30. Immunology 1 – Diversity, Specificity, & B cells

MIT OpenCourseWare

12 May 202051:36

EducationalLearning

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TLDRThe script discusses the immune system and how it fights disease. It explains the two levels of immunity - innate, which is immediate and non-specific, and adaptive, which is delayed and specific. Adaptive immunity has humoral and cell-mediated branches. It achieves specificity through complementarity-determining regions on antibodies and T cell receptors. Diversity is generated by recombination of gene segments during B and T cell development. The script also covers immune memory, which allows faster, stronger responses to pathogens previously encountered, a key principle behind vaccination.

Takeaways

😊 Immunity helps the body resist disease and is the principle behind vaccination
🧬 Innate immunity is immediate and non-specific, while adaptive immunity is delayed and specific
💉 Vaccines leverage immune memory to prepare the body to fight future infections
🔬 Antibodies bind antigens with high specificity due to hypervariable complementarity-determining regions
🧬 V(D)J recombination of immunoglobulin gene segments generates antibody diversity
📈 Somatic hypermutation further increases antibody diversity and binding affinity
🧬 Each B cell expresses a single unique antibody encoded in its genome
🧠 Long-lived memory B cells allow stronger, faster secondary immune responses
📉 Tighter binding antibodies are generated upon secondary exposure to an antigen
💊 Engineered antibodies like Herceptin can treat diseases like HER2+ breast cancer

Q & A

What is the principle behind vaccination?
-The principle behind vaccination is that vaccines work by putting in attenuated or inactivated foreign agents into the body, such that the body is able to remember them later on when exposed to the real infectious agent, and is able to fight it off more effectively.
What are the two levels of immunity?
-The two levels of immunity discussed are innate immunity, which is inborn and provides an immediate immune response, and adaptive immunity, which adapts based on exposure to foreign agents and provides a delayed but more specific immune response.
What are antibodies also known as?
-Antibodies are also known as immunoglobulins or IGs, and are proteins involved in the humoral immune response mediated by B cells.
How does the immune system achieve high specificity?
-The immune system achieves high specificity through complementarity-determining regions (CDRs) on antibodies, which are areas of high sequence variability that allow antibodies to recognize and bind to specific foreign substances.
How is diversity generated in the immune system?
-Diversity is generated through V(D)J recombination, which shuffles different gene segments to produce a large variety of antibodies, as well as junctional imprecision during recombination and somatic mutations.
What is the difference between a primary and secondary immune response?
-The primary response is slower with a longer lag time, lower antibody production, and weaker antibody affinity, while the secondary response is faster, has greater antibody production, and stronger antibody affinity due to immunological memory.
What are some effector functions of antibodies?
-Some effector functions of antibodies include: neutralization of foreign substances, inducing phagocytosis, recruiting cells to kill infected cells, and treating diseases like HER2+ breast cancer.
What causes immunological memory?
-Immunological memory results from irreversible V(D)J recombination leading to the persistence of memory B cells that retain antibodies specific to previously encountered antigens.
What is somatic mutation?
-Somatic mutation refers to an elevated mutation rate at the immunoglobulin locus during the activation of the T cell response, which further increases the diversity of antibodies.
What is allelic exclusion?
-Allelic exclusion ensures that each B cell only expresses a single antibody variant by suppressing recombination of the second allele if a functional antibody is produced from the first allele.

Outlines

00:00

🧬 Overview of immunity and vaccination history

Introduces key concepts related to immunity - resistance to disease from prior exposure. Traces first example of vaccination back to 18th century English physician Edward Jenner, who realized farmhands exposed to cowpox became immune to smallpox. This led to development of first vaccine.

05:02

🚨 Innate vs adaptive immunity

Contrasts immediate, non-specific innate immunity which provides constant surveillance, with delayed, specific adaptive immunity which adapts based on exposure. Breaks down adaptive immunity into antibody-mediated humoral immunity and cell-mediated immunity.

10:03

🔬 Antibody and T cell receptor structure

Explains structural details of antibodies/B cell receptors vs T cell receptors. Antibodies are Y-shaped proteins composed of 2 heavy & 2 light chains with hypervariable complementarity-determining regions that bind antigens. T cell receptors are simpler α/β heterodimers that bind peptide antigens presented on MHC.

15:07

🎯 Antibody specificity and diversity generation

Emphasizes crucial specificity of adaptive immune system to recognize foreign but not self antigens. Diversity of antibodies generated by V(D)J recombination of immunoglobulin gene segments during B cell maturation, combined with imprecision in recombination junctions and somatic hypermutation.

20:09

🧠 Immunological memory

Memory B cells retain antibodies against previously encountered pathogens, allowing faster, stronger secondary immune response on re-exposure. Memory key for effective vaccines to prime immune system against infectious agents.

Mindmap

Keywords

💡immunity

Immunity refers to the body's resistance to disease, often through prior exposure. This is a central theme of the video, which discusses how the immune system builds resistance and 'memory' to infectious agents. The concept of immunity underlies vaccination, as exposing someone to a weakened pathogen allows their immune system to develop protection.

💡innate immunity

Innate immunity is the first line of defense against pathogens. It is present at birth and does not change based on prior exposures. Innate immunity involves immediate, non-specific responses like inflammation and phagocytosis. The video contrasts innate and adaptive immunity.

💡adaptive immunity

Adaptive immunity develops throughout life and adapts to pathogens encountered. It involves B and T lymphocytes and immunological 'memory'. A key difference from innate immunity is that adaptive responses become stronger and more tailored on secondary exposures.

💡antibodies

Antibodies, also called immunoglobulins, are Y-shaped proteins produced by B cells. They bind to specific antigens, marking pathogens for destruction. The video discusses the structure of antibodies and how junctional diversity in their genes allows the immune system to target myriad antigens.

💡B cells

B cells produce and display antibodies on their surface. Each B cell makes antibodies against a single antigen. When a B cell binds its cognate antigen and receives signals from a T helper cell, it proliferates and secretes antibodies tailored to that antigen.

💡T cells

T cells, contrasted with B cells, have simpler antigen receptors that only bind peptide fragments presented on MHC molecules. When activated, T cells release cytokines that amplify immune responses. Certain T cells also directly kill infected cells.

💡antigens

Antigens are substances like toxins or surface proteins that provoke an immune response. The video discusses how antibodies and T cell receptors bind antigens with extreme specificity, allowing precise immune reactions.

💡V(D)J recombination

V(D)J recombination shuffles gene segments to produce diverse B cell receptors. Recombination activating genes mediate the rearrangement of variable (V), diversity (D) and joining (J) gene segments, increasing antigen receptor variation exponentially.

💡immunological memory

Immunological memory allows stronger, faster secondary immune responses through memory B cells that persist after initial infection. Memory depends on the diversity of lymphocyte antigen receptors and underlies effective vaccination.

💡monoclonal antibodies

Monoclonal antibodies are identical antibodies produced by a single B cell lineage. The video mentions their use as research reagents and therapies like Herceptin against the HER2 antigen in breast cancer.

Highlights

Immunity is the resistance to disease, based on prior exposure

Innate immunity is inborn and has an immediate response to infections

Adaptive immunity changes with exposure, takes time to respond, and is highly specific

Humoral immunity involves antibodies secreted into body fluids

Cell-mediated immunity involves T cells that mature in the thymus

Antibodies can recognize many types of molecules, T cell receptors only recognize peptides

Each B cell expresses one unique antibody with unique antigen specificity

Antibody diversity is generated by V(D)J recombination of gene segments

Junctional imprecision during recombination further increases diversity

Somatic mutations also contribute to antibody diversity

V(D)J recombination allows one heavy and one light chain gene to be expressed per B cell

Immune system memory allows faster, stronger responses to subsequent infections

Memory results from irreversible V(D)J recombination and memory B cells

Antibodies can neutralize or induce phagocytosis of pathogens

Engineered antibodies are used as targeted cancer therapies

Transcripts

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