Lecture 22 Studyguide - Immunology PDF

Memory B and T lymphocytes Goals of adaptive immunity 1. Clear antigen and associated microbes 2. Prepare long-term defense against re-infection The text seems to be discussing the concept of memory B and T lymphocytes, which are key players in the adaptive immune system. These cells are formed in r...

Memory B and T lymphocytes Goals of adaptive immunity 1. Clear antigen and associated microbes 2. Prepare long-term defense against re-infection The text seems to be discussing the concept of memory B and T lymphocytes, which are key players in the adaptive immune system. These cells are formed in response to exposure to antigens (foreign substances) and provide longterm protection against reinfection by the same antigen. The goal of adaptive immunity is twofold: first, to clear the immune system of antigens and associated microbes during an active infection, and second, to prepare the immune system for future encounters with the same antigen, thereby providing long-lasting protection. The process of forming memory cells begins with a primary immune response. During this response, naive B and T cells, which have not encountered antigens before, are activated by antigen-presenting cells (such as dendritic cells). These activated cells then proliferate and differentiate into effector cells, which carry out the immune response by producing antibodies (in the case of B cells) or by directly attacking infected cells (in the case of T cells). Alongside the effector cells, a small population of B and T cells differentiate into memory cells. These memory cells have a longer lifespan and remain in the body even after the infection is cleared. They "remember" the specific antigen that triggered their formation. 1 When the body encounters the same antigen again in the future (a secondary infection), the memory B and T cells quickly mount a robust immune response. This secondary response is faster and more efficient than the primary response because the memory cells are already primed to recognize and combat the antigen. The text also mentions the concept of "contraction" in the context of T cells. After the peak of the immune response, the population of effector T cells decreases through a process called contraction. This helps maintain the balance of the immune system and prevents it from becoming overly activated. Overall, memory B and T lymphocytes are crucial components of the adaptive immune system, providing long-term protection against recurrent infections by "remembering" previous encounters with specific antigens. If there are specific parts of the text that aren't clear, please let me know, and I can provide further explanation! 1 Specialized features of memory lymphocytes Long-term survival Quick response to reinfection Distribution to appropriate location(s) Certainly! Let's break down the specialized features of memory lymphocytes as discussed in the text: 1.Long-Term Survival: Memory lymphocytes, whether they are memory B or T cells, are characterized by their ability to survive for long periods within the body. Unlike the effector cells that are short-lived and decline after the infection is cleared, memory cells persist for extended durations, sometimes for the lifetime of the individual. This prolonged survival ensures that the immune system retains a "memory" of past encounters with specific antigens. 2.Quick Response to Reinfection: One of the primary functions of memory lymphocytes is to mount a rapid and robust immune response upon encountering the same antigen again. This rapid response is crucial for effectively combating pathogens during secondary infections. Memory cells are already primed to recognize and respond to the antigen, allowing the immune system to react swiftly and prevent the infection from establishing itself. 3.Tissue Distribution: Memory lymphocytes exhibit specialized patterns of distribution within the body. Some memory cells migrate to specific tissues or organs where they are most likely to encounter the antigen upon reinfection. For example, memory cells formed in response to a respiratory virus may localize in the respiratory tract tissues, ready to respond quickly to reinfection in that area. This tissue-specific distribution enhances the efficiency of the immune response by positioning memory cells strategically where they are most needed. 2 4. Circulation: In addition to tissue-specific distribution, some memory lymphocytes circulate continuously throughout the body via the bloodstream. These circulating memory cells act as a surveillance system, constantly patrolling various tissues and organs to detect and respond to any reemergence of the antigen. This ensures widespread coverage and readiness to combat infections regardless of the site of reinfection. Overall, memory lymphocytes possess specialized features that enable them to provide long-lasting protection against specific pathogens. Their ability to survive for extended periods, mount rapid responses to reinfection, and strategically distribute within the body contributes to the effectiveness of the adaptive immune response in preventing recurrent infections. Despite the complexities involved, understanding these specialized features is crucial for unraveling the mechanisms underlying immune memory and developing strategies for enhancing immune protection. 2 Properties of memory cells: long-term survival Occurs in absence of antigen (antigen is strongest survival signal for effector lymphocytes) Long-term survival depends on: 1. Increased expression of anti-apoptotic (pro-survival) proteins For example: BCL-2 blocks apoptosis in absence of survival signals 2. Slow proliferation Reduces chance of damage associated with cell cycle and metabolic activity Also seen in HSCs and other stem cells For memory T cells, these features depend on IL-7 signaling => High levels of IL-7 receptor now used as marker for memory T cells The text discusses the property of long-term survival exhibited by memory cells, whether they are memory B or T lymphocytes. Here's a detailed breakdown of the key points: 1.Survival in the Absence of Antigen: Long-term survival of memory cells occurs in the absence of antigen. After the primary immune response, most effector cells undergo programmed cell death since they are no longer needed to combat the infection. However, a small population of memory cells persists for extended periods to provide immunological memory. 2.Increased Expression of Anti-Apoptotic Proteins: To sustain their long-term survival, memory cells exhibit increased expression of certain anti-apoptotic proteins. Apoptosis is a programmed cell death process regulated by a balance between pro-survival and pro-apoptotic proteins. Memory cells tilt this balance in favor of survival by upregulating proteins like BCL-2, which blocks apoptosis signaling pathways. BCL-2 is a crucial pro-survival protein that prevents memory cells from undergoing apoptosis even in the absence of external survival signals provided by antigens. 3.Slow Proliferation Rate: Memory cells also demonstrate a relatively slow rate of proliferation or infrequent cell division compared to effector cells. This reduced frequency of cell division minimizes the risk of DNA damage 3 associated with replication errors, chromosome segregation errors, and other abnormalities that may occur during cell cycle progression. Slow proliferation helps protect the genomic integrity of memory cells, ensuring their long-term viability and functionality. 4. Lower Metabolic Activity: Memory cells exhibit lower metabolic activity compared to actively proliferating cells. This lower metabolic rate reduces the production of potentially damaging metabolic byproducts, which could harm cellular components, including DNA. By maintaining a lower metabolic activity, memory cells minimize the risk of accumulating damage that could compromise their survival and function. 5.Comparison with Stem Cells: The text draws a comparison between the slow proliferation observed in memory cells and that seen in stem cells, particularly hematopoietic stem cells. Stem cells also exhibit slow proliferation to protect their genomic integrity and ensure the maintenance of a functional stem cell pool. The similarities in proliferation patterns suggest shared mechanisms for controlling cell division and maintaining cellular integrity in both memory cells and stem cells. 6.Signaling through IL-7: For memory T cells specifically, their long-term survival depends on signaling from the cytokine interleukin-7 (IL-7). Memory T cells express relatively high levels of the IL-7 receptor, indicating their responsiveness to IL-7 signaling. In response to IL-7 signals, memory T cells upregulate the expression of proteins, including anti-apoptotic factors like BCL-2, which promote their survival and maintenance. This IL-7 signaling pathway plays a crucial role in supporting the long-term persistence of memory T cells. In summary, the long-term survival of memory cells is facilitated by a combination of increased expression of antiapoptotic proteins, slow proliferation rate, and lower metabolic activity. These features ensure the longevity and functionality of memory cells, allowing them to provide durable protection against recurrent infections. Additionally, signaling through cytokines like IL-7, particularly in memory T cells, further supports their survival and persistence in the absence of antigenic stimulation. 3 Properties of memory cells: response to reinfection Compared to naïve lymphocytes, memory lymphocytes: Exhibit a more rapid response to antigen* Ø Time to effector functions in mice: memory T cells = 1-3 days, naïve T cells = 5-7 days Are less dependent on costimulation * Ø Can respond to antigens presented by variety of APCs in peripheral tissues Are in greater number (typically ~100-fold) Consist of effector subsets (e.g., CD4+ or CD8+ T cells or even Th1, Tfh, etc.) Express high-affinity antigen receptors of appropriate isotype (memory B cells) *Cytokine and effector molecule genes often epigenetically modified to be accessible Certainly! Let's delve into the properties of memory cells regarding their response to reinfection as discussed in the text: 1.Rapid Response to Antigen: Memory lymphocytes, whether B or T cells, exhibit a significantly faster response to antigen re-encounter compared to naive lymphocytes. This rapid response is characterized by the time it takes from detecting the antigen to the generation of functional effector cells capable of defending against the infection. In mice, memory T cells can achieve effector functions within one to three days, whereas naive T cells typically require five to seven days to reach the same stage. 2.Reduced Dependence on Co-stimulation: Memory cells are less reliant on co-stimulation for activation compared to naive lymphocytes. Co-stimulation refers to additional signals, such as those provided by molecules like B7 and CD28, which are necessary for the activation of naive lymphocytes. Memory cells, having undergone prior activation, exhibit decreased dependence on these co-stimulatory signals. As a result, memory cells can respond to antigen presentation by various antigen-presenting cells (APCs) in peripheral tissues, enhancing their ability to rapidly mount an immune response. 3.Increased Numbers: Memory lymphocytes are typically present in greater numbers than naive lymphocytes 4 specific to the same antigen. While memory cells do not exist in millions of additional numbers, they are present at approximately 100 times the quantity of naive cells recognizing the same antigen. This increased abundance of memory cells increases the likelihood of a rapid and effective immune response upon re-exposure to the antigen. 4. Pre-existing Differentiation: Memory cells have already undergone certain differentiation processes, which primes them for a quicker response to reinfection. Memory T cells, for instance, may have already differentiated into specific effector subsets, such as TH1 cells or T follicular helper cells, streamlining their response to antigenic stimulation. Similarly, memory B cells have undergone processes like affinity maturation and isotype switching, resulting in the expression of high-affinity antigen receptors and specific antibody isotypes. These pre-existing differentiations enable memory cells to respond more swiftly and efficiently upon encountering the antigen again. 5.Epigenetic Modifications: Memory cells exhibit epigenetic modifications to genes involved in effector functions, allowing for rapid gene expression and effector molecule production upon reactivation. These modifications render the genes more accessible to transcription factors, facilitating a quicker response compared to naive cells, where genes may be tightly packaged and require time-consuming unpackaging processes for gene expression. In summary, memory lymphocytes possess several features that contribute to their rapid response to reinfection. These include reduced dependence on co-stimulation, increased abundance, pre-existing differentiation, and epigenetic modifications that facilitate rapid gene expression. These mechanisms collectively enable memory cells to mount a swift and effective immune response upon encountering the antigen, providing enhanced protection against recurrent infections. 4 4 Properties of memory cells: response to reinfection => Subsequent exposure to an antigen will produce a more robust response in comparison to the initial exposure => Basis of vaccination: best vaccines generate memory B cells and memory T cells Certainly! Let's further discuss the properties of memory cells regarding their response to reinfection, focusing on the robust and rapid secondary response: 1.Robust Secondary Response: Upon re-exposure to the same antigen (antigen X), memory cells mount a significantly more robust immune response compared to the initial exposure. This secondary response is characterized by a quicker and more potent reaction, resulting in a rapid increase in antibody titers (in the case of B cells) and a heightened cellular immune response (in the case of T cells). This heightened response is a hallmark of immunological memory and is crucial for effectively combating recurrent infections. 2.Mechanisms Driving the Robust Response: The robust secondary response is facilitated by several mechanisms. These include the presence of a larger pool of memory B and T cells specific to antigen X, which ensures a greater number of cells ready to respond immediately upon re-exposure. Additionally, memory cells have undergone preexisting differentiation processes and possess epigenetic modifications that enable rapid activation of effector functions, leading to a quicker and more efficient immune response. 3.Vaccine-Induced Memory Cells: The concept of vaccine-induced memory cells is essential in understanding the significance of memory cells in vaccination. Vaccines containing antigenic components of pathogens stimulate the 5 immune system to generate memory B and T cells specific to those antigens. This ensures that upon subsequent exposure to the pathogen, the immune system can mount a rapid and robust secondary response, effectively preventing or mitigating the infection. 4. Importance of Memory B and T Cells in Vaccination: Effective vaccines are designed to elicit strong memory B and T cell responses. Memory B cells are responsible for the rapid production of antibodies upon re-exposure to the pathogen, providing immediate protection against infection. Memory T cells, on the other hand, recognize and eliminate infected cells, further bolstering the immune response. A successful vaccination strategy aims to generate robust memory B and T cell responses to confer long-lasting immunity against the target pathogen. 5.Variability in Vaccine Effectiveness: Different vaccines may vary in their ability to induce memory B and T cell responses. Some vaccines may primarily stimulate antibody production (B cell response), while others may elicit strong cellular immune responses (T cell response). The effectiveness of a vaccine in generating memory cells may influence the need for booster doses and the duration of protective immunity. Vaccination strategies aim to optimize memory cell generation to ensure durable protection against infections. In summary, memory B and T cells play a crucial role in mounting a rapid and robust secondary immune response upon reexposure to a pathogen. Understanding the mechanisms underlying memory cell responses is essential for the development of effective vaccination strategies aimed at conferring long-lasting immunity against infectious diseases. 5 Properties of memory cells: locations in the body Memory cells can migrate to nearly any tissue => respond to antigen at infection site Migration facilitated by expression of certain CAMs and chemokine receptors Memory T cells tend to become residents in various peripheral tissues Memory B cells may: Remain in lymphoid organ of origin Circulate through blood and lymphoid organs Become residents in various regional immune systems Certainly! Let's break down the properties of memory cells regarding their locations in the body and why the brain would be expected to contain few or no memory cells: 1.Migration Capability: Memory lymphocytes, including both memory B and T cells, have the ability to migrate to various tissues throughout the body. Unlike some immune cells that remain confined to specific anatomical locations, memory cells can travel through the bloodstream and extravasate into tissues in response to chemotactic signals. 2.Local Response to Infection: Once in a tissue, memory cells can respond to antigenic challenges at the site of infection. This localization allows memory cells to provide rapid and targeted immune responses in peripheral tissues where infections occur. 3.Brain as an Immunologically Privileged Site: The brain is considered an immunologically privileged site due to the presence of the blood-brain barrier (BBB), which tightly regulates the passage of molecules and cells between the bloodstream and the brain tissue. The BBB restricts the entry of immune cells, including lymphocytes, into the brain parenchyma under normal physiological conditions. 4.Limited Presence of Immune Cells in the Brain: In healthy individuals, the brain parenchyma contains few 6 immune cells, including lymphocytes. The presence of lymphocytes in the brain is typically limited to specialized regions such as the meninges and perivascular spaces, where the BBB is less restrictive. Even in these regions, the number of lymphocytes is relatively low compared to other tissues in the body. 5. Absence of Memory Cells in the Brain: Given the limited access of immune cells to the brain and the sparse presence of lymphocytes in brain tissue, it would be expected that the brain contains few or no memory cells. Memory lymphocytes primarily reside in peripheral tissues where they can rapidly respond to antigenic challenges. The brain, being an immunologically privileged site, lacks the conditions necessary for the accumulation and maintenance of memory cells. In summary, memory lymphocytes have the capability to migrate to various tissues in the body and respond to antigenic challenges at the site of infection. However, the brain is considered an immunologically privileged site with limited access for immune cells, including memory cells. Therefore, it would be expected that the brain contains few or no memory cells under normal physiological conditions. 6 Possible development pathways for memory cells (T cell example) Linear pathway Branched pathway Develop from effector cell Develop from antigenstimulated cell Assumed to depend on signal-induced changes in gene expression but details yet to be established Certainly! Let's elaborate on the possible development pathways for memory cells, using the example of memory T cells: 1.Expression of Cell Adhesion Molecules (CAMs): Memory T cells express specific sets of proteins known as cell adhesion molecules (CAMs) that facilitate their migration to various tissues in the body. CAMs play a crucial role in allowing cells to adhere to other cells or extracellular matrix components, enabling them to traverse through tissues. For instance, CAMs such as integrins and ICAMs aid leukocytes in attaching to endothelial cells and squeezing through blood vessel walls to enter tissues. 2.Expression of Chemokine Receptors: Memory T cells also express chemokine receptors, which are cell surface receptors that bind to chemokines, signaling proteins produced at sites of infection or inflammation. Chemokines act as chemoattractants, guiding memory T cells towards locations where antigenic challenges are occurring. Memory T cells express specific chemokine receptors that allow them to respond to chemotactic signals and migrate towards infected tissues. 3.Residency in Peripheral Tissues: Memory T cells tend to become resident in peripheral tissues after their 7 activation. Once they migrate to a particular location in the body, such as the respiratory tract in the case of a respiratory virus, they often remain in that region, poised to respond rapidly to reinfection. This residency allows memory T cells to provide localized immune protection against pathogens that may re-infect the same tissue. 4. Variability in Memory B Cell Locations: Unlike memory T cells, memory B cells exhibit more variability in their tissue residency patterns. Some memory B cells may remain in secondary lymphoid organs like lymph nodes and the spleen, where they continue to surveil for antigen. Others may circulate through the bloodstream, patrolling the body and potentially encountering antigens in various tissues. Additionally, some memory B cells may become resident in specific locations, such as the gut-associated lymphoid tissue (GALT), where they contribute to local immune responses, especially those involving mucosal immunity. 5.Dynamic Response to Reinfection: Despite their residency patterns, both memory T and B cells retain the ability to respond dynamically to reinfection. If a reinfection occurs, memory cells can mobilize from their resident locations and migrate towards the site of infection, guided by chemotactic signals. This ability ensures that memory cells can swiftly mount an immune response wherever it is needed in the body. In summary, memory T cells and B cells exhibit specific migration patterns and residency tendencies in different tissues of the body. While memory T cells often become resident in peripheral tissues, memory B cells display more variability in their locations, including residency in lymphoid organs, circulation in the bloodstream, and residence in specialized immune sites like the GALT. Despite their residency, memory cells retain the ability to respond dynamically to reinfection, allowing them to provide rapid and targeted immune protection against pathogens. 7 It seems like you're discussing the active area of research surrounding COVID-19, particularly in understanding the immune response generated by the virus and vaccines. The titles you mentioned indicate a focus on memory cells and their role in combating COVID-19. This research aims to uncover how memory cells are generated, their potency, and their longevity in providing immunity to SARS-CoV-2. While there's substantial ongoing research in this area, it's important to note that due to the relatively short time since the emergence of COVID-19, there's still much to learn about the duration and effectiveness of memory cell responses. Long-term studies will be crucial in determining the persistence and efficacy of memory cells against SARS-CoV-2 infection. As research progresses, we can expect to gain deeper insights into the mechanisms of immune memory and how they contribute to both natural infection and vaccination against COVID-19. These findings will likely inform future strategies for combating the virus and developing more effective vaccines. 8