CONNECTIVE TISSUE BY ADEKEYE ADESHINA 2015

CONNECTIVE TISSUE Outline: • Definition • Formation/components of CT • Function of CT • Extracellular matrix • Cells of CT • Classification of CT

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Connective tissue is formed primarily of Extracellular matrix (ground substance and protein fibers) Connective tissue cells ORIGIN The CT originate from the mesenchyme, an embryonic tissue formed by elongated undifferentiated cells, the mesenchymal cells Functions Connective tissue supports organs and cells Acts as a medium for exchange of nutrients and wastes between the blood and tissues Protects against microorganisms Repairs damaged tissues Stores fat.

EXTRACELLULAR MATRIX (ECM)

It is the major constituent of Connective tissue It consist of different combinations of protein fibers (collagen, reticular, and elastic) and ground substance.

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Ground substance is a colorless, highly hydrophilic, transparent, gel-like material in which the cells and fibers of connective tissue are embedded. It is a complex mixture of glycosaminoglycans, proteoglycans, and glycoproteins Ground substance serves as lubricant Prevent invasion of tissues by foreign agents, and resists forces of compression.

FIBERS: • are long, slender protein polymers present in different proportions in different types of connective tissue. • predominantly composed of collagen, constitute tendons, aponeuroses, capsules of organs and membranes that envelop the central nervous system (meninges)

• Collagen and reticular fibers are both formed by the protein collagen • Elastic fibers are composed mainly of the protein elastin. • These fibers are distributed unequally among the types of connective tissue. •

• 1. Collagen fibers : there are at least 25 different types of collagen, the most common collagen types in connective tissue proper are type I and type III collagen, both consisting of many closely packed tropocollagen fibrils. • Chief examples among its various types are present in the skin, bone, cartilage, smooth muscle, and basal lamina.

• Collagen is the most abundant protein in the human body, representing 30% of its dry weight.

• Collagens that Form Long Fibrils I-Skin, tendon, bone, dentin Function:Resistance to tension II-Cartilage, vitreous body Function:Resistance to pressure III-Skin, muscle, blood vessels Function:Structural maintenance in expansible organs Others include V and XI (Cartilage)

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Fibril-associated collagens IX, XII and XIV Examples include Cartilage, vitreous body, Embryonic tendon, skin, Fetal skin and tendon Collagen that forms anchoring fibrils VII Example include Epithelia Collagen that forms networks Example include all basement membranes

Collagen fibers have great tensile strength, which imparts both flexibility and strength to tissues containing them. Bone, skin, cartilage, tendon, and many other structures of the body contain collagen fibers.

The levels of organization in collagen fibers

NOTE: Collagen is the most abundant structural protein of the ECM

• 2. Reticular fibers are extremely thin (0.5–2.0 m) in diameter and are composed primarily of type III collagen. • they have higher carbohydrate content than other collagen fibers. • 3. Elastic fibers are coiled branching fibers 0.2 to 1.0 m in diameter that sometimes form loose networks. These fibers may be stretched up to 150% of their resting length. They are composed of elastin and microfibrils of fibrillin

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.Cells of Connective Tissue Some originate locally and remain in the connective tissue (fixed cells) Fixed connective tissue cells include fibroblasts Pericytes adipose cells mast cells fixed macrophages.

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whereas others originate elsewhere (HSC in Bone marrow) and remain only temporarily in connective tissue (transient cells) Transient connective tissue cells include Certain macrophages, Lymphocytes Plasma cells Neutrophils Eosinophils Basophils

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4 Major cell components of the connective tissues Fibroblast : originate locally from undifferentiated mesenchymal cells Macrophage Mast cell Plasma cell

• Note: MMP originate from hematopoietic stem

cells in bone marrow, circulate in the blood and then move into connective tissue where they remain and execute their functions

Origin of connective tissue cells. Cells arising from undifferentiated mesenchymal cells are formed in connective tissue and remain there

Lineages of connective tissue cells

A. Fixed Cells of Connective Tissue

• 1. FIBROBLASTS arise from mesenchymal cells and are the predominant cells in connective tissue proper. • It originate locally from undifferentiated mesenchymal cells and spend all their life in this tissue • They often possess an oval nucleus with two or more nucleoli. • They may differentiate into other cell types under certain conditions.

• Fibroblasts synthesize collagen, elastin, glycosaminoglycans, proteoglycans and multiadhesive glycoproteins. • Fibroblasts are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. • Two stages of activity—active and quiescent

• Active fibroblasts are spindle shaped (fusiform) and contain well-developed rough endoplasmic reticulum (RER) and many Golgi complexes. • Myosin is located throughout the cytoplasm, and actin and -actinin are located at the cell periphery. • Clinical consideration: Fibroblasts undergo mitosis only during wound healing.

•The active fibroblast has an abundant and irregularly branched cytoplasm. •The active fibroblast has an abundant and irregularly branched •I cytoplasm. •Its nucleus is ovoid, large, and pale staining, with fine chromatin and a prominent nucleolus. • The cytoplasm is rich in rough endoplasmic reticulum, and the Golgi complex is well developed A connective tissue layer (dermis) shows several fibroblasts H&E stain

•Quiescent fibroblasts are elongated cells with thin cytoplasmic extensions and condensed chromatin. •Pararosaniline–toluidine blue (PT) stain

•Active (left) and quiescent (right) fibroblasts. •External morphological characteristics and ultrastructure of each cell are shown. •Fibroblasts that are actively engaged in synthesis are richer in mitochondria, lipid droplets, Golgi complex, and rough endoplasmic reticulum than are quiescent fibroblasts (fibrocytes)

• 2. PERICYTES are derived from embryonic mesenchymal cells and may retain a pluripotential role. • . They possess characteristics of endothelial cells as well as smooth muscle cells because they contain actin, myosin, and tropomyosin, suggesting that they may function in contraction. • . They are located mostly along capillaries and may function as contractile cells that modify capillary blood flow. • . During blood vessel formation and repair, they may differentiate into smooth muscle cells as well as endothelial cells. • In response to injury, pericytes may give rise to endothelial cells, fibroblasts and smooth muscle cells of blood vessel walls.

3. ADIPOSE CELLS (adipocytes) • Arise from mesenchymal cells and perhaps from fibroblasts • They do not normally undergo cell division because they are fully differentiated cells. • However, they do increase in number in early neonatal life. • They are surrounded by a basal lamina and are responsible for the synthesis, storage and release of fat.

TYPES OF ADIPOSE CELLS • a. Unilocular adipose cells (white adipose tissue) contain a single large fat droplet. • (1) These cells have plasmalemma receptors for insulin, growth hormone, norepinephrine and glucocorticoids to control the uptake and release of free fatty acids and triglycerides. • (2) They are surrounded by a basal lamina and are responsible for the synthesis, storage and release of fat. • b. Multilocular adipose cells (brown adipose tissue) are smaller than unilocular adipose cells and the fat is stored as many small fat droplets, and thus the spherical nucleus is centrally located.

4. MAST CELLs

arise from myeloid stem cells in bone marrow and usually reside near small blood vessels. • They possess a central spherical nucleus; their cytoplasm is filled with coarse, deeply stained metachromatic granules • Their surfaces are folded, and in electron micrographs they have a well-developed Golgi complex, scant RER, and many dense lamellated granules. Two populations of mast cells exist. • Mast cells function in the localized release of many bioactive substances with roles in the inflammatory response, innate immunity, and tissue repair

• Connective tissue mast cells possess secretory granules containing heparin. • The other population, the smaller mucosal mast cells whose secretory granules contain chondroitin sulfate, is located in the mucosa of the alimentary canal and of the respiratory tract.

Simplified representation of the connective tissue cell lineage derived from the multipotential embryonic mesenchyme cell

• B. Transient Cells of Connective Tissue • 1. Macrophages are the principal phagocytosing cells of connective tissue. • They are responsible for removing large particulate matter and assisting in the immune response. • They also secrete substances that function in wound healing.. • MACROPHAGES originate in the bone marrow as monocytes, circulate in the bloodstream, then migrate into the connective tissue, where they mature into functional macrophages.

Macrophages have specific name in certain organs for example, they are called Kupffer cells in the liver, Osteoclast in bone and microglia cell in the CNS. Macrophages in the connective tissue have the following features: • They contain abundant lysosomes required for the breakdown of phagocytic materials. • Active macrophages have numerous phagocytic vesicles (or phagosomes) for the transient storage of ingested materials. • The nucleus has an irregular outline.

• 2. Lymphoid cells • Arise from lymphoid stem cells during hemopoiesis • They are located throughout the body in the subepithelial connective tissue and accumulate in the respiratory system, gastrointestinal tract and elsewhere in areas of chronic inflammation. • a. T lymphocytes (T cells) initiate the cell-mediated immune response. • b. B lymphocytes (B cells), following activation by an antigen, differentiate into plasma cells, which function in the humoral immune response. • c. Natural killer cells (NK cells) lack the surface determinants characteristic of T and B lymphocytes but may display cytotoxic activity against tumor cells

• 3. Plasma cells • are antibody-manufacturing cells that arise from activated B lymphocytes and are responsible for humoral immunity. • a. These ovoid cells contain an eccentric nucleus possessing clumps of heterochromatin, which appear to be arranged in a wheel-spoke fashion. • b. Their cytoplasm is deeply basophilic because of an abundance of RER. • c. A prominent area adjacent to the nucleus appears pale and contains the Golgi complex (negative Golgi image). • d. They are most abundant at wound entry sites or in areas of chronic inflammation..

• 4. Granulocytes • are white blood cells that possess cytoplasmic granules and arise from myeloid stem cells during hemopoiesis. • At sites of inflammation, they leave the bloodstream and enter the loose connective tissue, where they perform their specific functions .

• a. Neutrophils phagocytose, kill, and digest bacteria at sites of acute inflammation. • b. Eosinophils bind to antigen–antibody complexes on the surface of parasites (e.g.,helminths) and then release cytotoxins that damage the parasites. • They are most prevalent at sites of chronic or allergic inflammation. • c. Basophils are similar to mast cells

CLASSIFICATION OF CONNECTIVE TISSUE • Based on the proportion of cells to fibers & on the arrangement and type of fibers • Embryonic connective tissue • Connective tissue proper • Specialized connective tissue.

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A. Embryonic connective tissue It is a loose tissue formed during early embryonic development 1. Mucous tissue (Wharton jelly) is a loose connective tissue that is the main constituent of the umbilical cord and fetal tissues. has an abundance of ground substance composed chiefly of hyaluronic acid It consists of a jellylike matrix with very few collagen fibers in which LARGE STELLATE FIBROBLASTS are scatterly embedded. 2. Mesenchymal tissue is found only in embryos. It consists of a gel-like amorphous matrix containing only a few scattered reticular fibers, in which star-shaped, pale-staining mesenchymal cells are embedded

Mucous tissue.

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B. Connective tissue proper (Adult Connective Tissue) It has a considerable structural diversity because the proportion of cells to fibers and of ground substances varies from tissue to tissue. This variable cell to ECM ratio is the basis for the subclassification of adult connective tissue into two type of connective tissue proper. 1. Loose (or areolar) connective 2. Dense connective tissue

• Loose connective tissue • contains more cells than collagen fibers • generally found in the mucosa and submucosa of various organs and surrounding blood vessels, nerves and muscles, papillary layer of the dermis, hypodermis, linings of the peritoneal, pleural cavities, glands, mucous membranes supporting the epithelial cells. • Well vascularized, flexible, and not very resistant to stress.

• It usually supports epithelial tissue • It is more abundant than dense connective tissue • The most numerous cells are fibroblasts and macrophages, but other types of connective tissue cells are also present. • Collagen, elastic, and reticular fibers also appear in this tissue.

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Dense connective tissues contains more of collagen fibers than cells. is adapted to offer resistance and protection. When the collagen fibers are preferentially oriented as in tendons, ligaments and the cornea, the tissue is called Dense regular connective tissue. • When the collagen fibers are randomly oriented- as in the dermis of the skin, the tissue is called dense irregular

longitudinal section of dense regular connective tissue of a tendon

Loose and dense irregular connective tissue within the esophagus

Section of loose connective tissue. Many fibroblast nuclei are interspersed with irregularly distributed collagen fiber

Section of immature dense irregular collagen tissue.

Dense irregular connective tissue from human dermis contains thick bundles of collagen fibers, fibroblast nuclei

• NOTE: • Reticular and elastic fibers predominate in irregular connective tissue. • Reticular connective tissue • contains reticular fibers, which form the stroma of organs of the lymphoid-immune system (e.g lymph nodes and spleen), the hematopoietic bone marrow and the liver. Function • Provides a delicate meshwork to allow passage of cells and fluid. • Elastic connective tissue • contains irregularly arranged elastic fibers in ligaments of the vertebral column. Function • Provides elasticity.

Light micrograph of reticular tissue (silver stain)

• C. The Special connective tissue • comprises types of connective tissue with special properties not observed in the embryonic or adult connective tissue proper. There are four types of special connective tissue 1. Adipose tissue 2. Cartilage 3. Bone 4. Hematopoietic tissue (bone marrow)

• Adipose tissue has more cells (adipose cell or adipocytes) than collagen fibers and ground substance. • This type of connective is the most significant energy storage site of the body. • The hematopoietic tissue is found in the marrow of selected bones

• Esssentially, cartilage and bone are dense connective tissues with specialized cells and ground substance. • An important difference is that cartilage has a noncalcified ECM whereas the ECM of bone are calcified • Assignment • List the cell of mononuclear phagocyte system and their function