The Necessity of the Immune System
Stanford・2 minutes read
The course on immunology led by David Lewis at Stanford University covers topics like the immune system's evolution, pathogens like Staphylococcus aureus and malaria's impact on global health, showcasing the complexity and importance of understanding the immune system's intricacies in relation to diseases like autoimmunity, vaccines, aging, and cancer. The immune system, with innate and adaptive responses, utilizes cells like T and B cells, dendritic cells, and regulatory T cells to recognize, target, and eliminate pathogens while maintaining a delicate balance to prevent overreactions and autoimmune diseases.
Insights
- The course on immunology led by David Lewis emphasizes the intricate workings of the immune system, from distinguishing friend from foe to the evolution of immune responses against pathogens.
- The adaptive immune system, with T and B cells generating specific receptors through VDJ recombination, plays a crucial role in tailoring immune responses to encountered pathogens, providing memory recall for durable immunity.
- Understanding the immune system's complexities, such as the role of innate and adaptive immunity, thymic selection of T cells, and the significance of antibodies in humoral immunity, is essential for addressing diseases, vaccines, aging, and cancer.
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Recent questions
What topics are covered in the course?
Various topics like immunology, aging, and cancer biology.
Who leads the presentation on immunology?
David Lewis, an expert in immunology and pediatrics.
What is the role of the innate immune system?
Provides immediate, stereotyped responses to pathogens.
How do T cells recognize pathogens?
By binding to pathogen-derived peptides presented by MHC molecules.
What is the significance of memory CD8 T cells?
Provide long-term immunity and improved responses upon reinfection.
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Summary
00:00
"Stanford Medical Course: Immune System Essentials"
- Phil Pisa, Dean of the School of Medicine at Stanford University, welcomes new attendees to the third quarter of the course, highlighting the exciting and interconnected nature of the upcoming presentations.
- The course will run for ten weeks, starting promptly at 6:30 pm and ending at 8:20 pm each Tuesday, with opportunities for questions and dialogue at the end of each session.
- The course originated from a Stanford undergrad's suggestion and has evolved into a comprehensive three-quarter event, celebrating the medical school's fiftieth anniversary.
- The syllabus for the quarter, curated by Cathy Gilliam, will be available online the next day, covering topics such as immunology, movement, obesity, aging, memory, cancer biology, and stem cells.
- David Lewis, an expert in immunology and pediatrics, will lead the presentation on immunology, discussing the evolution and importance of the immune system in protecting against pathogens.
- Lewis humorously introduces the defensive strategies of the immune system, likening it to military tactics in distinguishing friend from foe, mobilizing defenses, and demobilizing once the threat is eliminated.
- Examples of significant pathogens like Staphylococcus aureus, Mycobacterium tuberculosis, and Neisseria meningitidis are highlighted for their impact on immune system evolution and disease.
- The course emphasizes the balance between harmful pathogens and beneficial commensal bacteria in the body, underscoring the importance of the immune system in maintaining this equilibrium.
- Lewis delves into the complexities of the immune system, discussing innate and adaptive immunity, historical observations, and the integration of immune responses to protect against infections.
- The presentation aims to provide an overview of why the immune system is essential, how it functions, potential vulnerabilities, and strategies for addressing immune system dysfunctions.
17:55
"Immune System: Pathogens, Antimicrobial Therapy, and Response"
- The immune system distinguishes between harmless commensals and true pathogens in the gut.
- Fungi, with a nucleus in their cells, are harder to treat than bacteria due to overlapping antimicrobial therapy side effects.
- Pneumocystis, a pathogen affecting those with immune system issues, was a major cause of death in HIV patients.
- Malaria, caused by parasites, remains endemic in the tropics, with up to half a billion cases annually and 1 to 3 million deaths, mostly children in sub-Saharan Africa.
- Schistosomiasis, caused by large worms, is prevalent in Africa and Asia, requiring a unique immune strategy for elimination.
- Viruses, like software viruses, replicate inside cells causing acute infections like influenza, with pandemics potentially leading to substantial deaths.
- Herpes viruses, like cytomegalovirus, can cause lifelong infections and serious issues, particularly in pregnant women.
- The innate immune system, present in sponges to humans, provides immediate, stereotyped responses to pathogens, activated by trauma or damage.
- Innate immunity includes barriers like skin, antimicrobial peptides, phagocytes, cytokines, and toll-like receptors recognizing pathogen-specific products.
- Complement proteins tag pathogens for destruction by phagocytes, attracting white blood cells and creating holes in bacteria, distinguishing between self and pathogens.
37:00
Evolution of Immune System Responses to Pathogens
- The adaptive immune system evolves with repeated exposure, improving its response each time.
- The innate immune system has a finite number of receptors, such as toll-like receptors and inflammasomes.
- Innate immunity shows subtle differences with age, with newborns starting slower but stabilizing through childhood to old age.
- Survival during plagues like the one in Athens remains a mystery due to unknown pathogens and variable immune responses.
- Immune-enhancing agents like vitamin C and echinacea have subtle effects on innate immunity, with controlled trials showing no significant benefits.
- Adaptive immunity tailors responses to specific pathogens encountered, generating unique immune responses.
- The adaptive immune system generates millions of specific receptors through VDJ recombination in T and B cells.
- T cells develop in the thymus, while B cells mature in the bone marrow, both creating diverse receptors to recognize pathogens.
- T cells recognize pathogen-derived peptides presented by MHC molecules, activating immune responses.
- CD4 T cells regulate immune responses, while CD8 T cells specialize in killing viruses, both activated by specific receptors recognizing pathogen peptides.
55:33
Thymus purges self-reactive T cells for immunity.
- T cells lack intrinsic knowledge of the peptides they encounter, leading to potential autoimmune reactions if they bind to self-proteins.
- The thymus gland plays a crucial role in purging T cells reactive to self-proteins by expressing various body proteins for evaluation.
- Thymic epithelial cells form a meshwork that developing T cells interact with to identify self-reactive cells, eliminating about 25% of them.
- T cells with strong reactions to self-proteins are triggered to die in the thymus, ensuring only non-reactive cells leave to combat pathogens.
- T cells that pass thymic selection become antigenically naive, waiting in the periphery for foreign antigens to encounter.
- Dendritic cells act as sentinels, capturing foreign proteins, presenting them in lymph nodes for T cell recognition, initiating an immune response.
- Lymphocyte recirculation allows T cells to move between lymph nodes, constantly surveilling the body for foreign proteins.
- Adaptive immunity provides memory recall, enhancing immune responses upon re-exposure to pathogens, with durable immunity lasting for years.
- Immune system effectiveness declines with age due to reduced thymic function, impacting responses to new infections in the elderly.
- Autoimmune diseases may result from defects in negative selection processes or inappropriate triggers by infections, but their pathogenesis remains complex and not fully understood.
01:13:42
Immune Responses: Cells, Infections, and Immunity
- Bacteria form granulomas to contain infections, seen under a microscope with a t-helper one response, often linked to tuberculosis.
- T-helper two cells combat large worms by inducing gut contractions, mucus production, and eosinophils to attack parasites.
- CD4 T cells coordinate these responses, with TH17 cells producing interleukin 17 to recruit neutrophils against bacteria.
- The immune system must control responses to prevent overreactions, especially in the gut with numerous commensal bacteria.
- Regulatory T cells in pregnancy prevent rejection by inducing tolerance to maternal cells in the fetus.
- Cytokines from innate immune cells direct naive CD4 T cells to become specific T helper cells based on the infection type.
- Mismatched signals can lead to ineffective responses, as seen in leprosy where T helper two cells are induced instead of T helper one cells.
- CD8 T cells act as "double-oh-seven" killers, releasing proteins to induce apoptosis in virally infected cells with surgical precision.
- Memory CD8 T cells provide long-term immunity and improved responses upon reinfection, potentially targeting tumors as well.
- B cells secrete antibodies to tag pathogens for destruction, with a simpler mechanism than T cells but requiring diverse antibody production through VDJ recombination.
01:31:39
"Antibodies: Versatile Defenders in Immune System"
- Genes encoding immunoglobulin differ from T-cell receptors, allowing antibodies to be secreted into body fluids.
- Antibodies recognize 3D shapes, like a lock-and-key system, rather than peptide MHC complexes.
- Antibodies can bind to any three-dimensional molecule, not limited to proteins, enhancing versatility.
- B cells produce antibodies through activation triggered by antigens, leading to the creation of plasma cells.
- Antibodies, part of humoral immunity, tag bacteria and fungi for destruction, aiding in pathogen elimination.
- Streptococcus pneumoniae, with an outer capsule evading the immune system, necessitates antibody binding for tagging.
- Specific antibodies are crucial for infections like measles, showcasing the exquisite specificity of antibodies.
- Monoclonal antibodies, specific to one type, are used in therapies like treating B-cell lymphomas effectively.
- Mimicking infections through vaccines can enhance immune responses, activating the immune system for defense.
- Immunodeficiencies, like genetic defects affecting neutrophils or T cells, illustrate the critical role of the immune system.
01:50:29
Gut CD4 T cell decline impacts immunity
- CD4 T cells in the gut start declining within two weeks of infection, leading to a decrease in total body numbers, with the virus also affecting other immune cells like dendritic cells, essentially removing the master regulators of the immune system.
- The gut is considered a major site of viral dissemination and immune destruction, with the GI tract being one of the largest parts of the immune system, highlighting the complexity and importance of understanding the immune system's intricacies in relation to diseases like autoimmunity, vaccines, aging, and cancer.
