Understanding Cutaneous Immunology

Introduction:

Mammals have numerous layers of ectodermal tissue that make up their skin, an organ of the skeletal system that protects the underlying muscles, bones, ligaments, and internal organs. Skin is the outermost layer of the body that contains a complex network of different cell types that engage in plastic and dynamic cellular communication. It serves as a barrier against several external diseases and environmental toxins. In addition, the skin performs vital homeostatic duties such as preventing water loss and supporting body temperature regulation. The cellular composition and structure of the skin joined together to fight physical and chemical threats from the outside world.

What Is a Cutaneous Immune System?

The term cutaneous, which comes from the Latin word cutis, means of the skin. The skin has an immune system that defends the body against toxins, infections, cancer, and other diseases which attempt to prevent autoimmunity. It also sometimes refers to skin-associated lymphoid tissue (SALT), which includes peripheral lymphoid organs like the spleen and lymph nodes.

What Are the Parts of the Cutaneous Immune System?

The cutaneous immune system consists of an innate and adaptive immune system. The immune cells are commonly found in the epidermis and dermis layers of the skin. Cutaneous dendritic cells (Langerhans cells) and keratinocytes (skin cells) are the primary immune cells in the epidermal layer. The dermis layer contains dermal dendritic cells and lymphocytes (T cells, B cells, and natural killer cells) along with blood vessels and lymph vessels.

In epidermal layer consist of cutaneous dendritic cells (Langerhans cells) and keratinocytes (skin cells)

• Keratinocytes - The epidermis mostly consists of keratinocytes. They serve as the body's first line of defense against infection in the innate immune system. They have toll-like receptors (TLRs) and pattern-recognition receptors (PRRs) that recognize conserved chemicals on pathogens and start an inflammatory response.

• Dendritic Cell - Dendritic cells in the dermis and epidermis have a role in innate and adaptive immune responses. Toll-like receptors (TLRs) found on dendritic cells can be activated by microorganisms.

The dermis layer contains dermal dendritic cells and lymphocytes (T cells, B cells, and natural killer cells) along with blood vessels and lymph vessels.

• Neutrophils and Macrophages - Macrophages are phagocytic cells that can distinguish between molecules within the body (self) and from outside. Activated macrophages recruit neutrophils to circulate and visit areas of infection or inflammation. The first cells to respond to infection are neutrophils. They directly fight bacteria by using phagocytosis and degranulation of poisonous chemicals.

• Natural Killer Cells (NK cells) - Natural killer cells are cytotoxic lymphocytes that may destroy cancerous cells and virally-infected cells without needing antigen presentation. Interferons or other cytokines released by macrophages activate natural killer cells.

What Are the Three Lines of Defense of the Immune System?

A pathogen must pass through three immune system protection layers to infect the body.

1. Physical Barrier -

• The initial line of defense is the innate immune system, which can be broadly split into chemical and physical barriers and nonspecific resistance. Physical barriers, such as the skin and mucosa of the digestive and respiratory tracts, aid in eliminating pathogens and preventing tissue and blood infections. Additionally, substances secreted by the skin or mucosa, such as sweat, saliva, tears, and mucus, aid in creating a fundamental barrier against invasive microorganisms. The skin is an impermeable physical and mechanical barrier to prevent numerous infections from entering the body. Similar to this, the mucosa or mucous membranes lining the immediate internal systems aid in trapping germs by secreting mucus.

• Additionally, viruses and environmental toxins are captured by earwax and the hairs inside the nasal cavity. Gastric juice, urine, and vaginal secretions are some examples of acidic fluids that can kill bacteria by lowering the pH of the environment. Additionally, lysozyme, present in tears, sweat, and saliva, functions as a critical antibacterial agent to eliminate infections.

2. Nonspecific Innate Response -

• The second line of protection comes into contact with viruses once they successfully pass the physical barriers. This innate immune response primarily uses immune cells and proteins to recognize and eliminate any pathogen that enters the body. An important function of the innate immune system is called phagocytosis, which uses a distinct class of immune cells called phagocytes. Neutrophils and macrophages are the two different types of phagocytes. The blood and tissues both contain these cells. Phagocytes initially identify and bind pathogens before using the plasma membrane to enclose and engulf pathogens inside the cell. As a result, a distinct internal compartment (phagosome) is formed, which later unites with the lysosome, a different kind of cellular compartment. Pathogens are ultimately destroyed by being broken up into pieces by the digesting enzymes found inside lysosomes.

• In a phagosome, pathogens are digested into pathogenic pieces and indigestible components, the latter of which is excreted by exocytosis. However, the pathogenic pieces are visible on the surface of phagocytes, which are then identified and eliminated by cytotoxic T cells. Complement proteins are activated at the site of infection, attracting other white blood cells (neutrophils, eosinophils, and basophils), which causes an inflammatory reaction (swelling, redness, and pain).

3. Specific Adaptive Response -

• The third line of defense aims to eliminate specific pathogens that the immune system has previously encountered (adaptive or acquired immune response). The adaptive immune response occurs around the body, not at the infection site. B lymphocytes (B cells) and T lymphocytes are the two primary types of white blood cells (lymphocytes) that make up the adaptive immune system (T cells). T cells are involved in cell-mediated immunological responses, whereas B cells are involved in antibody-mediated immune responses (humoral immunity). B cells are activated in antibody-mediated immunity when they contact a known antigen. The antigen is subsequently taken up and digested by activated B cells, and MHC (major histocompatibility complex)-bound antigenic fragments are then displayed on the surface of the B cell.

• The interaction of the antigen and MHC further stimulates helper T cells, which release cytokines (interleukins) to promote the maturation of antigen-presenting B cells into antibody-producing B cells. (plasma cells).

• To maintain the immune system ready for the next attack, some B cells are now converted into memory cells. The plasma cells that make antibodies secrete them into the bloodstream, where they carry out several tasks. T cells are activated during cell-mediated immunity when they come into contact with antigen-presenting cells like B cells or dendritic cells. The subsequent release of cytokines by activated T cells helps to promote T cell development further.

• By rupturing the cell membrane, T cells that develop into cytotoxic or killer T cells mostly eliminate cancer cells, damaged cells, and cells exposed to pathogens. As opposed to this, T cells that develop into helper T cells enable B cells to carry out antibody-mediated immune responses.

What Are the Conditions Associated With Skin Immunity?

The conditions associated with the immunity of the skin include:

• Scleroderma.

• Psoriasis.

• Dermatomyositis.

• Epidermolysis bullosa.

• Bullous pemphigoid.

Conclusion:

A mechanical and immunological barrier to the environment is formed by the skin, one of the largest organs. The adaptive immune system and innate immune system cells are present in the skin immune system. Skin immunological responses are often initiated by signals from the innate immune system, whereas cells and cytokines from the adaptive immune system maintain the inflammation. Although they can potentially lead to inflammatory skin disorders, skin immune responses ensure effective host protection against pathogens. The complexity of skin inflammatory responses is due to considerable cross-talk between pathogens, tissue cells, and many immune cell types.