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Connective Tissue http://jpkc.fudan.edu.cn/s/426/main.htm Prof. Hong CHEN, MD, PhD Office: Room 304, Building 9 East Tel: 54237019-9304 Mobile: 18602109425 Email: hchen30@hotmail.com; hchen@graduate.hku.hk QQ: 2572491042 WeChat: chenhong990543 General Characteristics of Connective Tissue (CT) • Few cells, more ECM. • No polarity, inside located in the body as its inner environment • Rich in blood and lymph vessels, nerves. • Originated from mesenchyme • Supply a matrix for connection, support, nutrients, protection, etc. Embryonic Mesenchyme • An embryonic tissue from mesoderm • Formed by elongated undifferentiated cells, called MESENCHYMAL CELLS – Many thin cytoplasmic process – Oval nuclei with prominent nucleoli and fine chromatin • More viscous ground substances (hyaluronan) with few collagen fibers • Have the multi-potentials in differentiation Differentiation of Mesenchymal Cells √ √ Mucous Tissue • Mainly in the umbilical cord and fetal tissue • Jellylike tissue, as Wharton’s jelly – Rich in hyaluronic acid – Few cells or fibers Classification of CT • Embryonic Connective Tissues: Mesenchyme, Mucous CT • Connective tissue proper: Loose CT Dense irregular/regular CT • Specialized Connective Tissue: Adipose tissue Reticular tissue Cartilage, Bone, Blood Composition of Connective Tissue ---- Cells, ECM (Fibers, Ground Substances) Cells • • • • • • • Fibroblasts Macrophages Plasma cells Mast cells Fat cells or Adipocytes Undifferentiated Mesenchymal Cells Leukocytes Fibroblasts • Most common cells • Have two levels of activity: active or quiescent. • For active: fibroblasts – With more abundant & irregular cytoplasm process – Have a basophilic cytoplasm rich in RER, Golgi. – Synthesize and secrete • collagen and elastin forming fibers • GAGs, proteoglycans and multiadhesive glycoproteins comprising the ground substances • For quiescent: fibrocytes (small, slim spindle-shaped, fewer processes, less RER) Granulation tissue after a wound Fibroblasts • Most common cells • Have two levels of activity: active or quiescent. • For active: fibroblasts – With more abundant & irregular cytoplasm process – Have a basophilic cytoplasm rich in RER, Golgi. – Synthesize and secrete • collagen and elastin forming fibers • GAGs, proteoglycans, and multiadhesive glycoproteins comprising the ground substances • For quiescent: fibrocytes (small, slim spindle-shaped, fewer processes, less RER) Granulation tissue after a wound Fibroblasts & Fibrocytes ↑ ↑ ↑ Collagen bundles Large active nuclei, basophilic cytoplasm, more abundant & irregular cytoplasm process, more RER, Golgi Small, slim spindle-shaped, fewer processes, less RER Fibroblast (TEM) • Typical features of a protein-secreting cell: rich in RER, Golgi • Long cytoplasmic extensions • Extracellularly abundant collagen or other fibers Fibrocyte (TEM) • Inactive fibroblast, with fewer cytoplasmic processes • Inactive in synthesis and secretion of materials making ECM • Reversible to the fibroblast, in case of injury and other repairing situations Macrophages (1) • Derived from monocytes • More cytoplasmic projections or pseudopodia involved in amoeboid movement • Cytoplasm: – Acidophilic – More lysosomes, phagosomes and residual bodies. Macrophages (2) • Function : – Phagocytotic activity – Antigen processing and presenting to immune cells – Secretion of growth factor, cytokine, and the others • The mononuclear phagocyte system: see Table 5-2 – All derived from monocytes of the blood – Localized outside of blood vessels Macrophages Macrophages Macrophages (TEM) Macrophage w/ RBC (SEM) Macrophage w/ RBC(1) Macrophage w/ RBC(2) Macrophage w/ RBC(3) Plasma Cells • Differentiated from B lymphocytes • Eccentrically spherical nucleus as “cartwheel” or “clock face” • Large and ovoid cells with intensely basophilic cytoplasm due to its richness in RER. • Producing antibodies: – IgG, IgM, IgA, IgD, IgE Plasma Cells • Most localized in intestinal mucosa, respiratory tract, and that with chronic inflammations. Plasma Cell Mast Cells • More near small blood vessels • 20 - 30 μm in diameter • Cytoplasm full of basophilic secretory granules, METACHROMASIA (change the color of some basic dyes from blue to purple or red) – Histamine – Heparin – Eosinophil chemotactic factors, ECF • Function similar to basophilic leukocytes • Play an important role in allergic reactions, such as asthma Mast Cell Mast Cell (TEM) Mast Cell (TEM) Secretion of Mast Cell Allergens: pollen or bee venom Fibers • Collagen Fibers • Elastic Fibers • Reticular Fibers Collagen Fibers • The most abundant fibers with various diameters • Fresh in white • Bright pink in HE staining • Composed of collagen fibrils • Formed by collagen type I & III • Have 60-70 nm periodicity of transverse striations Collagen Fibrils (TEM, longitudinal section) Collagen Fibrils (TEM, Cross section) Production of Collagen Fiber by Assembly of Type I Collagen Type I collagen molecules Fibrils Fibers Bundles Gap region Procollagen subunit Procollagen molecule intertwined A 67 nm periodicity of cross striations Gap region Elastic Fibers • Fresh in yellow, called yellow fibers • Bright pink in HE, purpleblue in Weigert staining • Thinner in diameter, coiled in free ends • Composed of microfibrils and core elastins • More resilience Elastic Fibers Elasticity Elastic Fibers (Weigert Staining) Elastic Fibers (Weigert Staining) Elastin & Microfibril Reticular Fibers also called Argyrophil Fibers • Extremely thin, more branch, extensive networks • Not visible in HE, easily stained in silver, Argyrophil fibers • Collagen type III, 60-70 nm periodicity of transverse striations • Localized in basal lamina • Set up a network in various organs (liver, hematopoietic organs) Ground Substances as both lubricant and a barrier to the penetration of invaders Sulfated GAGs (side chains) Globular proteins Core protein (vertical rod) Glycoproteins Proteoglycans Branched chains of monosaccharides Ground Substances Proteoglycans Hyaluronic acids axis Core proteins Link protein Sulfated GAGs Ground Substances – Glycoproteins for cell recognization, adhesion, and migration Fibronectin Lamini Classification of CT • Connective tissue proper: – Loose CT: the cells as the majors – Dense CT: the fibers as the majors • irregular: • regular: – Tendon:collagen fibers – Ligament: elastic fibers, elastic tissues • Specialized Connective Tissues: – Adipose tissue – Reticular tissue – Cartilage, Bone, Blood • Embryonic Connective Tissues: – Mesenchyme, Mucous CT Dense Irregular Connective Tissue Loose CT (L) & Dense Irregular CT (D) Dense Regular Connective Tissue Long, parallel bundles of collagen fibers and fibrocytes in a tendon Dense Regular Connective Tissue Long, parallel bundles of collagen fibers and fibrocytes in a tendon Classification of CT • Connective tissue proper: – Loose CT: the cells as the majors – Dense CT: the fibers as the majors • Specialized Connective Tissues: – Adipose tissue: adipocytes + ECM • White adipocytes: – unilocular (one large central droplet) – more common • Brown adipocytes: – multilocular (multiple small lipid droplets) – Reticular tissue • Embryonic Connective Tissues: – Mesenchyme, Mucous CT White Adipose Tissue unilocular (one large central droplet) White Adipocytes White Adipose Tissue by osmium tetroxide Brown Adipose Tissue multilocular (multiple small lipid droplets) Classification of CT • Connective tissue proper: – Loose CT: the cells as the majors – Dense CT: the fibers as the majors • Specialized Connective Tissues: – Adipose tissue: adipocytes + ECM – Reticular tissue: • reticular cells • reticular fibers • Embryonic Connective Tissues: – Mesenchyme, Mucous CT Reticular Tissue Reticular fibers: irregular black lines Reticular cells: heavily stained and dark SUMMARY • General Characteristics • Classification • Cells • Fibers • Ground substances General Characteristics of Connective Tissue (CT) • Few cells, more ECM. • No polarity, inside located in the body as its inner environment • Rich in blood and lymph vessels, nerves. • Originated from mesenchyme • Supply a matrix for connection, support, nutrients, protection, etc. Cells • Fibroblasts (fibrocytes): the major cell producing ECM • Macrophages: the short-lived cells derived from monocytes function as APC & phagocytosis • Plasma cells: the short-lived cells derived from B lymphocytes function as antibody-producing cells • Mast cells: more METACHROMASIA granules • Adipocytes (Fat cells): storage of triglycerides by forming adipose tissue • Undifferentiated Mesenchymal Cells: stem cell • Leukocytes Fibers • Collagen Fibers: – The most important & abundant fibers – Fibrils of Type I collagen bundled together – 60-70 nm periodic crossbanding • Reticular Fibers – – – – Fibrils of Type III collagen bundled together 60-70 nm periodic crossbanding Stained by silver as dark lines, as Argyrophil fibers Abundant in immune and lymphoid tissues • Elastic Fibers, or sheets called elastic lamellae – Composed of the proteins Elastin and fibrillin – Exist in a stretchable conformation Ground Substances as both lubricant and a barrier to the penetration of invaders Sulfated GAGs (side chains) Globular proteins Core protein (vertical rod) Glycoproteins Proteoglycans Branched chains of monosaccharides Classification of CT • Connective tissue proper: Loose CT Dense irregular/regular CT • Embryonic Connective Tissues: Mesenchyme, Mucous CT • Specialized Connective Tissue: Adipose tissue Reticular tissue Review Questions 1 • Compare and contrast the different types of connective tissues as listed in the following table: Types Loose connective tissue Dense connective tissue Adipose tissue Reticular tissue Fibers Cells Matrix Distribution Function Review Questions 2 & 3 • Summarize the structure and function of the fibroblasts, macrophages, mast cells, and plasma cells. • Describe the mononuclear phagocytic system. 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