Connective Tissue

Loose connective tissue (aka areolar tissue): loosely arranged fibers plus cells of various types. The cells are separated widely by intercellular ground substances. They are located under epithelia that cover the body surfaces and line the internal surfaces, as well as being associated with epithelium of glands, and surrounding blood vessels, muscles, and nerves. It also plays a role in immunity, inflammation, and diffusion of nutrients, oxygen, CO2, and waste.

Dense connective tissue: contains more collagen than cells. Include the following types:

• Regular dense connective tissue: contains collagen fibers preferentially oriented and densely packed. It is found in tendons, ligaments, and cornea.
• Irregular dense connective tissue: contains collagen fibers randomly oriented, as well as reticular and elastic fibers. It is found in the dermis of the skin and in the submucosa of hollow organs (i.e. intestine), providing resistance to stretching and tearing.

Extracellular Matrix: complex and intricate structural network surrounds and supports cells within the connective tissue. It consists of fibers (collagen, elastic, and reticular) and ground substance (proteoglycans).

Collagen Fibers are made up of fine fibrils, which exhibit a 68 nm banding pattern due to precipitation of the TEM stain. They are the most abundant fibers of connective tissues, appearing wavy in LM. They stain easily with Eosin, and other acidic dyes. Collagen fibrils are assembled extracellularly.

• Fibroblasts (and closely related myofibroblasts), which are the principal cells of connective tissue. They synthesize collagen, elastin, reticular fibers, and complex carbohydrates of ground substance.
• Macrophages, also known as tissue histiocytes. They are phagocytic cells derived from monocytes in the bone marrow. They possess lysosomes and finger-like projections. Secretion (proteases and GAGases) helps migration of macrophages into the connective tissue. Their main functions are phagocytosis (i.e. defense and clean up of cell debris) and play a role in immune reaction by presenting (via MHC II) concentrated antigens derived from phagocytosed foreign cells or proteins to CD4+ T lymphocytes. They are called antigen-presenting cells (APC). They may fuse to form a large cell with up to 100 nuclei, and phagocytose exceptionally large bodies. These cells are called Foreign body giant cells or Langhan’s cells. The Mononuclear Phagocytic System (MPS) include macrophages (Histiocyte) in connective tissue, perisinusoidal macrophages (Kupffer cell) in the liver, alveolar macrophages (Dust cell) in the lungs, Osteoclasts in bone, Microglias in the central nervous system (CNS), Langerhan’s cells (APC) in the epidermis, Hofbauer cells in the placenta, fibroblast-derived macrophages in the lamina propria of the intestine, and macrophages in the spleen, lymph nodes, bone marrow, and thymus.
• Adipose cells
• Mast cells are large ovoid connective tissue cells containing granulated cytoplasm. They are related to the blood basophil cells, which contain similar cytoplasmic granules. Their precursors migrate to connective tissues and differentiate into mast cells. The cytoplasmic granules contain vasoactive and immunoreactive substances. These are released upon stimulation by an antigen to which the individual cell has already been sensitized (i.e. an antigen-antibody reaction). They are distributed mainly in small blood vessels, skin, and capsules of organs. They are ABSENT from the brain and spinal cord, which protects them from damage due to edema from allergic reactions. The four substances released are Histamine (causing edema), Slow-reacting substance of anaphylaxis [SRS-A] (bronchospasm), Eosinophil and neutrophil chemotactic factors (attract eosinophils and neutrophils to the site of inflammation), and Heparin.
• Undifferentiated mesenchymal cells (adult stem cells)

• Lymphocytes, which are principally involved in immune responses. They are the smallest free cells (diameter of 6-8μm), containing a thin rim of cytoplasm that may not be seen with LM. Normally, there are only a small number of lymphocytes found in all connective tissue, which then increases dramatically at sites of inflammation. They are most numerous in the lamina propria of respiratory and GI tracts (immunosurveillance).
• Neutrophils
• Eosinophils
• Basophils
• Monocytes
• Plasma cells, which are a prominent component of loose connective tissue of the GI tract, respiratory tract, salivary glands, lymph nodes, and hematopoietic tissue. They have display many characteristics of protein synthesis and secretion, including strong basophilia in the cytoplasm, multiple rER, extensive Golgi complex, prominent nucleolus, and the heterochromatin in the nucleus is radially arranged to resemble spokes in a wheel (cartwheel).