CHAPTER 2 IMMUNO - Innate Immunity

IRF3, IRF7, and NF-κB.

It binds to STING and initiates signaling for type I IFN gene expression.

Pro-interleukin-1β (pro-IL-1β) to active IL-1.

It stimulates autophagy for degrading organelles and pathogens.

Innate immunity features various types of invariant receptors, such as Toll-like receptors and RIG-like receptors.

It serves to eliminate damaged cells and initiate tissue repair.

They are encoded by inherited genes and are identical across all cells expressing them.

Through the epithelial barriers of the skin and gastrointestinal, respiratory, and genitourinary systems.

Cyclic guanosine monophosphate – adenosine monophosphate (cGAS).

The stimulator of IFN genes (STING) pathway.

TLRs, C-type lectin receptors (CLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), and cytosolic DNA sensors (CDSs).

To provide early defense against infections.

Cytokines known as colony-stimulating factors (CSFs).

Microbes cannot easily evade innate immunity by mutation, while they can evade adaptive immunity by mutating antigens, which are not essential for their survival.

They stimulate expression of cytokines and proteins involved in inflammatory and antiviral responses.

They recognize microbial dsDNA and activate signaling pathways for antimicrobial responses.

TLRs (Toll-Like Receptors) are located on cell surfaces and endosomes, recognizing microbial proteins, lipids, and polysaccharides.

A nucleotide oligomerization domain (NOD).

High mobility group box protein 1 (HMGB1) and extracellular adenosine triphosphate (ATP).

Rare autosomal recessive diseases characterized by recurrent infections.

Herpes simplex virus infections.

They accumulate and activate at infection or tissue injury sites to kill extracellular microbes and eliminate damaged tissues.

Inflammatory bowel disease.

Healthy cells express molecules that block innate immune responses.

How innate immunity recognizes microbes and damaged cells, how its components combat different microbes, and how it stimulates adaptive immune responses.

Cells that produce cytokines and help in the defense against infections.

Polypeptides with an N-terminal formylmethionine, a specific feature of bacterial proteins.

Production of cytokines, adhesion molecules, and stimulation of adaptive immunity.

They recognize shared microbial structures, making innate immunity a highly effective defense mechanism against pathogens.

NLRP1, NLRC4, or AIM2.

NOD1 and NOD2.

A type of host defense that is always present and functional, ready to recognize and eliminate microbes and dead cells.

Innate immunity provides immediate defense against infections, while adaptive immunity requires antigen stimulation and takes several days to develop.

To activate inflammatory responses in the presence of pathogens.

They recognize nucleic acids released from ingested microbes.

TBK1 (TANK-binding kinase 1).

4000 to 10,000 per μL.

Antimicrobial substances produced by epithelia.

1. Physical barrier to infection, 2) Killing of microbes by antibiotics, 3) Killing of microbes by intraepithelial lymphocytes.

Innate immunity has nonclonal receptors that recognize the same microbe, while adaptive immunity has diverse antigen receptors formed by gene rearrangement.

By eliminating or inactivating self-reactive lymphocytes upon encounter with self antigens.

Macrophages that are always present in most healthy organs and tissues.

They release histamine and other mediators during allergic responses and inflammation.

They are signaling molecules that mediate and regulate immunity and inflammation.

Keratin forms a physical barrier, while mucus provides a chemical barrier against infection.

Gasdermin D.

About 1,000 molecular patterns.

They provide physical barriers and produce antimicrobial substances.

Different dipeptides derived from bacterial cell wall peptidoglycan.

NF-κB transcription factor.

In intestinal Paneth cells in the small bowel.

By expressing receptors for complement activation products and antibodies that coat microbes.

They are responsible for engulfing and destroying microbes.

The innate immune system responds in essentially the same way and does not remember prior encounters.

Defense at every stage of microbial infections.

Phagocytosis of fungi and bacteria, and inflammatory responses to these pathogens.

DAMPs and PAMPs in the cytosol.

They presumably react against infectious agents that breach the epithelia, although their specificity is poorly understood.

Viral RNA.

Various PAMPs or DAMPs through pattern recognition receptor signaling.

Molecules released from damaged or necrotic host cells that the innate immune system recognizes.

It moves to the nucleus to induce type I IFN gene expression.

Systemic inflammatory diseases called interferonopathies.

Cytosolic viral RNA.

Innate immunity instructs the adaptive immune system to respond effectively to different microbes.

Resident macrophages, dendritic cells, and mast cells.

The innate immune response combats microbes immediately upon infection.

MD2 protein.

Double-stranded RNA (dsRNA) and unmethylated CG-rich (CpG) oligonucleotides.

To enter the nucleus and stimulate the production of proteins for inflammation and antiviral defense.

The regeneration of cells and restoration of tissue structure.

A form of programmed cell death characterized by cell swelling, loss of plasma membrane integrity, and release of inflammatory cytokines.

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.

IL-18.

Polymorphonuclear leukocytes (PMNs).

Cellular Receptors.

Receptors that recognize specific patterns on microbes to initiate immune responses.

Innate immunity has more limited and generalized responses compared to the specific responses of adaptive immunity.

Stimulation of type I interferon (IFN) production.

It blocks microbial invasion, destroys microbes, and assists in clearing dead tissues and repairing damage.

Monocytes are less abundant than neutrophils and can differentiate into macrophages during inflammatory reactions.

Stem cells in the yolk sac of the fetal liver.

Caspase-1.

They can identify and destroy infected or cancerous cells without prior sensitization.

Chemical signals from damaged tissues and pathogens attract phagocytes.

Autoinflammatory syndromes, gout, and potentially atherosclerosis.

Innate immunity receptors are encoded in the germline with limited diversity, while adaptive immunity receptors are produced by somatic recombination and have greater diversity.

Nuclear factor κ B (NF-κB) and interferon regulatory factors (IRFs).

Cyclic di-GMP (c-di-GMP) and cyclic di-AMP (c-di-AMP).

Dectins, which are carbohydrate-recognizing proteins.

Founding members of families of structurally homologous cytosolic receptors for bacterial and viral products.

Antimicrobial substances called defensins.

Natural killer (NK) cells.

They initiate the process of inflammation.

Progenitors in the yolk sac or fetal liver during fetal development.

A wide variety of stimuli, including crystalline substances like uric acid.

10 different TLR proteins.

They protect against infection at interfaces like skin, gastrointestinal tract, respiratory tract, and genitourinary tract.

Nuclear damage, cholesterol crystals, extracellular ATP, reduced potassium ion concentration, and reactive oxygen species.

ATP, bacterial products, crystals, potassium efflux, and reactive oxygen species.

Keratin in the skin and secreted mucus in various systems.

Inflammation and antiviral defense.

Detecting intracellular pathogens and stress signals.

Epithelia and mucus that provide physical barriers and antimicrobial molecules.

It is present in all multicellular organisms, including plants, invertebrates, and vertebrates.

Structurally diverse products of microbes.

Neutrophils produce low levels per cell; macrophages produce large amounts requiring transcriptional activation.

Receptors used by the innate immune system to detect microbes and damaged cells.

Promotes migration and antimicrobial activities of phagocytes.

Antimicrobial peptides produced by epithelial cells that kill bacteria and some viruses.

Innate immunity receptors are nonclonal, meaning identical receptors are present on all cells of the same lineage.

Innate immunity can recognize healthy host cells and often does not react to them.

About 100 types capable of recognizing around 1000 PAMPs and DAMPs.

Only several hours.

Neutrophils rapidly induce reactive oxygen species, while macrophages have less prominent activity.

Interleukin-1β (IL-1β) and IL-18.

They react against microbes that enter the circulation and promote their destruction.

A Drosophila protein called Toll, known for its role in development and fungal infection protection.

Epithelial cells, sentinel cells, circulating phagocytes, innate lymphoid cells, NK cells, and plasma proteins.

RIG-I and MDA-5.

They are the first and most numerous cell type to respond, particularly to bacterial and fungal infections.

Bacterial pneumonias.

To capture and present antigens to T cells, bridging innate and adaptive immunity.

Shared structures not present in normal host cells, such as bacterial endotoxin and peptidoglycans.

Endosomal TLRs, specifically TLR-3, TLR-7, TLR-8, and TLR-9.

Bacterial LPS (endotoxin) made by gram-negative bacteria.

T cell lineage lymphocytes that express antigen receptors of limited diversity, found in epithelial layers.

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.

Neutrophils live for 1-2 days, while macrophages can live for days, weeks, or even years.

Viral nucleic acids in the cytosol, signaling an immune response.

They block viral replication within host cells.

It evolved receptors specific for microbial structures and products of damaged cells, not substances in healthy cells.

They enter extravascular tissues and differentiate into macrophages.

A ligand-binding domain composed of leucine-rich motifs and a TIR domain.

dsRNA.

Type I interferons (IFNs).

Neutrophils respond rapidly and are short-lived; macrophages respond more slowly and have prolonged activity.

Multiprotein complexes that assemble in the cytosol of cells in response to microbes or cell injury.

They engulf and destroy microbes and damaged cells.

To recognize cell wall components of bacteria.

It is a group of proteins that enhance the ability to clear microbes and promote inflammation.

The process by which phagocytes engulf and destroy pathogens.

By interacting with a mitochondrial membrane protein called MAVS.