Author: Dr Yuliya Velykoredko, skin science Resident, and Dr Michal Bohdanowicz,Dermatology Resident,University that Toronto, Canada. DermNet new Zealand Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, new Zealand. Copy editors: Gus Mitchell/Maria McGivern. September 2017.

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What is the immune system of the skin?

The skin has actually an immune system that protects the human body from infection, cancer, toxins, and attempts to avoid autoimmunity, in enhancement to gift a physical barrier against the outside environment.

The skin immune device is sometimes called skin-associated lymphoid tissue (SALT), which contains peripheral lymphoid organs favor the spleen and also the lymph nodes.

Skin immune device


Reprinted through permission indigenous Macmillan Publishers.

How walk the skin immune device function?

The immune device of the skin has elements of both the natural (nonspecific) and also adaptive (specific) immune systems.Immune cells inhabit the epidermis and dermis.

The key immune cell in the epidermis are:

Epidermal dendritic cells (Langerhans cells)Keratinocytes (skin cells).

The dermis has actually blood and also lymph vessels and numerous immune cells, including:

Dermal dendritic cellsLymphocytes: T cells, B cells, natural killer (NK) cellsMast cells.

There is consistent trafficking of immune cells in between the skin, draining lymph nodes, and blood circulation. The skin microbiome likewise contributes to the homeostasis of the skin immune system.

What is the skin’s natural immune response?

The natural immune solution is immediateand is no dependent on previous immunological memory.


Keratinocytes room the predominant cells in the epidermis. Lock act together the very first line of natural immune defence against infection. Castle express Toll-like receptors (TLRs), which room pattern-recognition receptors (PRRs) that detect conserved molecule on pathogens and also trigger an inflammatory response.

Keratinocytes communicate with the rest of the immune mechanism through:

Signalling cytokines (eg, interleukin–1β )Chemokines, which entice other immune cell to the epidermisDirect activation the primed T lymphocytesand NK cells (through significant histocompatibilitycomplex ns ).

Macrophages and also neutrophils

Macrophages room phagocytic cells that have the right to discriminate between the body"s cells (self) and foreign molecules. ~ phagocytosis by macrophages, an invading pathogen is killed inside the cell. Set off macrophages recruit neutrophils to go into the circulation and travel to sites of epidemic or inflammation.

Neutrophils space the very first cells come respond to infection.They directly attack microorganisms by phagocytosis and by degranulation of toxic substances.

Dendritic cells

Epidermal and dermal dendritic cell are associated in both the innate and adaptive immune responses. Throughout the inherent response:

Dendritic cell possess TLRs that deserve to be activated by microbial componentsPlasmacytoid dendritic cells (pDCs) produce large amounts that interferon-γ (IFN-γ) in solution to viral infection.

Natural killer cells

NK cells are cytotoxic lymphocytes the can get rid of virally infected cells and also cancer cell without antigen presentation or priming.

NK cells space activated by interferons or various other cytokines exit from macrophages. NK cell express inhibitor receptors that recognise MHC–I and also prevent undesirable attacks on self. They deserve to kill target cells v the perforin-granzyme pathway, i m sorry induces apoptosis (programmed cell death).

Mast cells

Mast cells are activated in response to allergic reactions and produce cytoplasmic granules filled through pre-formed inflammation mediators, such together histamine. They relax these granules when their high-affinity immunoglobulin E (IgE) receptor (FcεRI) top top the mast cell surface ar reacts upon call with stimuli such together allergens, venoms, IgE antibodies, and medications.

These mediators can result in pruritic weals due to increased vascular permeability (urticaria). In rarely cases, mast cabinet activation have the right to lead to anaphylaxis,characterised through bronchoconstriction, dizziness, and also syncope.


Eosinophilsenter the skin in pathological problems such as parasitic infestationsand atopic dermatitis.Eosinophils space attracted come immunoglobulins such together IgE that space bound tocomplement protein on the surface of large organisms such together helminths.

The eosinophils release cytoplasmic cytotoxic granules to death the parasite (an inherent immune response) andpromote Th2 helper T cell differentiation upon relax (an adaptive immune response).

Complement system

Thecomplement systemis an enzymatic cascade of over 20 different proteins normally uncovered in the blood. As soon as an epidemic is present, the device is sequentially triggered leading to events that assist destroy the invading organism.

The enhance system can likewise attract neutrophils to the site of infection.

What is the adaptive immune response?

The adaptive immune an answer is specific to a virus and bring away a much longer time come elicit. Adaptive immunity requires the manufacturing of specific T lymphocytes to recognize an antigen v precision and B cell to produce specific antibodies that bind to the microbe in a "lock-and-key" fashion.

Antigen presentation

Dendritic cell (Langerhans cells and macrophages), or antigen–presenting cell (APCs), identify antigens and also present them to immature T cells. Epidermal Langerhans cells usage their dendrites (arm-like projections) to survey the environment, especially in the stratum corneum. The Langerhans cells bind pathogens to their TLRs, travel to draining lymph nodes, and present antigens come naïve lymphocytes. Antigen presentation calls for internalisation that the pathogen, processing inside the cell, and display the a short peptide top top the surface of the APC on a major histocompatibility complex (MHC) molecule.

There room two major types the MHC: MHC-I and MHC-II.

MHC-I is found on all cells in the body and is offered to display endogenous substances, such together viral or tumour proteins.MHC-II is uncovered on APCs (dendritic cells, monocytes/macrophages and B cells) and also is provided to display foreign non-self molecules.

T cells

The skin contains resident T cells and also recruits turn T cells. T cells space unable come recognise pathogens directly. The receptor ~ above the surface ar of a T cell binds to the peptide/MHC complex on the surface of the APC. Effective antigen presentation permits for naïve T cell to mature right into effector T cells, i m sorry in turn identify into 2 varieties: cytotoxic CD8+ T cells and CD4+ T helper (Th) cells.

Cytotoxic CD8+ T cell recognise and also bind to MHC-I molecules. They bind to the Fas death receptor, a protein ~ above the cabinet membrane surface ar that initiates the perforin–granzyme pathway and also cytokine-mediated pathways to induce apoptosis, which directly kills virally infected cell or tumour cells.

CD4+ Th cells recognise and bind come MHC-II molecules. Castle activate B cells to produce certain antibodies. ~ above re-exposure come the exact same antigen, memory T cells deserve to respond easily by division and clonal expansion.

Th cells include theTh1, Th2, Th17 and also Th22 subtypes. Each subtype is associated with certain signalling cytokines and also effector functions.

Th1 cells develop a cell-mediated immune response to death intracellular pathogens.

Th1 cells create IFN-γ and can activate macrophages and stimulate NK cells.

Th2 cabinet activation leads to B cabinet stimulation and antibody production.

Th2 cells create cytokines IL-4, IL-5, IL-6 and also IL-10.They have the right to stimulate eosinophil activation.

Th17 cells produce IL-17 and IL-22 and also play a duty in protection from bacterialinfections and fungalinfections. Th22 cells produce IL-22 and tumour necrosis factor alpha (TNF-α), i m sorry induces inflammation. Both Th17 and Th22 cells play a role in the pathogenesis of psoriasis. Various other T cabinet populations, such as regulatory T cell (Tregs), fine-tune the immune an answer by managing immune cells solution to foreign and also self-antigens and prevent autoimmunity reactions.

B cells

B cells space responsible for producing a storage of former antigen exposure come ensure a faster immune solution and a lasting immunity. B cells create antibodies (immunoglobulins) that can bind to particular antigens. Antibody effector features are:

Neutralisation — antibodies binds to the virus and prevents adherence/infectionOpsonisation — the coating the the antigen surface ar by antibodies and the subsequent uptake through phagocytic cells

To develop antibodies, B cells require cytokine signalling and stimulatory signal from Th cells. This takes location in secondary lymphoid guts such as lymph nodes.

The B cells and also T cells must bind via the B cell receptor (BCR) and also the T cabinet receptor, respectively. This is mediated by co-stimulatory signals on Th cells.The proliferation that B cells leader to the manufacturing of a certain antibody, either IgG, IgA or IgE, depending upon the antigen.

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Upon re-exposure to the same antigen and follicular dendritic cells, B cells space activated come produce particular antibodies.This process allows for the generation of memory B cells and long-lived plasma cells because that long-lasting immunity from infection.