Connective Tissue: Active and Non-Active Cells

• Connective tissue is from the mesoderm layer it is made of cells and ground substance (matrix) and fibers.
• Active cell carries out the function and synthesis of protein
• Non-active cells are in a state of rest.

Active cells

• Basophilic cytoplasm
• Pale nucleus
• Abundant rough ER (RER), ribosomes, Golgi apparatus, and mitochondria (Mito).
• Euchromatin

Non-active cells

• Acidophilic cytoplasm
• Deep basophilic nucleus
• Heterochromatin
• Few organelles
• Edema occurs when fluid enters the interstitial matrix and then exits the connective tissue

Connective Tissue Matrix

• Supports and physically connects other tissues and cells for organs
• Gives metabolic support through interstitial fluid for nutrient and waste diffusion
• Originates from embryonic mesenchyme, developing from the mesoderm
• Interstitial fluid is also known as ground substance
• Ground substance: adhesive glycoproteins, and proteoglycans
• Adhesive glycoproteins: Stick cells to the matrix below them
• Fibroblasts are active cells that form fibers of the connective tissue
• Fibrocytes are inactive fibroblasts that can change when needed, such as in the event of bleeding.
• Myofibroblasts close wounds by drawing the edges of the cut skin together,
• Reticular cells are mutated fibroblasts that make reticular fibers in the stroma
• Connective tissue is made of cells, fibers, and matrix
• Cells of the CT exist on a matrix that facilitates cell growth

Types of fibers

• collagen
• reticular
• elastic

Types of Connective Tissue

• CT is categorized into 3 types by the nature of the intercellular matrix:
• Connective tissue proper: soft matrix
• Cartilage: rubbery matrix
• Bone: solid matrix

Connective Tissue Proper

• Supports, binds, and connects various tissues and organs
• 6 types of connective tissue proper include areolar, adipose, yellow elastic, white collagenous, mucoid, and reticular

Types of Connective Tissue Cells

• Resident (Fixed): Fibroblasts, Fixed macrophages, Adipocytes, and Mesenchymal Cells
• Transient (Wandering): Mast Cells, Plasma Cells, Leukocytes, Melanocytes

Fibroblasts

• Most common cells in connective tissue proper, produce and maintain the tissue's extracellular components
• Develop from mesenchymal cells and pericytes
• Large, ovoid, euchromatic nucleus
• Prominent nucleolus
• Numerous in areolar connective tissue
• Branched cell with multiple processes
• Basophilic cytoplasm
• Cytoplasm is rich in RNA, endoplasmic reticulum, Golgi apparatus, and mitochondria
• Fibroblasts can divide
• Form collagen, elastin, and reticulin for connective tissue fibers and also form the mucoprotein of the connective tissue matrix
• Number increases during wound healing or connective tissue damage
• Myofibroblasts are fibroblasts that can close wounds during injury

Fibrocytes

• Mature fibroblasts so also are inactive
• Small spindle-shaped cells with dense nuclei
• Acidophilic cytoplasm
• Few cell organelles
• Unable to divide

Macrophages

• Highly developed phagocytic ability, derived from circulating monocytes
• Specializes in protein fiber turnover,apoptotic cell and tissue turnover, and other particulate material
• Located in areas where there is inflammation
• Branched cells with many processes
• Irregular membrane due to pseudopodia
• Unclear cytoplasm, rich in lysosomes, basophilic in staining, and rich in cell inclusions and phagocytosed particles.
• Small kidney-shaped nucleus, rich in chromatin, and darkly stained
• Present in most organs and are sometimes called histiocytes by pathologists
• Histiocyte cells can be stained with vital stain as Trypan blue
• The TEM shows they have irregular surfaces with pleats, protrusions, and indentations indicative of their active pinocytotic and phagocytic activities.
• They have well-developed Golgi complexes and many lysosomes
• Monocytes cross the epithelial wall of small venules to enter connective tissue, differentiating, maturing, and acquiring the morphologic features of a macrophage
• Monocytes formed in the yolk sac during early embryonic development circulate to developing organs and can become a resident in the tissue
• Long-living cells that survive a long time despite their low activity; when activated due to organ damage, they quickly increase in number through proliferation and recruitment of additional monocytes from bone marrow

Adipocytes

• Fat cells in connective tissue of many organs specialized for lipid storage or heat production.
• Tissue with a large adipocyte population is called adipose, insulates and cushions organs and skin.
• Specialized in concentrating triglycerides, storing little other lipids
• Active metabolically, respond to nervous and hormonal stimuli
• Release hormones and various important substances.
• Adipose tissue is now recognized as an endocrine organ at the center of nutritional homeostasis.

Types of Adipocytes

• Uni-Locular adipocytes: are more common
• Multi-locular adipocytes

Uni-locular adipocytes

• Contains one large cytoplasmic droplet of whitish yellow fat
• Inactive
• Specialized for fat storage
• Stores but doesn't synthesize
• Peripheral nucleus that is crescent-shaped
• Has a signet-ring appearance, with the lipid droplet displacing and flattening the nucleus

Multi-locular adipocytes

• Multiple lipid droplets interspersed among abundant mitochondria
• Cells have multiple lipid droplets interspersed among abundant mitochondria, giving darker appearance
• Primarily produce heat
• Richly supplied with blood like other cells in the connective tissue

Plasma cells

• B-lymphocyte-derived and produce antibodies
• Life Span on average 10-20 days
• Large, oval cells with basophilic cytoplasm, rich in RER
• Large Golgi apparatus near the nucleus; appears pale in routine histologic preparations (-ve Golgi image)
• Spherical and eccentric nuclei
• Prominent nucleoli and peripheral heterochromatin resemble a cartwheel, or clock-face look

Antibodies

• Specific for the antigens that stimulated a clone of B cells to react only with that antigen
• Their average life span ranges from 10–20 days.
• They are derived from B lymphocytes and responsible for the synthesis of immunoglobulin antibodies.
• They neutralize harmful effects caused by antigens.
• Antibody complexes are quickly removed from tissues by phagocytosis.

Mast Cells

• Small cells that develop in bone marrow and differentiate in connective tissue
• Large, ovoid connective tissue cells (20-30 μm in diameter) with a spherical nucleus and cytoplasm filled with large, intensely basophilic granules.
• Not easily identified in human tissue sections without special fixatives, such as toluidine blue, to preserve granules.
• Granules intensely stain and metachromatically due to the heparin, a highly sulfated proteoglycan, and histamine content.
• The cytoplasm small amounts of rER, mitochondria, and a Golgi apparatus.
• Cell surface contains numerous microvilli and folds.
• Nuclei are generally at one end and not central.

Types of mast cells

• Heparin secretory: in the connective tissue of skin and secrete anticoagulant heparin, which is an anticoagulant
• Histamine secretory: in the mucosa lining the respiratory and digestive tracts, secrete histamine.
• Both types of mast cells contain specific receptors for IgE on their surface.

Functions of mast cells

• Considered paracrine cells
• Secrete heparin or histamine or release chemical mediators of immediate hypersensitivity, which may cause anaphylactic shock

Undifferentiated mesenchymal cells

• Give rise to all connective tissues, originate from mesoderm
• Undifferentiated and have large nuclei
• Prominent nucleoli and fine chromatin
• Spindle-shaped, with scant cytoplasm extended into two or more thin cytoplasmic processes

Leukocytes

• Migrate from blood between endothelial cells of venules to enter connective tissue
• This increases greatly during inflammation
• Inflammation begins with the local release of chemical mediators from cells, the ECM, and proteins in blood plasma, all acting on blood vessels, mast cells, macrophages, and other cells to induce inflammation, such as migration of immune cells
• Mostly function for a few hours or days, undergoing apoptosis.
• Lymphocytes and phagocytic antigen-presenting cells will leave the interstitial fluid of CT and enter the blood or lymph to move to selected organs

Pigment cells and melanocytes

• Pigment cell precursor, is called the melanoblast with the mature pigment cell called the melanocyte.
• Two types of pigment produced by melanocytes: eumelanin (brown or black) and pheomelanin (yellow/red)
• Migrate to the stratum Basale of epidermis and neural crest derived.
• Melanocytes also are observed in the eye (uvea), the inner ear, vaginal epithelium, meninges, bones, and heart.
• Melanin is a dark pigment primarily responsible for skin tone and is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation.
• Darker skin tones have more melanosomes than lighter skin tones, and Melanin protects against UV radiation by blocking it from entering the skin
• The DOPA test is used to differentiate between melanocytes and pigmented cells.

Connective tissue originates from the mesoderm layer and consists of cells, ground substance (matrix), and fibers. Active cells have basophilic cytoplasm and abundant organelles, while non-active cells have acidophilic cytoplasm and fewer organelles. Edema occurs when fluid enters the interstitial matrix.