stromal fibroblastic cells, endothelial cells, epidermal keratinocytes Þ regulate immune response either as targets, or producers of adhesion molecules, pro-inflammatory chemokines (IL8, etc), and cytokines (IL1, IL6, TGF)
Summary of skin immune response
Langerhans’ cells (LCs) and dermal macrophages of the skin are dendritic cells. They differ from lymphoid tissue LCs in two ways:
(1) they uptake antigen both by pinocytosis and via cell-surface receptors
(2) they lack co-stimulatory activity
Once they uptake antigen from the outside of the body LCs migrate from the epidermis, cross the dermis, and enter the lymphatic system
They float to a lymph node where in paracortical region they become mature dendritic cells which can no longer ingest Ag, but can now co-stimulate T-cells
These mature LCs now bind T-cells via weak LFA:ICAM interactions, if an appropriate TCR matches with the cell’s MHC-II receptor the LFA:ICAM affinity becomes stronger, and the T-cell becomes educated to the foreign antigen
These T-cells lose expression of the L-selectin molecule that mediates homing to the lymph nodes, and increase expression of the integrin VLA-4 which binds VCAM-1 on endothelial cells
Cytokines induce expression of VCAM-1 on endothelial cells at sites of infection. Upon antigen re-exposure the T-cells migrate to the site and mediate an immune response.
– Genetic disease of autoreactivity, hyper IgE, and deficient cell mediated immune responsiveness in skin.
Atopic Triad: Atopic Dermatitis, Asthma, Hay fever
. Characterized by red, papulovesicular, oozing, and crusted lesions early on (such lesions are prone to bacterial S. Aureus superinfection, which produces a yellow crust (impetiginization)) that, with persistence, eventuate into raised, scaling (hyperkeratotic), dry plaques (acanthosis)
If it doesn’t itch it isn’t AD
. In childhood located on face and extensor aspects of extremities, with age localizes to popliteal and antecubital fossae, neck and postauricular area, and hands.
Note
: other forms of eczema include Primary Irritant Dermatitis (caused by repeated trauma such as rubbing) and Contact Dermatitis (caused by topically applied Ags, delayed hypersensitivity). Wet work and/or contact with irritating agents are one of the most common causes of disability in the U.S.
Histological
– Spongiosis – "accumulation of edema fluid within the intercellular spaces of the epidermis" with or without secondary epidermal hyperplasia. Stratum corneum gets altered. Epidermis gets infiltrated by lymphocytes and MF s. Dermis gets infiltrated by lymphocytes, macrophages and LCs. Mast and endothelial cell activation.
Mechanism
– Type I (anaphylactic) and Type II (cell-mediated) Hypersensitivity reactions happen together.
LCs in both epidermis and dermis lose distinction and acquire same phenotype – gain ability to activate patient’s own T-cells (autoreactivity)
For some reason this leads to the overproduction of Type II helper T-cells (TH2) – the type of cells which activate B cells via IL-4 and IL-5
Because there is a low level of TH1 cells CD8+ T-cells aren’t produced thus leading to poor responses to viral and fungal infections
Also, because of the high levels B cells a lot of IgE is produced leading to Type I hypersensitivity upon further exposures to Ag.
Treatment
Emolliation (grease on skin) blocks leakage/evaporation of water via skin.
Corticosteroids – reduce inflammation
Phototherapy – particularly useful for UVA
Antihistamines, antidepressants, anesthetics – used for pruritus.
Systemic Antibiotics – to protect against staph colonization and superinfection
Cyclosporine (systemic steroid) – blocks immune system, only used in severe cases.
Topical FK506 – topical immunosuppresent only blocks immune system in specific places.
Psoriasis
– CHRONIC INFLAMMATORY PROCESS
Clinical
– Genetic disease of autoreactivity. Onset is teens to middle age, disease is chronic
Lesions begin as a red pinpoint papule, evolving into an elevated erythematous plaque with silvery scale
Plaques can coalesce and become confluent over large areas including scalp, elbows, knees, buttocks, thighs, abdomen, palms, and soles
Nails usually fall off (onycholysis)
Disease can extend to total body exfoliative erythroderma
Psoriatic arthritis
(destructive, debilitating rheumatoid lesions) may be associated.
Histological
– Epidermal hyperplasia with elongated rete pegs due to keratinocyte hyperproliferation, alternating with a thinned suprapapillary epidermis due to overgrowth and outward pressure of vascular papillary dermal capillary loops
Hyperkeratosis, parakeratosis (hyperkeratosis with retention of nuclei of keratinocytes), infiltration of leukocytes, minimal spongiosis
Mechanism
– macrophages capable of activating T-cells without addition of exogenous antigen are present
Unlike AD, TH1 cells predominate producing IFN (macrophage activator), and lymphokines which cause keratinocyte hyperproliferation
The keratinocytes release cytokines which exacerbate this cycle
High relative risk with HLA-Cw6 gene.
Treatment
– hydrating creams, ointments, topical corticosteroids and vitamin D (calciportriol)
Phototherapy
Immunosuppressive meds may be used systemically (ie methotrexate, cyclosproine)
Experimental therapies target activated T cells, APC costimulatory molecule, and adhesion molecule for leukocyte trafficking.