Immunology in the skin

Summary

The skin, as the body's primary barrier, hosts a complex ecosystem of immune cells and skin cells that work together to maintain homeostasis and respond to threats. It comprises the epidermis, dermis, and subcutaneous tissue, with commensal microbes aiding in protection and healing. Keratinocytes form the epidermal barrier, while dendritic cells and T cells in the dermis and epidermis play crucial roles in immune response. Specialized immune cells like Langerhans cells and various T cell subsets contribute to defense and can become disregulated, leading to skin disorders such as psoriasis. The script delves into the intricate balance of the skin's immune system and its potential for both protection and disease.

Takeaways

• 🛡️ The skin acts as the body's primary barrier against physical harm and pathogens, maintaining tissue homeostasis and inducing immune responses.
• 🌱 The skin is composed of the epidermis, dermis, and subcutaneous fatty region, and hosts commensal bacteria, fungi, and viruses beneficial for protection and healing.
• 🔬 The epidermis is made up of specialized epithelial cells called keratinocytes, which are continuously replenished and form the skin's barrier.
• 🧬 In the dermis, fibroblasts secrete elastin and collagen fibers, creating a dense extracellular matrix, while blood and lymphatic vessels support the skin's functions.
• 🕵️‍♂️ Langerhans cells in the epidermis are specialized dendritic cells that sample antigens and have both anti-inflammatory and activatory roles.
• 🔎 Dendritic cells in the dermis efficiently capture dead cells and present antigens to T-cells, acting as immune sentinels.
• 💪 T-cells are the immune effectors in the skin, with memory T-cells being more abundant in healthy skin than in the blood, ready for rapid reactivation.
• 🔄 CD8 T-cells in the epidermis are cytotoxic, killing target cells upon activation, while CD4 T-cells in the dermis have a more regulatory role.
• 🤒 Other immune cells like natural killer cells, eosinophils, and mast cells may be involved in allergic reactions in the skin.
• 🚨 Dendritic cells and keratinocytes sense tissue damage through receptors that recognize pathogen-derived or host-derived molecules.
• 🛡️ Keratinocytes produce antimicrobial peptides and inflammatory mediators that activate immune cells and recruit additional immune effectors.
• 🔄 Activated T-cells migrate to lymph nodes, where they are primed to differentiate into effector cells that return to the skin to control infections.
• 🛑 Memory CD8 cells persist in the epidermis to provide immunity against future encounters with the same pathogen.
• 🤕 Skin disorders like psoriasis can result from disregulated immune responses, with genetic and environmental factors contributing to the disease's onset.
• 🧬 Genetic studies have linked psoriasis susceptibility to specific genes, including those associated with the Th17 subset of T-cells, which produce IL-17 and play a role in psoriasis pathogenesis.

Q & A

What is the primary function of the skin in the human body?

The skin serves as the body's primary barrier against physical insults and microbial pathogens, helping to maintain tissue homeostasis and induce immune responses.

What are the main components of the skin structure?

The skin is composed of the epidermis, dermis, and a subcutaneous fatty region.

What beneficial effects do commensal bacteria, fungi, and viruses living on the skin have?

Commensal bacteria, fungi, and viruses on the skin have beneficial effects in protecting against pathogens and aiding in wound healing.

What are the specialized epithelial cells in the epidermis called, and what is their role?

The specialized epithelial cells in the epidermis are called keratinocytes, which are continuously replenished and are largely responsible for the skin's barrier function.

What do fibroblasts in the dermis secrete that contributes to the extracellular matrix?

Fibroblasts in the dermis secrete elastin and collagen fibers that form a dense extracellular matrix.

How do Langerhans cells in the epidermis function in the immune response?

Langerhans cells in the epidermis sample antigens and can have both anti-inflammatory and activatory roles, depending on the context.

What is the role of dendritic cells in the dermis regarding antigen presentation?

Dendritic cells in the dermis are highly efficient at capturing dead cells and presenting antigens, such as viruses or other intracellular pathogens, to T cells.

What types of T cells are predominantly found in the epidermis and dermis, and what are their functions?

CD8 T cells, which can become cytotoxic and kill target cells upon activation, are mostly found in the epidermis. In the dermis, helper CD4 T cells, which have a more modulatory role in the immune response, are predominant.

How do immune cells, such as dendritic cells and keratinocytes, respond to tissue damage?

Dendritic cells and keratinocytes sense tissue damage through receptors that recognize pathogen-derived molecular patterns or host-derived molecules exposed by cell death, such as DNA.

What is the process that leads to the formation of acute psoriatic lesions?

Acute psoriatic lesions form when stressed keratinocytes might release self DNA, which, in complex with an antimicrobial peptide, activates dermal plasmacytoid dendritic cells to secrete high amounts of the antiviral mediator IFN, along with pro-inflammatory IL1 Alpha.

How do genetic studies contribute to our understanding of psoriasis?

Genetic studies have identified psoriasis-associated susceptibility genes, some of which link the subset of T cells that produce IL17 to psoriasis pathogenesis.