Acute Phase Response and COVID-19 Quiz
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Questions and Answers

What marker has been associated with areas of hypoperfusion in patients with acute respiratory distress syndrome?

  • Interleukin-8
  • C-reactive protein
  • Ferritin:transferrin ratio
  • D-dimer (correct)

An increased ferritin:transferrin ratio in hospitalized patients with Covid-19 is indicative of what condition?

  • Dysregulated iron homeostasis (correct)
  • Effective anti-interleukin-6 therapy
  • Reduced complement activation
  • Decreased risk of ICU admission

What has the complement pathway been identified as in the context of COVID-19?

  • A therapeutic target (correct)
  • A pathway leading to decreased inflammation
  • A negative marker for disease progression
  • A marker for successful anti-interleukin-6 therapy

Which biomarker when decreased, does not correlate with clinical benefit of anti-interleukin-6 therapy?

<p>C-reactive protein (D)</p> Signup and view all the answers

What is considered a 'holy grail' for timely intervention in the context of disease progression?

<p>The accurate prediction of disease progression (C)</p> Signup and view all the answers

Which of the following is NOT classified as an acute-phase protein, according to the text?

<p>Interferon (B)</p> Signup and view all the answers

What is a primary function of the acute-phase response?

<p>To amplify antimicrobial resistance and tissue repair (C)</p> Signup and view all the answers

In the context of Covid-19, which acute-phase protein has NOT been explicitly mentioned as a diagnostic tool or prognostic indicator in the text?

<p>STING (C)</p> Signup and view all the answers

What is identified as the first line of resistance against microbial pathogens?

<p>Innate immunity (B)</p> Signup and view all the answers

Acute-phase proteins are considered key components of which type of immunity?

<p>Humoral innate immunity (B)</p> Signup and view all the answers

Molecular strategies used by the cellular arm to sense microbial moieties and tissue damage include all EXCEPT:

<p>Interferon genes (STING) (A)</p> Signup and view all the answers

What term does the text use to describe acute-phase proteins in the context of humoral innate immunity?

<p>Ante-antibodies (B)</p> Signup and view all the answers

Besides infection, what other type of condition is NOT mentioned as having applications for acute-phase proteins?

<p>Diabetes (C)</p> Signup and view all the answers

Which of the following best describes the role of haptoglobin and hemopexin?

<p>They act as soluble scavengers of free hemoglobin and heme, respectively. (D)</p> Signup and view all the answers

What is a key function of the innate immune system in response to SARS-CoV-2?

<p>Recognizing viral components and activating both innate and adaptive immunity. (A)</p> Signup and view all the answers

Which cellular sensors are involved in the innate immune response to SARS-CoV-2?

<p>Membrane C-type lectins, endosomal TLRs, and the cGAS-STING pathway. (D)</p> Signup and view all the answers

How does SARS-CoV-2 open reading frame 8 (ORF8) impact the immune response?

<p>It inhibits interferon production through epigenetic mechanisms. (D)</p> Signup and view all the answers

Which acute-phase protein has been shown to bind to the spike protein of SARS-CoV-2?

<p>MBL (B)</p> Signup and view all the answers

Which of the following is NOT a function of pentraxins?

<p>Directly inhibiting complement activation (C)</p> Signup and view all the answers

What is the significance of free heme in the context of inflammation?

<p>It is a source of redox-active iron and can intercalate into lipids, causing toxicity. (D)</p> Signup and view all the answers

In severe inflammatory conditions like macrophage-activation syndrome and Covid-19, for what is ferritin used?

<p>A marker of the severity of the condition and related prognosis. (D)</p> Signup and view all the answers

What is a key difference between the production of PTX3 and C-reactive protein in inflammatory conditions?

<p>PTX3 is stored in neutrophil granules for rapid release, while C-reactive protein production is downstream of the cytokine cascade. (D)</p> Signup and view all the answers

Besides the spike protein, what other SARS-CoV-2 component is a target for acute-phase binding proteins?

<p>The nucleocapsid. (D)</p> Signup and view all the answers

Genetic polymorphisms of which pentraxins have been associated with increased susceptibility to fungal and bacterial infections?

<p>PTX3 and SAP (D)</p> Signup and view all the answers

Which of the following best describes the role of pentraxins in managing apoptotic cells?

<p>They facilitate non-inflammatory disposal of cells by binding to phospholipids and sNRNPs. (B)</p> Signup and view all the answers

With which complement molecules do pentraxins interact?

<p>C1q, ficolins, and mannose-binding lectin (MBL) (B)</p> Signup and view all the answers

In which cellular component is PTX3 stored, ready for immediate release?

<p>Neutrophil granules (D)</p> Signup and view all the answers

What is the main characteristic of the AA protein that leads to its aggregation into insoluble fibrils?

<p>Its hydrophobicity from the folding of a β sheet. (A)</p> Signup and view all the answers

Why is the complement system considered a central player in innate immunity?

<p>It is an evolutionarily conserved system crucial for humoral innate immune responses. (B)</p> Signup and view all the answers

Which transcription factors are activated by interleukin-1 and interleukin-6 to regulate acute-phase protein synthesis in the liver?

<p>STAT3, nuclear factor κB, and CCAAT/enhancer-binding proteins (C), STAT3, nuclear factor κB, and CCAAT/enhancer-binding proteins (D)</p> Signup and view all the answers

What is a shared structural characteristic of pentraxins?

<p>A cyclic multimeric structure with a conserved 200-amino-acid pentraxin domain (B)</p> Signup and view all the answers

Which of the following is NOT a short pentraxin?

<p>PTX3 (C)</p> Signup and view all the answers

Which of the following is a primary mediator in the cytokine cascade, as shown in Figure 3A?

<p>interleukin-6 (A)</p> Signup and view all the answers

According to Figure 3A, what is one effect of glucocorticoids in the cytokine cascade?

<p>Activation of the hypothalamus–pituitary–adrenal axis (C)</p> Signup and view all the answers

According to Figure 3A, what is a result of the production of acute-phase proteins in the liver?

<p>Amplification of systemic innate immunity (A)</p> Signup and view all the answers

According to Figure 3B, which cells are primarily derived from leukocytes?

<p>SAA (B)</p> Signup and view all the answers

Based on Figure 3B, which of the following acute-phase proteins are derived from both liver and leukocytes or stromal cells?

<p>PTX3 (C)</p> Signup and view all the answers

According to Figure 3B, which of the following is NOT derived from liver cells?

<p>C1q (C)</p> Signup and view all the answers

According to Figure 3B, which of the following is NOT derived from leukocytes or stromal cells?

<p>CRP (A)</p> Signup and view all the answers

Which process(es) is/are associated with acute-phase proteins derived from all the cells according to Figure 3B?

<p>All of the above (D)</p> Signup and view all the answers

What is the function of acute-phase proteins in relation to complement as shown in Figure 3B?

<p>To activate complement (C)</p> Signup and view all the answers

Which of the following cells is NOT a cellular source of acute-phase proteins as listed in the figure 3B?

<p>Osteocytes (B)</p> Signup and view all the answers

What is the main proposed function of tumor necrosis factor (TNF) and interleukin-1 according to figure 3B?

<p>Stimulate acute-phase protein synthesis (D)</p> Signup and view all the answers

What is the function of complement molecules in humoral innate immunity according to figure 3B?

<p>Pathogen and tissue-damage recognition (A)</p> Signup and view all the answers

Which acute-phase protein is also known as Interleukin 1 receptor antagonist?

<p>Interleukin 1 receptor antagonist (IL-1Ra) (B)</p> Signup and view all the answers

What is the primary function of acute-phase protein synthesis in the body?

<p>To act as a key feature of innate immune functions of the liver (D)</p> Signup and view all the answers

What is the role of serum amyloid A (SAA) in the context of host insults?

<p>It has concentration dependent functions during host insults. (D)</p> Signup and view all the answers

What does an acidic microenvironment influence the pattern recognition molecule PTX3?

<p>It sets it in a tissue repair mode. (D)</p> Signup and view all the answers

What mechanism is associated with the activation of intracellular complements?

<p>An alarm-raising mechanism (D)</p> Signup and view all the answers

What did Bodin et al show regarding antibodies to human serum amyloid P?

<p>They eliminate visceral amyloid deposits. (D)</p> Signup and view all the answers

What is a key role of cytokines in the body, according to the material?

<p>Regulating inflammation and immunity (B)</p> Signup and view all the answers

What has been shown regarding recombinant human pentraxin 2 protein?

<p>It has been tested in the long-term treatment of idiopathic pulmonary fibrosis. (B)</p> Signup and view all the answers

Flashcards

Acute-phase proteins

A group of proteins whose levels increase significantly in the blood during infection, inflammation, or tissue damage.

C-reactive protein (CRP)

A key acute-phase protein that helps in identifying and responding to infection, inflammation, and tissue damage.

Humoral innate immunity

A major component of the humoral innate immune system that acts as a first line of defense against pathogens.

Cellular innate immunity

An essential part of the immune system responsible for recognizing and responding to pathogens and tissue damage through immune cells like macrophages and neutrophils.

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Pattern Recognition Receptors (PRRs)

A crucial step in the innate immune response where immune cells identify and bind to foreign molecules (like bacteria, viruses) or damaged cells.

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Acute-phase response

A process that amplifies the immune response to fight pathogens and repair damaged tissues.

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Molecular sensing

A specialized mechanism that helps the innate immune system sense and respond to threats using receptors that recognize specific molecular patterns associated with pathogens or damage.

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Acute-phase proteins in clinical diagnostics

The production of several acute-phase proteins, such as CRP, fibrinogen, and ferritin, are increased during inflammation.

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D-dimer in COVID-19

Increased levels of D-dimer, a protein fragment released during blood clotting, may indicate blood clots, which can contribute to serious complications in COVID-19.

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Iron Dysregulation in COVID-19

Anemia and elevated ferritin levels (a protein that stores iron), may be associated with serious COVID-19 cases, possibly due to how the body regulates iron during infection.

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Increased Complement in COVID-19

An excess of complement components in the blood is a hallmark of COVID-19. This suggests that the complement system, a part of the immune response, plays a role in the disease's progression.

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C-reactive Protein (CRP) and COVID-19

Elevated levels of C-reactive protein (CRP) are a common indicator of inflammation. This protein can be particularly useful in identifying patients who may benefit from specific treatments like anti-IL-6 therapy.

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Markers of Tissue Inflammation in COVID-19

Proteins like PTX3 and interleukin-8 are produced in infected tissues and may more accurately indicate how a patient is responding to treatment than inflammation markers like CRP.

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What are Pentraxins?

Pentraxins are a family of proteins that play a crucial role in the innate immune response. They are characterized by their distinctive pentameric structure and their ability to bind to various pathogens, promoting inflammation and initiating the complement cascade.

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What are the three main types of Pentraxins?

C-reactive protein, Serum Amyloid P (SAP), and PTX3 are three major types of pentraxins that act as pattern recognition molecules. They are all involved in the detection and clearance of various pathogens, apoptotic cells, and other danger signals in the body.

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Haptoglobin and Hemopexin

Acute-phase proteins that bind free hemoglobin and heme, respectively. They act as scavengers, preventing the harmful effects of these molecules.

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Free Heme

A highly toxic molecule that can damage cells and tissues. It's a source of redox-active iron and can disrupt cell membranes.

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What does Pentraxins bind to?

Pentraxins bind to various pathogens like bacteria, fungi, and viruses, and activate the innate immune system to fight off infection.

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What else do Pentraxins bind to besides pathogens?

Pentraxins also bind to apoptotic cells (cells that are dying) and promote their removal in a non-inflammatory manner, preventing unnecessary inflammation.

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Pattern-Recognition Molecules (PRMs)

A group of proteins that recognize and bind to specific patterns on pathogens, triggering an immune response. They're like the first responders of the immune system.

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How do Pentraxins enhance the immune response?

Pentraxins interact with different complement molecules like C1q, ficolins, and mannose-binding lectin (MBL), leading to a broader and more effective recognition of pathogens and their elimination.

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Mannose Binding Lectin (MBL)

A protein that binds to the spike protein of SARS-CoV-2, potentially contributing to the immune response.

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MBL and PTX3

A protein that recognizes glycosylated spike protein of SARS-CoV-2, potentially contributing to the antiviral response.

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What is the difference between the release of PTX3 and C-reactive protein?

PTX3 is released immediately from neutrophil granules upon infection, while C-reactive protein production in the liver is activated later by inflammatory cytokines.

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What is the link between Pentraxins and susceptibility to infections?

Genetic variations in PTX3 and SAP have been linked to increased susceptibility to infections, particularly fungal and bacterial infections, suggesting their role in the host's defense against these microbes.

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SARS-CoV-2 Open Reading Frame 8 (ORF8)

A viral protein that inhibits the production of interferons, important proteins that fight viral infections.

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What is the Complement System?

The complement system is a key player in the innate immune response, acting as a cascade of proteins that are activated to eliminate pathogens and promote inflammation.

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cGAS–STING Pathway

A pathway that triggers the innate immune response to viral infections. It involves sensors that detect viral nucleic acids.

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Interferon

A crucial protein involved in the innate immune response to viral infections. It's like a "master switch" that activates the immune system.

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What is interleukin-6?

A key regulator of acute-phase protein synthesis in the liver, primarily known for its role in inflammation.

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What is interleukin-1?

A crucial cytokine that also plays a key role in triggering the production of acute-phase proteins in the liver.

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What is C-reactive protein (CRP)?

A protein that acts as a 'danger signal', indicating tissue damage and activating immune responses.

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What is serum amyloid P component (SAP)?

A protein responsible for recognizing and binding to damaged cells, activating complement pathways and promoting immune responses.

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What is pentraxin 3 (PTX3)?

A critical protein in the innate immune response, known for its role in recognizing and binding to pathogens.

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What are acute-phase proteins?

A family of cell signaling proteins, produced by the liver, that increase during infection or inflammation.

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What is the liver's role in the immune response?

The primary source of acute-phase proteins.

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What are pattern-recognition molecules?

They are part of the immune system's 'first responders', triggered by infections or tissue damage.

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What are examples of pattern-recognition molecules?

Toll-like receptors (TLRs) and inflammasomes.

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What are cytokines?

They are a group of signaling proteins, like TNF, interleukin-1, and interleukin-6, that are important for mediating inflammatory responses.

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What is the hypothalamic-pituitary-adrenal (HPA) axis?

It plays a crucial role in regulating the production of glucocorticoids, which are involved in the body's stress response.

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What are coagulation factors?

Proteins produced by the liver that are involved in tissue remodeling and repairing damaged tissues.

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What are complement molecules?

They are a group of proteins involved in the complement activation pathway, a crucial immune response mechanism that helps fight infections.

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What are the main functions of complement molecules?

Recognizing pathogens and tissue damage, and activating the complement pathway.

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Mendelian randomization

A large-scale study that combines individual participant data from multiple studies , usually addressing a common research question.

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Study Notes

Humoral Innate Immunity and Acute-Phase Proteins

  • Inflammation is a complex process encompassing tissue reactions triggered by microbial recognition and tissue damage, also involved in dysmetabolic conditions like diabetes and obesity
  • Inflammatory reactions amplify innate resistance and aid tissue repair
  • Acute-phase proteins are molecules (e.g., C-reactive protein) produced in response to local or systemic inflammation
  • C-reactive protein was initially associated with infections and can recognize Streptococcus pneumoniae's C-type polysaccharides.
  • The acute-phase response includes decreased albumin production, altered iron metabolism, and hormonal changes
  • Acute-phase proteins are valuable diagnostic tools for various conditions like infections, cardiovascular diseases, cancer, neurodegeneration, and dysmetabolism
  • During the COVID-19 pandemic, acute-phase proteins like C-reactive protein, fibrinogen, and ferritin have aided medical management and prediction of outcomes.

Cellular and Humoral Innate Immunity

  • Innate immunity comprises cellular and humoral arms
  • Cellular arm detects microbial moieties, tissue damage, and dysmetabolism using pattern-recognition molecules (e.g., TLRs, inflammasomes).
  • The humoral arm uses molecules like pentraxins, collectins, and ficolins to activate complement, opsonize microbes, and regulate inflammation.
  • These molecules function as 'ante-antibodies'

Acute Phase Proteins: Production, Structure, and Function

  • Acute-phase proteins are mainly produced by the liver
  • Certain cells in peripheral tissues also produce some acute-phase proteins like macrophages and endothelial cells
  • Inflammatory cytokines (e.g., interleukin-1, interleukin-6, TNF) induce acute-phase protein production in the liver
  • Key acute-phase proteins like C-reactive protein, serum amyloid A, pentraxin 3 (PTX3), and fibrinogen play critical roles in responding to microbial pathogens and tissue damage.

Molecules and Functions of Pentraxins

  • Pentraxins (like C-reactive protein, serum amyloid P, and PTX3) form a family of evolutionarily conserved proteins
  • Their structure involves a cyclic multimeric structure with a conserved pentraxin domain.
  • These proteins have diverse functions, including binding to various microbes, complement molecules, and extracellular matrix proteins, enhancing clearance of these elements.
  • PTX3 is elevated in inflammatory conditions, including infections, and can be used as a predictor for disease severity or outcomes.

The Complement System

  • The complement system is a network of soluble molecules produced mainly by the liver, which plays a crucial role in humoral innate immunity.
  • Key molecules like C3, C4, C9, and factor B have activating roles, while C1 inhibitor and C4BP are negative regulators.
  • The complement system plays a role in both the activation and regulation of inflammatory responses
  • The system's activation is linked to the acute-phase response, especially concerning inflammation and tissue repair.

Acute-Phase Proteins and Iron Homeostasis

  • Acute-phase proteins, including hepcidin, ferritin, haptoglobin, and hemopexin, are involved in regulating iron metabolism
  • Key functions for these molecules include binding or trapping iron, preventing its use by pathogens, and controlling host-cell iron availability to regulate the immune response
  • Iron is crucial for host-cell functions, but pathogens can also require it for their growth - acute-phase proteins aid in this regulation by modulating iron availability.

Acute-Phase Proteins in Covid-19 and other Conditions

  • Acute-phase proteins (e.g., CRP, PTX3, fibrinogen) have been recognized as indicators for Covid-19 severity, prognosis and disease outcome, in addition to other conditions.
  • Levels can predict hospitalization, need for intensive care, and even mortality.
  • These molecules are also associated with other inflammatory diseases like arthritis or cardiovascular conditions, where elevated levels could suggest more severe inflammatory processes or poor prognosis
  • Understanding patterns of acute-phase proteins in relation to disease development and severity can advance our capabilities for patient-tailored approaches.

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Humoral Innate Immunity and Acute-Phase Proteins PDF

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Test your knowledge on the acute-phase response and its implications in COVID-19. This quiz covers various biomarkers, their roles in disease progression, and the acute-phase proteins involved in immune response. Challenge yourself with these essential concepts in critical care medicine.

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