1. Immune system Lecture 2011

2. Immune system Innate - non-specific (no immunisation required) o physical barriers (skin, mucosa, cilia) o biological barriers (symbionts) o chemical barriers (pH, mucus) o soluble factors (lysozyme, interferons, proteins ac.ph., complement) o Cells: phagocytes, granulocytes o (rapid answer, restrictive flexibility, non-specific reaction, no memory ) adaptive – specific (immunisation required) o Cells: T - lymfocytes (directly kill cells/ virus- infected, foreign cells, microorganisms) o B – lymfocytes (produce) o Antibodies (delayed answer, high flexibility, high specifity, memory and immunity)

3. Organs and cells of immune system internet Bone marrow Thymus Tonsils and adenoids Lymph nodes Spleen Peyer´s patches Appendix Lymphatic vessels

4. Cells of immune system (effect) non-specific intracelullar killing macrophages (mononuclear phagocyte system) “activating macrophages“! produce cytokins APC! neutrophils extracellular killing NK-cells (CD16, CD56), “large, granular lymfocytes“ (perforins, apoptosis), not MHC restricted eosinophils (granules with cytotoxic proteins) specific B-lymphocytes (receptor: Ig) o T-lymphocytes (receptor:TCR in complex with CD, Ag split in peptide fragments in complex with MHC presented by APC (T c ) MHC I+Ag (T H ) Ag +MHC II presenting by APC

5. Cell origin: Hemocytoblast (pluripotent stem cell) M yeloid lineage Erythrocytes Plateletes Granulocytes Monocytes Dendritic cells Mast cells Lymphoid lineage B-lymphocytes T-lymphocytes NK-cells

6. Tissues and organs of immune system cells: blood, lymph, lymphoid tissue lymphoid tissue: lymphoid nodules,MALT primary or central lymphoid organs: thymus bone marrow secondary or peripheral: encapsulated: lymph nodes spleen non-capsulated: Peyer´s patches appendix tonsils

7. Cells of immune system LYMPHOCYTES Can exist without contact with another cells (cytokines!) Migrate through tissues, blood and lymph 2kg in organism/ 2- 3 grams in blood

8. Lymphocytes organT-lymph %B-lymph % thymus1000 bone marrow1090 spleen4555 lymph nodes6040 blood8020 NK

9. Cells of immune system Antigen presenting cells (APC) heterogenous group of cells macrophages dendritic cells Langerhans´ cells (skin) B-lymfocytes M-cells (GIT)

10. Dendritic cells APC originate in bone marrow, progenitor c. precursors are seeded through the blood to (T- regions) or to non-lymphoid organs (Langerhans cc. in the skin) high ability to be attracted to sites of antigen challenge and travel via lymph vessels to peripheral organs, presenting Ag to T-lymph (satelite lymph node, initiate immune response) X folicular dendritic cc – origin just in stroma of nodes, not presenting Ag, but retain Ag/Ab in membrane – B-lymph and i. memory

11. Thymus immature lymphocytes from bone marrow settled the thymus pre- and postnatally, undergoing -terminal differentiation and proliferation elimination 95% (apoptosis), negative selection and positive selection cortex (blood-thymus barries) x medulla (postcapillary venules – mature lymphocytes leave thymus to T- regions in peripheral organs) reticular epithelial stroma, reticular cells! Dual embryonic origin - endoderm (3rd pair of pharyngeal pouches) + mesenchym (lymphocytes), Intensive growth till puberty Inborn defect: di George syndrom- thymus aplasia

12. Thymus anatomy Superior and anterior inferior mediastinum lobus dx. et sin. lobuli, cortex, medulla (lobuli thymici accessorii) weight at birth (12-14g)

13. Thymus – cortex (85% T-cells) epithelial cells – cortical (stromal cells) secretory granules,desmosomes,3D network, express MHC I, MHC II T-cells double negative, proliferation,gene rearrangement pre-TCR along with coreceptors CD4 and CD8 double positive (CD4 and CD8), positive selection( CD4 or CD8)  macrophages negative selection, apoptotic T-cc dendritic cells corticomedullary venules (functional thymocytes exit to circulation to T-regions

14. Thymus – medulla (25% T-cells) Fully matured T-cells (single positive) Epithelial cells Hassal´s corpuscles (onion –like structures, degenerated cells Macrophages Dendritic cells NO blood-thymus barrier

15. Blood – thymus barrier Cortical epithelial cells Basal lamina Endothelial cells Macrophages Only present in cortex

16. Thymus involution Gradual involution from puberty After 50th year, adipose tissue

17. Lymph node organs of lymphoid tissue in the course of lymphatics filter of Ag (microorganisms, tumor cells) coming in the lymph before its return to blood circulation recirculation: lymphocytes return to node via high endothelial venules reticular connective tissue stroma cortex (lymphatic nodules, B-lymph) paracortex (T-lymph)

18. Lymph node Cortex: Subcapsullary sinuses Lymphatic follicules Interfollicular sinuses Paracortex Medulla Lymphatic cords Medullary sinuses

19. Spleen largest lymphoid tissue accumulation filter of Ag (microorganisms, tumor cells) that penetrate blood, producing antibodies and activated lymphocytes White pulp, PALS (T-lymph) + lymhatic nodule (B-lymph) Marginal zone (between red and white pulp, active macrophages) Red pulp – lymphatic cords of Billroth + venous sinuses

20. Vascular supply Splenic artery Trabecular artery Central artery (surrounded by PALS) Penicilar artery (in red pulp) Venous sinuses Trabecular veins Splenic vein

21. Spleen – proliferation in germ center of lymhatic follicle (PCNA)