Connective Tissue Proper

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Connective tissue compoments

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Cells + extracellular fibers + ground substance

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Mesenchyme

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Embryonic tissue from the mesoderm that differentiates into connective tissue proper, cartilage, bone, or hematopoietic and lymphoid cells

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Mesenchymal Stem Cells form:

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Fibroblasts, endothelium, mesothelium, adipocyte, chondroblast, osteoblast, muscle

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Hematopoietic Stem Cells form:

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erthyrocyte, lymphocyte, monocyte, granulocytes, megakaryocytes

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Fibroblasts

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Make fibers and ground substance (collagenous, elastic, and reticular fibers)

LM: oval-shaped cell with pale eosinophilic cytoplasm, an oval nucleus. Enlarges when highly active

TEM - well-developed rER and Golgi

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Macrophage Function

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From monocytes-lives up to 2-3 months

1. Phatocytosis
2. Antigen-presenting cell to CD4+ T helper as a major histocompatibility complex
3. Release lymphokines to induce inflammatory reactions

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Macrophage Structure

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Ruffled border, pale pink cytoplasm with vaculoes, horseshoe to oval nucleus with peripheral heterochromatin.

TEM- well-developed Golgi with many lysosomes

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Kupffer cells

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Macrophage in liver sinusoids

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Langerhans cells

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Macrophage in epidermis

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alveolar (Dust cells)

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Macrophage in lung alveoli

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Osteoclasts

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Macrophage in bone

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Microglia

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Macrophage in CNS

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Dendritic cells

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Macrophage in spleen and lymph nodes

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Pleural and peritoneal macrophages

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In serous cavities

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Langhans 'foreign body giant' cells

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Produced by fusion of multiple macrophages

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Hofbauer cells

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Placental APCs

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Mast cells

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Secretes vasoactive and chemotactic mediators in inflammatory and allergic responses

Binds to two IgE immunoglobulins from B plasma lymphocytes

LM: stains metachromatically with basic dyes. Found near blood vessels. Round cell with small oval nucleus. Cytoplasm has large secretory vesicles

TEM - large, electron-dense granules. Well-developed Golgi

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Histamine

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increases vascular permeability and vasodilation; causes mucus secretion and smooth muscle contraction in bronchioles

Secreted by mast cells

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Heparin

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anticoagulant (sulfated GAG)

secreted by mast cells

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Chemotactic factors

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Attracts eosinophils, neutrophils, and macrophages

secreted by mast cells

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Leukotrienes and Prostoglandins

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Not in granules. Lead to prolonged smooth muscle contraction

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Cytokines

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TNF alpha and interluekins - signalling molecules used in inflammatory responses

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Pericytes

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Mesenchymal stem cells. Surrounded by own basal 'external' lamina with dual capability to synthesize ECM components and to contract smooth muscle cells

Outside endothelium - contain myofilament bundles with rER and Golgi

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Plasma cells

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Activated B lymphocytes that produce monoclonal antibodies. Round cell shape with eccentric nucleus and a purple, cytoplasmic tail. Has wagon-wheel heterochromain in nucleus

TEM - well developed rER and swollen Golgi cisternae

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Eosinophils

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allergies, inflammation

Bi-lobed nucleus with bright red granules.

Hamburgers. Has major basic protein - toxic to parasites

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Neutrophils

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Respond to acute inflmation. Chemotaxis and phagocytosis.

Ovoid cell with multi-segmented nucleus with pale granules.

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Collagen fibers

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Triple helix (procollagen)
Monomers(preprocollagen) synthesized by fibroblasts, chrondroblasts, osteoblasts, pericytes, smooth muscle, and epithelial cells

Made with repeating sequence of Gly-X-Y (where X and Y are hydroxlyated proline and lysine)

Procollagen peptidase removes some amino acids, leaving tropocollagen, the definitive molecule in all collagen subtypes

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Type 1 Collagen

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Present in dense connective tissue, including tendons, aponeuroses, and ligaments - makes eosinophilic bundles. Stains brown with silver stains.

Forms large fibers that are visible by LM. Predominantly in dermins, bone, tendons, ligaments, capsules, fascia, cornea, and teeth

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Type 2 Collagen

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Predominates in cartilage (hyaline and elastic), intervertebral disks, vitreous body

Forms thin fibers visible with TEM, but not LM.

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Type 3 Collagen

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Reticular fibers predominate in lymphatic and hematopoietic tissues.

Forms thin fibers visible with TEM, but not LM.

Present in organ stroma (spleen, liver, lung, lymph nodes, adipose, marrow), papillary dermis, CV and lymphatic vessels, lamina reticularis

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Collagen fibrils

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Spontaneously assemble from collagen subtypes 1-IV with a 4-fold staggered overlap with 68 nm banding periodicity.

Lysine residues are covalently bound

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Collagen fibers

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Made of fibrils. Visible ropes via H&E.

Attach to PM integrins via linker proteins (fibronectin and laminin)

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Metalloproteinases

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Degrades extracellular collagen. Zn-dependent proteases. Degrades during growth, development, implantation, and repair, as well as in pathological processes like tumor growth, metastasis, and injury

Collagenases, gelatinases, elastases

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Type IV collagen

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Do not form fibrils. Part of the basal lamina (lamina densa)

Stop at procollagen stage follwoing secretion, remainin uncleaved. Not visible with TEM without immunohistochemical localization.

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Interactions of collagens

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Non-fibrillar collagens interact with fibrillar ones to form complex integrated collagen networks

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Type X Collagen

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Part of the growth plate; found in the zone of hypertrophy. Useful as a marker, along with VEGF.

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Reticular fibers

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Made mostly of type III collagen fibers - made by fibroblasts, reticular cells in lymphatic and hematpoietic tissues, Schwann cells (endoneurium), and smooth muscle cells (tunica media, muscularis mucosa)

form branching networks, but not fiber bundles

PAS-positive. Stain black with silver

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Elastic fibers

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Fibrillin around tropoelastin core.

See with silver and PAS (fibrillin is a glycoprotein)

Let's organs distend yet return to a particular shape

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Ground substance

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Hydrated gel filling interstitial space between cells and fibers. Allows diffusion of nutrients and gases.

Proteoglycans and Glycoproteins

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Glycosaminoglycans

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Negatively-charged - attract water to form a hydrated gel that gives turgor to the matrix and resists compression

Bind to a core protein to form proteoglycans (except hyaluronic acid - forms aggrecan)

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Disaccharide units of GAGs

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Heparin
Chondroitin sulfates
Keratan sulfate
Heparan sulfate
Dermatan sulfate
Hyaluronic acid

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Hyaluronic acid

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Non-sulfated, aggrecan backbone. Links to proteoglycan core proteins via linker proteins to form an aggrecan

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Glycoprotein

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Used by cell to bind to extracellular matrices. Integrins link actin to basal lamina.

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Fibronectin

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Adhesion and migration of cells.

Chondronectin mediates chondrocyte binding to type II collagen

Osteonectin mediates osteocyte binding to type I collagen

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Laminin

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Attachment factor produced by epithelial cells mediating cell attachment to basement membranes via binding to type IV collagen via integrin receptors

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Wharton's jelly

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amorphous, mucoid CT found in umbilical cord and subdermal CT of embryo. Mostly ground substance with few collagen type III fibers and fibroblasts

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Loose areolar connective tissue

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Small amount of loosely arranged collagen with abundant ground substance and/or cells.

Lamina propria, spaces around blood vessels and lymphatics, mesentery

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Dense Irregular Connective Tissue

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Collagen oriented in 2 or more directions with greater fiber to cell/GS density than loose. Fibroblasts are common. Structural support

organ capsules & septa, dermis, submucosa, epineurium, periosteum, perichondrium

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Dense Regular Connective Tissue

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Very densely packed and oriented for stress/force. Fibroblasts (tendinocytes) only cells normally present between fasicular bundles

Tendons (straight), ligaments(wavy), aponeuroses(orthogonal sheets of parallel fibers)