1.1.1.5 The connection between keratinocytes and t...
（1）Desmosomes：The epidermal keratinocytes are mainly connected by desmosomes.Other connection methods include adhesion connections，gap connections，and tight connections.Desmosomes are the main structure of the connection between keratinocytes，formed by the dense and thickened local cell membranes of adjacent cells.Under the electron microscope，the desmosomes are disc-shaped and have a paired button-like structure with a diameter of 0.2-0.5μm and a thickness of 30-60 nm.There is a 20-30 nm wide electronic transparent gap in the center，containing low-density tension filaments.The dense layer with higher electron density in the center of the gap is called the central layer；a deeper dyed interline can be seen in the middle of the central layer，which is a highly osmiophilic layer.There is a thickened disc-shaped attachment plate on the inner side of adjacent cell membranes constituting desmosomes，with a length of 0.2-0.3μm and a thickness of about 30 nm.Many tension filaments with a diameter of about 10 nm are attached to the attachment plate in loops and then folded back into the cytoplasm.In addition，there are thinner filaments（transmembrane filaments）that emerge from the inside of the attachment plate，extend into the intercellular space，and are interlaced with the filaments in the central layer（Figure 1-4）.The main proteins that make up desmosomes include：①transmembrane proteins，mainly composed of desmoglein and desmocolin，which form the electronically transparent intercellular space and intercellular contact layer of desmosomes；②desmoplakin in the cytoplasm is a component of the disc-shaped attachment plate，mainly composed of desmoplakin and desmosomal porphyrin.Desmosomes themselves have a strong resistance to tension，and the continuous network of tension filaments between adjacent cells strengthens the connection between cells.The destruction of desmosome structure can cause keratinocytes to separate from each other，forming dermal blisters or bullous skin diseases，such as pemphigus.
（2）Hemidesmosome：It is the main connection structure between the basal cells and the underlying basement membrane zone.It is formed by the irregular protrusions of the basal keratinocytes and the basement membrane zone interlocking with each other to form a similar structure of a half desmosomes，but its constituent proteins are very different from desmosomes.Under the electron microscope，the inner part of the hemidesmosome is a highdensity adhesion spot，and the keratin tension filaments of the basal cells are attached to it；the outer part of the cell membrane is a subbasal dense spot.The dense spots on both sides and the central cell membrane form a sandwich-like structure.The dense spots contain bullous pemphigoid antigen 1/2（BPAG1/BPAG2），integrin，and other proteins（Figure 1-5）.
（3）Basement membrane zone：Basement membrane zone is located between the dermis and the epidermis.Under the optical microscope，Basement membrane zone is dyed by PAS as a 0.5-1.0μmpurple-red homogeneous band，and the silver dip dyeing method can dye it to black.There are also basement membrane bands between the skin appendages and the dermis and around the blood vessels.The basement membrane zone under the electron microscope is composed of 4 layers：cell membrane layer，transparent layer，dense layer，and dense lower layer.
①Cell membrane layer：It is mainly composed of the cytoplasmic membrane on the dermis side of the basal keratinocytes，with a thickness of about 8 nm.The hemidesmosomes span between them.The hemidesmosomes are connected with the tension filaments in the cytoplasm through attachment spots.The other side adhere to the transparent layer with the help of a variety of transmembrane proteins（e.g.，BPAG2，integrin α6β4），to form a rivetlike connection in the basement membrane band.
②Transparent layer：Transparent layer is located under the cell membrane at the bottom of hemidesmosomes and basal cells，with the thickness of 35-40 nm.It appears transparent due to low electron density.The main components are the extracellular matrix composed of laminin and its isomers and anchor filaments.The anchor filaments can pass through the transparent layer to a dense layer，which has a connection and fixation effect.(https://www.daowen.com)
③Dense layer：It is a ribbon-like structure with a thickness of 35-45 nm.The main component is type Ⅳ collagen and a small amount of laminin.Type Ⅳ collagen molecules are cross-linked to form a highly stable continuous three-dimensional grid，which is an important supporting structure of the basement membrane zone.
④Dense lower layer：Dense lower layer，called mesh plate as well，can migrate with the dermis without obvious boundaries；the main component is type Ⅶ collagen.Anchor fibrils traverse in the dense lower layer，combine with anchor spots，connect the dense layer and the underlying dermis，and maintain the connection between the epidermis and the underlying connective tissue.
The four-layer structure of the basement membrane zone is organically combined through various mechanisms.In addition to tightly connecting the dermis and the epidermis，it also has the functions of penetration and barrier.There is no blood vessel distribution in the epidermis.Nutrients in the blood can enter the epidermis through the basement membrane zone，and the epidermal metabolites can enter the dermis through the basement membrane zone.Under normal circumstances，the basement membrane zone restricts the passage of macromolecules with a molecular weight greater than 40000.But when it is damaged，inflammatory cells，tumor cells，and other macromolecular substances can also enter the epidermis through the basement membrane zone.The abnormal structure of the basement membrane zone can cause the dermis to separate from the epidermis，forming subepidermal blisters or bullae.The representative disease is pemphigoid（see extended reading 2）.