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.
