Innate Immunity: Key Concepts and Receptors in Host Defense

What is inflammation in the context of the immune response?

Inflammation is one of the two principal immune responses involving the accumulation and activation of leukocytes and plasma proteins at sites of infection or injury, working together to kill extracellular microbes and eliminate damaged tissue.

What are damage-associated molecular patterns (DAMPs)?

DAMPs are molecules released from damaged or necrotic host cells that the innate immune system recognizes to eliminate damaged cells and initiate tissue repair.

What are pathogen-associated molecular patterns (PAMPs)?

PAMPs are microbial molecules that stimulate innate immunity, indicating the presence of infectious agents and shared by microbes of the same type.

What are Toll-like receptors (TLRs) and their function?

TLRs are receptors homologous to a Drosophila protein 'toll', present in humans (9 types) to detect extracellular microbes, activating transcription factors that express cytokines and endothelial adhesion.

What role do NK cells play in the innate immune system?

NK cells mediate innate immune defense against intracellular viruses by killing virus-infected cells and can be altered by encounters with microbes to improve future responses.

How does the innate immune system recognize microbes?

The innate immune system recognizes structures shared by various classes of microbes that are not present on normal host cells, using receptors specific to different bacteria, viruses, or fungi.

What types of receptors do phagocytes have?

Phagocytes have bacterial endotoxin receptors for lipopolysaccharides (LPS) and other receptors for peptidoglycans, which are not produced by mammalian cells.

What is the significance of double-stranded RNA (dsRNA) in the innate immune response?

Mammalian cells recognize dsRNA, which is produced during the replication of many viruses but not in mammalian cells, indicating viral infection.

What are Pattern Recognition Receptors (PRRs)?

PRRs are receptors of the innate immunity that recognize structures shared with PAMPs in microbes, essential for the survival and infectivity of these microbes.

How does the innate immune system differ from the adaptive immune system in terms of receptor diversity?

The innate immune system has receptors encoded by inherited genes that are identical in all cells, while the adaptive immune system has clone cells with diverse receptors.

How many types of innate immune receptors can recognize PAMPs and DAMPs?

There are approximately 100 types of innate immune receptors that can recognize around 1000 PAMPs and DAMPs.

What is the role of healthy cells in the innate immune response?

Healthy cells express molecules that block innate immune responses, preventing recognition and reaction by the innate immune system.

What is the function of inflammasomes in the immune response?

Inflammasomes are multiprotein complexes that assemble in response to microbes or cell injuries, activating inflammatory cytokines and producing pro-IL-1B.

What is pyroptosis?

Pyroptosis is a form of programmed cell death in macrophages and dendritic cells triggered by inflammasome activation, resulting in cell swelling, loss of plasma membrane integrity, and release of inflammatory cytokines.

What are autoinflammatory syndromes?

Autoinflammatory syndromes are conditions characterized by uncontrolled spontaneous inflammation due to mutations in inflammasomes, which can be treated with IL-1 antagonists.

What distinguishes the adaptive immune system's response to self-antigens?

The adaptive immune system discriminates between self and non-self, producing lymphocytes that recognize self-antigens, which either die or are inactivated upon encountering self-antigens.

What is the role of the complement system in the innate immune response?

The complement system is an example of how healthy cells express molecules that inhibit innate immune responses, preventing damage to self-tissues.

How do microbes evade adaptive immunity?

Microbes evade adaptive immunity by mutating antigens that are not essential for their survival, allowing them to avoid being targeted by the adaptive immune response.

What is the relationship between innate immune receptors and microbial structures?

Innate immune receptors are specific for structures of microbes that are often essential for their survival and infectivity, but they do not kill the microbes directly.

How do TLRs contribute to the immune response?

TLRs activate transcription factors that lead to the expression of cytokines and endothelial adhesion molecules, enhancing the immune response to detected pathogens.

What happens to macrophages and dendritic cells during pyroptosis?

During pyroptosis, macrophages and dendritic cells swell, lose their plasma membrane, and release inflammatory cytokines as a result of inflammasome activation.

What is the significance of the recognition of lipopolysaccharides (LPS) by phagocytes?

Phagocytes recognize LPS, a component of bacterial cell walls, which is crucial for initiating an immune response against gram-negative bacteria.

What is gout characterized by?

Deposition of urate crystals and inflammation.

What role do inflammasomes play in atherosclerosis?

They contribute to the inflammatory processes involved in atherosclerosis.

What are cytosolic RNA and DNA sensors?

Cytosolic proteins that recognize microbial RNA or DNA and signal the production of inflammatory and antiviral cytokines.

What are NOD-like receptors (NLRs)?

A large family of innate receptors that sense DAMPs and PAMPs in the cytosol and initiate signaling to promote inflammation.

What do cytosolic DNA sensors (CDSs) recognize?

Microbial double-stranded DNA (dsDNA) in the cytosol.

What pathway do cytosolic DNA sensors induce for type 1 IFN production?

The STING pathway.

What is the function of STING in the immune response?

STING stimulates autophagy and induces type 1 interferon production.

How does autophagy contribute to the innate immune system?

It degrades organelles in lysosomes and delivers cytosolic microbes for destruction.

What are interferonopathies?

Inflammatory diseases caused by cytosolic DNA sensors failing to recognize excess self DNA due to mutations.

What are lectins (Dectins) and their function?

Receptors in plasma membranes that recognize fungal glucans and promote phagocytosis of fungi and bacteria.

What is the role of Formyl Peptide Receptor 1?

A cell surface receptor in phagocytes that recognizes polypeptides and promotes migration and phagocyte attack.

What are the epithelial barriers in innate immunity?

Layers of epithelial cells in skin, GI tract, respiratory tract, and genitourinary tract that prevent infection.

What substances do epithelial barriers produce to prevent infection?

Keratin, mucous, and antimicrobial peptides (defensins and cathelicidins).

What are the two types of phagocytes?

Neutrophils and monocytes.

What are the characteristics of neutrophils?

Most abundant leukocytes in blood, respond rapidly to infections, and live for several hours.

What is the role of monocytes in the immune response?

They ingest microbes and differentiate into macrophages during inflammation.

What are the two stages of macrophages?

Blood monocyte and macrophage.

What are the functions of macrophages?

Initiate tissue repair, clear dead tissue, ingest/destroy microbes, and produce cytokines.

What are the two pathways of macrophage activation?

Classical macrophage activation and alternative (M2) macrophage activation.

What is the role of dendritic cells in immunity?

They respond to microbes, produce cytokines, and bridge innate and adaptive immunity.

What are mast cells and where are they found?

Bone-marrow derived cells with granules, found in skin, mucosal tissues, and connective tissues.

How do mast cells contribute to inflammation?

They release histamine and other mediators that cause vasodilation, increase capillary permeability, and stimulate inflammation.

What types of pathogens do mast cells defend against?

Helminths, venoms, and other pathogens, and they are also involved in allergic diseases.

What are Innate Lymphoid Cells (ILCs)?

Tissue resident cells that produce cytokines like helper T-lymphocytes, do not express T-cell antigen receptors, and are always present in tissues.

What are the three groups of Innate Lymphoid Cells?

Th1, Th2, and Th17.

How are Innate Lymphoid Cells triggered?

They are triggered by damaged epithelial cells and other cells at infection sites, providing early infection defense.

What is the primary function of Natural Killer (NK) Cells?

To recognize and destroy cells infected with viruses, some other cells, and stressed cells, as well as to help eliminate tumors.

How do cytokines influence NK cells?

Cytokines secreted by macrophages or dendritic cells increase the ability of NK cells.

Describe the interaction between macrophages and NK cells.

Macrophages ingest microbes and produce IL-12, which activates NK cells. NK cells then secrete IFN-y, activating macrophages to kill microbes.

What is Antibody-dependent Cellular Cytotoxicity (ADCC)?

A process mediated by NK cells that involves the recognition and killing of antibody-coated cells.

Which receptor on NK cells is involved in ADCC?

Receptor CD16, which activates the Fc region of immunoglobulin (Ig) bound to cells.

What role do inhibitory receptors play in NK cell function?

Inhibitory receptors block signaling by activating receptors for self class 1 MHC, protecting cells from being destroyed by NK cells.

Name two major families of NK cell inhibitory receptors in humans.

Killer cell immunoglobulin-like receptors (KIRs) and a receptor of CD94 and lectin subunit NKG2.

What is the significance of ITIMs in NK cell receptors?

ITIMs are motifs that inhibit signaling, helping to regulate NK cell activity.

How do viruses evade destruction by NK cells?

Viruses inhibit MHC expression, preventing CTLs and NKs from killing them, which can make NK cells more effective.

What is the complement system?

A collection of membrane-associated proteins important in defense against microbes, many of which are proteolytic enzymes.

What are the three pathways to activate the complement cascade?

Alternative pathway, Classical pathway, and Lectin pathway.

What triggers the Alternative pathway of the complement cascade?

Activation of complement proteins on microbial surfaces.

How is the Classical pathway of the complement cascade triggered?

By antibodies binding to microbes or antigens.

What activates the Lectin pathway of the complement cascade?

Carbohydrate-binding plasma proteins, such as mannose-binding lectin or ficolins, binding to carbohydrate ligands on microbes.

What is the central component of the complement pathways?

The plasma protein called C3.

What are the three main functions of the complement system?

Opsonization and phagocytosis, inflammation, and recruitment of leukocytes.

How does C3b function in opsonization?

C3b coats microbes and promotes binding to phagocytes that contain C3b receptors.

What is the role of C5a and C3a in inflammation?

They act as chemoattractants for leukocytes (neutrophils and monocytes) and activate endothelial cells and mast cells.

What is the role of leukocytes and plasma proteins in inflammation?

They promote movement into tissues during inflammation.

What is the outcome of cell lysis in the immune response?

It culminates in the formation of a polymeric protein complex that inserts into microbial cell membranes, disturbing permeability and causing osmotic lysis.

What is the function of Plasma MBL in innate immunity?

It recognizes microbial carbohydrates, coats microbes for phagocytosis, or activates the lectin pathway.

What is C-reactive protein (CRP) and its role in the immune response?

A five-headed molecule that binds to microbes, opsonizes them, or activates the classical pathway.

What happens to Plasma MBL and CRP levels during infection?

Their circulating levels increase.

What are cytokines and their role in innate immunity?

Soluble proteins that mediate inflammatory and immune reactions, responsible for communication between leukocytes and other cells.

What are interleukins?

Molecularly defined cytokines that bind to high-affinity receptors on target cells.

What is septic shock and what causes it?

A condition caused by high levels of TNF produced in response to bacterial PAMPs, leading to low blood pressure and metabolic disturbances.

How does the innate immune system eliminate microbes?

By inducing an acute inflammatory response and antiviral defense mechanisms.

What is the role of neutrophils and monocytes in the acute inflammatory response?

They defend against extracellular bacteria and fungi.

How are intracellular bacteria eliminated in the immune response?

By phagocytes activated by TLR and cytokines.

What is the function of type 1 interferons (IFNs) in antiviral defense?

They inhibit viral replication and help establish an antiviral state.

What is the significance of neutrophil extracellular traps (NETs)?

They contain antimicrobial substances that trap and kill bacteria and fungi.

What is Chronic Granulomatous Disease (CGD)?

An immunodeficiency disorder characterized by a deficiency in phagocyte oxidative enzymes, leading to an inability to eradicate intracellular microbes.

What is the role of macrophages in tissue repair?

They, along with helper T-cells and ILCs, are involved in the tissue repair process.

What are danger signals in the context of adaptive immune response activation?

Stimuli that warn the adaptive immune system of microbial presence and host cell damage.

What are adjuvants and their purpose in vaccines?

Substances administered with antigens to elicit an innate immune response that provides a second signal to activate the adaptive immune response.

What are costimulators in the immune response?

Surface molecules in macrophages and dendritic cells that activate T cells by binding to naïve T cells.

How do pathogenic microbes resist innate immunity?

They evolve mechanisms, such as Listeria producing proteins that help escape phagocytic vesicles and inhibit ROS and NO.

What is the relationship between innate immune responses and the activation of naïve T and B lymphocytes?

Innate immune responses generate signals required to activate naïve T and B lymphocytes, with full activation requiring two signals.

What is the acute inflammatory response's role in innate immunity?

It defends against extracellular bacteria and fungi through the action of monocytes and neutrophils.

What is the effect of reactive oxygen species (ROS) in phagocytes?

They are toxic to ingested microbes and are produced during the oxidative burst.

What is the role of macrophages in phagocytosis?

They produce nitric oxide and other reactive substances to kill microbes in phagolysosomes.