10.3 Skin-associated lymphoid tissue (SALT)
3 min read•july 25, 2024
The skin is our first line of defense against pathogens and environmental threats. Skin-associated lymphoid tissue (SALT) is a complex network of immune cells and structures that work together to protect us from harm and maintain skin health.
SALT includes various cell types like keratinocytes, , and . These cells coordinate to detect threats, initiate immune responses, and maintain a delicate balance between protection and tolerance in the skin.
Structure and Function of Skin-Associated Lymphoid Tissue (SALT)
Structure of skin-associated lymphoid tissue
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- Layers of the skin involved in SALT form protective barrier against pathogens and environmental insults
- Epidermis outer layer composed of stratified squamous epithelium (keratinocytes)
- Dermis underlying layer rich in connective tissue, blood vessels, and immune cells
- Cellular components of SALT work together to maintain skin immunity
- Keratinocytes produce antimicrobial peptides and cytokines (defensins, cathelicidins)
- Langerhans cells patrol epidermis capturing and presenting antigens
- orchestrate immune responses in deeper skin layers
- T cells including provide rapid response to known pathogens
- contribute to early defense and tissue homeostasis
- Structural features enhance barrier function and regulate immune responses
- Tight junctions between keratinocytes prevent paracellular transport of molecules
- Basement membrane separating epidermis and dermis regulates cell migration and signaling
- Molecular components contribute to innate and adaptive immunity
- Antimicrobial peptides directly kill microbes and modulate immune responses (, )
- Cytokines and chemokines coordinate immune cell recruitment and activation (, )
Role of Langerhans cells
- Origin and location establish unique niche in skin immunity
- Derived from embryonic precursors self-renew in epidermis
- Reside in epidermis forming network of sentinel cells
- Antigen capture and processing initiate immune responses
- Extend dendrites to sample antigens from environment and microbiome
- Internalize and process antigens for presentation to T cells
- Migration to lymph nodes bridges innate and adaptive immunity
- Activation by danger signals triggers migration out of epidermis
- -dependent movement to lymph nodes guided by chemokine gradients
- activates naive T cells
- Express and II molecules for antigen display
- Present antigens to naive T cells in lymph nodes initiating adaptive responses
- Cytokine production shapes immune environment
- Secrete , , and promoting and T cell differentiation
- Tolerance induction maintains skin homeostasis
- Can promote regulatory T cell development preventing excessive inflammation
Immune Mechanisms in Skin Health and Disease
Skin-resident memory T cells
- Generation of skin-resident memory T cells provides long-term protection
- Develop from effector T cells after infection or vaccination creating tissue-specific immunity
- Location and retention ensure rapid response to local threats
- Reside in epidermis and dermis strategically positioned for surveillance
- Express CD69 and CD103 for tissue retention anchoring cells in skin
- Rapid response to pathogens enhances local immunity
- Provide immediate protection upon re-exposure to known antigens
- Secrete cytokines and chemokines to recruit other immune cells amplifying response
- Long-term persistence maintains protective barrier
- Maintain protective immunity for extended periods without recirculation
- Heterogeneity allows diverse immune functions
- Include both CD4+ and CD8+ T cell subsets with distinct roles in immunity
Immunology of skin disorders
- characterized by chronic inflammation and hyperproliferation
- T cell-mediated autoimmune response targets skin antigens
- Overproduction of IL-17 and IL-22 drives inflammatory cascade
- Keratinocyte hyperproliferation leads to plaque formation
- Neutrophil infiltration contributes to tissue damage
- involves allergic inflammation and barrier dysfunction
- Th2-driven immune response promotes allergic sensitization
- Increased IgE production mediates hypersensitivity reactions
- Impaired skin barrier function allows penetration of allergens and irritants
- Overexpression of thymic stromal lymphopoietin (TSLP) promotes Th2 responses
- Common features highlight shared pathways in skin inflammation
- Chronic inflammation persists due to dysregulated immune responses
- Dysregulation of immune cell populations alters tissue homeostasis
- Altered cytokine profiles drive pathological changes in skin
- Therapeutic approaches target specific immune pathways
- Immunosuppressive drugs (corticosteroids, calcineurin inhibitors) broadly suppress inflammation
- Biologics targeting specific cytokines or receptors (anti-TNF, anti-IL-17) offer precise intervention
Key Terms to Review (27)
Antigen Presentation: Antigen presentation is the process by which immune cells display antigens on their surface to enable T cells to recognize and respond to pathogens or infected cells. This crucial mechanism bridges innate and adaptive immunity, allowing for a targeted immune response against specific threats.
Atopic Dermatitis: Atopic dermatitis is a chronic inflammatory skin condition characterized by dry, itchy, and inflamed skin. It often occurs in individuals with a personal or family history of allergic diseases, such as asthma or hay fever, and is linked to an abnormal immune response in the skin. The condition highlights the important relationship between skin-associated lymphoid tissue and immune regulation.
CCL20: CCL20, also known as chemokine C-C motif ligand 20, is a small cytokine that plays a critical role in immune responses by guiding the migration of immune cells, particularly lymphocytes and dendritic cells, to sites of inflammation. This chemokine is primarily produced by epithelial cells in tissues such as the skin and mucosal surfaces, where it helps maintain the balance of immune cell populations and facilitates the body's response to pathogens.
Ccr7: CCR7, or C-C chemokine receptor type 7, is a critical surface protein that plays a vital role in the migration and homing of immune cells, particularly T cells and dendritic cells, to lymphoid tissues. It is essential for the proper functioning of the immune system, as it helps guide these cells to sites where they can effectively initiate an immune response, including in the context of T cell subsets and skin-associated lymphoid tissue.
Commensal bacteria: Commensal bacteria are microorganisms that reside on or within the human body without causing harm, often providing beneficial effects to their host. They play an essential role in maintaining the balance of the immune system and preventing pathogenic infections, particularly in environments like the skin where skin-associated lymphoid tissue is present.
Cutaneous hypersensitivity: Cutaneous hypersensitivity is an exaggerated immune response occurring in the skin, typically manifested as inflammation, redness, or itching when exposed to specific allergens or irritants. This hypersensitivity can involve various immune cells, such as T cells and mast cells, and is often associated with conditions like allergic contact dermatitis and atopic dermatitis.
Dermal dendritic cells: Dermal dendritic cells are specialized immune cells located in the dermis of the skin that play a crucial role in the initiation and regulation of immune responses. They are vital for capturing and presenting antigens to T cells, thus helping to activate adaptive immunity while also maintaining tolerance to harmless substances. These cells bridge the innate and adaptive immune systems, contributing to skin-associated lymphoid tissue functions.
Dermal layer: The dermal layer, also known as the dermis, is the thick layer of living tissue located beneath the epidermis in the skin. It plays a crucial role in providing structural support, housing blood vessels, nerves, and various cells involved in immune responses. The dermal layer is essential for maintaining skin integrity and facilitating communication between the skin and the immune system.
Epidermal layer: The epidermal layer is the outermost part of the skin, primarily composed of keratinized stratified squamous epithelium. This layer serves as a critical barrier protecting underlying tissues from environmental hazards, pathogens, and water loss while playing a significant role in the immune response through interactions with skin-associated lymphoid tissue.
IL-1: IL-1, or Interleukin-1, is a pro-inflammatory cytokine that plays a key role in the immune response by promoting inflammation and activating immune cells. This cytokine exists in two forms, IL-1α and IL-1β, both of which are crucial for initiating and regulating various immune processes, including the response to infections and the development of autoimmune diseases. Its involvement in inflammation links it to the mechanisms of tissue immunity and can impact disorders associated with chronic inflammation.
IL-12: IL-12 is a cytokine produced primarily by antigen-presenting cells, such as dendritic cells and macrophages, that plays a crucial role in the immune system by promoting the differentiation of T cells and enhancing the activity of natural killer (NK) cells. This cytokine is key in driving the Th1 response, which is essential for combating intracellular pathogens and fostering cellular immunity.
Il-1β: IL-1β, or Interleukin-1 beta, is a pro-inflammatory cytokine produced mainly by activated macrophages and plays a critical role in the immune response by promoting inflammation. It is involved in a range of biological activities including the activation of immune cells, the stimulation of inflammatory responses, and the regulation of various immune pathways. Its importance is highlighted in both innate immunity through pattern recognition receptors and its influence on skin-associated lymphoid tissue, where it helps coordinate local immune responses.
Immune surveillance: Immune surveillance is the process by which the immune system monitors and detects abnormal cells, such as cancerous or infected cells, to eliminate them before they can proliferate. This ongoing mechanism relies on various immune cells, particularly T cells and natural killer (NK) cells, that patrol tissues and recognize alterations in cell surface markers or signs of distress. Effective immune surveillance is crucial for maintaining tissue homeostasis and preventing the development of tumors.
Inflammation: Inflammation is a biological response of the immune system to harmful stimuli, such as pathogens, damaged cells, or irritants. It serves to protect the body by initiating healing processes, recruiting immune cells to the site of injury or infection, and facilitating the removal of harmful agents. This complex response can be acute or chronic and is crucial for maintaining homeostasis and defense mechanisms.
Innate lymphoid cells: Innate lymphoid cells (ILCs) are a group of immune cells that play a critical role in the early immune response, serving as the bridge between the innate and adaptive immune systems. These cells are essential for maintaining tissue homeostasis, responding to infections, and contributing to inflammation. They are primarily found in tissues like the skin and mucosal surfaces, particularly in areas such as skin-associated lymphoid tissue, where they help regulate immune responses against pathogens while maintaining tolerance to commensal organisms.
K. a. j. j. g. h. van der burg: K. A. J. J. G. H. van der Burg is a prominent researcher known for contributions to the understanding of skin-associated lymphoid tissue (SALT). His work has shed light on the complex interactions between the immune system and skin, focusing on how SALT functions in immune responses and its role in skin health and disease.
Langerhans cells: Langerhans cells are specialized dendritic cells found primarily in the skin that play a crucial role in the immune system by capturing and presenting antigens to T cells. These cells are essential components of skin-associated lymphoid tissue (SALT), acting as sentinels that help initiate immune responses against pathogens while maintaining tolerance to harmless substances.
LL-37: LL-37 is a human antimicrobial peptide that plays a crucial role in the innate immune response, particularly in the skin. It is part of the cathelicidin family, which is produced by various cells, including keratinocytes, and helps protect against bacterial infections by disrupting microbial membranes and promoting wound healing.
Memory T cells: Memory T cells are a specialized subset of T lymphocytes that persist long-term after an initial immune response, enabling a quicker and more effective response upon re-exposure to the same antigen. These cells are crucial for adaptive immunity, as they allow the immune system to 'remember' past infections or vaccinations, leading to improved protection against pathogens in the future.
MHC Class I: MHC Class I molecules are cell surface proteins that present endogenous antigens to CD8+ T cells, playing a crucial role in the immune system by enabling the recognition of infected or cancerous cells. These molecules are essential for distinguishing self from non-self, and their interactions with T cells are fundamental in the activation and differentiation of adaptive immune responses.
MHC Class II: MHC Class II molecules are proteins found on the surface of certain immune cells that play a crucial role in the adaptive immune response by presenting antigens to CD4+ T helper cells. These molecules specifically present processed extracellular antigens, enabling T cells to recognize and respond to pathogens such as bacteria and parasites, thus connecting them to the immune system's ability to differentiate between self and non-self.
Psoriasis: Psoriasis is a chronic autoimmune skin condition characterized by the rapid proliferation of skin cells, leading to the formation of thick, scaly patches on the skin's surface. This condition results from an overactive immune response, which involves skin-associated lymphoid tissue (SALT) playing a crucial role in the inflammation and abnormal skin cell turnover that defines psoriasis.
Skin microbiome: The skin microbiome refers to the diverse community of microorganisms, including bacteria, fungi, viruses, and other microbes, that reside on the surface of the skin. This complex ecosystem plays a crucial role in maintaining skin health, protecting against pathogens, and influencing immune responses. The balance within this microbial community can be disrupted by various factors, leading to skin disorders and impacting overall immune function.
T cells: T cells, or T lymphocytes, are a type of white blood cell that plays a central role in the adaptive immune response. They originate from hematopoietic stem cells in the bone marrow but mature in the thymus, where they develop the ability to recognize specific antigens presented by other cells. T cells are crucial for cell-mediated immunity, helping to eliminate infected or cancerous cells and orchestrating the immune response.
T. M. O'Neill: T. M. O'Neill is a prominent researcher known for contributions to understanding skin-associated lymphoid tissue (SALT) and its critical role in immune responses. His work highlights how SALT, which includes structures like epidermal Langerhans cells and dermal lymphocytes, acts as a frontline defense against pathogens while maintaining tolerance to harmless antigens.
Tnf-α: TNF-α, or Tumor Necrosis Factor-alpha, is a pro-inflammatory cytokine produced mainly by macrophages that plays a crucial role in immune responses, inflammation, and the regulation of cell survival and apoptosis. This cytokine connects various aspects of the immune system, including its interactions with pattern recognition receptors, its influence in skin-associated lymphoid tissue, its involvement in autoimmune disorders, and its critical functions as a signaling molecule in immune responses.
β-defensins: β-defensins are small cationic peptides that play a crucial role in the innate immune response, particularly in the skin. They are produced by various cells, including keratinocytes, and are known for their antimicrobial properties against a wide range of pathogens. In the context of skin-associated immunity, β-defensins contribute to the first line of defense by disrupting microbial membranes and modulating inflammatory responses.