Trigger 4 - Vaccination for Type 1 Diabetes Flashcards
Infection of beta cells with enterovirus leads to ____________, which causes autoimmune attack against beta cells.
Insulitis
The overriding immune cell population involved in Type 1 Diabetes is __________.
Cytotoxic CD8+ T cells
What is the mechanism by which Fas receptor induces apoptosis in beta cells?
A. Caspase-3 activation
B. Perforin release
C. Jak-STAT signaling
D. NF-kB translocation
A. Caspase-3 activation
Which cytokines are involved in the immune response against beta cells?
A. IL-6 and IL-8
B. IL-1B, TNF-a, and IFN-y
C. IL-2 and IL-4
D. IL-10 and TGF-beta
B. IL-1B, TNF-a, and IFN-y
True or False: Fas expression on CD8+ T cells is influenced by IFN-y and IL-1B stimulation.
True
True or False: NO production, induced by IL-1B, IFN-y, and TNF-a synergy, leads to ATP depletion and cell death.
True
Define “Insulitis” in the context of Type 1 Diabetes.
Insulitis refers to the autoimmune attack against beta cells, involving the infiltration of immune cells, such as T and B lymphocytes, macrophages, and dendritic cells, into the pancreatic islets.
Define “FasL/Fas” and its role in the apoptosis pathway.
FasL/Fas refers to the interaction between Fas ligand (FasL) on CD8+ T lymphocytes and Fas receptor on beta cells. This interaction activates the apoptotic pathway through the recruitment of Fas-associated death domain (FADD) and subsequent activation of caspase-8.
Describe the role of perforin and granzyme in CD8+ T cell-mediated apoptosis of beta cells.
Perforin and granzyme released from CD8+ T cells play a crucial role in beta cell apoptosis. Perforin induces pore formation in the beta cell membrane, allowing the entry of granzyme. Granzyme activation leads to the activation of Bid, initiating the mitochondrial death pathway and ultimately causing apoptosis.
Describe the mechanisms by which cytokines IL-1B and IFN-y contribute to beta cell death in Type 1 Diabetes.
IL-1B binds to its receptor, leading to the activation of NF-kB and MAPK pathways. IFN-y, on the other hand, induces the dimerization of Jak1 and Jak2, leading to the recruitment of STAT1. These pathways converge to regulate the expression of pro-apoptotic elements, including caspases, Fas, and iNOS.
Perforin and granzyme, released from CD8+ T cells, mediate beta cell apoptosis through the formation of pores in the membrane via a __________ mechanism.
Ca2+
The synergy of IL-1B, IFN-y, and TNF-a leads to the production of __________, which elicits DNA damage and activates PARP, ultimately inducing cell death.
NO (Nitric Oxide)
Which immune cell population is the predominant one in insulitis during Type 1 Diabetes?
A. B lymphocytes
B. Macrophages
C. Cytotoxic CD8+ T cells
D. Dendritic cells
C. Cytotoxic CD8+ T cells
What is the role of FADD in the FasL/Fas-mediated apoptosis pathway?
A. Cleavage of caspase-3
B. Recruitment of perforin
C. Activation of Bid
D. Formation of pores in the membrane
A. Cleavage of caspase-3
True or False: Insulitis involves the infiltration of immune cells, including only T lymphocytes and macrophages.
False
True or False: Fas expression is influenced by IL-2 and IL-4 stimulation.
False
Define “Cytotoxic CD8+ T cells” and explain their role in Type 1 Diabetes.
Cytotoxic CD8+ T cells are a subset of T lymphocytes that play a crucial role in Type 1 Diabetes by mediating the autoimmune attack on beta cells. They release perforin and granzyme, leading to beta cell apoptosis.
Define “Nitric Oxide (NO)” and describe its role in beta cell death.
Nitric Oxide (NO) is a signaling molecule produced during the synergy of IL-1B, IFN-y, and TNF-a. NO induces DNA damage and activates PARP, contributing to beta cell death through ATP depletion.
Describe the steps involved in Fas receptor activation and its downstream effects on beta cells.
Fas receptor activation involves trimerization and recruitment of Fas-associated death domain (FADD), followed by caspase-8 activation. Caspase-8 then cleaves caspase-3, initiating the mitochondrial death pathway by cleaving Bid, leading to beta cell apoptosis.
Describe the role of cytokines IL-1B, TNF-a, and IFN-y in the immune response against beta cells during early insulitis.
These cytokines, secreted by immune cells like CD8+ cytotoxic T cells and CD4+ helper T cells, contribute to the progression of insulitis. IL-1B activates NF-kB and MAPK pathways, while IFN-y regulates the expression of pro-apoptotic elements, leading to beta cell death. TNF-a also plays a role in this synergistic process.
Insulitis is defined as the presence of at least __________ CD45+ cells/islets in a minimum of 3 islets.
15
Peri-insulitis involves infiltrates of immune cells at the __________ of the islets.
Periphery
What is the main role of CD45+ cells in insulitis?
A. Beta cell destruction
B. Insulin production
C. Immune cell infiltration
D. Islet regeneration
C. Immune cell infiltration
What percentage of islets typically show insulitis in a T1D pancreas?
A. 5-10%
B. 10-30%
C. 30-50%
D. 50-70%
B. 10-30%
True or False: Insulitis indicates a non-inflammatory state in the pancreatic islets.
False
True or False: Younger patients with Type 1 Diabetes generally exhibit less insulitis in their pancreas.
False
Define “Peri-insulitis” and “Intra-insulitis” in the context of insulitis sub-categories.
Peri-insulitis involves infiltrates of immune cells at the periphery of the islets, while intra-insulitis involves infiltrates within the parenchyma of the islets. These sub-categories help describe the localization of immune cell infiltration in insulitis.
Describe the factors that contribute to insulitis in Type 1 Diabetes.
Insulitis in Type 1 Diabetes is influenced by genetic and environmental factors. While the exact cause is unknown, the infiltration of immune cells, including T and B lymphocytes, macrophages, and dendritic cells, can lead to the destruction of beta cells responsible for insulin production within the islets.
Describe the variation in the proportion of islets showing insulitis in a T1D pancreas based on age and disease duration.
In a T1D pancreas, the proportion of islets showing insulitis is typically low, ranging from 10-30%. This variation is influenced by factors such as age and the duration of the disease, with younger patients generally exhibiting more insulitis.
The inflammatory lesion of pancreatic islets, characterized by the presence of T and B lymphocytes, macrophages, and dendritic cells, is known as __________.
Insulitis
Peri-insulitis involves infiltrates of immune cells at the __________ of the islets.
Periphery
What is the significance of the presence of at least 15 CD45+ cells/islets in insulitis definition?
A. It indicates disease remission
B. It signifies an autoimmune attack
C. It measures insulin production
D. It represents a non-inflammatory state
B. It signifies an autoimmune attack
Which factors contribute to the development of insulitis in Type 1 Diabetes?
A. Genetic and environmental factors
B. Age and gender
C. Insulin resistance
D. Diet and exercise
A. Genetic and environmental factors
True or False: The proportion of islets showing insulitis in a T1D pancreas is consistent across all age groups.
False
True or False: Intra-insulitis involves infiltrates at the periphery of the islets.
False
Define “Insulitis” and explain its role in the development of Type 1 Diabetes.
Insulitis is an inflammatory lesion characterized by the presence of immune cells in and around pancreatic islets. It signifies an autoimmune attack on beta cells, leading to the destruction of insulin-producing cells and contributing to the development of Type 1 Diabetes.
Define “Intra-insulitis” and describe its significance in the context of insulitis sub-categories.
Intra-insulitis involves infiltrates within the parenchyma of the islets. This sub-category helps describe the localization of immune cell infiltration, providing insights into the distribution of inflammatory cells in the pancreatic tissue.
Describe the variation in the proportion of islets showing insulitis based on age and disease duration in Type 1 Diabetes.
The proportion of islets showing insulitis in a T1D pancreas varies, typically ranging from 10-30%. This variation is influenced by factors such as age and disease duration, with younger patients and those with longer disease durations exhibiting different levels of insulitis
Describe the role of immune cells, including T and B lymphocytes, macrophages, and dendritic cells, in insulitis and its impact on beta cells.
Insulitis involves the infiltration of immune cells, including T and B lymphocytes, macrophages, and dendritic cells, in and around pancreatic islets. This autoimmune attack on beta cells can lead to their destruction, impacting insulin production and contributing to the pathogenesis of Type 1 Diabetes.
Chronic infections are often associated with the formation of biofilm-like structures, which display resistance to antibiotics, making treatment __________.
Difficult
Enteroviruses, such as Coxsackievirus B, have an affinity for B-cells, and B-cells are thought to express receptors needed for the binding and internalization of the virus (True/False).
True
What is the main consequence of chronic infections in beta-cells caused by enteroviruses?
A. Rapid symptom onset
B. Increase in insulin secretion
C. Reduction in glucose-induced insulin secretion
D. Activation of immune response
C. Reduction in glucose-induced insulin secretion
What is the primary mechanism through which acute infections caused by pathogens like Pseudomonas aeruginosa result in rapid and severe disease?
A. Formation of biofilm-like structures
B. Evasion of host defense
C. Virulence factors
D. Quorum sensing
C. Virulence factors
True or False: Chronic infections involving biofilm-like structures make it challenging for the immune system, and these communities can persist for a long time without complete eradication.
True
True or False: Enteroviruses, once in the B-cell, can affect the molecular machinery of the cell, leading to a decrease in autoimmune response against the ß-cell.
False
Define “Biofilm” and explain its significance in chronic infections caused by pathogens like Pseudomonas aeruginosa.
Biofilm is a structured community of bacterial cells enclosed in a self-produced matrix, often forming on surfaces. In chronic infections, biofilm-like structures formed by bacteria, such as Pseudomonas aeruginosa, contribute to resistance against antibiotics, making treatment challenging for medical interventions.
Define “Quorum Sensing” and describe its role in chronic infections.
Quorum sensing is a communication system used by bacteria to coordinate behavior within a population. In chronic infections, bacteria in biofilm communities exhibit traits of quorum sensing, contributing to resistance to environmental stressors and persistent infections.
Describe the mechanisms through which enteroviruses can lead to a reduction in glucose-induced insulin secretion in beta-cells.
Enteroviruses, having an affinity for B-cells, can enter the body and specifically target B-cells. Once inside, the virus can replicate and affect the molecular machinery of the cell, leading to an upregulation of HLA molecules and an increase in the autoimmune response against the ß-cell. This process results in a reduction in glucose-induced insulin secretion.
Describe the characteristics of chronic infections, focusing on the formation of biofilm-like structures and their impact on the immune system.
Chronic infections involve the formation of biofilm-like structures by bacteria, making them resistant to antibiotics. These structures are challenging for the immune system, allowing bacterial communities to persist for a long time without complete eradication. This resilience is attributed to characteristics such as resistance to environmental stressors and quorum sensing.
Chronic infections often involve bacterial communities that adopt a biofilm strategy, displaying phenotypes and traits characteristic of biofilm communities, such as resistance to environmental stressors and __________.
Quorum sensing
Acute infections caused by pathogens like Pseudomonas aeruginosa can result in rapid and severe disease due to the presence of various virulence factors that enable rapid replication, tissue damage, and evasion of host defense (True/False).
True
What is the main consequence of chronic infections associated with biofilm-like structures in beta-cells?
A. Increased autoimmune response
B. Rapid symptom onset
C. Resistance to environmental stressors
D. Reduction in glucose-induced insulin secretion
D. Reduction in glucose-induced insulin secretion
How do enteroviruses enter the body, including the pancreas?
A. Only through inhalation
B. Through various routes, including oral
C. Exclusively through blood transmission
D. Via skin contact
B. Through various routes, including oral
True or False: Chronic infections associated with biofilm-like structures can persist for a long time without complete eradication due to their resilience against environmental stressors.
True
True or False: Acute infections often involve gradual onset and persist for an extended period.
False
Define “Quorum Sensing” and explain how it contributes to the characteristics of biofilm communities in chronic infections.
Quorum sensing is a communication system used by bacteria to coordinate behavior within a population. In chronic infections, biofilm communities exhibit quorum sensing, contributing to their resilience, environmental stressor resistance, and prolonged persistence.
Define “Viral Replication” and describe its impact on beta-cells during enterovirus infections.
Viral replication refers to the process by which viruses replicate within host cells. In the context of enterovirus infections in beta-cells, viral replication can up-regulate the expression of HLA molecules, intensifying the autoimmune response against the ß-cell.
Describe the consequences of acute infections caused by pathogens like Pseudomonas aeruginosa, emphasizing the role of virulence factors in disease progression.
Acute infections caused by pathogens like Pseudomonas aeruginosa result in rapid and severe disease due to the presence of virulence factors. These factors, such as toxins and secretion systems, contribute to rapid replication, tissue damage, and evasion of host defenses.
Describe the mechanisms through which chronic infections associated with biofilm-like structures impact the immune system and resist eradication.Chronic infections with biofilm-like structures challenge the immune system by displaying resistance to antibiotics. The bacterial communities in biofilm states persist for extended periods, exhibiting traits such as resistance to environmental stressors and quorum sensing, making them challenging to eradicate completely.
Chronic infections with biofilm-like structures challenge the immune system by displaying resistance to antibiotics. The bacterial communities in biofilm states persist for extended periods, exhibiting traits such as resistance to environmental stressors and quorum sensing, making them challenging to eradicate completely.
Positive strand RNA viruses have genomes that are single strands of RNA with a __________ polarity, allowing them to be directly translated into proteins by the host cell’s ribosomes.
Positive
The lack of proofreading activity of RdRP in +ssRNA viruses results in a significant genetic diversity, allowing them to adapt to new hosts and environments __________.
Rapidly
What is the main function of RNA dependent RNA polymerase (RdRp) in positive single-stranded RNA viruses?
A. Encapsulating viral RNA
B. Synthesizing a complementary negative strand RNA
C. Translating viral proteins
D. Facilitating endocytosis
B. Synthesizing a complementary negative strand RNA
Which component of +ssRNA viruses is crucial for host cell attachment in enveloped viruses?
A. RNA genome
B. Capsid
C. Envelope
D. Viral proteins
C. Envelope
True or False: +ssRNA viruses typically alter cellular processes to evade immune detection, such as replicating with double membrane vesicles that conceal double-stranded RNA intermediates.
True
True or False: RNA dependent RNA polymerase (RdRp) synthesizes a positive strand RNA template to serve as a template for the synthesis of new viral genomes.
False
Define “Capsid” and explain its role in +ssRNA viruses.
Capsid is a protein shell composed of capsomers that encapsulates the RNA genome of +ssRNA viruses. It protects the viral RNA and is essential for the structure of the virion.
Define “Immune Evasion” in the context of +ssRNA viruses and provide an example of a mechanism they use for evasion.
Immune evasion in +ssRNA viruses involves altering cellular processes to avoid immune detection. An example is replicating with double membrane vesicles that conceal double-stranded RNA intermediates, which are triggers for an antiviral response.
Describe the process of entry for +ssRNA viruses, including how the viral DNA is released into the host cell’s cytoplasm.
+ssRNA viruses enter host cells by binding to specific receptors on the cell surface, followed by endocytosis or direct fusion with the cell membrane. The viral DNA is released into the cell’s cytoplasm after uncoating, which occurs when the virus escapes from the endocytic vesicle.
Describe the diversity observed in +ssRNA viruses and explain its significance in their ability to adapt to new hosts and environments.
+ssRNA viruses exhibit high mutation rates due to the lack of proofreading activity of RdRp. This creates significant genetic diversity, allowing them to adapt rapidly to new hosts and environments.
+ssRNA viruses typically alter cellular processes to evade immune detection, such as replicating with double membrane vesicles that conceal double-stranded RNA __________.
Intermediates
What is the primary function of the envelope in enveloped +ssRNA viruses?
A. Protection of RNA genome
B. Synthesis of viral proteins
C. Host cell attachment
D. Encapsulation of RNA-dependent RNA polymerase
C. Host cell attachment
Which viral protein is crucial for recognition of host cell receptors and is key to the infectivity of enveloped +ssRNA viruses?
A. RNA-dependent RNA polymerase
B. Structural proteins
C. Surface glycoproteins
D. Capsid proteins
C. Surface glycoproteins
True or False: +ssRNA viruses typically alter cellular processes to evade immune detection, such as replicating with double membrane vesicles that conceal single-stranded RNA intermediates.
False
True or False: The lack of proofreading activity of RdRp in +ssRNA viruses results in a stable and unchanging genetic makeup.
False
Define “RNA-dependent RNA Polymerase (RdRp)” and explain its role in the replication of +ssRNA viruses.
RNA-dependent RNA polymerase (RdRp) is an enzyme that synthesizes a complementary negative strand RNA from the positive strand RNA genome of +ssRNA viruses. This negative strand RNA serves as a template for the synthesis of new positive strand RNA genomes.
Define “Immune Evasion” and describe how +ssRNA viruses achieve immune evasion in their life cycle.
Immune evasion in +ssRNA viruses involves strategies that alter cellular processes to avoid detection by the host immune system. An example is replicating with double membrane vesicles, concealing double-stranded RNA intermediates that would trigger an antiviral response.
Describe the process of release for enveloped +ssRNA viruses, explaining how new virions are assembled and released from the host cell.
New virions are assembled by encapsulating newly synthesized RNA with structural proteins to form a capsid. In enveloped viruses, the capsid is cloaked with a segment of the host cell membrane, creating a viral envelope. New virions are then released from the host cell by lysis or budding. Enveloped viruses typically exit through budding, enabling effective evasion of the immune system.
Describe the role of mRNA vaccines in combating +ssRNA viruses like SARS-CoV-2, emphasizing the delivery mechanism and immune response elicited.
mRNA vaccines deliver genetic material to cells, prompting the production of viral proteins, such as the spike protein of SARS-CoV-2. This triggers an immune response, providing protection against future viral infections. Other vaccines use vectors to deliver genetic material for +ssRNA viral antigens, stimulating a similar immune response.
Enteroviruses are small, non-enveloped, single-stranded RNA viruses, typically ranging in size from __________.
24-30nm
Viral RNA is translated into a polypeptide by host ribosomes, and the negative RNA strand is used for duplicates, resulting in the formation of double-stranded RNA (True/False).
False
What is the primary function of Natural Killer (NK) cells in the innate response to enterovirus infection?
A. Directly killing infected cells
B. Producing interferons
C. Synthesizing viral proteins
D. Enhancing MHC Class 1 expression
A. Directly killing infected cells
Which immune cells bridge the adaptive and innate responses by acting as phagocytes and presenting antigens to T lymphocytes?
A. Macrophages
B. Cytotoxic T cells
C. B Cells
D. Dendritic cells
D. Dendritic cells
rue or False: Interferons released by infected cells bind to IFN receptors on nearby cells, promoting the production of antiviral proteins and preventing viral replication.
True
True or False: Viruses up-regulate MHC Class 1 on infected cells to avoid recognition by Natural Killer (NK) cells.
False
Define “Innate Response” and explain its role in the cellular defense against enterovirus infection.
Innate response is the immediate, nonspecific defense mechanism activated when a cell is infected. It includes the release of interferons, production of antiviral proteins, and activation of Natural Killer cells to prevent viral replication and spread.
Define “Antigen-Presenting Cell” and describe how macrophages function as antigen-presenting cells during enterovirus infection.
Antigen-presenting cells are cells that display fragments of pathogens on their surface to activate the adaptive immune response. Macrophages recognize viruses, engulf them, and break them down using lysosomal enzymes. Fragments of the virus are then presented on the cell surface as antigens for T lymphocytes.
Describe the role of dendritic cells in the cellular response to enterovirus infection, highlighting their function in connecting the adaptive and innate immune systems.
Dendritic cells act as phagocytes during enterovirus infection and present antigens to T lymphocytes. By presenting antigens, dendritic cells bridge the adaptive and innate immune responses, connecting the initial recognition of the virus with the activation of the adaptive immune system.
Describe the adaptive immune response to enterovirus infection, focusing on the roles of cytotoxic T cells (CD8+ T cells) and B cells.
Cytotoxic T cells recognize viral fragments on MHC Class 1 molecules on infected cells and release cytotoxic factors, resulting in apoptosis or cell lysis. B cells, upon activation by T helper cells, differentiate into memory cells and plasma cells, the latter of which releases antibodies to neutralize the virus.
Enteroviruses are comprised of 60 copies of VP1 to VP4 and are typically encountered by most children by the age of __________.
6 months
The adaptive immune response involves activated B cells differentiating into memory cells and plasma cells, with plasma cells releasing __________ to combat enterovirus infection.
Antibodies
What is the primary role of interferons released during the innate response to enterovirus infection?
A. Directly killing infected cells
B. Enhancing MHC Class 1 expression
C. Preventing viral replication
D. Synthesizing viral proteins
C. Preventing viral replication
Which viral proteins are synthesized and packed into the virion during the normal action of enteroviruses?
A. VP1-VP4
B. MHC Class 1
C. CD8+ T cells
D. Interferons
A. VP1-VP4
True or False: During the normal virus action, the negative RNA strand is utilized for duplicates, resulting in the formation of double-stranded RNA.
False
True or False: Dendritic cells primarily act as cytotoxic T cells during enterovirus infection.
False
Define “Exocytosis” and explain how it contributes to the release of virions during enterovirus infection.
Exocytosis is a cellular process where cells release particles outside the cell. In enterovirus infection, new virions are released out of the cell by exocytosis, allowing for the infection of new cells.
Define “Memory Cells” and describe their role in the adaptive immune response to enterovirus infection.
Memory cells are long-lived cells formed during the adaptive immune response. In enterovirus infection, activated B cells differentiate into memory cells, providing immunological memory for a faster and more effective response upon subsequent encounters with the virus.
Describe the process of endocytosis during the entry of enteroviruses into host cells, highlighting how it facilitates the release of positive-stranded RNA.
Enteroviruses enter the cell via endocytosis, and within the endosome, the positive-stranded RNA is released. This process allows the viral RNA to enter the host cell’s cytoplasm for further translation and replication.
Describe the role of Natural Killer (NK) cells in the innate response to enterovirus infection, emphasizing their actions against infected cells and the release of interferon gamma.
Natural Killer (NK) cells are activated if there’s insufficient MHC Class 1 on infected cells. They release granules and perforin, leading to cell death. Additionally, NK cells secrete interferon gamma (IFN-γ), protecting adjacent cells from viral infection and aiding in the activation of T-cell-mediated immunity.
Enteroviruses are a type of virus with __________ RNA.
Positive single-stranded RNA
What hypothesis is mentioned regarding the potential role of coxsackie viruses in triggering T1D?
A. Genetic mutation hypothesis
B. Domino effect hypothesis
C. Double-stranded RNA hypothesis
D. Immune system evasion hypothesis
C. Double-stranded RNA hypothesis
The PROVENT vaccine focuses on which enterovirus, identified as possibly leading to T1D?
A. Rhinovirus
B. Poliovirus
C. Coxsackie virus B
D. Hepatitis C virus
C. Coxsackie virus B
True or False: The increase in T1D, especially in children, is primarily attributed to genetic factors.
False
True or False: The PROVENT vaccine, a polyvalent inactivated Coxsackie virus B vaccine, is currently in Phase 2 of clinical trials.
False
Define “Autoimmunity” in the context of T1D and explain how it relates to the destruction of insulin-producing Beta cells.
Autoimmunity refers to the immune system’s attack on the body’s own cells. In T1D, autoimmunity leads to the destruction of insulin-producing Beta cells in the pancreas, resulting in a lack of insulin production.
Define “Polyvalent” in the context of the PROVENT vaccine and describe its significance in targeting enterovirus strains.
Polyvalent refers to a vaccine that targets multiple strains or types of a virus. In the context of the PROVENT vaccine, being polyvalent allows it to target all 5 strains of Coxsackie virus B, potentially preventing T1D associated with these strains.
Describe the role of interferons in the innate response to enterovirus infection and how they contribute to preventing viral replication.
When a cell is infected, it releases interferons, which bind to IFN receptors on nearby cells. This triggers the production of antiviral proteins, preventing the replication of the virus within the cell. Interferons also increase the expression of MHC Class 1 on the cell surface.
Describe the current status and key findings of the PROVENT vaccine study, emphasizing its potential impact on preventing Coxsackie virus B infection and T1D.
As of the most recent studies on the PROVENT vaccine, it is still in Phase 1 trials and has shown positive results. The vaccine is well-tolerated, induces high levels of coxsackie virus neutralizing antibodies, and has not shown severe side effects in volunteers. Further work is needed, but the study is looking promising for preventing Coxsackie virus B infection and, subsequently, T1D.
What is the proposed hypothesis regarding the potential link between coxsackie viruses and T1D development?
A. Genetic mutation hypothesis
B. Domino effect hypothesis
C. Double-stranded RNA hypothesis
D. Immune system evasion hypothesis
C. Double-stranded RNA hypothesis
According to recent studies, what type of RNA does enterovirus possess?
A. Double-stranded RNA
B. Negative single-stranded RNA
C. Positive single-stranded RNA
D. Ribosomal RNA
C. Positive single-stranded RNA
True or False: The PROVENT vaccine, currently in Phase 1 trials, has already demonstrated its effectiveness in preventing Coxsackie virus B infection and T1D.
False
True or False: The increase in T1D, especially in children, is hypothesized to be influenced by environmental factors, such as viruses, rather than solely genetic factors.
True
Define “Autoimmune-Mediated Cell Destruction” and explain its role in the pathogenesis of Type 1 Diabetes.
Autoimmune-mediated cell destruction refers to the immune system’s attack on the body’s own cells, particularly pancreatic insulin-producing Beta cells in the context of Type 1 Diabetes. This process leads to the destruction of these cells and a subsequent lack of insulin production.
Define “Polyvalent Inactivated Vaccine” and describe how the PROVENT vaccine, targeting Coxsackie virus B, fits this category.
A polyvalent inactivated vaccine targets multiple strains or types of a virus and is made from viruses that have been killed or inactivated. The PROVENT vaccine, focusing on all 5 strains of Coxsackie virus B, is polyvalent and inactivated, aiming to prevent T1D associated with these strains.
Describe the role of interferons in the innate response to enterovirus infection, emphasizing how they contribute to preventing viral replication and enhancing immune responses.
Interferons released during enterovirus infection bind to IFN receptors on nearby cells, triggering the production of antiviral proteins. This prevents viral replication within the infected cell and increases the expression of MHC Class 1 on the cell surface. Interferons also enhance immune responses by activating Natural Killer cells and aiding in T-cell-mediated immunity.
Describe the significance of the PROVENT vaccine in preventing T1D linked to Coxsackie virus B, including key findings from human trials and its potential impact on public health.
The PROVENT vaccine, focusing on Coxsackie virus B, has shown positive results in human trials, inducing high titres of coxsackie virus neutralizing antibodies. While still in Phase 1 trials, it holds potential for preventing T1D associated with these virus strains. If successful, the vaccine could have a significant impact on public health by reducing the incidence of T1D linked to enterovirus infections.
According to the information provided, which platforms are most utilized for receiving diabetes self-care services through social networks?
A. Facebook, Twitter, LinkedIn
B. WhatsApp, Telegram, Instagram
C. Snapchat, TikTok, Pinterest
D. YouTube, Reddit, Tumblr
B. WhatsApp, Telegram, Instagram
What factor showed a significant association with the use of self-care services through social networks?
A. Gender
B. Age
C. Education level
D. Diabetes duration
C. Education level
True or False: Over 95% of the treatment process for diabetes is carried out by healthcare professionals during clinic visits.
False
True or False: Younger patients, those with higher education, type 2 diabetes, and over 21 years of diabetes history were less likely to use information services on social networks.
False
Define “HbA1c” and explain its significance in diabetes management.
HbA1c, or Hemoglobin A1c, is a measure of average blood glucose levels over the past two to three months. It is a crucial indicator in diabetes management, providing insights into long-term glycemic control. Lower HbA1c levels are associated with better diabetes management and reduced risk of complications.
Define “Meta-analyses” and describe how they contribute to understanding the impact of online services through social networks on diabetes management.
Meta-analyses are comprehensive analyses that combine and synthesize data from multiple studies. In the context of diabetes management, meta-analyses provide a systematic review of studies examining the impact of online services through social networks. They help in drawing meaningful conclusions and identifying trends in the effectiveness of such services.
Describe the role of social networks in improving diabetes self-care processes, highlighting specific benefits such as real-time communication, training, and feedback between patients and professionals.
Social networks play a crucial role in improving diabetes self-care processes by facilitating real-time communication and feedback between patients and healthcare professionals. They also offer training opportunities, contributing to enhanced patient knowledge and information about managing diabetes.
Describe the utilization patterns of different social networks for receiving diabetes self-care services, emphasizing the popularity of platforms like WhatsApp, Telegram, and Instagram among participants.
WhatsApp (88.5%), Telegram (59.5%), and Instagram (46.3%) emerge as the most utilized social networks for receiving diabetes self-care services. Less commonly used platforms include IGap (0.9%), Baleh (1.4%), and Myspace (2.3%). The findings underscore the prevalence of specific platforms in facilitating diabetes-related communication and support.
Define: Positive-Sense Single-Stranded RNA Virus
A virus with a single-stranded RNA genome that can be directly translated into proteins by the host cell’s ribosomes.
Describe: Immediate Replication in +ssRNA Viruses
Upon entering a host cell, the viral RNA is immediately utilized to make viral proteins.
Fill in the Gap: +ssRNA Viruses Encode ______ for Replicating Their Genome
RNA-dependent RNA polymerase (RdRp).
Define: Negative-Sense Single-Stranded RNA Virus
A virus with a single-stranded RNA genome that requires transcription into positive-sense RNA before translation.
Describe: Genome Packaging in –ssRNA Viruses
The negative-sense RNA is tightly packaged with nucleoproteins and RdRp within the virion
–ssRNA Viruses Bring Their Own ______ Since Host Cells Cannot Transcribe –ssRNA.
A) DNA polymerase
B) RNA-dependent RNA polymerase (RdRp)
C) Ribosomes
D) Helicase
B) RNA-dependent RNA polymerase (RdRp).
Define: Double-Stranded RNA Virus
A virus with a genome containing RNA strands of both positive and negative sense.
Describe: Replication in dsRNA Viruses
Replicate within a capsid and require unique mechanisms to ensure that each segment is replicated and packaged into new virions.
Fill in the Gap: Many dsRNA Viruses Have ______ Genomes, Meaning Their Genetic Material Is Divided Into Several Separate RNA Molecules.
Segmented
Describe: Mutation Rates in RNA Viruses
All RNA viruses have high mutation rates due to the lack of proofreading in their RNA polymerases, leading to significant genetic diversity.
What Is a Major Challenge in Developing Effective Vaccines Against RNA Viruses?
A) Low replication rates
B) Lack of host recognition
C) High mutation rates
D) Stable genome
C) High mutation rates
Define: Type 1 Diabetes
Type 1 diabetes is a chronic autoimmune condition primarily due to genetic factors.
Describe: Inheritance and Genetic Predisposition
Genetic predisposition increases the risk of developing diabetes. Variants in HLA-DQA1, HLA-DQB1, and HLA-DRB1 genes contribute to this predisposition.
Fill in the Gap: HLA Complex Helps Immune Systems Distinguish Between ______ and Proteins Made by Foreign Invaders.
The body’s own protein.
Which HLA Genes Increase the Risk of Developing Type 1 Diabetes?
A) HLA-A
B) HLA-DQA1
C) HLA-B
D) HLA-C
B) HLA-DQA1.
Describe: Non-HLA Gene Markers
INS gene and PTPN22 gene contribute to most diabetes risk after HLA alleles. CTLA4 gene reduces control in the proliferation of T-cells.
Define: Environmental Factors in Type 1 Diabetes
Environmental factors impact the development of type 1 diabetes and can trigger or accelerate its progression.
Describe: Viral Infections and Type 1 Diabetes
Enteroviruses, especially Coxsackie virus B1 (CBV1), may act through direct cytolytic effects or initiate autoimmune processes leading to beta-cell destruction. CBV3/CBV6 infections might have a protective effect.
Type 1 diabetes is a chronic autoimmune condition primarily due to _______ factors.
a) Environmental
b) Genetic
c) Both a and b
d) None of the above
c) Both a and b
How can viral infections impact Type 1 Diabetes development?
Enteroviruses, especially Coxsackie virus B1 (CBV1), may act through direct cytolytic effects or initiate autoimmune processes leading to beta-cell destruction.
Which strains of enteroviruses are linked to a higher risk of beta-cell autoimmunity and T1D manifestation?
Coxsackie virus B1 (CBV1) infections.
Which HLA genes are associated with an increased risk of Type 1 Diabetes?
Variants of HLA-DQA1, HLA-DQB1, and HLA-DRB1 genes.
How does the HLA complex contribute to Type 1 Diabetes risk?
It helps the immune system distinguish between the body’s own proteins and those made by foreign invaders, increasing the risk of inappropriate immune response to beta cells.
What is the potential protective effect of breastfeeding against T1D?
Breastfeeding is suggested to have a protective effect, although results are conflicting.
Which dietary factors may increase the risk of beta-cell autoimmunity and T1D?
Early introduction of cow milk protein, cereals, and certain fruits, berries, and roots.
What is the association between cod liver oil, Omega-3 Fatty acids, and T1D risk?
Cod liver oil and Omega-3 Fatty acids show conflicting evidence, but some studies suggest a reduced risk of T1D.
Besides HLA alleles, which non-HLA gene markers contribute to the risk of diabetes?
INS gene and PTPN22 gene contribute significantly to diabetes risk after HLA alleles.
What does the CTLA4 gene regulate, and how does it relate to T1D risk?
The CTLA4 gene reduces control in the proliferation of T-cells, potentially influencing T1D risk.
How does geographical location relate to the incidence of Type 1 Diabetes?
Further away from the equator, populations are more likely to have a higher incidence of diabetes.
How does weight gain in infancy relate to T1D risk in later childhood?
Weight gain in infancy is shown as a risk factor for T1D in later childhood.
What are the effects of rapid weight gain and growth in infancy on T1D risk?
Rapid weight gain and growth in infancy are associated with increased beta cell load, insulin resistance, and potential stress on beta cells, contributing to T1D risk.
How does the gut microbiota potentially influence autoimmune diabetes?
Decreased MyD88 protein in NOD mice, showing the absence of commensal microbes, is linked to increased autoimmune diabetes.
What association has been observed between the intestinal microbiome and diabetic children?
Diabetic children have been observed to have less diverse and unstable microbiomes in the intestinal microbiome.
hich enterovirus strain is associated with a higher risk of beta-cell autoimmunity and T1D manifestation?
A) Coxsackie virus A
B) Coxsackie virus B1 (CBV1)
C) Poliovirus
D) Enterovirus D68
B) Coxsackie virus B1 (CBV1)
Which HLA genes are linked to an increased risk of Type 1 Diabetes?
A) HLA-A and HLA-B
B) HLA-C and HLA-DPA1
C) HLA-DQA1, HLA-DQB1, and HLA-DRB1
D) HLA-G and HLA-E
C) HLA-DQA1, HLA-DQB1, and HLA-DRB1
What dietary factor is suggested to have a protective effect against Type 1 Diabetes, although results are conflicting?
A) Early introduction of cow milk protein
B) Cereal introduction
C) Breastfeeding
D) Cod liver oil supplementation
C) Breastfeeding
Besides HLA alleles, which gene markers contribute significantly to the risk of diabetes?
A) INS gene and PTPN22 gene
B) CTLA4 gene and IL-6 gene
C) TNF-alpha gene and IL-1 gene
D) FOXO3 gene and SIRT1 gene
A) INS gene and PTPN22 gene
What geographical factor is associated with a higher incidence of Type 1 Diabetes?
A) Proximity to the ocean
B) Distance from the equator
C) Altitude above sea level
D) Latitude
B) Distance from the equator
How is weight gain in infancy related to Type 1 Diabetes risk in later childhood?
A) Protective factor
B) No correlation
C) Risk factor
D) Variable impact
C) Risk factor
What does the CTLA4 gene regulate in the context of Type 1 Diabetes?
A) Beta-cell function
B) Insulin production
C) Proliferation of T-cells
D) HLA gene expression
C) Proliferation of T-cells
How might rapid weight gain and growth in infancy contribute to Type 1 Diabetes risk?
A) Reducing insulin resistance
B) Decreasing beta cell load
C) Stress on beta cells
D) Enhancing immune response
C) Stress on beta cells
What role does the gut microbiota play in Type 1 Diabetes development?
- A) Increased MyD88 protein leads to decreased risk
- B) Commensal microbes decrease autoimmune diabetes risk
- C) Absence of commensal microbes may increase autoimmune diabetes risk
- D) Gut microbiota has no impact on Type 1 Diabetes
C) Absence of commensal microbes may increase autoimmune diabetes risk
Question: What is the primary cause of Type 1 Diabetes?
a) Genetic factors
b) Environmental factors
c) Autoimmune condition
d) Lack of physical activity
c) Autoimmune condition
Type 1 diabetes affects almost __________ people in the UK, with approximately __________ being children.
400,000; 10%
Insulitis
Definition: _____________________________
Description: _____________________________
Insulitis is a designated hallmark feature of type one diabetes, characterized by the infiltration of immune cells, particularly CD8 positive cytotoxic T cells, selectively killing beta cells within the pancreatic islets.
True or False: Monitoring of Type 2 Diabetes involves examining the pancreas directly.
False
What is the worldwide cost of diabetes to the NHS per day?
a) £22 million
b) £5 million
c) £50 million
d) £10 million
a) £22 million
According to the geographical prevalence of diabetes, what trend is observed in relation to the distance from the equator?
a) Decrease in diabetes incidence
b) Increase in diabetes incidence
c) No correlation with diabetes incidence
b) Increase in diabetes incidence
In the research of Type 1 Diabetes, what is NOT examined clinically in blood samples?
The pancreas
Question: How many children worldwide are living with Type 1 Diabetes?
a) 100,000
b) 500,000
c) 1 million
d) 250,000
b) 500,000
What is a notable feature of the destruction of beta cells in Type 1 Diabetes?
a) Destruction occurs uniformly
b) Destruction is selective
c) Destruction is instantaneous
d) Destruction is only genetic-driven
b) Destruction is selective
Why is it important to identify and intervene during stage 2 of Type 1 Diabetes?
a) Stage 2 is irreversible
b) Prevents clinical diagnosis
c) Stage 2 is symptom-free
d) Stage 2 is the final stage
b) Prevents clinical diagnosis
What factors contribute to the increase in the prevalence of diabetes, especially in children?
a) Genetic factors
b) Environmental factors
c) Dietary habits
d) Lack of physical activity
b) Environmental factors
What is the role of glucagon in patients with Type 1 Diabetes?
a) Raises blood glucose levels
b) Lowers blood glucose levels
c) Stimulates insulin production
d) Inhibits insulin secretion
a) Raises blood glucose levels
What is the role of the Islets of Langerhans in the pancreas?
a) Filtration of blood
b) Digestion of nutrients
c) Production of hormones
d) Storage of bile
c) Production of hormones
At what age is a particular mass of beta cells in the pancreas achieved for normal individuals?
a) Birth
b) 2 years
c) 10 years
d) Puberty
b) 2 years
What immune cells are particularly attracted to the pancreas in people with Type 1 Diabetes, leading to insulitis?
a) CD4 positive helper T cells
b) CD20 positive B cells
c) CD8 positive cytotoxic T cells
d) CD68 positive macrophages
c) CD8 positive cytotoxic T cells
In Type 1 Diabetes, there is a slow decline in the mass of beta cells over time, starting after a triggering event. This decline is ___________________.
Non-uniform and varies from individual to individual
What immune cells are present within the insulitic infiltrates in Type 1 Diabetes?
a) CD45 positive cells
b) CD20 positive cells
c) CD4 and CD8 positive cells
d) All of the above
d) All of the above
What is the significant association between enterovirus infection and type 1 diabetes?
a) Enteroviruses directly cause diabetes
b) Enterovirus infection triggers autoimmunity leading to diabetes
c) Enteroviruses prevent diabetes development
d) Enteroviruses have no relation to diabetes
b) Enterovirus infection triggers autoimmunity leading to diabetes
Enteroviruses are respiratory viruses with a genome made of __________ and are encountered by individuals by the age of __________.
RNA; 6 months
Where can viral protein one be detected in individuals with and without type 1 diabetes?
a) Detected in islets of both groups
b) Detected only in islets of individuals with diabetes
c) Detected only in islets of individuals without diabetes
d) Absent in both groups
a) Detected in islets of both groups
What is the role of double-stranded RNA (dsRNA) in type 1 diabetes?
a) Prevents viral replication
b) Causes viral replication
c) Triggers autoimmunity
d) Detected only in alpha cells
c) Triggers autoimmunity
In persistent enteroviral infection, the virus retains its genome in a __________ form, hiding away in the nucleus.
Double-stranded genomic
According to the information provided, how is vaccination related to diabetes prevention?
a) Vaccination is a cure for diabetes
b) Vaccination prevents enterovirus infection
c) Vaccination immunizes individuals from being susceptible to diabetes
d) Vaccination triggers autoimmunity
c) Vaccination immunizes individuals from being susceptible to diabetes
Viral protein one immunopositivity is restricted to __________ within the islets in type one diabetes.
Beta cells
What is the role of protein kinase R in enteroviral infecting cells?
a) Promotes viral replication
b) Prevents protein synthesis
c) Enhances apoptosis
d) Increases viral protein production
b) Prevents protein synthesis
Mda5 is a driver of interferon expression and is mainly present in __________ in control islets.
Alpha cells
Where is dsRNA detected in islet cells in type 1 diabetes?
a) Detected in both alpha and beta cells
b) Detected only in alpha cells
c) Detected only in beta cells
d) Absent in both alpha and beta cells
c) Detected only in beta cells
Define: Autoimmunity
Autoimmunity is a condition where the immune system mistakenly targets and attacks the body’s own cells, tissues, or organs, leading to inflammatory responses and potential damage.
Describe: Protein Kinase R
Protein Kinase R is an enzyme induced in viral infecting cells. It plays a crucial role in stopping protein synthesis to prevent viral replication, leading to translational arrest. Additionally, it contributes to the depletion of anti-apoptotic proteins in cells.
hat is the genome structure of enteroviruses?
a) DNA
b) RNA
c) Both DNA and RNA
d) Proteins
b) RNA
Enteroviral infections detected in islets in type one diabetes are atypical as viral protein one immunopositivity is restricted to __________ within the islets.
Beta cells
Describe Mda5
Mda5, also known as melanoma differentiation-associated protein 5, is a protein that serves as a driver of interferon expression. It is expressed in endocrine cells and is mainly present in alpha cells in control islets.
Define: Double-Stranded RNA (dsRNA)
Double-stranded RNA (dsRNA) is a molecule composed of two RNA strands with complementary sequences. In the context of enteroviral infections, the presence of dsRNA is associated with viral persistence and triggers immune responses.
Where can viral protein one be detected in individuals with and without type 1 diabetes?
a) Detected in islets of both groups
b) Detected only in islets of individuals with diabetes
c) Detected only in islets of individuals without diabetes
d) Absent in both groups
a) Detected in islets of both groups
In persistent enteroviral infection, the virus retains its genome in a double-stranded form, hiding away in the __________.
Nucleus
Describe Insulitic Infiltrates
Insulitic infiltrates are immune cell accumulations within the pancreatic islets, particularly CD8 positive cytotoxic T cells. This infiltration is a hallmark feature of type 1 diabetes, indicating the selective destruction of beta cells.
What is the relationship between enteroviral infection and diabetes, based on the provided information?
a) Enterovirus causes diabetes directly
b) Enterovirus prevents diabetes
c) Enterovirus triggers events that accumulate to diabetes
d) Enterovirus has no relation to diabetes
c) Enterovirus triggers events that accumulate to diabetes
Define: Polydipsia
Polydipsia is a medical term referring to excessive thirst and the intake of abnormally large amounts of fluids
Describe beta cells
Beta cells are specialized cells found in the pancreatic islets of Langerhans. They play a critical role in maintaining glucose homeostasis by synthesizing, storing, and releasing insulin, a hormone that regulates blood sugar levels.
How is the enterovirus primarily spread?
a) Airborne transmission
b) Bloodborne transmission
c) Faecal-oral route
d) Sexual transmission
c) Faecal-oral route
An autoimmune response in Type 1 Diabetes leads to the death of __________ cells.
Beta cells
Describe Coxsackie B Virus
Coxsackie B Virus
What is the function of the Coxsackie and Adenovirus Receptor (CAR) in beta cells?
a) Prevents viral infections
b) Triggers apoptosis
c) Binds to enteroviruses and allows endocytosis
d) Regulates insulin secretion
c) Binds to enteroviruses and allows endocytosis
oxsackie and Adenovirus Receptor (CAR) is selectively and highly expressed on insulin secretary granules, allowing for endocytosis into the cell with __________.
Membrane recovery
Describe HLA gene
HLA genes (Human Leukocyte Antigen genes) play a significant role in polymorphism in Type 1 Diabetes. Variations, particularly in HLA class II genes, contribute to the genetic susceptibility to autoimmune diseases.
How do interferons exert their effects in the prevention against diabetes?
a) Directly attack viruses
b) Inhibit insulin secretion
c) Activate pro-inflammatory molecules through STAT1
d) Increase beta-cell vulnerability
c) Activate pro-inflammatory molecules through STAT1
What is the structure of insulin granules in beta cells?
a) Liquid-filled vesicles
b) Soluble crystalline hexameric insulin
c) Gas-filled sacs
d) Amorphous protein aggregates
b) Soluble crystalline hexameric insulin
How is Coxsackie B, the most prevalent enterovirus in diabetics, primarily transmitted?
a) Airborne transmission
b) Bloodborne transmission
c) Faecal-oral route
d) Vector-borne transmission
c) Faecal-oral route
What is the primary function of the Coxsackie and Adenovirus Receptor (CAR) in beta cells?
a) Synthesizing insulin
b) Recognizing antigens
c) Allowing endocytosis of enteroviruses
d) Regulating glucose levels
c) Allowing endocytosis of enteroviruses
Which type of genes, particularly in the HLA class II region, plays a significant role in genetic susceptibility to Type 1 Diabetes?
a) HLA class I genes
b) HLA class III genes
c) HLA class II genes
d) HLA class IV genes
c) HLA class II genes
What is the role of enterovirus in mediating an immune response against beta cells?
a) Directly killing beta cells
b) Activating pro-inflammatory molecules
c) Inhibiting insulin synthesis
d) Suppressing interferon release
b) Activating pro-inflammatory molecules
Where is double-stranded RNA (dsRNA) detected in islet cells in Type 1 Diabetes?
a) Detected in both alpha and beta cells
b) Detected only in alpha cells
c) Detected only in beta cells
d) Absent in both alpha and beta cells
c) Detected only in beta cells
What is one characteristic of the interferon viral footprint in beta cells?
a) Downregulation of MHC class I
b) Upregulation of MHC class I
c) Inhibition of insulin release
d) Decrease in beta cell antibodies
b) Upregulation of MHC class I
Coxsackie B has been linked to which of the following in diabetics?
a) Increased insulin production
b) Pancreatitis and beta-cell destruction
c) Inhibition of insulin secretion
d) Prevention of Type 1 Diabetes
b) Pancreatitis and beta-cell destruction
How does interferon signaling contribute to the prevention against diabetes?
a) Increases beta-cell vulnerability
b) Directly attacks viruses
c) Switches interferon signaling through STAT1
d) Suppresses pro-inflammatory molecules
c) Switches interferon signaling through STAT1
Why are individuals less likely to develop Type 1 Diabetes if they encounter Coxsackie B before another enterovirus?
a) Weaker immune response
b) Development of stronger immunity
c) Increased beta-cell vulnerability
d) No correlation with immunity
b) Development of stronger immunity
