I. GROUND SUBSTANCE  contains the following components:

A. Proteoglycans consist of a core protein that binds glycosaminoglycans (GAGs) and a link protein that binds hyaluronic acid.
B. GAGs consist of repeating disaccharide units that always contain either N-acetylglucosamine or N-acetylgalactosarnine as one of the repeating units.
1. Hyaluronic acid is found in most connective tissues.
2. Chondroitin sulfate is found in cartilage and bone.
3. Keratan sulfate is found in cartilage, bone, cornea, and intervertebral disk.
4. Dermatan sulfate is found in dermis of skin, blood vessels, and heart valves.
5. Heparan sulfate is found in basal lamina, lung, and liver.
C. Glycoproteins
1. Fibronectin and laminin are components of the basal lamina.
2. Chondronectin is found in cartilage.
3. Osteocalcin, osteopontin, and bone sialoprotein are found in bone.
D. Mineral (inorganic) component: none

II. FIBERS

A. Collagen contains two characteristic amino acids: hydroxyproline and hydroxylysine.

1. Synthesis of collagen involves intracellular and extracellular events.
a. Intracellular events include: 
(1) Synthesis of preprocollagen within rough endoplasmic, reticulum (rER)
(2) Hydroxylation of proline and lysine within rER, catalyzed by peptidyl proline hydroxylase and peptidyl lysine hydroxylase
(3) Glycosylation of hydroxylysine within rER
(4) Formation of triple-helical procollagen within rER (involves registration peptides) (5) Addition of carbohydrates within Golgi complex
(6) Secretion of procollagen
b. Extracellular events include:
(1) Cleavage of procollagen to form tropocollagen by extracellular peptidases
(2) Self-assembly of tropocollagen into fibrils (67nm periodicity)
(3) Cross-linking of adjacent tropocollagen molecules, catalyzed by lysyl oxidase

2. Collagen types

Table. Distribution of Collagen Types in the Body                                                                   
Collagen Type                       Location in Body                                                                      
I                                  Fibrocartilage, bone, dermis of skin, tendons;   most ubiquitous type of
                                   the collagen
II                                 Hyaline and elastic cartilage
III                                Liver, spleen, tunica media of blood vessels, muscularis externa of
                                   gastrointestinal tract, lymphatic system; reticular fibers
IV                                Basal lamina, anchoring plaques
V                                 Cornea
VI                                Dermal-epidermal junction (forms anchoring fibrils)                              

B. Elastic fibers consist of an amorphous core of elastin surrounded by microfibrils of fibrillin. Elastic fibers contain two unique amino acids, desmosine and isodesmosine, which are involved in cross-linking.

Ill. CELLS

A. Fixed cells are a stable population of cells that remain in the connective tissue:

I.  Fibroblasts
2. Adipocytes
3. Chondroblasts/chondrocytes
4. Osteoblasts/osteocytes

B. Free cells enter connective tissue from blood and are continuously replaced.

1. Macrophages are antigen-presenting cells that process antigen intracellularly and then incorporate an antigen-MHC complex on their cell surface. Osteoclasts are a type of macrophage found in bone.
a. Macrophages arise from monocytes in bone marrow.
b. They secrete interleukin-l, tumor necrosis factor (TNF), and granulocyte-macrophage colony stimulating factor (GM-CSF).
c. They are activated by lipopolysaccharide (a surface component of gram-negative bacteria) and interferon-y (produced by activated T lymphocytes).
d. They may form foreign body giant cells.
2. Neutrophils phagocytose bacteria, kill bacteria using enzymes contained in specific granules, and digest bacteria using enzymes contained in azurophilic granules (primary lysosomes).
3. Eosinophils destroy parasites (e.g., schistosomiasis, ascariasis, trichinosis) by secreting eosinophil cationic protein, major basic protein, and peroxidase. Eosinophils also reduce the severity of allergic reactions by degrading histamine.
4. B lymphocytes are involved in the humoral immune response and differentiate into plasma cells or long-lived memory cells.
5. Plasma cells are involved in the humoral immune response and synthesize anti, bodies.
6. T Lymphocytes are involved in the cell~mediated immune response and possess T-cell receptors on their surface that recognize antigens on other cells. T lymphocytes can exist as helper T cells (CD4 marker), cytotoxic T cells (CD8 marker), suppressor T cells (CD8 marker), or memory T cells.
7. Mast cells contain IgE receptors on their cell surface. Mast cells secrete histamine, which increases capillary permeability and contributes to hay fever and anaphylaxis; leukotrienes, which cause smooth muscle contraction in bronchioles and contribute to asthma; and heparin. Although morphologically similar, mast cells are not basophils.

IV. CLINICAL CONSIDERATIONS

A. Ehlers-Danlos syndrome is a genetic defect involving peptidyl lysine hydroxylase, an enzyme involved in the synthesis of type III collagen. The syndrome causes rupture of large bowel and/or large arteries.
B. Marfan syndrome is a genetic defect involving fibrillin (a component of elastic fibers). It results in ectopia lentis and a weakened tunica media of the aorta.
C. Homocystinuria is a genetic defect involving the enzyme cystathionine synthetase, resulting in abnormal crosslinking of collagen.
D. Osteogenesis imperfecta is a genetic defect involving type I collagen. It results in spontaneous fractures of bone and blue sclera of the eye.
E. Alport syndrome (hereditary nephritis) is a genetic defect involving type IV Collagen. It causes renal failure and deafness. 

Histology    Epithelial Tissue   Muscular Tissue    Nervous Tissue