Lecture 11 Midterm Review: Making Connections PDF

Lecture 11 Midterm Review: Making Connections 10/10/2024 Recap of Innate (and Adaptive) Immune System Physical Chemical Microbiological Innate Immune Adaptive barriers barriers barrier Cells Immunity Epithelial linings Acidic p...

Lecture 11 Midterm Review: Making Connections 10/10/2024 Recap of Innate (and Adaptive) Immune System Physical Chemical Microbiological Innate Immune Adaptive barriers barriers barrier Cells Immunity Epithelial linings Acidic pH Microbiota Macrophages B cells/Antibodies Mucosal linings Enzymes Neutrophils T cells Mucus AMPs NK cells Tears Complement Pathogen Pattern Recognition and Innate Immune Cell Function Image credit: Immunology by S. Juris. Oxford Press Pathogen Pattern Recognition and Innate Immune Cell Function Image credit: Immunology by S. Juris. Oxford Press  Innate immune cell functions targeting intracellular and extracellular pathogens Image credit: Immunology by S. Juris. Oxford Press Extracellular pathogens are commonly recognized by PRRs of innate immune cells present at the surface A B Image credit: Immunology by S. Juris. Oxford Press Extracellular pathogens are commonly recognized by PRRs of innate immune cells present at the surface A B Image credit: Immunology by S. Juris. Oxford Press Intracellular pathogens are commonly recognized by PRRs of innate immune cells present within the cytosol A B C Image credit: Immunology by S. Juris. Oxford Press Intracellular pathogens are commonly recognized by PRRs of innate immune cells present within the cytosol A B C Image credit: Immunology by S. Juris. Oxford Press  The Alternative Pathway of Complement Activation and Innate Immune Cell Action Image credit: Immunology by S. Juris. Oxford Press The Acute-Phase Response and Complement Activation Image credit: Immunology by S. Juris. Oxford Press Comparing and Contrasting the Structure and Function of Innate and Adaptive Immune System Receptors Image credit: Immunology by S. Juris. Oxford Press Lymphocyte Development in Primary Lymphoid Tissue Requires Recombination of Receptor Genes Image credit: Immunology by S. Juris. Oxford Press V regions are constructed from gene segments VJ VDJ V = variable D = diversity J = joining Fig. 5.3 Rearrangement of V, D, and J gene segments is guided by flanking DNA sequences Fig. 5.6 Enzymatic steps in V(D)J Recombination STEP 1: Synapsis – the process by which two distant selected coding segments and their adjacent RSSs are brought together by a chromosomal looping event and held in position for subsequent cleavage, processing, and joining. STEP 2: Cleavage – A lymphocyte-specific enzyme called the V(D)J recombinase creates double-stranded breaks at RSS-coding sequence junctions. The V(D)J recombinase is composed of two molecules each of two different proteins called RAG1 and RAG2 (recombination-activating gene). RAG genes are expressed only in developing B and T cells. RAG protein is inactivated in proliferating cells Fig. 5.8 Enzymatic steps in V(D)J Recombination STEP 3: Hairpin Opening and End Processing – After the formation of double-strand breaks, hairpins must be opened at coding junctions, and nucleotides may be added to or removed from coding ends to create even greater diversification. Artemis is an endonuclease that opens up the hairpins. A lymphoid-specific enzyme, called terminal deoxynucleotidyl transferase (TdT), adds nucleotides to broken DNA ends. STEP 4: Joining—The broken cording ends and signal ends are brought together and ligated by a double-strand break repair process found in all cells called nonhomologous end joining (NHEJ). Several ubiquitous proteins participate in NHEJ. KU70 and KU80 bind to the breaks and recruit the catalytic subunit of DNA-dependent protein kinase (DNA- PK), a DNA repair enzyme. DNA-PK also phosphorylates and activates Artemis. Ligation of the processed broken ends is mediated by DNA ligase IV and XRCC4. Fig. 5.8 Diversity of antigen receptor genes V D J segments segments segments Image Credit: Cellular and Molecular Immunology. 10 th Ed. Abbas, Lichtman, Pillai Can we solve this now? Secondary Lymphoid Tissue and the Adaptive Immune Response Image credit: Immunology by S. Juris. Oxford Press Action of Dendritic Cells in Draining Lymph Nodes Image credit: Immunology by S. Juris. Oxford Press Antigen processing and presentation HLA-DM Cathepsin S Image credit: Biorender.com  TCR binds to peptide and MHC Three properties are affected by MHC polymorphism: 1. The range of peptide bound, 2. the conformation of the bound peptide and 3. The direct interaction of the MHC molecule with with the TCR Image credit: Biorender.com T-Cell Activation and Signal Transduction Image credit: Immunology by S. Juris. Oxford Press  TCR signaling network Image credit: Biorender.com T cell co-stimulation Image credit: Biorender.com BCR signaling network Image credit: Biorender.com MHC diversity Codominance Image credit: Biorender.com Good luck with your exam! October 17th (Thursday), 10:10 – 11:15 AM, WMEM In-person, on your laptops (or paper!) Total # of questions = 45 Time allotted = 45 minutes MCQs, Fill-in-the-Blanks, T/F, Matching # of questions from each lecture = 5 except Lecture 1 = 2 questions Lecture 9 = 3 questions