Tissues and organs of immune system Lecture, SFST, 184 /2012

Immune/lymphoid system structures and cells innitiate and participate in the immune response lymphocytes mononunuclear – phagocyte system (antigen-presenting cells)

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)

Cells of immune system (effect) non-specific intracelullar killing macrophages (mononuclear phagocyte system) produce cytokines 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

Cells and their functions in immune response Immune response adnate non-specific neutrofiles macrophages kill bacteria eosinofiles parasites elimination NK-cells elimination of “non-self“ cells adaptive specific humoral B- lymphocytes plasma cells antibodies production cellular T- lymphocytes T-helper, CD4 macrophage s, B-cells activation, T- killer,CD 8 tumor cells and virus- infected cell elimination antigen- presenting cells - dendritic cells, macrophages

Periods of B and T lymphocytes differentiation in primary/central lymphoid organs (lymphopoiesis) 1.lymphopoiesis in fetal liver 2.progenitor B and T in bone marrow 3. T-cells precursors transport to the thymus 4.,5. imunocompetent, but virgin/naive B and T- lymphocytes to the periphery (blood, secondary lymphoid organs)

Origin of the cells from pluripotent stem cell - hemocytoblast dendritic cell

Antigen presenting cells (APC) heterogenous group of cells monocyte derived dendritic cells (its own progenitor) Langerhan´s cells (skin) M-cells (GIT, intestine) macrophages B-lymphocytes process Antigen and present epitope with MHC II molecule to T-lymphocytes

Dendritic cells principal APC originate in bone marrow from its progenitor stem cell precursors transported by blood to secondary lymphoid organs (T-zone) and non lymphoid organs (Langerhans cells in skin) endocytosis, processing and antigen presentation to T cells in closest lymphoid tissue (satelite node) – immune response X folicular dendritic cells – origin in situ, in the stroma of lymph nodes complex of antigen/antibody in membrane for long time immunological memory

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: capsulated: lymph nodes spleen non-capsulated: diffuse lymphoid system Peyer´s patches appendix tonsils

Lymphoid follicle/ nodule – B-zone primary and secondary lymphoid nodule germinal centre – imunoblasts (centroblasts, centrocytes), folicular dendritic cells, macrophages mantle zone - memory cells marginal zone - non activated B-cells

T- zone T-lymphocytes dendritic cells (APC for CD4+ a CD8+ T- lymphocytes) high endothelial venules for homing effect

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

Lymph node - histology 1. lymphoid tissue structure cortex (lymphatic nodules, B-zone paracortex (T- zone, high endothelial venules) medulla (B-lymphocytes, plasma cells) 2. lymph vessels arrangement (affererent lymphatic vessels – subcapsular sinus – cortical sinuses – medullary sinuses – efferent lymphatics) 3. reticular connective tissue stroma

Lymph node HE (x 30) retikulin (x 30)

Spleen largest lymphoid tissue accumulation filter of Ag (microorganisms, tumor cells) that penetrate blood, producing antibodies and activated lymphocytes

Spleen - histology red pulp white pulp, PALS (T-lymph) + lymhatic nodule (B-lymph) marginal zone (between red and white pulp, active macrophages) vascular supply – splenic artery – trabecular arteries – central artery – penicillar artery – sinusoids – trabecular veins – splenic vein reticular connective tissue stroma

White pulp – lymphoid tissue lymphoid nodules (B- zone) Malpighian bodies lymphoid tissue sheath surrounding central arteriole – periarteriolar lymphoid sheath – PALS ( T-zone) T-lymfocyty marginal zone – 100 um surronds white pulp marginal sinuses and lymphoid tissue macrophages, plasma cells, dendritic cells

Red pulp specialised vascularised connective tissue arterioles - terminal penicillar arterioles – capillaries – sinusoids – open circulation splenic cord, of Billroth - lymphocytes, macrophages, granulocytes, monocytes, erytrocytes, reticular cells

Spleen (x 42)

Thymus - histology terminal differentiation and proliferation of T- lymphocytes 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

Thymus HE (x 15) terminal differentiation and proliferation of T- lymphocytes elimination 95% (apoptosis), negative selection and positive selection cortex medulla

Thymus - structure reticular epithelium epithelial reticular cells, desmosomes paracrine secretion – thymic hormones - maturation of T cells cortex T - lymphocytes - differentiation, proliferation, selection in 98%, macrophages macrophages blood-thymus barrier – reticular cells medulla reticular epithelial cells, veins

Diffuse lymphoid system tonsils – aggregates of lymphoid nodules in entrance to the oral pharynx, partly capsulated and covering with epithelium – palatine tonsil, pharyngeal tonsil, lingual tonsil mucosa associated lymphoid tissue – MALT- lymphoid nodules – aggregates – Peyer´s patches in intestine (ileum)

Lymphocyte distribution organT-lymf %B-lymf % thymus1000 bone marrow1090 spleeen4555 lymph nodes6040 blood8020