1. ORGANS OF THE IMMUNE SYSTEM LYMPHOID ORGANS ORGANIZATION AND STRUCTURE OF THE IMMUNE SYSTEM GENERATION AND MIGRATION OF CELLS OF THE IMMUNE SYSTEM LYMPHOCYTE HOEMOSTASIS, RECIRCULATION THE ROLE OF LYMPHATICS IN THE TRANSPORTATION OF ANTIGENS INITIATION OF IMMUNE RESPONSE IN PERIPHERAL LYMPHOID ORGANS

2. ORGANIZATION OF THE IMMUNE SYSTEM CENTRAL (PRIMARY) LYMPHOID ORGANS –Bone marrow –Thymus DEVELOPMENT TO THE STAGE OF ANTIGEN RECOGNITION PERIPHERAL (SECONDARY) LYMPHOID ORGANS –Spleen –Lymph nodes –Skin-associated lymphoid tissue (SALT) –Mucosa-associated lymphoid tissue (MALT) –Gut-associated lymphoid tissue (GALT) –Bronchial tract-associated lymphoid tissue (BALT) ACTIVATION AND DIFFERENTIATION TO EFFECTOR CELLS BLOOD AND LYMPH CIRCULATION –Lymphatics – collect leaking plasma (interstitial fluid) in connective tissues –Lymph – cells and fluid –No pump– one way valves ensure direction – edema –Several liters (3 – 5) of lymph gets back to the blood daily – vena cava superior LYMPHOCYTES CONGREGATE IN SPECIALIZED TISSUES

3. GENERATION OF BLOOD CELLS BEFORE BIRTHAFTER BIRTH Spleen Liver Yolk sac Cell number (%) BIRTH months years Flat bones Tubular bones BONE MARROW TRANSPLANTATION

4. Pathogens Allergens Antigens Stem cells B-lymphocytes Antibodies T-lymphocytes Cellular immune response Helper Th Cytotoxic Tc Blood circulation Lymph circulation Bone marrow Thymus Nyirokerek CENTRAL PRIMARY LYMPHOID ORGANS Lymphatic vessels Spleen Lymph nodes PERIPHERAL SECONDARY LYMPHOID ORGANS ORGANIZATION OF THE IMMUNE SYSTEM WALDEYER RING Tonsils, adenoids Palatinal, pharyngeal lingual and tubar tonsils

5. THE BONE MARROW T cell precursors migrating to the thymus 2x10 7 HSC cell: assymetric division 7-8000/day self renewal B-precursor 2-3x10 8 Pre-B 2-3x10 7 B-cell 1-3x10 6 Mature naive B-lymphocytes Dendritic cell B-cell precursors Stem cell Stromal cell Bone Central sinus

6. STEM CELLS Unspecialized cells with unlimited proliferating capacity At least one differentiated cell Precursor/progenitor Self renewal + Assimmmetric division Or more differentiated cell Precursor/progenitor CHARACTERISTICS SELF RENEWAL ASSIMMETRIC DIVISION

7. Immature & mature B Central Sinus Progenitors Pre-B Stromal cells X X X EndoosteumEndoosteum Macrophage Scheme of B Cell Development in the Bone Marrow

8. DC mackrophage MYELOID PRECURSOR BONE MARROW HSC HEMATOPOIETIC STEM CELL mast DC monocyte neutrophil mast neutrophil TISSUES BLOOD B-cellT-cell NK-cell THYMUS B-cell LYMPHOID PRECURSOR LYMPHOID TISSUES BLOOD

9. Blood circulation Macrophage Hassal’s corpuscle Dendritic cell Thymocytes Epithelial cells Capsule Septum Mature naive T- lymphocytes STRUCTURE OF THE THYMUS

10. THYMUS INVOLUTION Up to puberty/adolescence the size of the thymus is increasing and naive T lymphocytes are produced in waves to ensure protective immune responses A sustained loss of tissue mass, cellularity and functionality of the thymus starts after puberty and lasts to middle age followed by a slower rate of involution extending to old age DN cells do not proliferate and differentiate Diversity of the TCR repertoire progressively becomes more limited The thymic tissue is replaced by fat deposits In old people naive peripheral T cells proliferate more extensively than those in younger individuals to compensate low cell numbers and reach their replicative limits earlier than in young people REDUCED RESISTANCE TO INFECTION AND TUMORIGENESIS Similar number of T cell progenitors to young individuals Limited IL-7 production, Bcl-2 expression and TCRβ rearrangement Replicative potential of thymic stromal cells is decreased The levels of nerve growth factor (NGF) secreted by medullary thymic epitelial cells (TEC) and IGF-1 produced by thymic macrophages decline