1. Connective tissue Functions of CT: a. Structural support
b. A medium for exchange (so it is vascular except dense CT.)
c. Helps in defense & protection of the body.
d. A site for storage of fat.
TYPES:
Mature CT Embryonic CT
a.CT. proper A.Mesenchymal B.Mucous
b. Specialized CT (cartilage, bone and blood).
Components of CT:
1-Cells.
2-Extracellular matrix (ground substances and fibers).

2. Extracellular Matrix of CT. proper
I-Ground substance It is an amorphous gel-like hydrated material composed of: 1. Glycosaminoglycans: are negatively charged, rod-like chains of repeating disaccharides that have the capability of binding large quantities of water. 2. Proteoglycans: constitute a family of macromolecules, each is composed of a protein core to which glycosaminoglycans are covalently bonded. 3. Glycoproteins: cell adhesive materials have binding sites for several components of the extracellular matrix a as well as for the integrin molecules of the cell membrane that facilitate the attachment of cells to the extracellular matrix. Ex. Fibronectin and laminin.

3. II-Fibers *Collagen fibers, are tough, firm, inelastic and possess great tensile strength. Each fiber is composed of fine subunits called tropocollagen whose α-chain amino acid sequences permit the classification of collagen into at least 15 different fiber types.They are stained with H&E as long wavy pink fiber bundles. By EM the fibers show cross-banding at regular intervals. Each fiber is formed of parallel aggregates of thinner fibrils. The fibrils are formed of smaller subunits called tropocollagen molecules. Each tropocollagen molecule is formed of polypeptide chains (α-chain)

4. Collagen synthesis By fibroblast.
It occurs by ribosomes on RER as indivedual preprocollagen chains(α-chains), then it enters the cisterna of RER to be modefied into procollagen molecules that leave RER as trnsfere vesicles to enter Golgi apparatus to be changed into tropocollagen molecules which arranged into fashioning fibrils that show banding specially in collagen type I, II, III, V and VII. Fibrillar structure is absent in type IV collagen.

5. Types of collagen fibers
Type I collagen: the most common type, forms thick fibers and is present in CT. proper, bone, dentin and cementum.
Type II collagen: forms slender fibers and is found in matrices of hyaline and elastic cartilage.
Type III collagen: is referred to reticular fibers. It is highly glycosylated thin fibers that stained with Silver or PAS
Type IV collagen: Lamina densa of the basal lamina.It does not possess a periodicity and not assembled into fibers instead it forms a meshwork of procollagen molecules matted together to form a supporting carpet of basal lamina.
Type V collagen: forms a very thin fibrils that associated with type I collagen and in the placenta.

6. Type VII collagen: forms small aggregates known as anchoring fibrils that secure the basal lamina to the underlying type I and III collagen fibers.
*Elastic fibers: are usually slender, long, and branching. They may form coarser bundles, as in ligaments, and fenestrated sheets, as in aorta. They are formed by fibroblasts and smooth muscle. They are composed of core of elastin and microfibrils of glycoprotein(fibrillin).

8. Collagen type I

9. CT.Cells I-Fixed cells: 1.Fibroblasts 2.Adipose cells. 3.Pericytes.
4.Mast cells.
5.Macrophages.
II-Transient cells:
1.Plasma cells.
2.Lymphocytes.
3.neutrophils, eosinophils and basophils.
4.Macrophages.
5.Monocytes.

10. CT. Cells

11. Fixed CT. Cells I-Fibroblasts
They are the most abundant CT. cells and derived from undifferentiated mesenchymal cells.
Types:
1- Active fibroblasts: are elongated, fusiform cells with pale blue-staining cytoplasm rich in RER and pale-stained large ovoid nucleus containing well-defined nucleolus.
2- Inactive fibroblasts (fibrocytes): are smaller and are more ovoid with acidophilic cytoplasm.
Fibrobalsts are responsible for the synthesis of almost of extracellular matrix.
They can differentiate into adipose cells, chondrocytes and osteoblasts.

13. Myofibroblast
Histologically : by LM they are similar to fibroblast, but by EM they have bundles of actin filaments as smooth muscle, but they have no basal or external lamina.

14. II-Adipose cells (fat cells or adipocytes):
They are derived from undifferentiated mesenchymal cells.
They are fully differentiated and do not undergo cell division.
There are 2 types:
A-Unilocular adipocytes, form white adipose tissue: they are large cells, they store fat as one droplet, which enlarge pushing the cytoplasm and the nucleus peripherally against cell membrane (signet-ring appearance). They have few mitochondria , few RER but abundant free ribosomes. The fat droplet is not bounded by a membrane. They have basal lamina-like substance.
B-Multilocular adipocytes, form brown adipose tissue:
Are small cells with multiple fat droplets, central spherical nucleus and many mitochondria.
* They function in the synthesis, storage and release of fat.

15. Adipocytes

16. Multilocular adipocytes

17. Classification of CT.
A-Embryonic CT:
1.Mesenchymal CT: Is present only in the embryo (in adult in pulp of teeth) and consists of mesenchymal cells in a gel-like ground substance containing scattered reticular fibers.
Mesenchymal cells are small cells with pale staining cytoplasm with small processes and a small pale nucleus with prominent nucleolus.
2.Mucous (mucoid) tissue:
It is formed of ground substance of hyaluronic acid, collagen types I &III and fibroblasts.
It is known as Wharton’s jelly and is found in umbilical cord and sub-dermal CT. of the embryo

18. Embryonic Mucous CT.

19. 2. Reticular CT: Type III collagen is its major component
2.Reticular CT: Type III collagen is its major component. Collagen forms mesh-like networks interspersed with fibroblast and macrophages. It forms the architectural framework of liver sinusoids, adipose tissue, lymph nodes, spleen, smooth muscle.It stained with silver

20. 3.Adipose tissue: It is divided into white (unilocular) adipose tissue and brown (multilocular) adipose tissue. It is rich in blood vessels

21. b. Dense regullar collagenous CT:
it is composed of coarse collagen bundles that oriented into parallel sheets. It has few ground substances and fibroblasts between collagen bundles.Ex. Tendons, ligaments and aponeuroses.

22. c.Dense regular elastic CT: it has coarse branching elastic fibers with only collagen fibers forming networks and scattered fibroblasts. Elastic fibers are arranged parallel to one another and form either thin sheets or fenestrated membranes as in large blood vessels, ligamenta flava and suspensory ligament of penis.

23. III-Pericytes
Are derived from mesenchymal cells partly surround the endothelial cells of capillaries and small venules. They have their own cell basal lamina. They have primary and secondary processes that wrap around blood capillary. They may differentiate into smooth muscle and endothelial cells

24. They are derived from bone marrow stem cells.
IV.Mast cells:
They are derived from bone marrow stem cells.
Their cytoplasm is rich in membrane-bound granules that stained metachromatically with toluidine blue.
The granules contain heparin, histamine, eosinophil chemotactic factor and neutrophil chemotactic factor.
They are present in subepithelial CT.,CT. around small blood vessels, and subepithelial CT. of digestive and respiratory tracts (mucosal mast cells that secrete histamine).
* Histamine causes vasodilatation and increase permeability of blood vessels. It causes bronchospasm and increase mucus production in respiratory tract.

25. Mast Cell

26. They are active mononuclear phagocytes.
V-Macrophages
They are active mononuclear phagocytes.
Some are fixed and others are transient .
They are irregular in shape and have filopodia.
Their cytoplasm Is basophilic with small eccentric indented nucleus, prominent RER, well developed Golgi and an abundance of lysosomes.
They derived from monocytes that localized in different regions, EX. in liver (Kupffer cells), in lung (dust cells), in CT.(macrophage), in skin (Langerhans cells) and in blood (monocytes).
Several monocytes can fuse together forming foreign-body giant cell.
They phagocytose foreign substances and debris.

27. Macrophage

28. Macrophages

29. Transient CT. cells I-Plasma cells
They are derived from B-lymphocytes after exposure to an antigen.
They secrete antibodies (protein in nature).
They are large ovoid cells with intensely basophilic cytoplasm that is rich in RER and Golgi (pale-staining region) adjacent to the nucleus. The nucleus has hetero-chromatin radiating out from the center (clock-face appearance).

30. Plasma Cell

31. II-Leukocytes
They are white blood cells that circulate in blood stream then migrate through capillaries to enter CT. during inflammations, invasion by foreign elements and immune response.

32. The loose CT of mucous membranes is called lamina propria.
B-Connective tissue proper
1- Loose (areolar CT):
It fills in the spaces of the body just deep to the skin, below the mesothelium lining of internal body cavity, adventitia of blood vessels and surrounds the parenchyma of glands.
The loose CT of mucous membranes is called lamina propria.
It is characterized by abundant ground substance and tissue fluid housing the fixed CT. cells, undifferentiated cells and collagen, reticular and elastic fibers.

33. Loose (Areolar ) CT.

34. Loose CT

35. 4. Dense CT:
It has many more fibers and fewer cells than ordinary CT.It is formed of three types:
a.Dense irregular collagenous CT: it is formed of randomly arranged collagen fibers, few ground substances and fibroblasts scattering between collagen fibers. It constitutes the dermis of skin, the sheath of nerves and capsules of spleen, testes, ovary and lymph nodes.

36. BASAL LAMINA AND BASEMENT MEMBRANE
Structure:
It is formed of:
1- Lamina densa: network of type IV collagen.
2- Lamina lucida (lamina rara):
an electron-lucent layer on one or both sides of the lamina densa.
It consists mainly of glycoprotein laminin.
Basal lamina:1+2 (E/M term)( nm thick)
It is visible only by E/M.
3- Reticular lamina (Lamina reticularis) ( Lamina fibro-reticularis).
Basement membrane: (is seen by L/M as PAS +ve structure)

37. Components of basement membrane:
1- Type IV collagen.
2- Proteoglycans:e.g. Heparan sulfate.
3- Glycoproteins:e.g. Laminin, Fibronectin
4- Type VII collagen: anchoring fibrils.
5- Type III collagen (Reticular fibers):
Produced by C.T. cells (Fibroblasts).

38. Sites (Distribution) of b.m.& External lamina:
Where cell types come into contact with C.T.
Cell types:e.g.1- Epithelium,
2- Muscle cells:
Smooth & skeletal muscle cells,
3- Adipose cells,
4- Schwann cells.
N.B. External lamina is a structure similar to b.m. That surrounds 2, 3 & 4.

39. Basement Membrane: 1- L.Rara. 2- L.Densa 3- L.Fibroreticularis

40. Basal lamina

41. Basal Lamina