Cells and tissues of the immune system Milan Číž Lymphoreticular tissue reticular connective tissue, loose cells reticular connective tissue – reticulocytes loose cells – different developmental stages of lymphocytes, macrophages, microphages thin lymphoid tissue – mainly reticulocytes dense lymphoid tissue – mainly lymphocytes Lymphoreticular tissue primary lymphoid organs secondary lymphoid organs lymphatic system Appendix Bone marrow Thymus Spleen Peyer’s patches Lymphatic vessels Tonsils Thoracic duct Lymphatic system • deffense mechanisms – lymph nodes • regulation of homeostasis • drainage of extracellular fluid from tissues • drainage of lipids to superior vena cava • drainage of metabolism products from the body (harmful, useless compounds) • transport of nutrients to blood lymphatic capillaries – lymphatic vessels – lymphatic nodes – thoracic duct – venous system Primary lymphoid organs formation, development and differentiation of immune cells thymus bursa Fabricii ~ bone marrow Primary lymphoid organs embryonal period – yolk sac fetal period – liver, spleen long bones → pelvis, vertebrates Primary lymphoid organs Bone marrow hematopoetic stem cells erythroid lineage lymphoid lineage myeloid lineage Primary lymphoid organs Thymus Primary lymphoid organs Thymus Newborn 2 years Adult Primary lymphoid organs Thymus Primary lymphoid organs Thymus Primary lymphoid organs Thymus Secondary lymphoid organs Lymphoid follicles formations of dense lymphoid tissue temporary Secondary lymphoid organs Lymph nodes Secondary lymphoid organs Lymph nodes Secondary lymphoid organs Lymph nodes Secondary lymphoid organs Lymph nodes Sekundární lymfoidní orgány Tonsils Waldeyer's tonsillar ring: - adenoids (pharyngeal tonsils) - roof of pharynx - palatine tonsils - sides of oropharynx between palatoglossal and palatopharyngeal arches - lingual tonsils - behind terminal sulcus (tongue) - tubal tonsils - roof of pharynx near to the outfall of Eustachian tube Secondary lymphoid organs Spleen Red pulp • reservoir of red blood cells (cca 1% of total blood volume) White pulp • lymphocytes, monocytes, macrophages (degrade 90% of erythrocytes in red pulp) • synthesis of antibodies • elimination of immunocomplexes Secondary lymphoid organs Peyer’s patches Secondary lymphoid organs Mucosa-associated lymphoid tissue (MALT) common defense mechanisms (movement of cilia, air and liquid flow, glandular secretions) organised lymphatic system (lymphoid follicles, induction of immune response) diffused lymphatic system (loose leukocytes and their effector mechanisms) GALT = gut-associated l.t. (Peyer’s patches, appendix) BALT = bronchial/tracheal-associated l.t. (tonsils) NALT = nose-associated l.t. VALT = vulvovaginal-associated l.t. Secondary lymphoid organs Mucosa associated lymphoid tissue Secondary lymphoid organs Mucosa associated lymphoid tissue lysozyme Cells of the immune system Cells of the immune system Cells of the immune system Mononuclear phagocytic system 5 – 10 % of all leukocytes 80 days preserved capability of mitosis large amoeboid cells with kidney-shaped nucleus Cells of the immune system Mononuclear phagocytic system Cells of the immune system Mononuclear phagocytic system - phagocytosis, killing, tissue regeneration, antigen presentation - characteristic nucleus - CD14 membrane marker - activated by cytokines - produce cytokines - eliminate malignant and altered self structures Cells of the immune system Dendritic cells heterogenous cell population (various phenotype and functional markers) catch antigens in peripheral tissue professional APC Cells of the immune system Polymorphonuclear phagocytic system - neutrophils (60 – 70% of all leukocytes) - basophils (0 – 1% of all leukocytes) - eosinophils (1 – 3% of all leukocytes) segmented nucleus CD66 membrane marker large quantity of diversely stained cytoplasmic granules live for several hours - days - first defense line against pathogenic microorganisms - chemotaxis - phagocytosis - reactive oxygen and nitrogen species generation - degranulation Cells of the immune system Polymorphonuclear phagocytic system Cells of the immune system Polymorphonuclear phagocytic system proliferation terminal differentiation Bone marrow Circulation Cells of the immune system Polymorphonuclear phagocytic system Cells of the immune system Monocytes/macrophages Neutrophils Morphology large mononuclear cells small cells with segmented nucleus Localization blood/tissues blood – recruited to the site of infection After killing bacteria migrate to local lymph nodes die by apoptosis, eliminated by macropahes Antigen presentation yes no (express MHC class II) (do not express MHC class II) Cells of the immune system Mast cells Skin, gastrointestinal tract Function similar to that of basophils in blood Release of histamine, heparin FceR Cells of the immune system Lymphocytes B lymphocytes T lymphocytes - TH lymphocytes - Treg lymphocytes ~ TS lymphocytes - TC lymphocytes NKT lymphocytes NK cells Cells of the immune system Lymphocytes Cells of the immune system Lymphocytes T lymphocytes TH1 lymphocytes: cooperate with macrophages, stimulate them to activated macrophages (inflammatory T lymphocytes; delayed type hypersensitivity), defense against intracellular pathogens TH2 lymphocytes: cooperate with B lymphocytes, induce multiplication of specific B lymphocyte clone and their differentiation into plasmatic cells TH17 lymphocytes: cooperate with neutrophils, defense against extracellular pathogens TH0 lymphocytes TH3 lymphocytes Cells of the immune system Lymphocytes TC lymphocytes: cytotoxic granules (perforin, granzymes) Fas-ligand TNF- (lymphotoxin) Cells of the immune system Lymphocytes NK cells large granular lymphocytes recognize cells, which express little MHC-I on their surface (cancer cells, cells infected by viruses) stimulatory (recognize surface, adhesion molecules) and inhibitory receptors (recognize MHC-I) Cells of the immune system Lymphocytes NK cells