Author: Dr. Yuliya Velykoredko, specialist in dermatology, and Dr. Michal Bohdanowicz, Specialist in Dermatology, University of Toronto, Canada. Editor-in-Chief of DermNet New Zealand: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Editors: Gus Mitchell/Maria McGivern. September 2017.
What is the skin's immune system?
The skin has an immune system that protects the body from itInfection,Krebs,Toxins, and tries to preventautoimmunity, in addition to being a physical barrier against the outside environment.
The skin's immune system is sometimes referred to as skin-associatedlymphaticTissue (SALT) that includesperipherallymphatic organs such as the spleen and theLymphnode.
immune system of the skin
Reprinted with permission from Macmillan Publishers.
How does the skin's immune system work?
The skin's immune system has elements of bothinnate(non-specific) and adaptive (specific) immune system.immune cellsinhabit theEpidermisAnddermis.
The main immune cells in the epidermis are:
- Epidermal dendritic Zellen(Langerhans cells)
- keratinocytes(skin cells).
The dermis has blood and lymphatic vessels and numerous immune cells, including:
- Dermaldendritic Zellen
- lymphocytes:T cells,B cells, natural killer (NK) cells.
- mast cells.
There is a continuous transport of immune cells between the skin, the lymph nodes and the bloodstream. The skinmicrobiomealso contributesHomeostasisof the skin's immune system.
What is the skin's innate immune response?
The innate immune response is immediate and notdependenton previousimmunologicalStorage.
Keratinocytes are the predominant cells in the epidermis. They act as the first line of innate immune defenses against infection. They express toll-like receptors (TLRs), which are pattern recognition receptors (PRRs) that recognize conservedlymoleculesAnpathogensand trigger oneflammableAnswer.
Keratinocytes communicate with the rest of the immune system through:
- Antimicrobial Peptides(cathelicidins and β-defensins)
- signallingcytokines(z.B,Interleukin–1β [IL–1β])
- Chemokine, which attract other immune cells to the epidermis
- Direct activation of primedT lymphocytesAndNK cells(through major histocompatibility complex I [MHC-I]).
are macrophagesphagocyticCells that can distinguish between the body's own cells (own cells) and foreign molecules. AfterPhagozytoseby macrophages, an intrusionpathogenis killed in the cell. Activated macrophages recruit neutrophils to enter the circulation and migrate to sites of infection orinflammation.
Neutrophils are the first cells to respond to infection. They attack directlymicroorganismsby phagocytosis and byDegranulationvonpoisonoussubstances.
Epidermal and dermal dendritic cells are involved in both innate and adaptive immune responses. During the innate response:
- Dendritic cells possess TLRs that can be activated by microbial components
- Plasmacytoid dendritic cells (pDCs) produce large amounts of interferon-γ (IFN-γ) in response to viral infection.
natural killer cells
NK cells arecytotoxicLymphocytes that can eliminate virus-infected cells and cancer cells withoutAntigenpresentation or priming.
NK cells are activated by interferons or other cytokines released by macrophages. express NK cellsInhibitorReceptors that recognize MHC-I and prevent unwanted attacks on itself. They can kill target cells via the perforin granzyme pathway that inducesApoptosis(programmed cell death).
In response, mast cells are activatedallergic reactionand producecytoplasmic granulesfilled with preformedflammablemediator, such asHistamine. They release these granules when they are high affinityImmunoglobulinE (IgE)receptor(FcεRI) on themast cellSurface reacts on contact with stimuli such as e.gAllergens, Poisons, IgEantibody, and medicines.
These mediators can lead toitching weltsdue to increasedvascular permeability(urticaria). In rare cases, mast cell activation can occurAnaphylaxis, characterized by bronchoconstriction, dizziness andSyncope.
Eosinophils enter the skinpathologicalconditions such asParasitenbefallAndatopic dermatitis.Eosinophils are attractedimmunoglobulinslike IgE that are boundadd to Proteinon the surface largeOrganismssuch asHelminths.
The eosinophils release cytoplasmic cytotoxic granules to kill themParasite(an innate immune response) and promote Th2 helpersT cell differentiationupon release (an adaptive immune response).
Thecomplement systemis aenzymaticCascade of over 20 different proteins normally found in the blood. When an infection is present, the system activates sequentially, resulting in events that help destroy the invasionOrganism.
The complement system can also attract neutrophils to the site of infection.
What is the adaptive immune response?
The adaptive immune response is specific to a pathogen and takes longer to elicit. Adaptive immunity requires the production of specific T lymphocytes to accurately identify an antigen and B cells to produce specific antibodies that bind to itMicrobesin a kind of "lock and key".
Identify dendritic cells (Langerhans cells and macrophages) or antigen presenting cells (APCs).Antigenand they present immature T cells. Epidermal Langerhans cells use theirsdendrites(Arm-like projections) for monitoring the environment, especially in theThe stratum corneum. The Langerhans cells bind pathogens to their TLRs, migrate to draining lymph nodes, and present antigens to naïve lymphocytes. Antigen presentation requires pathogen internalization, processing within the cell, and indication of a short circuitPeptideon the surface of the APC on a major histocompatibility complex (MHC)Molecule.
There are two main types of MHC: MHC-I and MHC-II.
- MHC-I is found on all cells in the body and is used for displayendogenousSubstances such as viral orTumorProtein.
- MHC-II is found on APCs (dendritic cells,monocytes/ macrophages and B-cells) and is used to represent foreign exogenous molecules.
The skin contains resident T cells and recruits circulating T cells. T cells are not able to directly recognize pathogens. The receptor on the surface of a T cell binds to the peptide/MHC complex on the surface of the APC. Effective antigen presentation allows naïve T cells to mature into effector T cells, which in turn differentiate into two variants: CD8+ cytotoxic T cells and CD4+ helper T cells (Th).
Cytotoxic CD8+ T cells recognize and bind to MHC-I molecules. They bind to the Fas death receptor, aproteinon the cell membrane surface, which initiates the perforin-granzyme pathway andcytokine-mediated pathways to induce apoptosis that directly kills virally infected cells or tumor cells.
CD4+ Th cells recognize and bind to MHC-II molecules. They activate B cells to produce specific antibodies. When re-exposed to the same antigen, memory T cells can respond rapidly by dividing andclonalExtension.
Th cells include the Th1, Th2, Th17, and Th22 subtypes. Each subtype is associated with specific signaling cytokines and effector functions.
Th1 cells produce a cell-mediated immune response to killintracellularpathogens.
- Th1 cells produce IFN-γ and can activate macrophages and stimulate NK cells.
- Th1 cells play a role in thepathogenesisvonpsoriasis.
Th2 cell activation leads toB cellexcitationantibodyProduction.
- Th2 cells produce the cytokines IL-4, IL-5, IL-6 and IL-10.
- You can stimulateeosinophilActivation.
- Th2 cells are involved in thisatopic eczema.
Th17 cells produce IL-17 and IL-22 and play a role in protecting againstbacterial infectionsAndfungal infections. Th22 cells produce IL-22 and tumorNecrosisFactor Alpha (TNF-α), which triggers inflammation. Both Th17 and Th22 cells play a role in the pathogenesis of psoriasis. Other T cell populations such as regulatory T cells (Tregs) tune the immune response by directing how immune cells respond to foreign andself antigensand prevent autoimmune reactions.
B cells are responsible for creating a memory of previous antigen exposure to ensure a faster immune response and lasting immunity. B cells produce antibodies (immunoglobulins) that can bind to specific antigens. Antibody effector functions are:
- Neutralization – Antibodies bind to the pathogen and prevent attachment/infection
- Opsonization – the coating of the antigen surface by antibodies and subsequent uptake by phagocytes
- Add toActivation.
To produce antibodies, B cells need cytokine signaling and stimulatory signals from Th cells. This takes place in secondary lymphoid organs such as lymph nodes.
- The B-cells and T-cells must bind via the B-cell receptor (BCR) and the T-cell receptor, respectively. This is mediated by costimulatory signals on Th cells.
- TheProliferationof B cells also leads to the production of a specific antibodyIgG,IgAor IgE, depending on the antigen.
Upon re-exposure to the same antigen andfollicularDendritic cells, B cells are activated to produce specific antibodies. This process allows for the generation of memory B cells and long-livedPlasmacells for long-lasting immunity against infections.