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Questions and Answers
Which of the following is NOT a condition that acute-phase proteins are used to diagnose?
Which of the following is NOT a condition that acute-phase proteins are used to diagnose?
What is the primary function of the acute-phase response?
What is the primary function of the acute-phase response?
Which of the following is an example of an acute-phase protein?
Which of the following is an example of an acute-phase protein?
What is the role of the cellular arm of innate immunity?
What is the role of the cellular arm of innate immunity?
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What are the molecular strategies used by the cellular arm of innate immunity to sense microbial moieties?
What are the molecular strategies used by the cellular arm of innate immunity to sense microbial moieties?
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Which of the following is NOT a type of receptor involved in innate immunity?
Which of the following is NOT a type of receptor involved in innate immunity?
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How do acute-phase proteins contribute to humoral innate immunity?
How do acute-phase proteins contribute to humoral innate immunity?
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What is the significance of the increasing use of molecular signatures in diagnosing and treating various conditions?
What is the significance of the increasing use of molecular signatures in diagnosing and treating various conditions?
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What is the primary function of Pentraxin 3 (PTX3) concerning urinary tract infections?
What is the primary function of Pentraxin 3 (PTX3) concerning urinary tract infections?
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In the context of sarcoidosis, what role does Pentraxin 3 (PTX3) play?
In the context of sarcoidosis, what role does Pentraxin 3 (PTX3) play?
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How does acute serum amyloid A (SAA) primarily contribute to the process of infection?
How does acute serum amyloid A (SAA) primarily contribute to the process of infection?
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What is the relationship between mannose-binding lectin (MBL) and community-acquired pneumonia?
What is the relationship between mannose-binding lectin (MBL) and community-acquired pneumonia?
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In autoimmune vasculitis, how is the protective effect of α1-antitrypsin affected by methionine oxidation?
In autoimmune vasculitis, how is the protective effect of α1-antitrypsin affected by methionine oxidation?
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What is a significant role that lectins play in the context of SARS-CoV-2 infection?
What is a significant role that lectins play in the context of SARS-CoV-2 infection?
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How is increased levels of antiplasmin related to long COVID?
How is increased levels of antiplasmin related to long COVID?
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What is the focus of study regarding multiple early factors in the context of post-acute COVID-19?
What is the focus of study regarding multiple early factors in the context of post-acute COVID-19?
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What is the role of Interleukin 1 receptor antagonist (IL-1Ra) in the body?
What is the role of Interleukin 1 receptor antagonist (IL-1Ra) in the body?
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What is the significance of serum amyloid A concentrations in COVID-19 patients?
What is the significance of serum amyloid A concentrations in COVID-19 patients?
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Which inflammatory markers were highlighted in relation to severe COVID-19 cases?
Which inflammatory markers were highlighted in relation to severe COVID-19 cases?
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What was the aim of the meta-analysis regarding COVID-19 patients mentioned?
What was the aim of the meta-analysis regarding COVID-19 patients mentioned?
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What feature of innate immune functions is emphasized in the context of the liver?
What feature of innate immune functions is emphasized in the context of the liver?
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What does an 'acidic microenvironment' do to PTX3?
What does an 'acidic microenvironment' do to PTX3?
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What was the reported outcome of long-term treatment with recombinant human pentraxin 2 protein?
What was the reported outcome of long-term treatment with recombinant human pentraxin 2 protein?
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Which aspect of intracellular complement activation is discussed?
Which aspect of intracellular complement activation is discussed?
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What role does ferritin play in severe pathologic inflammatory conditions?
What role does ferritin play in severe pathologic inflammatory conditions?
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Which acute-phase proteins act as soluble scavengers in the immune response?
Which acute-phase proteins act as soluble scavengers in the immune response?
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Which cellular sensor does NOT recognize viral nucleic acids in the innate immune response to SARS-CoV-2?
Which cellular sensor does NOT recognize viral nucleic acids in the innate immune response to SARS-CoV-2?
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What mechanism does the SARS-CoV-2 ORF8 component use to inhibit interferon production?
What mechanism does the SARS-CoV-2 ORF8 component use to inhibit interferon production?
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Which of the following is involved in the recognition of SARS-CoV-2 components?
Which of the following is involved in the recognition of SARS-CoV-2 components?
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What is the consequence of free heme in the context of SARS-CoV-2 infection?
What is the consequence of free heme in the context of SARS-CoV-2 infection?
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Which of the following is a function of the inflammasome in the immune response?
Which of the following is a function of the inflammasome in the immune response?
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MBL binds to which components as part of the immune response to SARS-CoV-2?
MBL binds to which components as part of the immune response to SARS-CoV-2?
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What role does the long pentraxin PTX3 play in critically ill patients?
What role does the long pentraxin PTX3 play in critically ill patients?
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What is the significance of PTX3 in predicting mortality outcomes?
What is the significance of PTX3 in predicting mortality outcomes?
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Which of the following diseases has been associated with genetic PTX3 deficiency?
Which of the following diseases has been associated with genetic PTX3 deficiency?
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According to the findings, which context is PTX3 suggested as a prognostic marker?
According to the findings, which context is PTX3 suggested as a prognostic marker?
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In what manner is PTX3 hypothesized to function within the innate immune defense?
In what manner is PTX3 hypothesized to function within the innate immune defense?
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Which protein class is PTX3 categorized under?
Which protein class is PTX3 categorized under?
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What type of clinical condition is primarily associated with the study of PTX3?
What type of clinical condition is primarily associated with the study of PTX3?
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What is the potential clinical application of measuring PTX3 levels?
What is the potential clinical application of measuring PTX3 levels?
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What role does C-reactive protein play in Covid-19?
What role does C-reactive protein play in Covid-19?
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What is the significance of Serum amyloid A in Covid-19?
What is the significance of Serum amyloid A in Covid-19?
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How does PTX3 relate to Covid-19?
How does PTX3 relate to Covid-19?
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What does the increase in Ferritin levels indicate in Covid-19 patients?
What does the increase in Ferritin levels indicate in Covid-19 patients?
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Which of the following proteins is known to decrease in patients with severe Covid-19?
Which of the following proteins is known to decrease in patients with severe Covid-19?
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How does the activation of the hypothalamus-pituitary-adrenal axis affect cytokine production?
How does the activation of the hypothalamus-pituitary-adrenal axis affect cytokine production?
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What role does alpha-1-antichymotrypsin have in Covid-19?
What role does alpha-1-antichymotrypsin have in Covid-19?
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What is the association of coagulation protein d-dimer in Covid-19?
What is the association of coagulation protein d-dimer in Covid-19?
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Which acute-phase protein is associated with a need for interleukin-6 inhibition in severe cases of Covid-19?
Which acute-phase protein is associated with a need for interleukin-6 inhibition in severe cases of Covid-19?
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How does transferrin level change in Covid-19 patients?
How does transferrin level change in Covid-19 patients?
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Which protein’s levels remain unchanged or slightly increased during Covid-19?
Which protein’s levels remain unchanged or slightly increased during Covid-19?
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Which of the following proteins plays a role in viral inhibition according to the outlined changes?
Which of the following proteins plays a role in viral inhibition according to the outlined changes?
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What is the association of haptoglobin levels in Covid-19?
What is the association of haptoglobin levels in Covid-19?
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What impact does interleukin-1Ra have in Covid-19?
What impact does interleukin-1Ra have in Covid-19?
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What is the significance of the proteins C1q, C3, and C4 in Covid-19?
What is the significance of the proteins C1q, C3, and C4 in Covid-19?
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Study Notes
Humoral Innate Immunity and Acute-Phase Proteins
- Inflammation encompasses diverse tissue reactions, often triggered by microbial recognition or tissue damage. Dysmetabolic conditions (like diabetes and obesity) also elicit these reactions.
- Inflammatory responses amplify innate resistance and aid tissue repair, restoring homeostasis.
- Systemic inflammation manifests in fever, altered leukocyte counts, cardiovascular changes, endocrine responses, and metabolic reorientation.
- Acute-phase proteins (APPs) are molecules produced during inflammation, particularly in the liver. C-reactive protein is a prototypic APP.
- APPs appear in the blood and other fluids during inflammation (either local or systemic), indicating a response. This response decreases albumin production by hepatocytes and changes iron metabolism.
- APPs serve as diagnostic tools for various conditions, including infection, cardiovascular disease, cancer, neurodegeneration, and dysmetabolism.
- APPs, like C-reactive protein, fibrinogen, and D-dimer, were vital during the COVID-19 pandemic, for monitoring disease and prognosis.
The Context of Cellular and Humoral Innate Immunity
- Innate immunity is the first line of defense against microbial pathogens.
- It activates adaptive immune responses and fosters tissue repair.
- Innate immunity includes a cellular and a humoral arm.
- The cellular arm senses microbial moieties and tissue damage via receptor interactions.
- The cellular arm results in cytokine production.
- The humoral arm's role is to help activate complement, opsonize pathogens, and regulate inflammation.
- Different types of molecules (pentraxins, collectins, and ficolins) are part of the humoral arm and function similar to antibodies (these are the ante-antibodies).
Upstream of the Acute-Phase Response: The Cytokine Cascade
- Microbial moieties, tissue damage, or dysmetabolism initiate a cytokine cascade.
- This cascade influences innate immunity and triggers the production of APPs. Interleukin-1, interleukin-6, and tumor necrosis factor (TNF) are primary inflammatory cytokines.
- Secondary mediators amplify inflammation, recruit leukocytes, shape innate immunity, and influence adaptive immune responses.
- Interleukin-6 plays a crucial role in directing the body's response to inflammation, including increasing APP production in the liver.
Main Acute-Phase Proteins and Their Role in Covid-19
- Various acute phase proteins exhibit specific patterns of change during inflammatory responses, including COVID-19.
- Some, like C-reactive protein, serum amyloid A, and pentraxin 3 (PTX3), show increased concentrations associated with disease severity in COVID-19.
- Many proteins are involved in coagulation and tissue repair processes, and their levels adjust during inflammation.
Acute-Phase Proteins, Coagulation, and Tissue Repair
- Various APPs are linked to coagulation and tissue repair.
- Fibrinogen, a crucial clotting factor, and its degradation products (D-dimer), are significant diagnostic markers in inflammatory states. including COVID-19.
- Acute phase proteins are also crucial elements to tissue repair
Hepatic and Non-Hepatic Sources of Acute-Phase Proteins
- The liver has traditionally been considered the primary source of APPs. However, other cells (like macrophages, endothelial cells, hepatocytes, stellate cells) participate in APP production.
- Production in peripheral tissues complements liver-derived APPs.
- Adipose tissue is a significant producer of APPs in response to inflammatory cues
Pentraxins (C-Reactive Protein, SAP, and PTX3)
- The pentraxins C-reactive protein (CRP), serum amyloid P component (SAP), and PTX3 are key molecules of the humoral arm of innate immunity
- They have similar functions, like mediating complement activation, opsonizing microbes, and promoting phagocytosis.
- Each pentraxin has unique properties and functions, e.g., CRP and SAP are generally produced by the liver, whereas PTX3 is produced by different tissues and cells, often in response to different stimuli.
Complement System and MBL
- The complement system is crucial in humoral innate immunity.
- It comprises ~50 molecules, largely produced by the liver to enhance the innate immune response to infection/damage.
- Mannose-binding lectin (MBL) is a liver-derived C-type lectin involved in pattern recognition and initiation of complement activation pathways.
Acute-Phase Proteins and Iron Homeostasis
- Iron metabolism plays a critical role in the host's response to pathogens because these microbes need iron to replicate/produce energy.
- Several acute-phase proteins help in iron regulation, either maintaining higher iron stores or restricting iron availability to pathogens.
- Hepcidin, ferritin, haptoglobin, hemopexin, and transferrin are key iron-metabolic regulators significantly influenced by the acute-phase reaction.
Acute-Phase Proteins and COVID-19
- Acute-phase proteins are used to monitor disease stages, predict severity, and guide treatment decisions in COVID-19.
- Levels of various acute-phase proteins might be helpful in detecting and following COVID-19.
- These levels can influence clinical decisions to direct therapy.
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Description
Explore the concepts of innate immunity, inflammation, and acute-phase proteins in this quiz. Understand how systemic inflammation affects various body systems and the diagnostic significance of acute-phase proteins like C-reactive protein. Test your knowledge on the responses to infection and dysmetabolic conditions.
