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Components of the Immune System Learn on your own: Spleen structure and function Mast cells and NK cells Self-Test Questions: A1: all A2: 1 - 4 A3: 1 - 3, 5 A4: 1, 2, 4 A5: all A6: both B1: none B2: 1, 2, 4, 5 C1: all C2: none C3: all D1: both D2: 2 & 3 D3: none Cells and Organs 1 “Hematopoiesis” = Formation of blood cells Stem cells self-renewing multipotent (less differentiated) progenitor cells (more differentiated vs blast cells vs mature (naïve) cells vs effector cells Site of hematopoiesis changes during development Cells and Organs 2 Why is apoptosis (programmed cell death) also Important? -- a normal and essential process Apoptosis vs Necrosis (cell lysis) Occurs during B- & T-cell development Also an important killing mechanism Prevents triggering of inflammation Apoptosis Cells and Organs 3 How can different cells be identified and separated? Cells possess different CD antigens With Immunofluorescence CD antigens can be stained with antibodies tagged with fluorescent molecules Flow cytometry and “fluorescence activated cell sorting” (FACS) can be used to count, sort and separate cell types See appendix 5 Cells and Organs 4 What are the 2 major categories of immune cells? 1- Lymphoid cells -- B- & T- cells -- NK cells 2- Myeloid cells -- Granulocytes -- Monocytes, macrophages, DC Lymphoid cells B-cells -- naïve carry B-cell receptor (membrane Ab) activated plasma cells secrete Ab T-cells -- Carry T-cell receptor (TCR) Tc cells are MHC-I restricted activated become CTLs TH cells are MHC-II restricted activated secrete cytokines (TH1 vs TH2) Cells and Organs 5 Myeloid cells A. Granulocytes -- degranulation Neutrophils -- multilobed -- rapid response Eosinophils -- bilobed -- eukaryotic parasites Basophils -- densely granular -- eukaryotic parasites -- type I hypersensitivities Neutrophil chase Cells and Organs 6 Granulocyte abnormalities can underlie disorders Eosinophilia -- too many eosinophils Causes Allergies Parasitic infections Neutropenia -- too few neutrophils Causes Leukemia Congenital Drug-induced Cells and Organs 7 B. Other myeloid cells Macrophages Develop from monocytes (in blood) -- within tissues Go by various names; e.g.: -- Kumpfer cells, Langerhans cells, microglial cells, etc -- tissue type specific How do macrophages kill pathogens? -- external & internal mechanisms -- enzymes and reactive molecules Act as “Professional-APCs” -- only to memory T-cells Cells and Organs 8 Dendritic Cells Functions: antigen… Capture Processing Presentation Antigen + T-cell interaction… “licensed DC” Only licensed DC can activate naïve T-cells Take on specialized functions -- determined by cytokines -- generate different types of T-cells Cells and Organs 9 What are the organs of the immune system? Primary lymphoid organs (naïve immune cell development) Bone marrow Thymus The “Nude Mouse” Secondary lymphoid organs (immune cell activation) Cells and Organs 10 Structure and function of 2O lymphoid tissues “Follicle” -- basic organizational unit -- may be within specialized organ 2O tissues carry out surveillance of systems -- respiratory : tonsils & MALT -- digestive : GALT -- circulatory : spleen -- lymphatic : lymph nodes -- skin : SALT What happens in these tissues AG presentation cell : cell interactions cell activation Cells and Organs 11 Immune Surveillance Circulation of cells and Interstitial fluid -- antigens / pathogens -- immune cells Cell extravasation -- Chemokines -- post-venous capillaries -- receptors -- adhesion proteins Leukocyte Rolling Cells and Organs Leukocyte Homing 12 Structure and function of lymph nodes Lymphatic vessels afferent efferent Cortex Follicles & Germinal centers 1O vs 2O B-cell activation Paracortex AG-presentation & T-Cell activation Medulla Plasma cell accumulation Cells and Organs 13 Mucosal-Associated Lymphoid Tissue (MALT) Widely distributed -- More about MALT in Chapter 12 e.g., Peyer’s patches (GALT) -- Protects Intestinal track -- M-cells Cells and Organs 14 Recent findings show effect of HIV on GALT Destruction of T-cells in gut Leads to destruction of GALT Ileum of: Uninfectected person HIV infected person GALT Image by Daniel Douek from Science (2005) 307: 1395 Cells and Organs 15