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Immune system Lecture 2011 Immune system  Innate - non-specific  adaptive – specific (no immunisation required) (immunisation required) o o o o o o physical barriers (skin, mucosa, cilia) biological barriers (symbionts) chemical barriers (pH, mucus) soluble factors (lysozyme, interferons, proteins ac.ph., complement) Cells: phagocytes, granulocytes (rapid answer, restrictive flexibility, non-specific reaction, no memory) Cells: T - lymfocytes (directly kill cells/ virusinfected, foreign cells, microorganisms) o B – lymfocytes (produce) o Antibodies (delayed answer, high flexibility, high specifity, memory and immunity) o Organs and cells of immune system  Bone marrow  Thymus  Tonsils and adenoids  Lymph nodes  Spleen  Peyer´s patches  Appendix  Lymphatic vessels Cells of immune system (effect)  non-specific  specific  intracelullar killing macrophages  B-lymphocytes (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) (receptor: Ig) o T-lymphocytes (receptor:TCR in complex with CD, Ag split in peptide fragments in complex with MHC presented by APC (Tc) MHC I+Ag (TH) Ag +MHC II presenting by APC Cell origin: Hemocytoblast (pluripotent stem cell) Myeloid lineage Erythrocytes Plateletes Granulocytes Monocytes Dendritic cells Mast cells Lymphoid lineage B-lymphocytes T-lymphocytes NK-cells 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 Cells of immune system LYMPHOCYTES  Can exist without contact with another cells (cytokines!)  Migrate through tissues, blood and lymph  2kg in organism/ 23 grams in blood Lymphocytes organ T-lymph % B-lymph % thymus 100 0 bone marrow 10 90 spleen 45 55 lymph nodes 60 40 blood 80 20 NK Cells of immune system Antigen presenting cells (APC)  heterogenous group of cells macrophages dendritic cells Langerhans´ cells (skin) B-lymfocytes M-cells (GIT) 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 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 Tregions 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 Thymus anatomy  Superior and anterior inferior mediastinum  lobus dx. et sin.  lobuli, cortex, medulla  (lobuli thymici accessorii)  weight at birth (12-14g) 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  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 Blood – thymus barrier Cortical epithelial cells  Basal lamina  Basal lamina  Endothelial cells   Macrophages  Only present in cortex Thymus involution  Gradual involution from puberty  After 50th year, adipose tissue 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) Lymph node  Cortex: Subcapsullary sinuses  Lymphatic follicules  Interfollicular sinuses   Paracortex  Medulla Lymphatic cords  Medullary sinuses  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 Vascular supply  Splenic artery  Trabecular artery  Central artery (surrounded by PALS)  Penicilar artery (in red pulp)  Venous sinuses  Trabecular veins  Splenic vein Spleen – proliferation in germ center of lymhatic follicle (PCNA)
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                            