.5
Overview of Innate Immunity
What mechanisms of defense does the innate immune system provide?
Defense at every stage of microbial infections.
p.13
Components of Innate Immunity
What are mannose receptors involved in?
Phagocytosis of fungi and bacteria, and inflammatory responses to these pathogens.
p.8
NOD-Like Receptors (NLRs) and Inflammasomes
What do NOD-like receptors (NLRs) sense?
DAMPs and PAMPs in the cytosol.
p.13
Epithelial Barriers in Innate Immunity
What is the function of intraepithelial T lymphocytes?
They presumably react against infectious agents that breach the epithelia, although their specificity is poorly understood.
p.11
Recognition of Microbes and Damaged Cells
What induces the synthesis of pro-IL-1β?
Various PAMPs or DAMPs through pattern recognition receptor signaling.
p.5
Recognition of Microbes and Damaged Cells
What are damage-associated molecular patterns (DAMPs)?
Molecules released from damaged or necrotic host cells that the innate immune system recognizes.
p.12
Cytokines and Signaling in Innate Immunity
What role does IRF3 play after phosphorylation?
It moves to the nucleus to induce type I IFN gene expression.
p.11
Cytosolic RNA and DNA Sensors
What diseases are associated with excessive accumulation of self DNA in the cytosol?
Systemic inflammatory diseases called interferonopathies.
p.2
Role of Innate Immunity in Stimulating Adaptive Immune Responses
What is the role of innate immunity in relation to the adaptive immune system?
Innate immunity instructs the adaptive immune system to respond effectively to different microbes.
p.6
Phagocytes: Neutrophils and Monocytes/Macrophages
Which cells detect microbes that breach epithelial barriers?
Resident macrophages, dendritic cells, and mast cells.
p.2
Overview of Innate Immunity
What is a key feature of the innate immune response in terms of its speed?
The innate immune response combats microbes immediately upon infection.
p.3
Recognition of Microbes and Damaged Cells
What are some examples of microbial molecules that stimulate innate immunity?
Double-stranded RNA (dsRNA) and unmethylated CG-rich (CpG) oligonucleotides.
p.8
Cytokines and Signaling in Innate Immunity
What is the role of NF-κB in TLR signaling?
To enter the nucleus and stimulate the production of proteins for inflammation and antiviral defense.
What is an essential part of tissue repair following an infection?
The regeneration of cells and restoration of tissue structure.
p.10
NOD-Like Receptors (NLRs) and Inflammasomes
What is pyroptosis?
A form of programmed cell death characterized by cell swelling, loss of plasma membrane integrity, and release of inflammatory cytokines.
p.4
Recognition of Microbes and Damaged Cells
What are PAMPs and their significance in innate immunity?
PAMPs (pathogen-associated molecular patterns) indicate the presence of infectious agents and are recognized by innate immune receptors, which are specific for these shared structures.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
What are neutrophils also known as?
Polymorphonuclear leukocytes (PMNs).
p.1
Cellular Receptors: Toll-Like Receptors (TLRs)
What are Toll-Like Receptors?
Receptors that recognize specific patterns on microbes to initiate immune responses.
p.3
Overview of Innate Immunity
How does the specificity of innate immunity differ from adaptive immunity?
Innate immunity has more limited and generalized responses compared to the specific responses of adaptive immunity.
p.11
Cytokines and Signaling in Innate Immunity
What is the outcome of RIG-I and MDA5 activation?
Stimulation of type I interferon (IFN) production.
p.2
Overview of Innate Immunity
What are the main functions of the innate immune response?
It blocks microbial invasion, destroys microbes, and assists in clearing dead tissues and repairing damage.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
What are monocytes and how do they relate to neutrophils?
Monocytes are less abundant than neutrophils and can differentiate into macrophages during inflammatory reactions.
p.14
Phagocytes: Neutrophils and Monocytes/Macrophages
What is the source of macrophages during early development?
Stem cells in the yolk sac of the fetal liver.
p.1
Components of Innate Immunity
What is a characteristic of Natural Killer cells?
They can identify and destroy infected or cancerous cells without prior sensitization.
p.1
Inflammation and Immune Reactions
What is involved in the recruitment of phagocytes to infection sites?
Chemical signals from damaged tissues and pathogens attract phagocytes.
p.10
NOD-Like Receptors (NLRs) and Inflammasomes
What diseases are associated with inflammasome activation?
Autoinflammatory syndromes, gout, and potentially atherosclerosis.
p.4
Components of Innate Immunity
How do the receptors of innate immunity differ from those of adaptive immunity?
Innate immunity receptors are encoded in the germline with limited diversity, while adaptive immunity receptors are produced by somatic recombination and have greater diversity.
p.7
Cytokines and Signaling in Innate Immunity
Which transcription factors are most important in TLR signaling?
Nuclear factor κ B (NF-κB) and interferon regulatory factors (IRFs).
p.12
Cytosolic RNA and DNA Sensors
What are some examples of second messenger molecules recognized by STING?
Cyclic di-GMP (c-di-GMP) and cyclic di-AMP (c-di-AMP).
p.12
Components of Innate Immunity
What receptors are involved in recognizing fungal glucans in innate immunity?
Dectins, which are carbohydrate-recognizing proteins.
p.7
NOD-Like Receptors (NLRs) and Inflammasomes
What do NOD and RIG refer to?
Founding members of families of structurally homologous cytosolic receptors for bacterial and viral products.
p.9
Components of Innate Immunity
What do Paneth cells express in response to ingested pathogens?
Antimicrobial substances called defensins.
p.3
Phagocytes: Neutrophils and Monocytes/Macrophages
Which cells mediate innate immune defense against intracellular viruses?
Natural killer (NK) cells.
p.6
Cytokines and Signaling in Innate Immunity
What is the role of cytokines in the immune response?
They initiate the process of inflammation.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
Where do tissue-resident macrophages derive from?
Progenitors in the yolk sac or fetal liver during fetal development.
p.9
NOD-Like Receptors (NLRs) and Inflammasomes
What type of stimuli can activate the NLRP3 inflammasome?
A wide variety of stimuli, including crystalline substances like uric acid.
p.6
Cellular Receptors: Toll-Like Receptors (TLRs)
How many different TLR proteins are there in humans?
10 different TLR proteins.
p.13
Epithelial Barriers in Innate Immunity
What physical and chemical barriers do epithelial cells provide?
They protect against infection at interfaces like skin, gastrointestinal tract, respiratory tract, and genitourinary tract.
p.10
NOD-Like Receptors (NLRs) and Inflammasomes
What types of cellular stress or damage does the NLRP3 inflammasome recognize?
Nuclear damage, cholesterol crystals, extracellular ATP, reduced potassium ion concentration, and reactive oxygen species.
p.11
Inflammation and Immune Reactions
What triggers the activation of the NLRP3 inflammasome?
ATP, bacterial products, crystals, potassium efflux, and reactive oxygen species.
p.14
Epithelial Barriers in Innate Immunity
What physical barriers do epithelial cells form?
Keratin in the skin and secreted mucus in various systems.
p.3
Overview of Innate Immunity
What types of reactions does the innate immune system primarily perform?
Inflammation and antiviral defense.
p.1
NOD-Like Receptors (NLRs) and Inflammasomes
What are NOD-Like Receptors responsible for?
Detecting intracellular pathogens and stress signals.
p.6
Epithelial Barriers in Innate Immunity
What are the earliest defense mechanisms at portals of entry for microbes?
Epithelia and mucus that provide physical barriers and antimicrobial molecules.
p.2
Overview of Innate Immunity
In what types of organisms is innate immunity present?
It is present in all multicellular organisms, including plants, invertebrates, and vertebrates.
p.8
Cellular Receptors: Toll-Like Receptors (TLRs)
What do different TLRs recognize?
Structurally diverse products of microbes.
p.14
Phagocytes: Neutrophils and Monocytes/Macrophages
What type of cytokine production is associated with neutrophils versus macrophages?
Neutrophils produce low levels per cell; macrophages produce large amounts requiring transcriptional activation.
p.6
Cellular Receptors: Toll-Like Receptors (TLRs)
What are pattern recognition receptors?
Receptors used by the innate immune system to detect microbes and damaged cells.
p.13
Cytokines and Signaling in Innate Immunity
What is the role of signaling by the formyl peptide receptor 1?
Promotes migration and antimicrobial activities of phagocytes.
p.13
Epithelial Barriers in Innate Immunity
What are defensins and cathelicidins?
Antimicrobial peptides produced by epithelial cells that kill bacteria and some viruses.
p.4
Components of Innate Immunity
What is the distribution of receptors in innate immunity?
Innate immunity receptors are nonclonal, meaning identical receptors are present on all cells of the same lineage.
p.4
Overview of Innate Immunity
How is the discrimination of self and nonself handled in innate immunity?
Innate immunity can recognize healthy host cells and often does not react to them.
p.5
Cellular Receptors: Toll-Like Receptors (TLRs)
How many types of innate immune receptors are estimated to exist?
About 100 types capable of recognizing around 1000 PAMPs and DAMPs.
p.14
Phagocytes: Neutrophils and Monocytes/Macrophages
What is the role of reactive oxygen species in neutrophils compared to macrophages?
Neutrophils rapidly induce reactive oxygen species, while macrophages have less prominent activity.
p.9
Cytokines and Signaling in Innate Immunity
What active forms of cytokines do inflammasomes generate?
Interleukin-1β (IL-1β) and IL-18.
p.6
Components of Innate Immunity
What role do plasma proteins, including those of the complement system, play in the blood?
They react against microbes that enter the circulation and promote their destruction.
p.6
Cellular Receptors: Toll-Like Receptors (TLRs)
What are Toll-Like Receptors (TLRs) named after?
A Drosophila protein called Toll, known for its role in development and fungal infection protection.
p.13
Components of Innate Immunity
What are the main components of the innate immune system?
Epithelial cells, sentinel cells, circulating phagocytes, innate lymphoid cells, NK cells, and plasma proteins.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
What role do neutrophils play in infections?
They are the first and most numerous cell type to respond, particularly to bacterial and fungal infections.
p.1
Components of Innate Immunity
What is the role of dendritic cells in innate immunity?
To capture and present antigens to T cells, bridging innate and adaptive immunity.
p.3
Recognition of Microbes and Damaged Cells
What types of microbial structures does the innate immune system recognize?
Shared structures not present in normal host cells, such as bacterial endotoxin and peptidoglycans.
p.8
Cellular Receptors: Toll-Like Receptors (TLRs)
Which TLRs recognize nucleic acids?
Endosomal TLRs, specifically TLR-3, TLR-7, TLR-8, and TLR-9.
p.6
Cellular Receptors: Toll-Like Receptors (TLRs)
What do TLR-4 specifically recognize?
Bacterial LPS (endotoxin) made by gram-negative bacteria.
p.13
Epithelial Barriers in Innate Immunity
What are intraepithelial lymphocytes?
T cell lineage lymphocytes that express antigen receptors of limited diversity, found in epithelial layers.
p.10
NOD-Like Receptors (NLRs) and Inflammasomes
What role does gasdermin D play in pyroptosis?
The N-terminal fragment oligomerizes to form channels in the plasma membrane, allowing the egress of IL-1β and influx of ions, leading to cell swelling and pyroptosis.
p.14
Phagocytes: Neutrophils and Monocytes/Macrophages
What are the main differences between neutrophils and macrophages regarding their life span in tissues?
Neutrophils live for 1-2 days, while macrophages can live for days, weeks, or even years.
p.1
Cytosolic RNA and DNA Sensors
What do cytosolic RNA and DNA sensors detect?
Viral nucleic acids in the cytosol, signaling an immune response.
p.3
Cytokines and Signaling in Innate Immunity
What do type I interferons (IFNs) do?
They block viral replication within host cells.
p.5
Components of Innate Immunity
How does the innate immune system differentiate between self and non-self?
It evolved receptors specific for microbial structures and products of damaged cells, not substances in healthy cells.
p.15
Phagocytes: Neutrophils and Monocytes/Macrophages
What happens to monocytes during inflammatory reactions?
They enter extravascular tissues and differentiate into macrophages.
p.8
Cellular Receptors: Toll-Like Receptors (TLRs)
What do all TLRs contain that is crucial for their function?
A ligand-binding domain composed of leucine-rich motifs and a TIR domain.
p.10
Cytosolic RNA and DNA Sensors
What cytokines do RLRs induce the production of when they sense viral RNA?
Type I interferons (IFNs).
p.14
Phagocytes: Neutrophils and Monocytes/Macrophages
How do neutrophils and macrophages differ in their response to activating stimuli?
Neutrophils respond rapidly and are short-lived; macrophages respond more slowly and have prolonged activity.
p.9
NOD-Like Receptors (NLRs) and Inflammasomes
What are inflammasomes?
Multiprotein complexes that assemble in the cytosol of cells in response to microbes or cell injury.
p.6
Phagocytes: Neutrophils and Monocytes/Macrophages
What is the function of phagocytes in tissues?
They engulf and destroy microbes and damaged cells.
p.8
Cellular Receptors: Toll-Like Receptors (TLRs)
What is the function of TLRs in the plasma membrane?
To recognize cell wall components of bacteria.
p.1
Components of Innate Immunity
What is the significance of the complement system?
It is a group of proteins that enhance the ability to clear microbes and promote inflammation.
p.1
Phagocytes: Neutrophils and Monocytes/Macrophages
What is phagocytosis?
The process by which phagocytes engulf and destroy pathogens.
p.10
Cytosolic RNA and DNA Sensors
How do RLRs initiate signaling for type I IFN production?
By interacting with a mitochondrial membrane protein called MAVS.
