1. Connective tissue 2009

2. Connective tissue Connective tissue consists of cells and extracellular matrix Connective tissue proper Cartilage Bone Adipose tissue

3. Connective tissue Mechanical (structural) role – supportive and connecting Defence – immune response and physical barrier Nutrition – vessels (blood supply) Storage of metabolites – Ca, fat Tissue repair after injury

4. Connective tissue proper Cells: Fixed: fibroblasts, reticular cells, adipocytes Blood derived: macrophages, plasma cells, mast cells, leucocytes Fibres: collagen, reticular and elastic Ground substance: glycoproteins and proteoglycans

5. Fibroblast Spindle -shaped cell with elliptic nucleus Proteosynthesis (GER and GA): collagen, elastin, proteoglycans and glycoproteins

6. Synthesis of collagen Preprocollagen with signal peptide – into RER Procollagen – hydroxylation of lysine and proline (RER) GA – packing nad secretion of procollagen, glycosylation, formation of disulphidic bounds Removal of nonhelical endings Tropocollagen Polymeration outside of cell Periodicity 64 nm

7. Types of collagens I. Bone, tendon, dentin, skin II. Hyalinne and elastic cartilage III. Reticular lamina (BM) and reticular fibres IV. Basale lamina V. Chorion and amnion

8. Elastin Proelastin – secretion of tropoelastin Interaction with fibrillin to organize immature elastic fibers Aggregation – mature elastic fibers Content of desmosin and isodesmosin (AA)- cross-linking of elastic fibers EM: microfibrils+MAGPs+fibrillin

9. Fibres Collagen fibres Reticular fibres (AgNO 3 ) Elastic fibres (resorcin fuchsin, orcein)

10. Clinical significance: Vitamine C – necessary for hydroxylation of collagen (hydroxyproline and hydroxylysine) Ehlers-Danlos syndrome – hyperelasticity of skin and hypermobility of joints – defect of procollagen peptidase or lysyl hydroxylase – impairment of cross-linking formation in collagen fibres

11. Clinical significance Marfan syndrome – autosomal dominant – defect of fibrillin – Myopy, lens ectopy, skeletal defects arachnodactyly, prolapse of the mitral valve, dilatation of aorta ascendens.

12. Ground substance Glycoproteins – fibronectin, chondronectin, laminin etc. Proteoglycans – Glycosaminoglycans – polysaccharides formed from hexosamine and uronic acide: chondroitin sulphate, heparan sulphate, dermatan suphate keratan sulphate Core protein, linker protein, hyaluronan molecule

13. Interaction between cells and matrix Integrins – receptors for molecules of extracellular matrix (hemidesmosomes and focal adhesions) Intracellular attachment to the cytoskeleton (paxilin, vinculin, talin, β-catenin)

14. Ground substance Hydratation of glycosaminoglycan molecules, presence of growth factors Degradation – metalloproteinases – collagenase, kathepsin, stromelysin, gelatinase, Significance : tumor invasion – degradation of basement membrane Cells decrease expression of integrines – attachment to BL

15. Regeneration After injury or impairment of tissue Cell division – scar formation Myofibroblasts – wound healing - wound contraction characteristics of both, fibroblast and smooth muscle cell Synthesis of growth factors (during development, too)

16. Macrophages Phagocytic cells, derived from monocytes Contain of lysosomes, phagosomes (vacuoles) Stainable by vital dyes – trypan blue Function: turn over the senescent fibers and ECM Antigen presenting cells (MHC) Production of cytokines – interleukin 1, TNFα

17. Macrophages Monocytes Histiocytes Osteoclasts Dendritic cells Mikroglia Kupffer cells Langerhans cells Epiteliod cells, multinuclear giant cells – segregation of foreign bodies

18. Mast cells Derives from bone marrow Vasoactive mediators: histamine, heparin, chemotactic mediators – leukotrienes Metachromasia

19. Mast cells Mucosal mast cells (lungs and gut) Connective tissue mast cells Activation – antigen - bounds to two IgE receptors Release – histamine, proteases, proteoglycans Synthesis of mediators derived from arachidonic acid- prostaglandins and leukotrienes

20. Plasma cells Activated B- lymphocytes – immunoblasts – plasma cells Proteosynthesis - GER and GA Cartwheel nucleus

21. Connective tissue Embryonic – mesenchyme, mucoid connective tissue – Wharton´s jelly Adult – loose and dense collagen connective tissue, reticular connective tissue, elastic connective tissue Special – white and brown adipose tissue

22. Connective tissue Collagen connective tissue Loose Dense Elastic Reticular White adipose tissue Brown adipose tissue

23. Embryonic connectives Mesenchyme – embryonic tissue starlike cells with little amount of ECM – allow cells to migrate Mucoid connective tissue – fetal – fibroblasts, collagen V, hyaluronic acid – umbilical cord (Warthon´s jelly), chorion

24. Collagen connective tissue Loose – many cells (blood deriveds, too) less fibers. Occurence in lamina propria, muscles ect. Dense – more fibres and less cells Regular (tendon, fascia, aponeurosis) Irregular (dermis)

25. Elastic connective tissue Bundles of elastic fibers, thin collagen fibers and fibroblasts Yellow ligament Suspensory ligament of the penis

26. Reticular connective tissue Three-dimensional network - reticular cells and fibers – microenvironment for haemopoesis and lymphatic organs: bone marrow, spleen, lymph nodes

27. Unilocular adipose tissue 50-150um, signet ring cell Excentric nuclei Only one big lipid droplet, it is not surrounded by membrane - triglycerids (Glut-4) Surrounded by basal lamina Hormone: insulin,GH, thyroxin, katecholamins, glucocorticods, prostaglandins,

28. Function: Insulator agains heat loss Reserve of energy Fills spaces and cushions Shock absorber in soles and mechanic support (kidney, eye). Synthesis: leptin, adiponectin, estrogens

29. Multilocular adipose tissue Multilocular Nucleus in the centra of cell, many mitochondria Present in fetuses and newborns

30. Multilocular adipose tissue Many vessels, sympathetic adrenergic inervation Function: thermogenesis – thermoregulation in newborns Uncoupling protein = thermogenin - in mitochondria - mitochondria produce heat instead of ATP