Podcast
Questions and Answers
Upon exposure to TNF-α, what intracellular event directly contributes to the upregulation of MHC molecule expression?
Upon exposure to TNF-α, what intracellular event directly contributes to the upregulation of MHC molecule expression?
- Direct phosphorylation of MHC molecules to enhance their stability on the cell surface.
- Increased production of IL-6, which synergistically enhances MHC expression.
- Inhibition of CIITA transcription, reducing MHC class II expression.
- Stimulation of NF-κB, leading to increased transcription of immune response genes, including those for MHC. (correct)
How does IFN-γ enhance antigen presentation via MHC class II molecules?
How does IFN-γ enhance antigen presentation via MHC class II molecules?
- By inducing the expression of CIITA, a transcription factor that activates MHC class II gene expression. (correct)
- By inhibiting the proteasome, preventing the degradation of antigens before they can bind to MHC class II.
- By increasing the rate of endocytosis, allowing for faster uptake of extracellular antigens.
- By directly binding to MHC class II molecules, stabilizing their structure on the cell surface.
In the context of viral infections, what is the primary role of IFN-α and IFN-β in regulating MHC expression?
In the context of viral infections, what is the primary role of IFN-α and IFN-β in regulating MHC expression?
- To primarily increase MHC class I expression, enhancing the immune response against viral pathogens. (correct)
- To induce the expression of MHC class II molecules on non-APCs, expanding antigen presentation.
- To suppress MHC class I expression, preventing over-activation of CD8+ T cells.
- To inhibit antigen processing, ensuring that viral peptides are not presented to T cells.
How do cytokines influence the expression of MHC molecules at the transcriptional level?
How do cytokines influence the expression of MHC molecules at the transcriptional level?
What is the functional consequence of MHC restriction in T cell activation?
What is the functional consequence of MHC restriction in T cell activation?
In the experiment by Zinkernagel and Doherty, what was the key observation that demonstrated MHC restriction of CD8+ T cells?
In the experiment by Zinkernagel and Doherty, what was the key observation that demonstrated MHC restriction of CD8+ T cells?
What is the primary role of antigen processing in the context of MHC presentation?
What is the primary role of antigen processing in the context of MHC presentation?
What is the function of 'Self-MHC restriction'?
What is the function of 'Self-MHC restriction'?
What is a key aspect of 'Antigen processing'?
What is a key aspect of 'Antigen processing'?
In the Rosenthal and Shevach experiment, that utilized guinea pig macrophages, what critical finding supported the concept of MHC restriction for CD4+ T cells?
In the Rosenthal and Shevach experiment, that utilized guinea pig macrophages, what critical finding supported the concept of MHC restriction for CD4+ T cells?
How does the cytokine IL-6 typically influence MHC expression in human neural stem progenitor cell lines, based on the information provided?
How does the cytokine IL-6 typically influence MHC expression in human neural stem progenitor cell lines, based on the information provided?
What is the significance of T cells undergoing ‘education’ or ‘selection’ in the thymus regarding self-MHC restriction?
What is the significance of T cells undergoing ‘education’ or ‘selection’ in the thymus regarding self-MHC restriction?
Considering the roles of different cell types in MHC-restricted antigen presentation, which cell type would be most effective at presenting antigens to CD4+ T cells to initiate an adaptive immune response?
Considering the roles of different cell types in MHC-restricted antigen presentation, which cell type would be most effective at presenting antigens to CD4+ T cells to initiate an adaptive immune response?
A researcher is studying the immune response in mice and wants to enhance MHC class I expression to improve the presentation of viral antigens. Which cytokine would be most effective for this purpose?
A researcher is studying the immune response in mice and wants to enhance MHC class I expression to improve the presentation of viral antigens. Which cytokine would be most effective for this purpose?
Which of the experiments directly demonstrated that LCMV (lymphocytic choriomeningitis virus)-specific cytotoxic T lymphocytes (CTLs) are MHC restricted, by observing that CTL kill the cellular target from LCMV-effective strain;
Which of the experiments directly demonstrated that LCMV (lymphocytic choriomeningitis virus)-specific cytotoxic T lymphocytes (CTLs) are MHC restricted, by observing that CTL kill the cellular target from LCMV-effective strain;
In the context of transplantation, why is MHC compatibility between a donor and recipient critical for graft survival?
In the context of transplantation, why is MHC compatibility between a donor and recipient critical for graft survival?
A researcher is investigating a novel cytokine and observes that it enhances the expression of MHC class II molecules. Which of the following mechanisms is most likely to be involved?
A researcher is investigating a novel cytokine and observes that it enhances the expression of MHC class II molecules. Which of the following mechanisms is most likely to be involved?
What accounts for the MHC restriction?
What accounts for the MHC restriction?
In a scenario where a patient's cells fail to express MHC class II molecules due to a genetic defect, which cell type's function would be most directly impaired?
In a scenario where a patient's cells fail to express MHC class II molecules due to a genetic defect, which cell type's function would be most directly impaired?
Following treatment with a novel drug, a researcher observes a decrease in the presentation of viral antigens via MHC class I molecules. Which of the following mechanisms is the most likely cause?
Following treatment with a novel drug, a researcher observes a decrease in the presentation of viral antigens via MHC class I molecules. Which of the following mechanisms is the most likely cause?
If a researcher wants to study the effects of costimulatory molecules on APCs, what molecule would they study?
If a researcher wants to study the effects of costimulatory molecules on APCs, what molecule would they study?
Which type of molecule is NOT involved in the regulation of MHC molecules?
Which type of molecule is NOT involved in the regulation of MHC molecules?
During a viral infection, a patient's cells do not upregulate MHC class I molecules effectively. Which of the following cytokines would be least helpful in restoring MHC class I expression?
During a viral infection, a patient's cells do not upregulate MHC class I molecules effectively. Which of the following cytokines would be least helpful in restoring MHC class I expression?
In an experimental setting, a researcher introduces a mutation in the gene encoding CIITA. What direct effect would this have on antigen presentation?
In an experimental setting, a researcher introduces a mutation in the gene encoding CIITA. What direct effect would this have on antigen presentation?
A research study reveals that a pathogenic bacterium produces a substance that inhibits the function of the TAP transporter. What effect would this substance have on MHC-mediated antigen presentation?
A research study reveals that a pathogenic bacterium produces a substance that inhibits the function of the TAP transporter. What effect would this substance have on MHC-mediated antigen presentation?
A researcher discovers that a particular cancer cell line has developed a mechanism to downregulate MHC class I expression. Which immune evasion strategy is the cancer cell line employing?
A researcher discovers that a particular cancer cell line has developed a mechanism to downregulate MHC class I expression. Which immune evasion strategy is the cancer cell line employing?
Why is understanding MHC restriction essential for developing effective vaccines?
Why is understanding MHC restriction essential for developing effective vaccines?
Considering that MHC molecules are central to immune responses, what could be a potential consequence of a mutation that impairs MHC class I expression?
Considering that MHC molecules are central to immune responses, what could be a potential consequence of a mutation that impairs MHC class I expression?
Flashcards
MHC Molecules
MHC Molecules
Proteins on cell surfaces presenting antigens to T cells.
Cytokines
Cytokines
Soluble proteins that regulate immune responses, affecting MHC expression.
CIITA
CIITA
Transcription factor activated by IFN-γ that upregulates MHC class II genes.
NF-κB
NF-κB
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Self-MHC Restriction
Self-MHC Restriction
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Antigen Processing
Antigen Processing
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Rosenthal and Shevach Experiment
Rosenthal and Shevach Experiment
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Zinkernagel and Doherty Experiment
Zinkernagel and Doherty Experiment
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Class II MHC Restriction
Class II MHC Restriction
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Class I MHC Restriction
Class I MHC Restriction
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IFN-γ
IFN-γ
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TNF-α
TNF-α
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Study Notes
- MHC molecule expression is regulated by cytokines by controlling the intensity of the light source.
- Cytokines induce formation of transcription factors that upregulate genes for protein development for chains of MHC class one and two molecules.
- Interferon gamma, beta, and alpha upregulate transcription factors that bind to the promoter region of MHC molecules.
- This process upregulates genes and proteins involved in antigen processing and presentation.
Inflammatory Cytokines and MHC Expression
- A dose-dependent increase in MHC class one and two is observed when cells are exposed to interferon gamma and TNF alpha.
- IL-6 did not increase MHC expression in the human neural stem progenitor cell line.
MHC Regulation and Adaptive Immune Response
- MHC describes the regulatory role of an MHC molecule to activate or recognize T and B cells when bound to appropriate MHC molecules.
- CD four and CD positive T cells are critical for MHC regulation of the adaptive immune response.
- MHC molecules are regulated by cytokines such as interferons (IFN-α, IFN-β, IFN-γ), tumor necrosis factor (TNF-α), and interleukins (IL-1, IL-6, IL-12).
- Cytokine regulation occurs during immune responses, particularly in inflammation.
- Cytokines enhance MHC molecule expression, improve antigen presentation, and activate the immune system.
Interferons (IFNs)
- Interferons, particularly IFN-γ, are key regulators of MHC expression.
- IFN-γ (produced by T helper 1 cells, NK cells, and CD8+ T cells) is the most potent inducer of MHC class I and class II molecules.
- IFN-γ enhances the expression of both MHC class I (important for CD8+ T cell responses) and MHC class II (important for CD4+ T cell responses).
- IFN-γ upregulates genes involved in antigen processing (e.g., proteasome components) and transport (e.g., TAP transporter).
- This results in more efficient presentation of cytosolic antigens.
- IFN-γ induces the expression of CIITA (Class II transactivator), a transcription factor that activates MHC class II gene expression.
- This enhances antigen presentation by professional antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells.
- IFN-α and IFN-β (type I interferons) primarily increase MHC class I expression, particularly during viral infections.
Tumor Necrosis Factor (TNF-α)
- TNF-α, produced by macrophages, dendritic cells, and T cells, plays an important role in regulating MHC expression.
- TNF-α enhances the expression of both MHC class I and II molecules, especially in response to infection or inflammation.
- TNF-α acts by stimulating NF-κB, a transcription factor that upregulates genes involved in immune responses, including those that control MHC expression.
- It also promotes the activation of immune cells like macrophages, further enhancing the expression of MHC molecules.
- TNF-α helps coordinate the immune response by inducing the expression of costimulatory molecules on APCs, crucial for T cell activation.
MHC Restriction
- MHC molecules are key regulators of immune system responsiveness.
- Immunomodulation is a key theme to understand several autoimmune and related diseases.
Rosenthal and Skeptic Experiment (1970s)
- Guinea pig macrophages from strain two were incubated with antigen.
- After macrophages processed and presented the antigen, they were incubated with T cells from the same strain or different strain animals.
- The magnitude of T cell proliferation was measured.
- These data confirmed that c4 positive T cells were only activated and proliferate in the presence of antigen presented by macrophages or APCs that share class two MHC alleles.
- CD 4t helper cells are class two MHC restricted.
- Primed T cells did not recognize macrophage antigen presentation from animals of different strains; thus, T cell proliferation did not occur.
Zinkernagel and Doherty Experiment (1974)
- Mice were immunized with lip acidic or meningitis virus.
- CD eight positive T cells were isolated from the spleen and incubated with virus-infected target cells of the same or different haplotype.
- The target cells were intracellularly labeled with CR 51.
- CD eight positive T cell killing was measured by the remains of the protein CR 51 in the cell culture media.
- Zinkernagel and Doherty found that CD positive T cells only killed syngeneic virus-infected target cells.
- The virus-infected target cells expressed class one MHC molecules encoded by the K or D regions of the MHC.
- CD eight positive T cells are class one MHC restricted.
Class One MHC Restriction
- T cells (CTLs) only kill target cells that are of the same haplotype and recognize antigen presented on MHC class one molecules.
MHC Restriction and T Cell Activation
- Experiments showed LCMV-specific CTL from effective strain A of mice were mixed with cells with two different mousestrain A and B, and these cells relatable is a chromium 51.
- CTL kill the cellular target from LCMV effective strain A.
- String B were not wise, but CTL at strain a.
- Experiments demonstrate that LCMV-specific CTL are MHC restricted for tubes immune genes of HCV mice.
- Only wise, not in cells from HDB mice, but had no effect of cells composed COVID, MHC, hepatitis, the CTL also did not lie to the uninfected cells from either strain A or B, because the virus antigen was not present.
- Two signals were needed, one from the supplement C and another from the antigen T cell to lyse cell, which identity restrictions.
Self-MHC Restriction
- Self-MHC (Major Histocompatibility Complex) restriction refers to the immune system's phenomenon where T cells specifically recognize and respond to antigens only when presented in the context of the individual's own MHC molecules.
- T cells undergo education in the thymus, learning to recognize self-MHC molecules.
- T cells that do not recognize self-MHC with appropriate specificity or those that recognize self-antigens too strongly are typically eliminated or rendered tolerant
- T cells are activated and respond to antigens only when presented in the context of MHC molecules compatible with the individual's genetic makeup.
- Key aspect of specificity and selectivity of the adaptive immune response.
Antigen Processing
- Antigen processing is a series of intracellular events within cells to break down antigens into smaller peptide fragments.
- These peptide fragments are then presented on the cell surface bound to major histocompatibility complex (MHC) molecules.
- Ensures that the immune system can recognize a wide range of antigens and mount specific immune responses.
- The recognition of antigens in association with MHC molecules is a key step in T cell activation and the initiation of adaptive immune responses.
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