Getting to know the skin

It is the largest organ of the human body, which reaches up to two square meters in an adult. Its main role is in protection, which is both physical and immunological protection, in regulating the homeostasis of the body, and in metabolism, it is more specific by interfering in the production of vitamin D. It consists of three layers: epidermis, dermis, and hypoderm.

Epiderm

Epidermis, which is epithelial cells called keratinocytes (92%) and the rest is Langerhans immune system cells, lymphocytes, melanocytes, etc., is formed by the accumulation of keratinocytes in hair follicles, sebaceous glands and sweat glands (eccrine-apocrine). They are considered the first line of defense from the lowest layer called basal or germinal. They are produced from cell stem cells (10% basal) which are multipotent cells (close to the hair follicle) and these germinals are connected to the basement membrane.

The second layer is the spinous epidermis, these cells strengthen each other and the basement membrane with their spiny appendages, which become closer to the surface with further development, where the granular cells (third layer) are said to be active in the production of some substances (ceramide). and other fats, proteins, and keratin) until this stage, it takes 14 days to reach the last layer, which is the corneum, and they stay for 14 days to be removed in the form of pus in the bathroom, which occurs in the course of evolution, a cell suicide (apoptosis), which is called cornification .

1- Keratinocytes, which are in the natural immunity of nature (anatomy and physiology, including natural antibacterial substances, thick and cornified, and good commensal bacteria, normal skin temperature and pH conditions) and natural can be created by itself and other existing cells

2- Langerhans, which is 3% of the cells of the derapiderm, which samples the antigen (allergen) and with the help of the specific receptor of the EGE molecule as a presenting cell (representing) the allergen to T cells, macrophages, or dendritic cells.

3- Merkel tubercle, which is near nerves, sebaceous glands and hair follicles, and although it is a type of keratinocyte, it is special, especially in sensitive and nerve-rich areas of the skin and face.

4- Melanocytes, which play a role in the regulation of the immune system, and the main job is to produce pigment

Unlike the epidermis, the dermis does not have many cells and two vascular networks on the surface

The papillary dermis is said to be twice as thick as the epidermis, where the epidermis penetrates in a finger-like manner and fills most of the volume of the dermis matrix, which also adheres to the basement membrane.

The reticular dermis, which is lower and is ten times thicker than the epidermis, and its matrix is ​​thicker and has more fibers. 72% of the matrix is ​​collagen 1 and 3 (there are 21 types of collagen).

Fibroblasts, which both make collagen and help in natural immunity and inflammation, are abundant in the papillary region along with mast cells. We have two types of mast cells: they produce trypase or chymase. In addition to allergies, mast cells also play a role in autoimmunity such as MS and RA. They are involved in the defense of bacteria and parasites, formation and repair, and they react to physical blows to the skin and mentally to the person.

We said that there are two large vascular networks in the skin that play a major role in thermoregulation. Vascular endothelium cells, which we call pericytes in the case of capillaries and blood vessels, play a role in both homeostasis and immunity, especially with the receptors they have in the passage of immune cells from The vessel wall plays a major role

There is a strong lymphatic network in the skin, which, in addition to debris, leads macromolecules to the lymph nodes of each region and then to the main path of the tracheic duct.

There are many nerves in the skin, which have a wide network in the surface and depth of the dermis, although they are more in the papillary dermis, the itch nerves are separate from pain, burning and heat, they are mainly C fiber, but it is also myelinated, but at the end, they are completely naked to work better and objects (corpus kole) in the skin called Meistner (for touch), Pacini (for vibration) and Veraphini (for stretching) nerves enter the sweat glands (apocrine and eccrine) and sebaceous glands and hair follicles. The role of sweat glands and sebaceous glands in better body immunity They have understood the hair follicle

It has three layers

1- Lamina lucida, which is hemi-desmosis, which is the filaments between the cytoplasmic membrane of basal cells and the membrane of cells, has different laminins and can be easily and quickly torn.

2- The lamina densa, which is the main membrane of the tissue, which contains type 4 collagen and proteoclycans, which are anchor plugs for the fibrils, and is thick

3- Fibril layer which is inside both main parts

The main part of this connection is the matrix, which means the same fibers that are the secretions of BazL cells or from fibroblasts.

Apply connection area

1- Keeping the epidermis firm and preventing it from separating

2-Interference in the growth of different cells

 3- Being semi-permeable

Hypo dermis

Hypodermis, which is the accumulation of fat and acts as a temperature insulator

Natural defense of the skin: is it natural or induced?

Natural defense

1- Normal flora, such as coriniforms and staph epidermidis, and a fungus called molasses, compete with pathogens.

2- The corneum layer, although the cell is dehydrated, fatless and dead (unsuitable for bacterial growth), but it is physically a barrier, and pathogens are thrown away during the pus bath.

3- Enzymes, peptides and immunoglobulin M (from sweat) active in fighting microbes

4- Fats such as sphingosine and free fatty acid that prevent the growth of bacteria by changing the pH and are basically antibacterial.

5-Lactic acid from the eccrine glands makes sweat pH acidic

6- The natural temperature of the body acts as an anti-bacterial

Induced natural defense

Pattern Recognition Receptor or PRR on the part of the body interferes with the pathogen associated molecular pattern on the part of the invader in immunity.

PRRs include toll-like receptors – maneuver receptor, CD1A and lipopolysaccharide receptor, which are both soluble, endocytic (inside the cell) and on the cell surface.

PAMPs included

 1-CPG Cytosine Phosphatide Guanine

 2- DNA of bacteria

3- RNA of influenza virus

4-Gram-positive lipotechoic acid

5- Gram-negative lipopolysaccharide

6- Peptidoglucan of bacteria 

7- Phosphoglycan of parasites

 8- Glucan of fungi such as fungal zymosan

1- Interleukin 1, which is always stored in keratinocytes and is released by physical trauma, let alone by contact with bacteria, and the reason why we have itching-scratching in defective ring eczema is that interleukin can lead to all 4 signs of inflammation, including pain- Swelling-heat and redness

Keratinocytes also have large amounts of PRRs, which can lead to the occurrence of PRRs on the level of leukocytes.

2- The order of peeling and frequent repairs, as in digestion, the parasites are removed by the shedding of intestinal mucus

3- Neutrophil cells and others must do their best before interfering with acquired immunity whenever an invader enters the skin.

4-Polypeptide such as interferon alpha, which is produced by keratinocytes and is anti-viral

5-Components of complement, vesponin, and anaphylotoxin, and CRP

6-PRR, which interacts with PAMP on behalf of cells and their secretions, on the part of bacteria, so that activities such as phagocytosis occur and lysosomes destroy the invader.

The most important PRRs are toll-like receptors, which cause chemotaxis of cells such as neutrophils and monocytes, and sometimes eosinophils in PRRs are also called mannose receptor and lipopolysaccharide receptor.

In the papillary, the activated Langerhans cells enter the lymph flow and reach the lymph nodes, and the lymphocytes are activated, and substances such as TNFα and interleukin

 1- They can act according to the corresponding PRR of the dendrite cell surface. 

Dendritic cell is the bridge between natural and acquired immunity, where the antigen (allergen) is delivered to the B or T lymphocyte cell to deal with it specifically.

After entering the Langerhans or dendritic cells into the lymph nodes, the acquired immunity acts, which have the role of presenting the antigen (allergen) and the acting cells are either T or B. Antibody production can be done with the help of T cells or his help. Unlike digestion and breathing in the skin, the production of antibodies is in the lymph nodes, not the site of inflammation, which reach them through the bloodstream. 

In the sweat glands, all 5 classes of immunoglobulin are found, and in the sebaceous glands we have EGA, in the skin we do not produce local IgE (unlike breathing).  

Acquired immunity is divided into 4 categories

Antibody-dependent cytotoxicity is mainly caused by EGG1 and EGA, or by fixing complement and secreted EGA as opsonin. Of course, we do not have a problem with congenital EGA defects because it is compensated by secreted IGM.

IGG4 and EGE with the help of T helper 2 and interleukin 4 and 13 lead to allergies. Antibodies against desmosome and hemidesmosome lead to immune blistering diseases of the skin, insect bites, drug reactions and diseases related to eosinophils, and simpler, the same as urticaria, angioedema, and anaphylaxis. There are categories

The formation of immune complex in connective tissue and autoimmune diseases also occurs in the skin, Arthur’s reaction

Cell-dependent cytotoxicity that Manto’s reaction in the tuberculin test and the formation of granuloma in tuberculosis sarcoid and transplant rejection and most importantly contact dermatitis

In the skin, we have functional memory T cells, E and normal T cells, and normal NK cells, but we do not have B and NKT lymphocyte cells.

Antigen-presenting cells in the skin include Langerhans, dendritic cells, and macrophages that activate resident T cells or bring them from the bloodstream because there are strong blood vessels, nerves, and lymphatics in the skin.

Neuropeptides of the nervous system play a role in innate and acquired immunity. In the function of induced innate immunity, the operation starts immediately, but in the case of acquisition, it takes a few days for the first time, and if there is a memory at work, one day, and sooner if the memory is repeated a lot.

 In acquired immunity according to the type of helper T cell, four pathways can be activated (preferably by looking at allergies)

A: Activation of T Helper1, which is the presence of tollic acid 4 (dendritic cell) and lipopolysaccharide formation of bacteria and the production of interleukin 12 and then normal immunity with the production of EGG, A, M and…

B: The activation of T Helper No. 17, which is a kind of normal route with the help of Interleukin 23, is not well known until today.  

C: Activation of T Helper 2, which is caused by the presence of histamine and toll-like 4 from dendritic cells, by switching the action of B cells towards the production of EGE and the production of allergies, and the reduction of the antibacterial activity of keratinocytes (infection on eczema)

The general and old definition of allergy, which is an acquired (new) hyperreactivity to harmless and previously neutral substances that leads to the creation of types of hypersensitivity.

A new and specific definition of allergy, which is a reaction that increases IGI and histamine and increases eosinophils through T Helper2, and the factor that causes this is called an allergen.

1- Autoallergens (autoantigens) which are from inside the body and the FC1 molecular receptor

IGE 2- Animal products

3- Plant products

4-Infections

 5-Chemical contact materials

 6- Foods 

7- Medicines 

8-Physical strikes

Gel-Combs classification, which has 4 types of hypersensitivities, specifies that one type (type 1) is specific and called allergy, but allergic diseases can be a combination, such as atopic dermatitis, which is type 1 and type 4, or all types are involved or beyond This is the division

It originates from the bone marrow (under the influence of interleukin 3 and after it is made, it develops under the influence of interleukin 5 and 9, which is inhibited by gamma interferon) and is in the sub-epithelial of the whole body and in the skin up to 10,000 per cubic millimeter. There is a lot of interest in being close to nerves, glands, and hair follicles. There are two main types that either secrete chymase or tryptase, but most of them produce both, which are in the skin of the entrances. The type that only secretes tryptase is in the intestines and breathing. The type that only secretes chymase is rare

Mast cell can attach the EGE molecule to its specific receptor on its surface without the intervention of the allergen and cause disease, and it can also directly attach to the B cell without the help of T Helper and produce EGE.

 Mast cell has products that other than histamine and heparin and… (pre-made ones) include various cell growth factors and cytokines such as TNFα and interleukin 4 and fat mediators (leukotrienes, prostaglandins and platelet activating factor) Ha) which are made after the order

Mast cell applications

1- Defense against parasites and bacteria

2- control the tonicity of the vessels and the permeability of the vessels

3- Role in repairing and inhibiting inflammation and angiogenesis

4- Understanding and responding to immunological factors such as EGE and TNFα and anaphylotoxin such as CDα

5- Understanding and responding to non-immunological factors such as heat – UV rays and mental stress

Mast cell plays an important role in the pathogenesis of autoimmunity such as MS and RA

 D: activation of T vessels that play a role in tolerance with the help of interleukin 10 (such as allergy vaccine treatment), actually energy 

  First of all, it should be said that the immune system and the nervous system have an active interaction with each other and regulate each other in strengthening and inhibiting each other. The inflammation caused by the involvement of the immune system with the pathogen must be stopped so that the new homeostasis can be replaced and we can repair and create granulation tissue. in the following ways

1- The absence of an invader means that PRR is not activated, so neither innate nor acquired immunity will work

2- Interleukin 1 antagonist is secreted from keratinocytes

3-TGBFβ from the macrophage itself causes the death of phagocytosing cells and the same substance from TRGs inhibits

T becomes Helper

4- Extracellular accumulation of adenosine and… reduces inflammation

5-interferon Ɣ inhibition of T Helper2

6-Interleukin 10 inhibition of T Helper1

7- Apoptosis of Langerhans and neutrophils

8-Tolerance that is either caused by suppressive T cells or unresponsiveness of T cells (anergy)