1. Cells and Organs1 Components of the Immune System Learn on your own: Spleen structure and function Mast cells and NK cells Self-Test Questions: A1: allC1: all A2: 1 - 4 C2: none A3: 1 - 3, 5 C3: all A4: 1, 2, 4 D1: both A5: all D2: 2 & 3 A6: bothD3: none B1: none B2: 1, 2, 4, 5

2. Cells and Organs2 “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

3. Cells and Organs3 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

4. Cells and Organs4 How can different cells be identified and separated? Flow cytometry and “fluorescence activated cell sorting” (FACS) can be used to count, sort and separate cell types See appendix 5 Cells possess different CD antigens With Immunofluorescence CD antigens can be stained with antibodies tagged with fluorescent molecules

5. Cells and Organs5 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 T H cells are MHC-II restricted activated secrete cytokines (TH 1 vs TH 2 )

6. Cells and Organs6 Myeloid cells A. Granulocytes -- degranulation Neutrophils -- multilobed -- rapid response Eosinophils -- bilobed -- eukaryotic parasites Basophils -- densely granular -- eukaryotic parasites -- type I hypersensitivities Neutrophil chase

7. Cells and Organs7 Granulocyte abnormalities can underlie disorders Eosinophilia -- too many eosinophils Causes Allergies Parasitic infections Neutropenia -- too few neutrophils Causes Leukemia Congenital Drug-induced

8. Cells and Organs8 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

9. Cells and Organs9 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

10. Cells and Organs10 What are the organs of the immune system? Primary lymphoid organs (naïve immune cell development) Bone marrow Thymus Secondary lymphoid organs (immune cell activation) The “Nude Mouse”

11. Cells and Organs11 Structure and function of 2 O lymphoid tissues “Follicle” -- basic organizational unit -- may be within specialized organ 2 O 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

12. Cells and Organs12 Leukocyte RollingLeukocyte Homing Immune Surveillance Circulation of cells and Interstitial fluid -- antigens / pathogens -- immune cells Cell extravasation -- Chemokines -- post-venous capillaries -- receptors -- adhesion proteins

13. Cells and Organs13 Structure and function of lymph nodes Lymphatic vessels afferent efferent Cortex Follicles & Germinal centers 1 O vs 2 O B-cell activation Paracortex AG-presentation & T-Cell activation Medulla Plasma cell accumulation

14. Cells and Organs14 Mucosal-Associated Lymphoid Tissue (MALT) Widely distributed -- More about MALT in Chapter 12 e.g., Peyer’s patches (GALT) -- Protects Intestinal track -- M-cells

15. Cells and Organs15 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 Image by Daniel Douek from Science (2005) 307: 1395 GALT