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PCB4233: Immunology Dr. Mauricio Rodriguez-Lanetty Email: [email protected] Phone: 305-3484922 Lecture 2 Skin Blood vessel Special forces of high specialization Troop (library) of soldiers (T/B cells) Recognition & Activation Skin Blood vessel Special forces of high specialization Immunological memory Troop (library) of soldiers (T/B cells) Skin Blood vessel Special forces of high specialization Immunological memory Troop (library) of soldiers (T/B cells) How these special cells (T/B) does not attack self cells in the body? Skin Blood vessel Special forces of high specialization Immunological memory Troop (library) of soldiers (T/B cells) Factory of T/B Cells Skin Blood vessel Special forces of high specialization Immunological memory Education Center for T-cells (Army Academy) Troop (library) of soldiers (T/B cells) Factory of T/B Cells Education Center for B-cells (Army academy) Skin Blood vessel Special forces of high specialization Immunological memory Education Center for T-cells (Army Academy) Troop (library) of soldiers (T/B cells) Don’t target/kill cells from your own body Education Center for B-cells (Army academy) Skin Blood vessel Special forces of high specialization Immunological memory Education Center for T-cells (Army Academy) Troop (library) of soldiers (T/B cells) Factory of T/B Cells Education Center for B-cells (Army academy) Skin Innate Immune System Blood vessel Adaptive Immune System Special forces of high specialization Immunological memory Education Center for T-cells (Army Academy) Troop (library) of soldiers (T/B cells) Factory of T/B Cells Education Center for B-cells (Army academy) Skin Innate Immune System Blood vessel Adaptive Immune System Special forces of high specialization Immunological memory Education Center for T-cells (Army Academy) Secondary lymphoid organs Troop (library) of soldiers (T/B cells) Factory of T/B Cells Education Center for B-cells (Army academy) Primary / Central lymphoid organs Skin Innate Immune System Blood vessel Adaptive Immune System Special forces of high specialization Immunological memory Education Center for T-cells (Army Academy) Troop (library) of soldiers (T/B cells) Factory of T/B Cells Education Center for B-cells (Army academy) Receptors with specificity for pathogens molecules Pattern Recognition Receptors (PRRs) This receptors recognize repeating patterns of molecular structure carried by microorganisms/pathogens on their surfaces The pathogen-associated molecular patterns that PRR recognize are called PAMPs (MAMPs) The pathogen-associated molecular patterns that PRR recognize are called PAMPs The Innate immune recognition by Toll-like receptors (TLR) •Toll-like receptors belong to an evolutionarily ancient recognition and signaling system •Discovered from embryonic development studies in fruitfly •Found to have a role in the defense against bacterial and fungal infections •In Drosophila is Toll, and the homologous protein in mammals and other animals are therefore known as Toll-like receptors There are 10 expressed TLR genes in mice and humans Infection stimulates macrophages to release cytokines and chemokines that initiate an inflammatory response Chemokines function mainly as chemoattractants for leukocytes, recruiting monocytes, neutrophils, and other effector cells from the blood to sites of infection Infection stimulates macrophages to release cytokines and chemokines that initiate an inflammatory response The recruitment of activated phagocytes to sites of infection is one of the most important functions of innate immunity Important cytokines secreted by macrophages in response to bacterial products Important cytokines secreted by macrophages in response to bacterial products Chemokines can be produced by a wide variety of cell types in response to bacterial products, viruses, and agents that cause physical damage. Thus, infection or physical damage to tissues sets in motion the production of chemokine gradients that can direct phagocytes to the sites where they are needed. Neutrophils • Normal adult releases1-3 x 1010 neutrophils per day from Bone Marrow • Primary function is phagocytosis and killing of pathogens • To do so neutrophils must gain access to tissues from the bloodstream – extravasation Neutrophils are the first cells to bind to inflamed tissue, and therefore to arrive in large numbers at a site of infection, with monocytes and immature dentritic cells being recruited later. Neutrophils moving through the circulation system: ROLLING Neutrophils leave the blood and migrate to sites of infection in a multi-step process Steps in neutrophil extravasation • Rolling. Recognition of inflamed tissue • Activation by chemoattractants • Arrest and adhesion • Transendothelial migration Same principles as for T cell migration in lymph nodes • Chemotaxis towards source of infection Macrophages and neutrophils are not only brought to potential sites of infection by chemokines but in the process they are also armed to deal with any pathogen they may encounter there. In particular neutrophils exposed to CXCL8 and cytokyne TNF-α are activated to produce the respiratory burst that generates oxygen radicals, nitric oxide, and to release their stored lysosomal contents. Some differences between INNATE and ADAPTIVE immunity That is all for today Thanks for coming! Reading Material Chapter 1 and 2