What happens to ITAMs when lymphocyte antigen receptors recognize their activating ligands?
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They become phosphorylated on tyrosine residues.
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What happens to ITAMs when lymphocyte antigen receptors recognize their activating ligands?
They become phosphorylated on tyrosine residues.
What do phosphorylated ITAMs promote?
Activation of cytosolic protein tyrosine kinases.
What is the role of class I MHC expression on healthy cells?
It protects them from destruction by NK cells.
What are the two major families of NK cell inhibitory receptors in humans?
Killer cell immunoglobulin-like receptors (KIRs) and receptors consisting of CD94 and NKG2.
What cells produce cytokines and other mediators during an acute inflammatory response?
Macrophages, dendritic cells, mast cells, and other cells in tissues.
What enzyme in macrophages catalyzes the conversion of arginine to nitric oxide (NO)?
Inducible nitric oxide synthase (iNOS).
What do ITIMs do when phosphorylated?
They promote activation of cytosolic protein tyrosine phosphatases, counteracting ITAM functions.
What do mediators like histamine and prostaglandins do during inflammation?
They increase the permeability of blood vessels, allowing plasma proteins to enter tissues.
What family do surfactant proteins in the lung belong to?
The collectin family.
What is the role of Innate Lymphoid Cells (ILCs) in early defense against infections?
ILCs may provide early defense against infections in tissues.
Where are microbicidal substances predominantly produced?
In lysosomes and phagolysosomes.
How do many viruses evade killing by CD8+ CTLs?
By blocking expression of class I MHC molecules in infected cells.
What are IL-1 and TNF's roles in inflammation?
They increase the expression of endothelial adhesion molecules and chemokines to promote leukocyte movement.
What is the function of C-reactive protein (CRP)?
It binds to phosphorylcholine on microbes and opsonizes them for phagocytosis by macrophages.
How are macrophages activated in innate immune responses?
By microbial products binding to TLRs and cytokines like NK cell-derived IFN-γ.
What role do lysosomal proteases play in the immune response?
They break down microbial proteins.
What happens when NK cells encounter infected cells with reduced class I MHC expression?
The NK cells become activated and eliminate the virus-infected cells.
What are the first steps in the acute inflammatory response?
Injury leading to barrier break and microbe entry.
What are the principal cellular targets of IFN-gamma?
NK cells and T cells.
What is the acute-phase response?
It is a protective response where circulating levels of plasma proteins increase rapidly after infection.
What do cell surface complement receptors promote in macrophages?
The phagocytosis of complement-coated microbes and activation of macrophages.
What happens to microbes after they are ingested into phagosomes?
They fuse with lysosomes, leading to their killing by enzymes and toxic substances.
What cytokine do Natural Killer (NK) cells produce that leads to dendritic cell and macrophage fusion?
IFN-gamma.
How do neutrophils and monocytes migrate to sites of infection?
By binding to venular endothelial adhesion molecules in response to chemoattractants.
What happens when an NK cell engages its inhibitory receptor?
The NK cell is not activated and does not kill the normal cell.
What is the principal effect of TGF-beta?
Inhibition of inflammation and differentiation of regulatory T cells.
What initiates the complement activation pathways?
The alternative pathway (microbe), classical pathway (microbe bound to antibody), and lectin pathway (microbe bound to mannose-binding lectin).
How do Fc receptors on macrophages function?
They bind antibody-coated microbes and perform similar functions to complement receptors.
What is the role of IL-12 in immune response?
It promotes IFN-gamma production and increased cytotoxic activity in NK cells and T cells.
What are neutrophil extracellular traps (NETs)?
Networks of chromatin extruded by dying neutrophils that trap and kill bacteria and fungi.
What initiates the sequence of events in leukocyte migration into tissues?
Cytokines TNF and IL-1 acting on the endothelium of venules.
How do leukocytes migrate toward the source of infection?
They migrate along extracellular matrix fibers directed by concentration gradients of chemoattractants.
What occurs when an NK cell binds to a virus-infected cell?
The NK cell is activated and kills the infected cell.
Which cells secrete cytokines in innate immunity?
Dendritic cells, macrophages, mast cells, and ILCs.
What is produced at the end of the complement activation process?
C3b, which initiates the formation of the membrane attack complex (MAC).
Which cytokine do NK cells secrete to activate macrophages?
Interferon-gamma (IFN-γ).
What are the principal cell sources of Tumor Necrosis Factor (TNF)?
Macrophages, T cells, and mast cells.
How do reactive oxygen species (ROS) contribute to microbe killing?
They are produced in phagolysosomes and kill microbes inside the cell.
What role do selectins play in the rolling of leukocytes?
They are adhesion molecules that bind circulating neutrophils and monocytes to the endothelium.
What are some examples of chemoattractants for leukocytes?
Chemokines, bacterial formyl peptides, and complement fragments C5a and C3a.
How do microbes evade killing by CTLs?
Viruses inhibit MHC expression, making it difficult for CTLs to recognize infected cells.
What initiates cellular reactions of innate immunity?
Cytokines secreted by various immune cells.
What are C3a and C5a known for?
They are inflammation-inducing by-products released during complement activation.
What are mast cells derived from?
Bone marrow.
Which cytokine is associated with activating endothelial cells and inducing fever?
Interleukin-1 (IL-1).
What percentage of lymphocytes in blood and secondary lymphoid organs are NK cells?
Approximately 5% to 20%.
What is chronic granulomatous disease (CGD)?
An immunodeficiency disorder caused by inherited deficiency of the phagocyte oxidase enzyme.
What do NK cells primarily kill?
Host cells infected by obligate intracellular microbes, such as viruses.
What activates the lectin pathway of complement activation?
Mannose-binding lectin (MBL) or ficolins binding to carbohydrate ligands on microbes.
What happens after neutrophils bind to the endothelium?
The flowing blood disrupts the binding; bonds reform downstream, allowing repetitive rolling.
What sequence of events facilitates the migration of blood leukocytes to infection sites?
Selectin-mediated rolling, integrin-mediated firm adhesion, and chemokine-mediated motility.
What is a characteristic of lymphocytes with limited diversity?
They express somatically rearranged antigen receptors but have limited diversity.
What cytokine do natural killer (NK) cells produce that activates macrophages?
Interferon-gamma (IFN-γ).
Where are mast cells commonly found?
In the skin, mucosal tissues, and most connective tissues.
What effects do chemokines have on leukocytes?
Increased integrin affinity, chemotaxis, and activation.
What consequence can arise from the release of enzymes and ROS into the extracellular space?
Injury to host tissues.
How do NK cells contribute to tumor destruction?
They kill tumor cells as part of their immune response.
What do NK cells use to induce apoptosis in infected cells?
They deliver contents of their cytoplasmic granules into the infected cells.
Why is the lectin pathway considered a component of innate immunity?
Because it is initiated by a microbial product in the absence of antibody.
What are leukocyte adhesion deficiencies (LADs)?
Inherited deficiencies in integrins and selectin ligands leading to defective leukocyte recruitment and increased susceptibility to infections.
What types of lymphocytes are involved in early defense against microbes?
γδ T cells, NK-T cells, mucosal-associated invariant T cells, B1 cells, and marginal zone B cells.
Which cytokine is involved in both innate and adaptive immunity?
Transforming growth factor beta (TGF-β).
What can activate mast cells?
Microbial products binding to TLRs, components of the complement system, or antibody-dependent mechanisms.
What are the primary roles of macrophages in host defense?
Ingesting and destroying microbes, clearing dead tissues, initiating tissue repair, and producing cytokines that regulate inflammation.
What initial process allows leukocytes to roll along the endothelial surface?
The interaction with selectins during weak tethering.
What is the source of Type 1 interferons (IFN-alpha and IFN-beta)?
IFN-alpha: dendritic cells, macrophages; IFN-beta: fibroblasts, epithelial cells.
What are interleukins?
Molecularly defined cytokines with specific numbers, e.g., interleukin-1.
What triggers the formation of neutrophil extracellular traps (NETs)?
Response to pathogens and inflammatory mediators.
What is the role of IL-12 in the activation of NK cells?
IL-12, produced by macrophages, activates NK cells to secrete IFN-γ.
What is the primary function of NK cells?
To eliminate infected cells and eradicate infections.
What is the central component of all three complement pathways?
C3, a plasma protein.
What role do phagocytes have in the immune response?
Phagocytes work with plasma proteins like complement to destroy offending agents.
What vasoactive amine do mast cell granules contain?
Histamine.
What cytokines do macrophages and dendritic cells produce at infection sites?
Tumor necrosis factor (TNF) and interleukin-1 (IL-1).
What receptors are involved in the activation of macrophages?
Pattern recognition receptors such as TLRs and NLRs, as well as phagocytic receptors like mannose receptors and scavenger receptors.
What defines the complement system?
A collection of circulating and membrane-associated proteins important in defense against microbes.
What is the function of Interleukin-10 (IL-10) in immune regulation?
Inhibition of cytokine and chemokine production and reduced expression of costimulators and class II MHC molecules.
How do cytokines typically act on target cells?
Most act on nearby cells (paracrine) or on the cells that produce them (autocrine).
What cytokine do activated NK cells secrete to enhance macrophage function?
Interferon-γ (IFN-γ).
What role does the proteolytic fragment C3b play in complement activation?
C3b covalently attaches to microbes and recruits downstream complement proteins.
What is phagocytosis?
The process of ingesting particles larger than 0.5 μm in diameter by phagocytes.
What effect does histamine have?
Causes vasodilation and increased capillary permeability.
How is the complement cascade activated?
Through the sequential activation of proteolytic enzymes.
What role do integrins play in leukocyte adhesion?
Integrins mediate firm adhesion of neutrophils to the endothelium.
What are the two pathways of macrophage activation?
Classical (M1) and alternative (M2) pathways.
What is the role of Interleukin-6 (IL-6) in the immune response?
Stimulates liver synthesis of acute-phase proteins and B cell proliferation.
What is the role of TNF and IL-1 in innate immunity?
They recruit blood neutrophils and monocytes to sites of infection.
Which cytokines enhance the killing functions of NK cells?
IL-15, type I interferons, and IL-12.
What are the three main functions of the complement system in host defense?
Opsonization and phagocytosis, inflammation, and cell lysis.
What triggers the process of phagocytosis?
Binding of membrane receptors to the microbe.
What additional substances do mast cells synthesize and secrete?
Lipid mediators (e.g., prostaglandins, leukotrienes) and cytokines (e.g., TNF).
How do chemokines affect leukocyte migration?
They activate leukocytes and stimulate their migration through the endothelium.
What triggers the alternative pathway of the complement system?
Activation of complement proteins on microbial surfaces where regulatory proteins are absent.
What induces classical macrophage activation?
Innate immune signals from TLRs and the cytokine IFN-γ.
Which cytokine supports the proliferation of NK cells and T cells?
Interleukin-15 (IL-15).
What systemic effects do TNF and IL-1 have?
They induce fever and stimulate liver cells to produce acute phase proteins.
What is the function of the activating receptor NKG2D on NK cells?
It recognizes stress-induced molecules resembling class I MHC proteins.
What is opsonization?
The process of coating a microbe with molecules recognized by receptors on phagocytes, promoting binding and ingestion.
What is formed when phagosomes fuse with lysosomes?
Phagolysosomes.
What role do mast cells play against pathogens?
They provide defense against helminths and protect against snake and insect venoms.
What are classically activated macrophages also known as?
M1 or pro-inflammatory macrophages.
What shape change occurs in leukocytes during migration?
Leukocytes become oval in shape as they migrate.
What typically initiates the classical pathway of the complement system?
Antibodies that bind to microbes or other antigens.
What can high concentrations of TNF lead to?
Thrombus formation on endothelium and reduced blood pressure.
How do C5a and C3a contribute to inflammation?
They act as chemoattractants for leukocytes and activators of endothelial cells and mast cells.
What is antibody-dependent cellular cytotoxicity (ADCC)?
The process by which NK cells kill antibody-coated cells.
What is the oxidative burst in phagocytes?
A process where phagocyte oxidase converts molecular oxygen into superoxide anion and free radicals to kill ingested microbes.
What are innate lymphoid cells (ILCs)?
Tissue-resident cells that produce cytokines similar to helper T lymphocytes without expressing TCRs.
What role do M2 macrophages play?
They are involved in tissue repair and terminating inflammation.
What are the low-affinity states of integrins associated with?
Unaffected leukocytes prior to activation.
What clinical syndrome can result from severe bacterial and fungal infections?
Septic shock, characterized by low blood pressure.
What determines the responses of NK cells?
The balance between activating and inhibitory receptors.
What is the result of complement activation on microbial cell membranes?
Formation of a polymeric protein complex that causes osmotic lysis.
What enzyme is involved in the oxidative burst?
Phagocyte oxidase.
In what immune responses are macrophages important?
Both the cell-mediated arm and the humoral arm of adaptive immunity.
How are ILCs classified?
Into three major groups based on their secreted cytokines corresponding to Th1, Th2, and Th17 subsets of CD4+ T cells.
What happens to leukocyte integrins upon activation by chemokines?
They transition to a high-affinity state for their ligands.
What role does mannose-binding lectin (MBL) play in innate immunity?
MBL recognizes microbial carbohydrates, coats microbes for phagocytosis, and activates the lectin pathway of complement.
What is a well-defined activating receptor of NK cells?
CD16, which recognizes the Fc region of bound IgG antibodies.
What functions do dendritic cells serve?
They initiate inflammation, stimulate adaptive immune responses, and capture and display protein antigens to T cells.
Where are ILCs always present?
In tissues.
What are ICAM-1 and VCAM-1?
Ligands for integrins expressed by activated endothelial cells.
How do dendritic cells connect innate and adaptive immunity?
By sensing microbes and interacting with lymphocytes, especially T cells.
What do leukocytes do once they adhere to the endothelium?
They crawl to and migrate through the junctions between endothelial cells.
What triggers the production of TNF in septic shock?
High levels of bacterial PAMPs.
Which cells produce IL-1 and IL-12 in response to microbial molecules?
Dendritic cells and macrophages.
What is the role of IL-12 in the immune response?
Activating NK cells, leading to increased killing activity and macrophage activation.
What cytokine do NK cells produce that activates macrophages?
IFN-γ.
What type of interferons do dendritic cells produce during viral infections?
Type I IFNs.
How do type I IFNs help during viral infections?
By inhibiting viral replication and preventing the spread of infection.
What is the main defense against extracellular bacteria and fungi?
The acute inflammatory response, involving neutrophils and monocytes.
How do phagocytes eliminate intracellular bacteria?
They are activated by TLRs and other innate sensors as well as by cytokines.
What mediators are released by mast cells and macrophages during inflammation?
Histamine, TNF, prostaglandins, and other mediators.
What are the characteristic features of acute inflammation?
Redness, warmth, and swelling.
What is the role of activated phagocytes in inflammation?
To engulf microbes and necrotic material and destroy potentially harmful substances.
