Lecture 3 VM 606 Innate Immunity.pdf

Innate Immunity VM 606 2023 Gregg A. Dean, DVM, PhD, DACVP  Objectives Describe Describe the function of primary and secondary lymphoid organs Understand Understand the basic concepts of cell signaling List the cellular and subcellular location and ligan...

Innate Immunity VM 606 2023 Gregg A. Dean, DVM, PhD, DACVP  Objectives Describe Describe the function of primary and secondary lymphoid organs Understand Understand the basic concepts of cell signaling List the cellular and subcellular location and ligands for key List pattern recognition receptors and their microbial/danger ligands Describe Describe the steps involved in innate recognition of pathogens Immune Organs  Function of immune organs Central (primary) lymphoid Peripheral (secondary) organs lymphoid organs Production of vertebrate Maintain naive immune cells lymphocytes Bone marrow Initiate adaptive immune Thymus response Lymph nodes Spleen Mucosal lymphoid tissues Bone marrow: origin of vertebrate immune cells  Hematopoietic stem cells (HSCs) Self-renew Proliferate Differentiate into HPCs Hematopoietic Hematopoietic progenitor cells (HPCs) Cells CD34 surface marker Do not self-renew Proliferate Differentiate into varied colony forming units Thymus: origin of T lymphocytes Lymph node structure Spleen Mucosa-Associated Lymphoid Tissue Innate vs. Adaptive Immunity Properties Innate Immunity Adaptive Immunity Specificity Non-specific Antigen specific Action time Immediate Delayed, 2-6 days after innate response Persistence Short-lived Long-lived Memory No Yes Antigens Conserved microbe-associated Diverse proteins, peptides, molecular patterns (MAMPs) carbohydrates Receptors Germ-line encoded Gene segments rearrange to create diversity  INNATE IMMUNITY PATTERN RECOGNITION RECEPTORS CELLULAR SOLUBLE Complement, Kinins Mast cells Vasoactive Amines Neutrophils Eicosanoids, Defensins Eosinophils Reactive Oxygen Species Basophils Lysosomal Enzymes Macrophages Cytokines, Chemokines Innate Lymphoid Cells Acute-phase Proteins RESPONSE Immediate Non-specific No memory PAMPs, DAMPs, & PRR Pathogen associated molecular patterns Danger-associated molecular patterns Pattern recognition receptors J Am Soc Nephrol. 2011 Mar; 22(3): 416–425. Cellular Locations for Pattern Recognition Receptors Discovery of Toll-like receptor 4 (TLR4) TLR Ligands and Location Pattern Recognition Receptors (PRR) TLR Signal Transduction Innate Recognition of Pathogens Watch  INNATE IMMUNITY PATTERN RECOGNITION RECEPTORS CELLULAR SOLUBLE Complement, Kinins Mast cells Vasoactive Amines Neutrophils Eicosanoids, Defensins Eosinophils Reactive Oxygen Species Basophils Lysosomal Enzymes Macrophages Cytokines, Chemokines Innate Lymphoid Cells Acute-phase Proteins RESPONSE Immediate Non-specific No memory THE CASE OF ANGEL: A YOUNG DOG WITH CHRONIC COUGHING AND REGURGITATION SIGNALMENT/CASE HISTORY 7-month-old spayed female Old English Sheepdog Purchased at 3 months of age by her owner, began coughing shortly afterwards, and has continued to do so ever since She sometimes expels froth during her fits of coughing, and she also vomits and regurgitates during coughing episodes and after meals. She has previously been seen by a veterinarian for dehydration and has been on and off antibiotic treatment for several months. She is currently on Clavamox 62.5 mg twice a day and Pepcid, and has received all her core vaccines, but is not on a heartworm preventative at present. During a recent episode of acute respiratory distress that occurred when the owner ran out of antibiotic, the referring veterinarian identified areas of consolidation in Angel’s left cranial lung lobe. PHYSICAL EXAMINATION Bright and alert Temperature 102.6°F (high normal) and respiratory rate was high at 85 breaths/minute She did not have any heart murmurs, and her mucous membranes were pink, with a capillary refill time of less than 2 seconds (normal). On auscultation her lung fields were clear, but a cough was elicited by tracheal palpation. Presumably the current antibiotic therapy had resolved the consolidation in her left lung lobe. Laurel J. Gershwin. Case Studies in Veterinary Immunology (p. 1). Garland Science.  Homework #1 LIST DIFFERENTIAL DISCUSS, WORK USE YOUR CLINICAL DIAGNOSES FOR ANGEL TOGETHER THINKING, NOT THE INTERNET!