Interferons and Coronavirus (L12)

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Questions and Answers

Which lipoprotein is involved in the recognition of pathogenic bacteria by dendritic cells?

TLR7

TLR9

TLR4

TLR1 (correct)

What type of RNA virus is SARS-CoV-2 classified as?

Double-stranded RNA virus

Negative-sense single-stranded RNA virus

Positive-sense single-stranded RNA virus (correct)

Enveloped double-stranded DNA virus

What is the consequence of the cytokine storm triggered by SARS-CoV-2?

Controlled immune response

Increased antibody production

Tissue damage (correct)

Enhanced virus replication

Which transcription factor is highly expressed in plasmacytoid dendritic cells (pDCs)?

IRF7 Signup and view all the answers

Which TLR (Toll-Like Receptor) is not expressed in human pDCs?

TLR3 Signup and view all the answers

What effect does the presence of cytokines during a virus infection typically have on the immune response?

Increases inflammation Signup and view all the answers

What is the primary role of type-I interferons (IFNs) in the immune response against viral infections?

To activate neighboring cells to produce antiviral responses Signup and view all the answers

What consequence arises from a lack of type-I or type-II IFN production in the body?

Enhanced replication of many viruses in host cells Signup and view all the answers

What is the function of IL-10 as induced by interferons during a viral infection?

To regulate immune responses and exert anti-inflammatory effects Signup and view all the answers

How do plasmacytoid dendritic cells (pDCs) contribute to the immune response against viruses?

By producing high levels of type-I interferons when activated Signup and view all the answers

Which of the following cells do NOT produce active type-I interferon?

Vero cells Signup and view all the answers

What factor contributes to the rapid production of interferons during viral infections?

Activation of Toll-like receptors TLR 7 and TLR 9 Signup and view all the answers

What is the primary function of type-I interferons in response to viral infections?

To regulate antiviral signaling pathways Signup and view all the answers

Which receptors are involved in recognizing RNA viruses within the cell?

RIG-1 and MDAs Signup and view all the answers

What characteristic of pathogenic recognition receptors (PRRs) is highlighted in their role against viruses?

They detect pathogen-associated molecular patterns (PAMPs). Signup and view all the answers

What was the significant finding in the 1957 study by Isaacs and Lindenmann about interferons?

Interferons provide protection to non-infected cells from viral infection. Signup and view all the answers

How do viral antagonists affect type-I interferons?

They block the signaling pathways of interferons. Signup and view all the answers

What is the significance of the localization of PRRs within the cell?

It is critical for the recognition of pathogen products. Signup and view all the answers

Which type of interferons are primarily studied in the context of antiviral responses?

Type-I interferons Signup and view all the answers

Which pathway is activated by DNA and RNA viruses that is critical for the immune response?

Type-I interferon signaling pathway Signup and view all the answers

What is required for the induction of interferon alpha and interferon beta?

Phosphorylation of transcription factors by kinases Signup and view all the answers

Which transcription factors are components of the ISGF3 complex?

STAT1, STAT2, and IRF9 Signup and view all the answers

What distinguishes the receptors for type 3 interferons from type 1 interferons?

Type 3 receptors are exclusively expressed in epithelial tissues Signup and view all the answers

Which of the following statements about IFN beta and IFN alpha is true?

IFN beta can trigger a stronger response due to its higher receptor affinity Signup and view all the answers

What role do interferon-sensitive response elements (ISREs) play?

They serve as binding sites for the ISGF3 complex Signup and view all the answers

How do type 1 and type 3 interferons induce similar responses despite using different receptors?

They activate the same transcription factors and pathways Signup and view all the answers

What can be inferred about the expression of IFN receptors in different cell types?

The expression of IFN receptors varies among cell types Signup and view all the answers

What is the primary function of the kinases activated by interferon signaling?

To phosphorylate and activate transcription factors Signup and view all the answers

What effect do type 3 interferons have in comparison to type 1 interferons?

They have less inflammatory effects Signup and view all the answers

Which type of tissue exhibits high expression of type 3 interferon receptors?

Epithelial tissues Signup and view all the answers

Study Notes

### Lipoproteins and Toll-like Receptors (TLRs)

Lipopolysaccharide (LPS) activates TLR4
Flagellin activates TLR5
IL-1 and IL-18 activate IL-1R and IL-18R respectively
Different types of dendritic cells (DCs) contain different TLR expression levels
- Plasmacytoid DCs (pDCs) express high levels of TLR7 and TLR9, recognizing viral RNA
- Human blood DCs express high amounts of TLR1, TLR2, TLR4, TLR5, TLR6
pDCs have high constitutive expression of IRF7
MyD88 and TRIF are essential signaling molecules for TLR signaling
TLR3 is activated by double-stranded RNA (dsRNA)
TLR4 is activated by lipopolysaccharide (LPS)
TLR7 and TLR8 are activated by single-stranded RNA (ssRNA)
TLR9 is activated by CpG DNA and located in endosomes
TLRs play roles in inducing interferon production

Coronavirus

Coronaviruses are enveloped, positive-sense single-stranded RNA viruses belonging to the Coronaviridae family
Coronaviruses can trigger cytokine storm (hyper inflammation) leading to tissue damage

### Interferons

Interferons are a family of cytokines that play a critical role in the antiviral response.
Interferons are induced by viral infection and other stimuli, leading to the production of antiviral proteins that inhibit viral replication.
Type-I interferons (IFN-α/β) are produced by a variety of cells, including dendritic cells, macrophages, and fibroblasts.
Type-III interferons (IFN-λ) are produced by epithelial cells and are primarily involved in antiviral defense at mucosal surfaces.
Type-II Interferons (IFN-γ) are produced primarily by T cells and Natural Killer cells and are important for immune regulation.

### Viral Evasion of Innate Immune Response

Viruses have evolved strategies to evade innate immune response, including blocking interferon production or signaling.
Viral antagonists can target different parts of the interferon signaling pathway.

### Interferon Signaling Pathway

Interferons bind to their receptors, initiating a signaling cascade that leads to the activation of transcription factors.
Activated transcription factors translocate to the nucleus and induce the expression of interferon-stimulated genes (ISGs).
ISGs encode antiviral proteins that block various steps in the viral replication cycle.
IFN receptors are localized in different cell types, leading to variations in interferon sensitivity and response.
IFN-β is more potent than IFN-α due to higher binding affinity to the receptor.
IFN-1 signaling uses the same pathways as IFN-3, leading to similar effects as IFN-3.
IFN-λ receptors are localized to epithelial cells, primarily important for antiviral defense at mucosal surfaces.

### Interferons and Immune Responses

Interferons can enhance immune response by promoting the activation of macrophages and dendritic cells.
Some ISGs act as antiviral factors attacking at early stages of viral replication.
Viruses may evolve to take advantage of ISGs to enhance viral replication.
Interferons can induce the production of other cytokines, such as IL-10, which can contribute to immune regulation and anti-inflammatory effects.

### Interferons and COVID-19

SARS-CoV-2 can infect epithelial cells that respond to type 3 interferons.
Interferon-lambda can act as an antiviral cytokine to the infection.
IFN-1 and IFN-3 can lead to different effects in critically ill patients.
Many studies have shown that critically ill patients have reduced IFN responses paired with a proinflammatory response.
Some studies have shown that type 3 interferon gamma can promote apoptosis and impaired epithelial proliferation, preventing tissue recovery.

### Effects of Interferons

Lack of type-I (or type-II) IFN production or signaling results in inefficient antiviral responses.
Viruses may not replicate in WT (IFN competent mice) but do replicate in IFN Receptor KO.
Many human viruses need to be adapted to mice for replication but replicate well in IFN-deficient mice.
To study whether IFNs are protective against a particular pathogen, one can use:
- IFN receptor KO cells and/or mice
- Cells that do not produce active IFN-I (e.g., Vero cells - do not produce but do respond)
- IFN production is determined by the presence of different types of dendritic cells that contain different expression levels of TLRs.
The use of Type-I IFN receptor KO cells and/or mice.
The use of cells that do not produce active IFN-I (e.g.Vero cells – do not produce but do respond).
IFN-I effects on regulation of other cytokines such as IL-10, IL-10 is a regulatory cytokine.
Interferons can induce IL-10 which can result in regulatory functions and antiinflammatory effects.
Interferons can promote induction of other cytokines important in viral infection such as IL-10.
- IL-10 is a regulatory cytokine.
Interferons can induce IL-10 which can result in regulatory functions and antiinflammatory effects.
Interferons can promote induction of other cytokines important in viral infection such as IL-10.
- IL-10 is a regulatory cytokine.
Interferons can induce IL-10 which can result in regulatory functions and antiinflammatory effects.
- IL-10 is a regulatory cytokine.
Interferons can induce IL-10 which can result in regulatory functions and antiinflammatory effects.

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Description

This quiz covers key concepts related to Toll-like receptors (TLRs) and their role in immune response, including specific TLR activation by various stimuli. Additionally, it explores characteristics of coronaviruses and their impact on cytokine production. Test your understanding of these important immunological concepts.