Skin Cells

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Skin Cells

Introduction

Skin is not a tissue but an organ. It is the largest organ present in our body. Skin is made up of a large number of multiple types of cells. Each type of cell plays a significant role that collectively adds to the function of the skin.

Skin not only acts as a barrier between the internal organs and external environment but also serves thermoregulatory and metabolic functions. In this article, we will talk about various types of skin cells, their structure, development, and functions. We will also discuss various disorders associated with these skin cells. So, keep reading.

Types of Cells

As mentioned earlier, skin is an organ having multiple tissue types. In this heading, we will have a general overview of important cell types present in the skin. These include:

  • Epithelial cells or keratinocytes
  • Melanocytes
  • Langerhans cells
  • Merkel Cells
  • Dermal connective tissue cells
  • Nerve endings

Skin is composed of two layers.

  • Superficial layer derived from the ectoderm of the embryo called the epidermis
  • Deep layer derived from the mesenchyme called the dermis

Both these layers join at the dermo-epidermal junction. At irregular intervals, finger-like projections formed by the dermal layer called the dermal papillae invaginate into the invaginations of the epidermal layer called epidermal ridges.

The first four types of cells are located in the epidermis while the rest of the cells are present in the dermis. Details of these cell types are mentioned below.

Keratinocytes

Keratinocytes or the epithelial cells are arranged in the form of multiple layer epithelium called the stratified squamous keratinized epithelium. These cells form the major portion of the epidermis. The thickness of the epidermis varies in different regions of the body. It is thickest at the palms and soles and is referred to as thick skin. The rest of the body organs are covered by a relatively thin layer of the epidermis called thin skin.

Layers of Keratinocytes

The size, shape, and function of keratinocytes vary in different layers of the epidermis. The epidermis is thought to consist of the following five layers of keratinocytes.

  • Stratum Basale: It is the lowest more layer of the epidermis. It is present at the dermo-epidermal junction. The basal layer consists of a single layer of cuboidal or sometimes columnar keratinocytes. These cells are basophilic in origin. The cells in this layer have two types of cell junctions. Desmosomes join the cells to each other in the basal layer while hemidesmosomes join them to the basement membrane. The cells in this layer contain Keratin intermediate filaments.
  • Stratum Spinosum: It is the thickest layer of the epidermis. It consists of polyhedral or polygonal keratinocytes. These cells have a spherical central nucleus. Keratin filaments in these cells are arranged to form microtubular structures called tonofibrils. These tonofibrils converge at desmosomes holding the keratinocytes together in the epithelial layer. Keratinocytes in this layer have slight extensions around the tonofibrils that result in the formation of the spine-like process, thus the name spinosum.
  • Stratum Granulosum: This layer consists of three to five layers of flat keratinocytes having an elongated nucleus. These cells are abundantly filled with basophilic granules called keratohyalin granules.These cells also have specialized Golgi-derived lamellar granules. These are small ovoid structures having multiple lamellae. These lamellae are filled with lipids.
  • Stratum Lucidum: This layer is present only in the thick skin. It consists of a translucent layer of flattened keratinocytes. These cells are highly eosinophilic and are connected via desmosomes.  They have lost nuclei and other organelles and are simple nags filled with keratin filaments.
  • Stratum Corneum: This layer contains 15 to 20 layers of squamous keratinocytes that are filled with keratin filaments.

Development

The epidermis is derived from the ectodermal layer. Its development occurs in different stages that ultimately result in the thickness of the epidermis.

The entire epidermis is derived from a single layer of ectodermal cells. These cells proliferate to form a layer of squamous cells that is called the periderm. In this way, two layers are formed:

  • The primordial ectodermal layer called the basal layer
  • Periderm

The cells in the periderm undergo keratinization and are continuously shed. They are replaced by new cells being formed by the basal layer.

The basal layer later becomes stratum germinativum producing new epidermal cells. These cells get pushed into the superficial layer. At the 11th week, an intermediate layer of cells has been formed between the basal layer and the periderm. By the 21st week, the periderm disappears and is replaced by the stratum lucidum.

Epidermal ridges are also formed by the proliferation of cells in stratum germinativum. These ridges are permanently established by the 19th week of gestation.

Functions

Here, we will talk about the functions performed by keratinocytes present in the different layers of the epidermis.

  • Formation of New Cells: Keratinocytes in the stratum basale are characterized by intense mitotic activity. These are the stem cells that give rise to the keratinocytes present in the rest of the layers of the epidermis. Some progenitor cells are also present in the deeper parts of the stratum spinosum. Both these layers containing the stem cells are called stratum germinativum.
  • Synthesis of Keratin: Keratin is abundantly present in the superficial layers of the skin. It is mainly formed by the cells in the stratum basale. As the new cells are formed, these cells move upward and undergo keratin differentiation. Keratin serves an important protective function in the skin.
  • Formation of Lipid Barrier around the Cells: It is done by the keratinocytes present in stratum spinosum. Recall that these cells contain abundant lamellar granules filled with lipids. Keratinocytes undergo exocytosis of these lamellar granules to form an impermeable lipid-rich layer around the cells. It results in the formation of a lipid barrier that serves as a barrier against water loss in the skin. It also contributes to the sealing effect of the skin.

Clinical Importance

Various clinical conditions are associated with the keratinocytes present in the epidermis. Some common skin conditions are discussed below.

Pemphigus Vulgaris

It is an autoimmune disease characterized by the destruction of desmosomes between the keratinocytes. It is mainly due to IgG antibodies directed against the desmoglein protein found in desmosomes. The patient presents with blisters on the skin and in the oral cavity.

In this disease, the separation of keratinocytes in the stratum spinosum results in the formation of superficial blisters. As the basal cells are attached to the basal layer via hemidesmosomes, they remain intact without any disruption.

The blisters formed in this case are thin-walled and rupture easily. Thus, they can cause considerable dehydration. Upon immunofluorescence, the fishnet pattern of keratinocytes can be seen.

Bullous Pemphigoid

It is also an autoimmune disease in which hemidesmosomes connecting the cells to the basal layer are destroyed. It is due to IgG antibodies that are directed against the collagen fibers present in the basement membrane.

This disease is characterized by skin blisters while the oral cavity is spared. The blisters, in this case, are deep, at the level of dermo-epidermal junction.

These blisters are covered by a thick layer of epithelium that does not rupture easily. It is a clinically mild disease as compared to pemphigus Vulgaris.

Immunofluorescence shows a linear pattern of antibodies along the basement membrane.

Dermatitis Herpetiformis

It is another autoimmune disease specific to the keratinocytes present in the skin. It is characterized by the deposition of IgA antibodies at the tips of dermal papillae. The patient presents with pruritic bullae that are grouped together.

Seborrheic Keratosis

It is a benign proliferation of squamous keratinocytes. It is a common benign tumor of the skin seen in elderly people. It presents as a raised, discolored plaque commonly on the extremities or the face. The plaque often has a coin-like, waxy, stuck-on appearance.

Upon histological examination, it is characterized by keratin pseudocysts. These are the keratin-filled cavities lined by fibrous tissue.

Basal Cell Carcinoma

It is a malignant tumor of the skin characterized by the malignant proliferation of the basal keratinocytes. It is the most common malignancy of the skin in humans.

It presents as a raised nodule having a central ulcerated appearance. The nodule is surrounded by markedly dilated vessels. It has the appearance of a pink, pearl-like papule. Classically, this lesion is seen in the upper lip.

Risk factors for basal cell carcinoma include enhanced exposure to UV light rays and UV-induced DNA damage. It may be due to prolonged exposure to sunlight. It is also seen in patients with albinism and xeroderma pigmentosum. It can be treated by early surgical excision.

Squamous Cell Carcinoma

It is the malignant proliferation of squamous epidermal cells that results in the formation of keratin pearls. Risk factors are the same as in basal cell carcinoma. Additionally, it can also be seen in patients on immunosuppressive therapy for a long period. Arsenic exposure and chronic inflammation are also important risk factors.

It usually presents as a nodular mass on the face, specifically involving the lower lip. The mass is often ulcerated. It can be treated by surgical excision.

Melanocytes

Melanocytes are specialized cells of the epidermis that release melanin, a dark brown or black pigment responsible for the color of skin. These cells are found in the epidermis (in basal layer), and hair follicles. In this part, we will discuss the development, function, and clinical significance of melanocytes.

Development

Melanocytes are derived from the neural crest cells. First, the neural crest cells specify into melanoblasts. After that, the melanoblasts migrate and proliferate, and eventually differentiate into melanocytes. Once formed, the melanocytes undergo a maturation process and start producing melanin. According to research, around 1000 to 2000 melanocytes are found per square millimeter of the skin. It means that approximately 5% to 10% of the cells in the epidermal basal layer are melanocytes.

Function

Melanocytes produce melanin in a process known as melanogenesis. In this process, an enzyme called tyrosinase which is a transmembrane enzyme, converts tyrosine into 3,4-dihydroxyphenylalanine. This chemical is then further processed and polymerized into different forms of melanin.

Melanin is found in the skin, eyes, hair, ear, and nasal cavity. An important piece of information is that the skin color variations between people are not due to differences in the number but due to differences in the activity of melanocytes. The main function of this black pigment is to protect the deeper layers of skin from UV radiation. Due to its black color, the melanin absorbs the UV light and hence the UV radiations are unable to pass through the epidermis.

Melanocytes also play a role in the immune system where they are considered to be immune cells. The immune functions of melanocytes are the presentation of antigen to T-cells and phagocytosis. Melanocytes are also involved in the production and release of proinflammatory mediators such as cytokines. These cytokines include IL-1, IL-3, IL-6, and IL-8.

Clinical Importance 

There are various conditions related to a disturbance in the production or function of melanocytes. Some of them are discussed below.

Melanoma

Melanoma or malignant melanoma is a type of cancer that develops from melanocytes. It is predominantly a cancer of the skin but it may also develop in the mouth and intestine. The primary cause of melanoma is exposure to UV radiation from the sun or tanning devices. Treatment of melanoma may involve surgery, radiotherapy, and chemotherapy. The survival rate of patients becomes very low if cancer spread to lymph nodes (metastasis).

Vitiligo

Vitiligo is a skin condition in which certain areas of skin lose their melanin and become white. In genetically susceptible individuals, certain factors such as autoimmune diseases trigger a response that results in the destruction of melanin. There is no cure for vitiligo but some treatment options exist that help to darken the white patches.

Albinism

Albinism is a congenital absence of pigmentation in the body due to decreased activity of tyrosinase or defective tyrosine transport. Individuals with albinism have very pale skin and eyes. Eyesight problems and increased susceptibility to skin cancers are some important problems seen in people with albinism.

Melasma

Melasma is a hyperpigmentation of skin strongly associated with pregnancy and the use of oral contraceptive pills. In this condition, melanocytes increase in number, and melanin production is also increased, resulting in patchy hyperpigmentation of the skin.

Addison disease

In Addison disease, the hormones that stimulate melanin production are elevated. This results in increased melanin production and darkening of the skin.

Langerhans cells

Langerhans cells are antigen-presenting cells derived from monocytes and found in all layers of the skin. These cells are most prominent in the stratum spinosum. An important feature of these cells is the presence of Birbeck granules. Langerhans cells make 2% to 8% of the cells present in the epidermis.

Function

Langerhans cells play an important role in the skin’s adaptive immunity. Langerhans cells work like dendritic cells: they bind the antigen, process it, and present the antigen to T lymphocytes. Under normal circumstances, these cells prevent an unnecessary immune response in the body. But when they sense danger signals, they stimulate allergic responses to protect the body.

Clinical Importance

Defects in the production or function of Langerhans cells cause various diseases and conditions in the body. Some of them are discussed below.

Langerhans cell histiocytosis

In Langerhans cell histiocytosis, there is an abnormal clonal proliferation of Langerhans cells. Abnormal cells derive from bone marrow and then migrate from the skin to lymph nodes. Some common signs and symptoms are fever, lethargy, weight loss, bone swelling, scaly erythematous skin lesions, and liver enlargement.

HIV

In HIV, Langerhans cells may be the initial target, reservoir, and/or vector for dissemination.

Dengue fever

The dengue virus that causes dengue fever, targets the Langerhans cells in the early phases.

Merkel Cells

Merkel cells are oval-shaped cells that are essential for light touch sensation. They are present in the skin but mostly they are present abundantly in the tips of fingers of humans. This makes the skin of the finger a highly sensitive skin which is necessary to do high skill activities.

Development and Function

The origin of Merkel cells has been a topic of debate in science. Previous researches have suggested that they arise from neural crest cells. But most recent studies indicate that they are epithelial in origin. Merkel cells are mostly found in the Stratum Basale and they are about 10 um in diameter.

Merkel cells are also called tactile epithelial cells. They work as mechanoreceptors that mediate the senses of light touch. They may also sense hair movement. They also contain dense core granules, that are suggestive of a neuroendocrine function.

Clinical Importance

Merkel cell carcinoma

Merkel cell malignancy is extremely rare and only 3 people in a population of 1,000,000 people develop this cancer. It is more common in older people and arises on the head, neck, and extremities. Merkel cell carcinoma arises in the form of a small red or blue nodule that may be painless or itchy. Prevention mainly involves the use of sunscreen and limiting sun exposure. Radiation therapy and surgery are the primary steps in the management of Merkel cell carcinoma.

Dermal connective tissue cells

Beneath the epidermis, a layer of connective tissue is present that supports the epidermis. This layer is called the dermis and it is mostly composed of collagen fibers, elastic fibers, and different types of cells. Dermis also contains blood vessels, sweat glands, and hair follicles.

The cells that are present in the dermis are fibroblast, macrophages, adipocytes, mast cells, leukocytes, stem cells, and Schwann cells. The upper papillary layer of the dermis contains more cells and the lower reticular layer contain fewer cells with abundant fibers. Here is an overview of some cells present in the dermal connective tissue.

Fibroblasts

Fibroblast is the primary cells of the dermis that synthesizes collagen and extracellular matrix. These cells play an important role in building a structural framework of tissues. Moreover, fibroblasts are also involved in tissue repair after injury.

Mast cells

Mast cells are known due to their role in the immune system. These cells contain many granules rich in heparin and histamine and thus play a key role in the inflammatory process. They release mediators such as histamine, cytokines, serotonin, etc., that are involved in inflammation.

Adipocytes

Adipocytes are derived from mesenchymal cells and they store energy as fats.

Stem cells

Some cells, present in the dermis, are able to develop into different types of cells. These cells mainly serve as a repair system for the body.

Summary

  • Skin is composed of two layers: the upper layer called the epidermis and the lower layer called the dermis. There are many types of cells present in the skin such as keratinocytes, melanocytes, Merkel cells, fibroblast, and Langerhans cells. Keratinocytes are from the major portion of the epidermis and are present in the form of different layers. These layers include stratum Basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.
  • Some important functions of keratinocytes are the formation of new cells, synthesis of a protein called keratin, and formation of a lipid barrier around the cells. Various skin conditions are associated with keratinocytes such as Pemphigus Vulgaris, Bullous Pemphigoid, Dermatitis herpetiform, Seborrheic keratosis, Basal cell carcinoma, and Squamous cell carcinoma.
  • Melanocytes are melanin-producing cells derived from neural crest cells and present in the epidermis. Melanocytes produce melanin which protects the body from harmful UV radiations. Moreover, melanocytes also play an important role in the immune system. Melanoma, vitiligo, melasma, albinism, and Addison disease are some conditions associated with the disturbance in melanocyte production or function.
  • Another type of cells present in the skin are Langerhans cells that are antigen-presenting cells. They play a key role in the skin’s adaptive immunity. In the epidermis, Merkel cells are also present that are involved in sensing light touch.
  • In the dermis, many cells are present such as fibroblasts, mast cells, macrophages, adipocytes, stem cells, and leukocytes. The primary cells of the dermis are fibroblasts that synthesize collagen fibres and provide a framework of tissues. Mast cells release inflammatory mediators while the adipocytes store energy in the form of fats.

References

  1. Junqueira’s Basic Histology: Text and Atlas, 15th Edition
  2. The Developing Human : Keith L. Moore, 11th Edition
  3. Fundamentals of Pathology : Hussain A Sattar