HCB Objectives 5 1. Connective Tissue: Resident cells: a. primitive mesenchymal cells (CT stem cells) b. fibroblast/fibrocyte (synthesize extracellular matrix molecules; important in wound healing, fibrosis (scarring), and differentiation into myofibroblasts (contraction and wound shrinkage) Thin cells with thin, elongated nuclei Migratory cells: a. macrophage (made from monocytes, phagocytize foreign particles especially if coated in IgG) Look big and strange; have many particles within b. mast cell (contain histamine, heparin, proteolytic enzymes for release in response to mechanical injury, inflammation, and allergens via IgE) causes allergic reaction, can cause anaphylaxis due to bronchoconstriction and drop in blood pressure Big cells with granular cytoplasm and nuclei c. lymphocyte (migratory cells, produce specific response by differentiating) Small cells with little cytoplasm and large nuclei d. plasma cell (differentiated B lymphocyte, produce antibodies) Cartwheel chromatin pattern, more cytoplasm than a lymphocyte e. eosinophil (bind IgE and phagocytize antibody tagged antigens; destroy cell membranes and can thus hurt host) Granular cytoplasm, bilobed nucleus f. neutrophil (phagocytize, best when antibody tagged, high numbers often signify acute infection) Clear nucleus, multinucleated 2. Clinical significance of white blood cells in CT: a. acute infection: macrophages (low numbers), neutrophils (high numbers) b. chronic infection: macrophages (high numbers), lymphocytes (high numbers), plasma cells allergy: mast cells recruit eosinophils to clean up (via IgE reception) 3. Extracellular matrix: Collagen: Most abundant, gives cells tensile strength. a. Type I Collagen: Main fiber in CT proper, abundant in bone, tendons, fascia, dermis, dense CT of organ capsules and septa synthesized in fibroblasts as procollagen, propeptide is cleaved after secretion to make tropocollagen which can form fibrils and then fibers broken down by collegenase (secreted by fibroblasts for normal turnover, neutrophils and macrophages in inflammatory process to get through basal lamina, some tumors to migrate across basal lamina and metastisize) b. Type II Collagen: In cartilage c. Type III Collagen: Also called reticular fibers, group into small bundles and form loose 3D structure (reticulum and reticular tissue). Found supporting lymph nodes, spleen, liver, and lamina propria (loose CT underlying mucosal epithelia) synthesized by mesenchymal reticular cells d. Type IV Collagen: NOT bundles, sheet-like network, present in basal lamina. Functions to bind laminin to basal lamina and extracellular matrix. Essential for basal lamina integrity. synthesized by epithelial cells and others cells making basal lamina. Elastic Fibers: Gives cells elasticity because of short hydrophobic segments prone to coiling upon themselves. Synthesized by fibroblasts and smooth muscle as tropoelastin, secreted and assembled with fibrillin as fibers (in skin) and sheets (walls of arteries). Proteoglycans: Highly charged to repel each other, attract Na+ and thus water to form hydrated gel. Provides space for molecules/small cells to travel. Synthesized in RER, composed of core protein with sugar side chains (different from glycoproteins (short sugar chains) because of long unbranched GAG polysaccharide chains). GAGs: dermatan sulphate proteoglycan (skin) aggrecan (cartilage, developing heart and brain) heparan sulphate proteoglycan (basal lamina) hyularonan o HUGE, exist unlinked to core protein o synthesized on fibroblast plasma membrane cavities of joints (lubricant) vitreous of eye (light transmission) cartilage, developing heart and brain (compression resistance) Adhesive Glycoproteins: a. Fibronectin: attaches cells to collagen, binds to integrins to attach cells to extracellular matrix. Essential for migration during inflammation, wound healing, macrophage, etc. b. Laminin: attaches cells to type IV collagen in basal lamina c. Chondronectin: attaches cells to collagen in cartilage d. Osteonectin: attaches cells to collagen in bone 4. Functional consequences of CT defects: a. Scurvy - Vitamin C deficiency (inability to form Type I Collagen triple helices; hemorrhages, impaired wound healing, etc.) b. Osteogenesis imperfecta - Mutation in Type I Collagen gene (decreased/defective synthesis of Type I Collagen yields brittle, fragile bones) c. Ehlers Danlos syndrome (type IV) – Mutation in Type III Collagen gene (defects in stability of organs, especially blood vessels in intestines) d. Alport syndrome – Mutation in Type IV Collagen (renal dysfunction due to defects in glomerular basal membranes) e. Marfan’s syndrome – Genetic defect in fibrillin (defects in all elastic fibers, aorta is more subject to rupture) 5. Basal lamina: made of type I and type IV collagen with laminin to bind integrins and type IV collagen. Function is to provide support and a boundary between CT and epithelia, skeletal muscles, adipocytes, and Schwann cells. 6. Types of CT: a. Loose CT: Reticular, elastic fibers prevail. Little type I collagen Underlies all types of epithelia and makes up most fascia b. Dense irregular CT: Type I collagen, irregularly arranged In capsules and septa of organs c. Dense regular CT: Type I collagen, regularly arranged Tendons, ligaments, intramuscular septa Connective tissue structure and likeliness for spread of infection: in loose CT, infection is more likely to spread (dense CT provides a barrier whereby connection can’t spread). However, the tissue surrounding loose CT must not have a barrier – if loose CT borders tight junctions, the infection won’t spread into the tissue. Instead, the loose CT will act as a conduit to send the infection to a different part of the body. 7. White fat: Unicellular, avascular, adipose tissue all in one globule surrounded by basal lamina in a cell. Used for storage and mobilization of lipids Brown fat: Multicellular, vascular, adipose tissue can be multiglobular in one cell. Used to produce heat (many mitochondria with ATP production uncoupled to produce heat; conducted through vasculature), generally in newborns, and is often not found in adults.