W2-6 TBL acute inflammatory response and complement

Questions and Answers

What types of injury can trigger inflammation?

Physical and chemical only

Physical, chemical, biological, and radiation

Physical, chemical, and biological only

Physical, chemical, biological, and psychological (correct)

Which of the following is not listed as a type of physical immunological insult?

Radiation

Frostbite

Viruses (correct)

Physical trauma

What is stated as the environment in which leukocytes perform at their best?

Chronic inflammation

Sepsis

Aseptic tissue repair

Inflammation (correct)

Which of the following is NOT listed as a chemical immunological insult?

Bacteria Signup and view all the answers

What does the text suggest about the relationship between immune responses and inflammation?

Inflammation is crucial for efficient immune responses Signup and view all the answers

According to the text, what types of injuries will be addressed in a separate series of activities provided by pathologists?

Responses to chemicals and trauma Signup and view all the answers

Which chemotactic factors enhance phagocytic cell recruitment?

C3a and C5a Signup and view all the answers

What effect does tumor necrosis factor α and prostagandins have on postcapillary veinules?

Induce vasodilation Signup and view all the answers

Which molecules stimulate the expression of selectins and their ligands on endothelial cells and circulating leukocytes?

IL-1β, TNF-α, and histamine Signup and view all the answers

What process enables leukocytes to leave the bloodstream and reach sites of infection or inflammation?

Transmigration Signup and view all the answers

What do leukocytes follow along the extracellular matrix in order to migrate?

Chemotactic gradients Signup and view all the answers

What is the interrelationship between the acute inflammatory response and the extrinsic coagulation pathway?

The acute inflammatory response activates the extrinsic coagulation pathway, and vice versa Signup and view all the answers

What stimulates the expression of tissue factor (TF) on the surface of endothelial cells, monocytes, and macrophages?

Tumor necrosis factor α and IL-1β Signup and view all the answers

Which factor leads to the activation of factor VII (factor VIIa) in the extrinsic coagulation pathway?

Tissue factor (TF) Signup and view all the answers

What is stimulated by thrombin stimulation of platelets in the extrinsic coagulation pathway?

Platelet activation, TF expression, chemokine release, endothelial and leukocyte adhesion molecules, and vascular leakage Signup and view all the answers

What stimulates leukocytes and endothelial cells to produce proinflammatory cytokines such as TNF-α, IL-1β, and IL-6?

Fibrin and fibrin/fibrinogen degradation products Signup and view all the answers

What do vasoactive peptides such as bradykinin induce?

Vasodilation Signup and view all the answers

What is a strong vasodilator capable of inducing vascular leakage?

Bradykinin Signup and view all the answers

Which type of macrophages is mainly involved in tissue repair?

M2 macrophages Signup and view all the answers

What is the primary function of M1 macrophages?

Pathogen clearance Signup and view all the answers

Which cells are the products of adaptive immunity and can be a source of IFN-γ during the innate stage of the immune response?

Natural Killer cells (NK cells) Signup and view all the answers

Which signal is absolutely necessary for macrophage activation for microbial killing?

IFN-γ Signup and view all the answers

What type of cells respond to macrophage synthesis and release of IL-12 by synthesizing and releasing IFN-γ?

Natural Killer (NK) cells Signup and view all the answers

Which type of cells are involved in pro-inflammatory responses and pathogen clearance?

M1 macrophages Signup and view all the answers

What is the primary function of M2 macrophages?

Tissue repair Signup and view all the answers

Which cells are the cellular sources of IFN-γ during the innate stage of the immune response?

Natural Killer cells (NK cells) Signup and view all the answers

What signal is necessary for macrophage activation for microbial killing, apart from IFN-γ?

TNF-α Signup and view all the answers

Which cells respond to macrophage synthesis and release of IL-12 by synthesizing and releasing IFN-γ?

Natural Killer (NK) cells Signup and view all the answers

Which type of cells are mainly involved in tissue repair and immune regulation?

M2 macrophages Signup and view all the answers

What is the primary function of classically activated macrophages (M1)?

Microbial killing Signup and view all the answers

Which of the following is required to activate macrophages?

IFN-γ and TNF-α Signup and view all the answers

What is the function of IL-12 cytokine?

Activation of Natural Killer cells (NK cells) Signup and view all the answers

Which cytokine is responsible for the activation of mast cells and chemotaxis?

C5a Signup and view all the answers

What is the role of endothelial cells in inflammation?

Release of soluble inflammatory mediators Signup and view all the answers

What is the function of IFN-γ cytokine?

Activation of macrophage microbicidal functions Signup and view all the answers

Which cytokine induces antiviral mediators?

IFN-α Signup and view all the answers

What are the non-specific signs and symptoms induced by proinflammatory cytokines released systemically?

Fever, muscle ache, joint pain, headache Signup and view all the answers

Which complement fragment is involved in the activation of mast cells and chemotaxis?

$C5a$ Signup and view all the answers

What is the function of TNF-α cytokine?

$Fever$, vasodilation, increased muscle and fat catabolism (cachexia) Signup and view all the answers

What is the role of neutrophils in inflammation?

Phagocytosis, release of DAMPs, microbial killing Signup and view all the answers

What is the function of IL-33 cytokine?

Nuclear alarmin cytokine released during tissue injury and involved in the control of the immune system Signup and view all the answers

What is the function of TNF-α cytokine?

Vasodilation and vascular permeability Signup and view all the answers

What is the function of the inflammasome?

It activates a caspase required for the proteolytic activation of the inactive precursor of InterLeukin-1-beta (IL-1ß) Signup and view all the answers

Which of the following is not a Pathogen-Associated Molecular Pattern (PAMP)?

Histones Signup and view all the answers

What is the main role of Nuclear Factor-kappa B (NF-κB) signaling pathway in inflammasome activation?

It signals for the synthesis of pro-IL-1ß in response to PAMP engagement Signup and view all the answers

Which type of cells contain inflammasomes?

Monocyte-derived phagocytic cells Signup and view all the answers

What is the function of alarmins and stressorins in the inflammatory response?

Act as Pathogen-Associated Molecular Patterns (PAMPs) Signup and view all the answers

Which of the following is a soluble inflammatory mediator?

Histamine Signup and view all the answers

What does PRR stand for in the context of the text?

Pathogen Recognition Receptor Signup and view all the answers

Which pathway is triggered by the engagement of the InterLeukin-1-Receptor (IL-1R) on the surface of macrophages?

NF-κB pathway Signup and view all the answers

What is the main target of the nuclear cytokine IL-33?

Mast cells Signup and view all the answers

What cellular injury releases DAMPs that attract tissue-resident phagocytic cells?

Macrophages Signup and view all the answers

What activates pro-IL-1ß by cleavage into biologically active IL-1ß?

Caspases Signup and view all the answers

What signaling pathway do Scavenger Receptors (SRs) activate?

Protein Kinase C (PKC) pathway Signup and view all the answers

What is engaged by IL-1ß released by the stimulated cell, triggering the activation of IL-1ß-responsive genes?

NF-κB pathway Signup and view all the answers

Which transcription factors are activated by the combined effect of NF-κB pathway and Mitogen-Activated Protein Kinase (MAPK) pathway?

NF-κB and Activator Protein 1 (AP-1) Signup and view all the answers

What do Tumor Necrosis Factor-alpha (TNF-α), IL-6, and CXCL8 (IL-8) belong to in the inflammatory cascade?

Pro-inflammatory cytokines Signup and view all the answers

What is involved in many autoimmune diseases due to gain of function of elements?

Inflammasome Signup and view all the answers

What are mainly induced by the working of soluble complement fragments, C5a & C3a, on microvasculature?

Vascular permeability and vascular leakage Signup and view all the answers

What does inflammation initiate in addition to vasodilation and fluid influx?

Microvascular thrombosis and kallikrein-kinin system activation Signup and view all the answers

What induces clotting mechanisms influencing immune cell recruitment and tissue repair?

Inflammatory signals Signup and view all the answers

Which type of macrophages is mainly involved in tissue repair and immune regulation?

M2 macrophages Signup and view all the answers

What is the main target of the nuclear cytokine IL-33?

Fibroblasts Signup and view all the answers

What does vasoactive peptides such as bradykinin induce?

Pain and inflammation Signup and view all the answers

What is engaged by IL-1ß released by the stimulated cell, triggering the activation of IL-1ß-responsive genes?

Interleukin-1-Receptor (IL-1R) Signup and view all the answers

What is involved in many autoimmune diseases due to gain of function of elements?

Inflammasomes Signup and view all the answers

What is required to activate macrophages?

Interferon-gamma (IFN-γ) Signup and view all the answers

What is the function of IL-1ß cytokine?

Initiation of the inflammatory response and fever Signup and view all the answers

What is the primary function of IL-6 cytokine?

Fever and synthesis of acute-phase reactants Signup and view all the answers

What is the main role of IL-33 cytokine?

Nuclear alarmin cytokine released during tissue injury Signup and view all the answers

What is the function of IL-2 cytokine?

Proliferation of T and B lymphocytes Signup and view all the answers

What is the primary function of TNF-α cytokine?

Vasodilation and chemotaxis Signup and view all the answers

What is engaged by IL-1ß released by the stimulated cell, triggering the activation of IL-1ß-responsive genes?

IL-1R Signup and view all the answers

Which type of cells respond to macrophage synthesis and release of IL-12 by synthesizing and releasing IFN-γ?

T lymphocytes Signup and view all the answers

What is the main function of M1 macrophages?

Activation of macrophage microbicidal functions Signup and view all the answers

What is the role of endothelial cells in inflammation?

Activation, expression of selectins & integrins, and production of adhesion molecules Signup and view all the answers

Which factor leads to the activation of factor VII (factor VIIa) in the extrinsic coagulation pathway?

Thrombin Signup and view all the answers

Which type of cells contain inflammasomes?

Macrophages Signup and view all the answers

What stimulates the expression of tissue factor (TF) on the surface of endothelial cells, monocytes, and macrophages?

TNF-α Signup and view all the answers

What is the primary function of classically activated macrophages (M1)?

Phagocytosis of microbes Signup and view all the answers

Which pathway is triggered by the engagement of the InterLeukin-1-Receptor (IL-1R) on the surface of macrophages?

NF-κB pathway Signup and view all the answers

What process enables leukocytes to leave the bloodstream and reach sites of infection or inflammation?

Diapedesis Signup and view all the answers

What is the function of alarmins and stressorins in the inflammatory response?

Activation of adaptive immunity Signup and view all the answers

Which of the following is a soluble inflammatory mediator?

Prostaglandins Signup and view all the answers

What is the main role of Nuclear Factor-kappa B (NF-κB) signaling pathway in inflammasome activation?

Activation of the inflammasome Signup and view all the answers

What does inflammation initiate in addition to vasodilation and fluid influx?

Activation of the coagulation cascade Signup and view all the answers

What cytokine induces antiviral mediators?

IFN-γ Signup and view all the answers

What is involved in many autoimmune diseases due to gain of function of elements?

NLR Signup and view all the answers

Which complement fragment is involved in the activation of mast cells and chemotaxis?

C5a Signup and view all the answers

What signaling pathway do Scavenger Receptors (SRs) activate?

MAPK pathway Signup and view all the answers

What are the non-specific signs and symptoms induced by proinflammatory cytokines released systemically?

Fever and fatigue Signup and view all the answers

What is the alternative nomenclature for designating the C3 convertase?

C4bC2b (syn. C4b2b) Signup and view all the answers

According to the text, what is the primary function of C2b fragment?

Activation of mast cells Signup and view all the answers

Why do many authors wish to maintain a coherent and logical nomenclature system based on released fragments being attributed to the ‘a’ suffix and the bound catalytically-active fragments, the suffix ‘b’?

To avoid confusion in nomenclature Signup and view all the answers

What is the suffix given to the smaller fragment that is released and solubilized?

'a' Signup and view all the answers

Which complement fragment is involved in the activation of mast cells and chemotaxis?

C3a Signup and view all the answers

What is deeply rooted and commonly in use, but considered one and the same?

C4b2a nomenclature Signup and view all the answers

What does the larger catalytic fragment remaining attached to C4b was named initially in the report on the activity of C2?

C2a Signup and view all the answers

Why do some authors develop alternative nomenclature by renaming the larger catalytic fragment C2b and the smaller released fragment C2a?

To avoid confusion with existing naming conventions Signup and view all the answers

What is considered to be rooted in semantics exclusively?

"C4b2a" nomenclature Signup and view all the answers

What was established as a result of both nomenclatures being deeply rooted and commonly in use?

Formation of two alternative nomenclatures Signup and view all the answers

What is the main function of the B cell receptor (BCR)?

Antigen recognition and signaling Signup and view all the answers

Which molecules confer the signaling capacity leading to the B cell’s response?

Igα/Igß, CD19, and CD21 Signup and view all the answers

What is the primary function of Complement Receptor type 1 (CR1)?

Phagocytosis Signup and view all the answers

Which receptor is involved in trapping antigens in germinal centers?

CR2 (CD21) Signup and view all the answers

What is the common pathway for the membrane attack complex (MAC) in the complement cascades?

C3 convertase formation Signup and view all the answers

In which complement cascade is the central event the cleavage of C3 by C3 convertase?

All three pathways Signup and view all the answers

What initiates the classical pathway of the complement system?

Antibodies Signup and view all the answers

Which molecule becomes coated with many molecules of C3b due to complement activation?

Immune complexes Signup and view all the answers

What are primarily involved in phagocytosis among the complement receptors?

CR1, CR3, & CR4 Signup and view all the answers

Where are mononuclear phagocytes, neutrophils, B and T cells primarily distributed?

Mononuclear phagocytes, neutrophils, NK cells Signup and view all the answers

Which of the following is the primary function of opsonization?

Triggering phagocytosis Signup and view all the answers

What triggers the lectin pathway of the complement cascade?

Plasma lectins binding to microbe carbohydrates Signup and view all the answers

What is the main role of complement-mediated cytolysis?

Microbial lysis Signup and view all the answers

Which complement fragment is involved in the activation of mast cells and chemotaxis?

C5a Signup and view all the answers

What is the function of complement fragment 3d (C3d) in the immune response?

Lymphocyte activation Signup and view all the answers

What triggers the classical pathway of the complement cascade?

Antibody binding to microbes Signup and view all the answers

What is the essential function of opsonins in the immune response?

Triggering phagocytosis Signup and view all the answers

Which complement proteins are primarily synthesized by hepatocytes?

Classical pathway proteins Signup and view all the answers

What is the theoretical trigger for the alternative (alternate) pathway of the complement cascade?

Spontaneous fixation of C3b on microbial surfaces Signup and view all the answers

How are most complement proteins activated to become active proteases?

Activation by proinflammatory cytokines Signup and view all the answers

What is the main function of soluble complement fragments C3a and C5a released in an inflamed site?

Attraction of leukocytes and induction of chemotaxis and inflammation Signup and view all the answers

Which chemokine is responsible for the chemotaxis of monocytes and macrophages, T lymphocytes, NK cells, and dendritic cells?

CXCL10 (IP-10) Signup and view all the answers

Which cytokine primarily induces antiviral mediators?

IL-18 Signup and view all the answers

Which chemokine mainly signals through CCR6 and is responsible for the chemotaxis of activated B cells, memory T cells, and immature dendritic cells in mucosa and skin?

CCL20 (MIP-3α) Signup and view all the answers

Which cytokine is involved in the proliferation and activation of eosinophils and is linked to Type I hypersensitivity reactions and asthma?

IL-5 Signup and view all the answers

What cytokine is responsible for the proliferation of NK and T lymphocyte progenitors?

IL-7 Signup and view all the answers

Which chemokine primarily signals through CXCR3 and is responsible for the chemotaxis of monocytes and macrophages, T lymphocytes, NK cells, and dendritic cells?

CXCL10 (IP-10) Signup and view all the answers

What is the main function of VEGF-A (vascular endothelial growth factor A)?

Angiogenesis and endothelial cell growth Signup and view all the answers

Which cytokine is mainly responsible for the inhibition of IL-12 expression?

IL-10 Signup and view all the answers

What is the primary function of platelet-activating factor (PAF)?

Involvement in inflammation and thrombotic cascades Signup and view all the answers

What is the main role of GM-CSF (granulocyte/macrophage colony stimulating factor)?

Maturation of granulocytes and monocytes Signup and view all the answers

What is the primary function of IFN-ß (Type I IFN)?

Antiviral state (intracellular response) Signup and view all the answers

What is the main function of CCL4 (MIP-1ß or macrophage inflammatory protein 1-ß)?

Fever induction Signup and view all the answers

What is the alternative nomenclature for C4bC2a (syn. C4b2a) C3 convertase, as mentioned in the passage?

C4bC2b (syn. C4b2b) C3 convertase Signup and view all the answers

Which fragment is given the suffix 'a' by convention, as mentioned in the passage?

Smaller released fragment Signup and view all the answers

Why do many authors develop alternative nomenclature for C2a/C2b as mentioned in the passage?

To avoid confusion and coherence with provided resources Signup and view all the answers

What was the larger catalytic fragment renamed to in the alternative nomenclature, as mentioned in the passage?

C2b Signup and view all the answers

What is the smaller released fragment renamed to in the alternative nomenclature, as mentioned in the passage?

C2a Signup and view all the answers

What is the suffix given to the larger catalytic fragment by convention, as mentioned in the passage?

'b' Signup and view all the answers

Which of the following is a function of opsonins in the immune response?

Promoting chemotaxis of antigens Signup and view all the answers

Associate the complement receptor CR1 with its function(s):

Clearance of immune complexes Signup and view all the answers

Associate the C5 convertase with the correct complement activation pathway(s):

Classical Signup and view all the answers

Which serine proteases are responsible for C4 and C2 proteolysis in the lectin pathway of complement activation?

MASP-1/MASP-2 Signup and view all the answers

Associate the convertase with its substrate:

$C3bBb$ Signup and view all the answers

What is the composition of the membrane-attack complex (MAC)?

$C56789n$ Signup and view all the answers

Associate the inhibitor with the correct complement activation pathway(s):

$C4BP$ Signup and view all the answers

A patient with a suspected complement deficiency has his complement activity tested. Both the CH50 and AH50 return results below normal values. A deficiency in which complement component could explain these results?

$C3$ Signup and view all the answers

A patient with a suspected complement deficiency has his complement activity tested. The CH50 returns results consistent with normal function but the AH50 returns results below normal values. A deficiency in which complement component could explain these results?

$Factor B$ Signup and view all the answers

What is an opsonin?

A molecule that binds the surface of an antigen to promote chemotaxis Signup and view all the answers

Associate the complement receptor with its function(s): CR2

B lymphocyte activation Signup and view all the answers

What initiates the alternative pathway of the complement system?

Spontaneous hydrolysis and cleavage of C3 Signup and view all the answers

What is the role of properdin in the alternative complement pathway?

Stabilization of the C3 convertase. Signup and view all the answers

What triggers the lectin pathway of complement activation?

Binding of mannose-binding lectin (MBL) to sugar molecules on pathogen surface. Signup and view all the answers

What is the function of the C5 convertase in the complement system?

Cleaves C5 into C5b and C5a. Signup and view all the answers

What is the role of plasma lectins or ficolins in the lectin pathway of complement activation?

Binds polysaccharides on the surface of microorganisms. Signup and view all the answers

What triggers the spontaneous cleavage of C3 in the alternative pathway?

Spontaneous hydrolysis in proximity to a complement-activating surface. Signup and view all the answers

What is the function of Factor D in the alternative complement pathway?

Cleaves Factor B to yield a C3bBb complex. Signup and view all the answers

What leads to binding of C3b to the activating surface in the alternative pathway?

Spontaneous hydrolysis and cleavage of C3. Signup and view all the answers

What is the primary function of the lectin pathway of complement activation?

Promotes opsonization and inflammation. Signup and view all the answers

What is required for further amplification stages in the alternative complement pathway?

The formation of further C3 convertase on the surface as a result of plasma Factor B and Factor D interaction. Signup and view all the answers

What is the role of C3a and C5a in the immune response?

Activate mast cell degranulation and release vasoactive and other inflammatory molecules. Signup and view all the answers

Which protein prevents the formation of excessive C3 convertases by binding to C4b?

C4 Binding Protein (C4BP) Signup and view all the answers

Which cell surface protein regulates the complement system by accelerating the decay of C3 and C5 convertases?

Decay-accelerating Factor (DAF) Signup and view all the answers

Which protein acts as a cofactor for Factor I that leads to inactivation of C3b and C4b?

C4 Binding Protein (C4BP) Signup and view all the answers

Which protein promotes the decay of C3 convertases and enhances the clearance of C3b from host cell surfaces?

Factor H Signup and view all the answers

What is the primary function of CD59 (Protectin) in the complement system?

Prevents the incorporation of C9 into the membrane attack complex (MAC) Signup and view all the answers

Which deficiency contributes to a greater susceptibility to infections in which the membrane-attack complex is an important defense mechanism?

Complement component deficiencies Signup and view all the answers

What is the consequence of deficiency in complement receptors 3 or 4 (CR3 or CR4)?

Increased susceptibility to infections with thin cell wall bacteria Signup and view all the answers

What is the role of Leukocyte Adhesion Deficiency (LAD) in individuals with this condition?

Recurring bacterial infections Signup and view all the answers

"Total complement activity test" (CH50) primarily tests for the function of which complement components?

$C1 - C9$ Signup and view all the answers

"Protectin" (CD59) primarily prevents the incorporation of which component into the membrane attack complex (MAC)?

$C9$ Signup and view all the answers

Which protein regulates the classical complement pathway by binding to $C4b$ and preventing excessive formation of $C3$ convertases?

C4BP Signup and view all the answers

What is the role of complement receptor deficiencies in contributing to pathologies?

Impaired leukocyte adhesion prior to transendothelial migration Signup and view all the answers

Which complement component is responsible for creating a large stable pore in the plasma membrane, leading to cellular lysis?

C9 Signup and view all the answers

What is the primary function of Complement Component 1 Inhibitor (C1 INH)?

Inhibiting the activation of C1 complexes Signup and view all the answers

Which complement component accelerates the decay of C3b and C4b by cleaving them into iC3b and C4c?

Factor I Signup and view all the answers

What is the role of Factor H in regulating the alternative complement pathway?

Accelerates the decay of C3b and C4b Signup and view all the answers

Which protein controls the lectin and classical pathways of complement activation by binding to and inactivating the active site of serine proteases?

Complement Component 1 Inhibitor (C1 INH) Signup and view all the answers

What is the function of MAC (Membrane Attack Complex) in complement activation?

Elaboration of stable pores in the target cell membrane Signup and view all the answers

Which complement component is responsible for mediating further inflammatory reactions when released in fluid-phase?

C5a Signup and view all the answers

What molecule binds serum $C7$ to form a $C5bC6C7$ complex, which penetrates and stabilizes in the membrane?

Serum C8 Signup and view all the answers

What is structurally homologous to perforin secreted by NK cells and cytotoxic T lymphocytes?

Serum C9 Signup and view all the answers

What is produced when MCP and CR1 act as cofactors for Factor I-mediated proteolytic cleavage of C3b?

iC3b Signup and view all the answers

Which proteins are reminiscent of C1q and initiate complement activation by binding to specific pathogen-associated molecular patterns?

Ficolins Signup and view all the answers

Which proteases cleave plasma C4 into fragments C4b and C4a in the lectin pathway of complement activation?

MASP1, MASP2, & MASP3 Signup and view all the answers

What is the complex that cleaves C4 and C2 in the lectin pathway of complement activation?

MASP complex Signup and view all the answers

Which complement pathway is activated by lectins or ficolins?

Lectin pathway Signup and view all the answers

What catalyzes the cleavage of numerous C5 molecules into C5b and C5a in the lectin pathway of complement activation?

C5 convertase Signup and view all the answers

Which proteins are homologous to the serine proteases MASPs of the lectin pathway?

C1r and C1s Signup and view all the answers

What is the function of lectins or ficolins in the lectin pathway of complement activation?

All of the above Signup and view all the answers

Study Notes

Acute inflammation is a process triggered by various types of injuries, which can be physical, chemical, biological, or psychological.
Table 1 in the text lists different types of immunological insults, including non-infectious (physical and chemical) and infectious causes.
Inflammation is an essential process that facilitates the immune system's effective response to injuries, whether during innate or adaptive immune responses.
Inflammation provides an environment for leukocytes to perform optimally, increasing their effectiveness and promoting the recruitment of leukocytes and soluble inflammatory mediators to the site of injury.
Swelling, warmth, redness, pain, and itching are the cardinal signs of inflammation, resulting from fluid influx, stimulation of sensory neurons, and the release of various inflammatory mediators.
The inflammatory response is initiated when injury is detected by pathogen recognition receptors (PRRs) and signaling PRRs engaged by Pathogen-Associated Molecular Patterns (PAMPs) or Damage-Associated Molecular Patterns (DAMPs).
The inflammasome is a multiprotein complex that activates caspases, which in turn activate the inactive precursor of Interleukin-1-beta (IL-1β) or Interleukin-18.
Inflammasome activation occurs through the juxtaposition of several inactive caspase subunits with several scaffold sensor subunits, usually Nucleotide-binding Oligomerization Domain-like Receptors (NOD-Like Receptors or NLRs).
The initial release of IL-1β requires the simultaneous synthesis of pro-IL-1β and caspase activation.
Once released by the stimulated cell, IL-1β engages its receptor on the surface of other cells, triggering the activation of IL-1β-responsive genes and the synthesis and release of numerous other pro-inflammatory factors.
Engagement of the Interleukin-1-Receptor (IL-1R) on the surface of macrophages triggers the NF-κB and MAPK pathways, leading to the activation of transcription factors NF-κB and AP-1.
Activation of these transcription factors results in the synthesis and release of various pro-inflammatory cytokines, chemokines, and inflammatory mediators, including Tumor Necrosis Factor-alpha (TNF-α), IL-6, CXCL8 (IL-8), LeukoTrienes (LT), and adhesion molecules among others.
The importance of the inflammatory response is evident from the large number of anti-inflammatory drugs and biologicals currently on the market, primarily monoclonal antibodies.

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Test your knowledge on the acute inflammatory response and complement system with this quiz. Explore the process of phagocytic cell recruitment and the role of chemotactic factors like C3a and C5a. Understand the release of proinflammatory mediators and the cascade of events in the immune response.