Immunology in the skin

nature video

18 Feb 201407:30

Summary

TLDRThe 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.

Outlines

00:00

🛡️ Skin's Immune Defense Mechanisms

The skin serves as the body's first line of defense against physical harm and pathogens. It is a unique environment where immune cells interact with skin cells to maintain tissue health and trigger immune responses. The skin is structured into the epidermis, dermis, and a subcutaneous fatty layer, and is home to beneficial commensal organisms that aid in protection and healing. The epidermis is composed of specialized epithelial cells called keratinocytes, which are continuously replenished and form the skin's barrier. In the dermis, fibroblasts produce extracellular matrix components and blood capillaries provide nourishment. The skin is populated by a variety of immune cells including Langerhans cells in the epidermis and dendritic cells in the dermis, which are crucial for antigen sampling and presentation. T cells, particularly memory T cells, are abundant in the skin and play a significant role in immune responses. Other immune cells like natural killer cells, eosinophils, and mast cells may also contribute to allergic reactions. The skin's immune cells can detect tissue damage and respond to it, while keratinocytes produce antimicrobial peptides for direct bacterial killing. Activated dendritic cells migrate to lymph nodes to prime naive T cells, which then differentiate into effector T cells to combat infections. Memory T cells persist to provide long-term immunity.

05:02

🔬 Psoriasis: An Autoimmune Skin Disorder

Psoriasis is a chronic inflammatory skin condition characterized by the formation of scaly, reddish plaques. It is influenced by a combination of environmental and genetic factors, with physical injury or inflammation potentially triggering acute lesions. The exact antigenic trigger is not known, but it is hypothesized that stressed keratinocytes might release self-DNA, which could activate plasmacytoid dendritic cells to secrete antiviral and pro-inflammatory cytokines. This leads to the differentiation and accumulation of T cells around blood vessels in the dermis, eventually causing epidermal infiltration and thickening. Specialized T cell subsets secrete mediators that stimulate keratinocyte proliferation, contributing to tissue remodeling and the amplification of the immune response. Without treatment, acute psoriatic lesions can become chronic. Genetic studies have linked psoriasis to susceptibility genes, some of which are associated with the Th17 subset of T cells, implicating them in the disease's pathogenesis. The skin's immune cells are thus vital for barrier function and defense against pathogens, but can also become dysregulated, leading to autoimmunity or allergies.

Mindmap

Keywords

💡Skin Barrier

The skin barrier refers to the skin's protective function as the body's primary defense against physical injuries and microbial pathogens. It is a key concept in the video, emphasizing the skin's role in maintaining homeostasis and inducing immune responses. The skin's barrier function is largely due to the outermost layer of dead cells called corneocytes, which are continuously replenished by basal keratinocytes.

💡Keratinocytes

Keratinocytes are highly specialized epithelial cells that make up the epidermis, the outermost layer of the skin. They are responsible for the skin's barrier function and are continuously replenished from a single layer of basal keratinocytes. In the video, keratinocytes are highlighted as crucial for the skin's ability to protect against pathogens and maintain tissue integrity.

💡Commensal Microbes

Commensal microbes are beneficial bacteria, fungi, and viruses that live on the skin and contribute to its health by aiding in protection against pathogens and wound healing. The video discusses the symbiotic relationship between the skin and these microbes, illustrating their role in maintaining skin health and immune function.

💡Dermis

The dermis is the layer of skin beneath the epidermis, composed of a dense extracellular matrix of elastin and collagen fibers secreted by fibroblasts. It is vital for the skin's structure and elasticity. In the video, the dermis is mentioned as the site where immune cells, blood capillaries, and lymphatic vessels are located, playing a critical role in the skin's immune response.

💡Langerhans Cells

Langerhans cells are a specialized subset of dendritic cells found in the epidermis that sample antigens and play a dual role in both anti-inflammatory and activatory responses. The video describes Langerhans cells as sentinels that project dendrites towards the cornified epithelial layer to sample bacterial antigens, highlighting their importance in the skin's immune surveillance.

💡Dendritic Cells

Dendritic cells in the dermis are highly efficient at capturing dead cells and presenting antigens to T cells, acting as immune sentinels. The video explains their role in activating the immune response by presenting antigens from pathogens such as viruses to T cells, which is essential for initiating an effective immune reaction.

💡T Cells

T cells, or T lymphocytes, are immune effector cells that play a central role in the adaptive immune response. The video mentions that healthy skin contains more T cells than blood, with most being memory T cells ready to react to previously encountered antigens. T cells in the epidermis are primarily CD8 cytotoxic T cells, while those in the dermis are mostly helper CD4 T cells, illustrating their diverse roles in the skin's immune response.

💡Inflammatory Mediators

Inflammatory mediators, such as interleukin 1 (IL-1), are signaling molecules that activate immune cells and contribute to the inflammatory response. The video describes how stressed keratinocytes release IL-1, which, along with other mediators, helps recruit neutrophils, macrophages, and T cells to the site of infection or tissue damage.

💡Psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by scaly, reddish plaques. The video discusses psoriasis as an example of a skin disorder where immune responses become disregulated, potentially due to the activation of plasmacytoid dendritic cells by self DNA released from stressed keratinocytes, leading to an overactive immune response.

💡Autoimmunity

Autoimmunity refers to a condition where the immune system mistakenly attacks the body's own tissues. In the context of the video, autoimmunity can occur when immune cells in the skin become activated by self-antigens, leading to skin disorders like psoriasis. The video explains how genetic factors and environmental triggers can contribute to the development of autoimmunity in the skin.

💡Memory T Cells

Memory T cells are a subset of T cells that persist in the skin after an immune response, providing long-term immunity against previously encountered pathogens. The video emphasizes the importance of memory T cells in the epidermis, which can rapidly respond to future infections with the same virus, showcasing the skin's adaptive immune capabilities.

Highlights

The skin serves as the body's primary barrier against physical and microbial threats, with a unique environment where immune cells interact with skin cells to maintain tissue homeostasis and induce immune responses.

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

The epidermis is composed of highly specialized epithelial cells called keratinocytes, which are continuously replenished from a single layer of basal keratinocytes.

Dead cells called corneocytes form the outermost layer of the skin, playing a significant role in its barrier function.

In the dermis, fibroblasts secrete elastin and collagen fibers, creating a dense extracellular matrix that supports the skin structure.

Lymphatic vessels in the dermis drain lymph fluid to lymph nodes, where immune cells are activated upon pathogen encounter.

Langerhans cells in the epidermis are specialized dendritic cells that sample antigens and have both anti-inflammatory and activatory roles depending on the context.

Dendritic cells in the dermis efficiently capture dead cells and present antigens to T cells, acting as immune sentinels.

Healthy skin contains more than twice the number of T cells found in the blood, with most being memory T cells capable of rapid reactivation.

CD8 T cells in the epidermis become cytotoxic upon activation, killing target cells and playing a crucial role in the immune response.

Helper CD4 T cells in the dermis have a modulatory role in the immune response, influencing the overall immune activity.

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 that can directly kill bacteria and contribute to the skin's defense mechanisms.

Activated dendritic cells migrate to lymph nodes to present antigens to naive T cells, initiating their activation and differentiation.

Memory CD8 cells persist in the epidermis to provide immunity for future encounters with the same virus, ensuring a rapid response.

Disregulated immune responses can lead to skin disorders such as psoriasis or atopic dermatitis, impacting skin health and appearance.

Psoriasis is a lifelong inflammatory skin disease characterized by scaly reddish plaques, influenced by a combination of environmental and genetic factors.

Genetic studies have identified psoriasis-associated susceptibility genes, some linking the subset of T cells that produce IL-17 to psoriasis pathogenesis.

Skin immune cells play a critical role in maintaining barrier function against pathogens but can also cause autoimmunity or allergies when activated by self-antigens or harmless antigens.

Transcripts

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