31. Immunology 2 – Memory, T cells, & Autoimmunity
TLDRThe video discusses various mechanisms by which the immune system distinguishes self from foreign to prevent autoimmune diseases, including negative selection against self-recognizing immune cells. It explains MHC antigen presentation, which displays peptides on cell surfaces for recognition by T cells, and contrasts MHC class I and II. The interaction between B cells and helper T cells is outlined, enhancing B cell function. Lastly, checkpoint inhibitor immunotherapy for cancer is described, which blocks receptors that tumors exploit to evade the immune system, though autoimmunity can result.
Takeaways
- 😀 The video discusses how immune cells can detect pathogens inside infected cells via antigen presentation of peptides on the cell surface
- 🧬 There are two classes of Major Histocompatibility Complex (MHC) molecules that display intracellular vs extracellular peptides to CD8+ and CD4+ T cells respectively
- 💉 Effective vaccines need to activate both humoral and cell-mediated immunity via B cell - T cell interactions
- 😡 The immune system has to distinguish between self and foreign antigens to prevent autoimmune diseases
- 😠 Negative selection via apoptosis removes self-reactive immune cells during development
- 🤝 Innate immune signals serve as a 'coincidence detector' to indicate foreign antigens to the adaptive immune system
- 🤯 Inhibitory receptors like CTLA-4 and PD-1 prevent overactive immune responses, and blocking them fights cancer
- 🦠 Listeria bacteria spread between cells by propelling themselves through the cell membrane
- 🔬 T cell receptor diversity is generated via V(D)J recombination like antibodies
- ✂ Proteasomes chop proteins into peptides that are displayed on MHC I molecules
Q & A
What is listeria and why is it dangerous?
-Listeria is an intracellular bacteria that can cause a nasty intestinal disease. It uses the host cell to reproduce and spread to other cells, avoiding the extracellular space and evading the immune system.
How does antigen presentation allow immune cells to see inside infected cells?
-Antigen presentation is the process by which peptides from inside the cell are displayed on the cell surface by MHC molecules. This allows T cells to observe what is happening inside the cell and mount an immune response.
What is the difference between MHC class 1 and class 2 molecules?
-MHC class 1 is expressed on all nucleated cells and presents peptides from the cell cytoplasm to CD8 T cells. MHC class 2 is restricted to antigen presenting cells and presents extracellular peptides to CD4 T cells.
How does interaction between B and T cells enhance immune function?
-When a B cell presents antigen to a helper T cell, the T cell induces affinity maturation, isotype switching, and differentiation of the B cell into plasma and memory cells. This enhances antibody production and memory.
What causes autoimmune diseases and how are self vs foreign antigens distinguished?
-Random generation of receptors can lead to self-recognition. Negative selection against self-reactive cells occurs in generative lymphoid organs. Innate immune signals also help discriminate self vs foreign.
What is the purpose of CD4 and CD8 co-receptors on T cells?
-CD4 and CD8 bind to MHC molecules along with the T cell receptor, providing specificity in targeting MHC class 2 vs class 1 peptide complexes.
How does rearrangement of T cell receptor genes occur?
-Like immunoglobulins, somatic recombination of V, D and J gene segments in the genome occurs. This creates diversity of antigen recognition.
How do cytotoxic T cells eliminate infected cells?
-When a CD8 cytotoxic T cell recognizes foreign peptide on MHC class 1, it releases cytotoxic materials that perforate and kill the infected cell.
What causes some advanced cancers to avoid immune detection?
-Some cancer cells express ligands for inhibitory receptors like PD1 on T cells. This suppresses T cell activity. Blocking these inhibitors restores anti-tumor immunity.
Why are adjuvants important for vaccines?
-Adjuvants like alum activate innate immune signals. This provides a 'danger' signal to more strongly prime adaptive immune responses to the vaccine antigen.
Outlines
🧬 Overview of immunity and intracellular pathogens
The professor introduces the concept of immunity in the context of intracellular pathogens like listeria. She shows a video of listeria bacteria moving around inside a cell, explains how they spread from cell to cell, and emphasizes why the immune system needs a way to detect these intracellular pathogens.
🟢 The major histocompatibility complex (MHC) and antigen presentation
The professor explains the role of major histocompatibility complex (MHC) in antigen presentation to display peptides on the cell surface for immune cells. She contrasts MHC class I, expressed in all nucleated cells, and MHC class II, expressed only in certain antigen-presenting cells, detailing their differences in structure, peptide sources, and recognition by T cells.
📋 CD8 vs CD4 T cell responses
Building on MHC class I vs class II, the professor explains that CD8 T cells recognize MHC class I, get signals something is wrong inside the cell, and act as killer/cytotoxic T cells. In contrast, CD4 T cells recognize MHC class II on antigen-presenting cells and act as helper T cells to enhance B cell immune function.
🤝 T and B cell interactions
Focusing on CD4 helper T cells and B cells in lymph nodes, the professor explains how their interaction leads to affinity maturation and tighter antigen binding by B cell antibodies, isotype switching to different effector antibodies, and B cell differentiation into plasma and memory B cells.
🌡️ Discriminating self vs. foreign antigens
The professor introduces the immune system's challenge in discriminating self vs. foreign antigens. She contrasts negative selection, deleting self-reactive immune cells, vs. positive selection and activation of foreign-reactive immune cells. She also covers mechanisms to distinguish self vs. foreign.
🚦 Inhibitory receptors CTLA-4 and PD-1
The professor concludes by discussing CTLA-4 and PD-1 as inhibitory receptors that prevent autoimmunity by downregulating T cell responses. This led to Nobel Prize-winning cancer immunotherapies that block these pathways to allow T cells to recognize and kill tumors.
Mindmap
Keywords
💡immunity
💡antigen presentation
💡MHC molecules
💡T cell receptor
💡B and T cell interaction
💡autoimmunity
💡negative selection
💡adjuvant
💡inhibitory receptors
💡immunotherapy
Highlights
Bacteria can spread between cells without going into extracellular space, enabling rapid infection
Antigen presentation displays peptides on cell surface for immune cells to recognize intracellular threats
Class I MHC presents cytoplasmic peptides to CD8 T cells; class II MHC presents extracellular peptides to CD4 T cells
CD8 cytotoxic T cells kill infected cells presenting foreign antigens on class I MHC
CD4 helper T cells enhance B cell antibody production against extracellular pathogens presented on class II MHC
B and T cell interaction leads to affinity maturation, isotype switching, and differentiation into memory B cells
VDJ recombination of TCR and BCR genes generates receptor diversity through genomic rearrangement, not splicing
Negative selection eliminates self-reactive lymphocytes; positive selection activates foreign-reactive ones
Lymphoid organs protected from foreign antigens to allow apoptosis of self-reactive lymphocytes
Innate immune signals distinguish foreign from self antigens for adaptive immune activation
Adjuvants in vaccines activate innate immunity to boost antigen-specific adaptive response
Inhibitory receptors like CTLA-4 and PD-1 prevent autoimmunity by limiting duration of immune responses
Blocking inhibitory receptors on T cells enables them to kill cancer cells expressing ligand
Inhibitor blockade immunotherapy risks autoimmune side effects without brakes on immune response
Balancing inhibition and activation of lymphocytes is key for effective, self-tolerant immunity
Transcripts
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