Skin immunology (psoriasis) Flashcards
Describe the epidermal barrier of the innate immune system
- The skin forms a barrier to invasion through production of many proteins including FILAGRIN
- Constitutively expressed ANTI-MICROBIAL PEPTIDES (AMPs) like DEFENSINS are also present in the barrier
- normal skin flora are competitive for binding spots on skin (prevent invasive microbes from latching on)
Describe the epidermal induction of local, non-specific immune responses
- The epidermis responds to activation of PROTEASE RECEPTORS and TOLL-LIKE RECEPTORS by producing cytokines that can activate the immune process;
- TUMOR NECROSIS FACTOR alpha
- INTERLEUKIN-1 (IL-1)
- CHEMOKINES (attract increased blood derived cells)
**results in new AMP production and blood borne immune cell activation
What blood derived cells play a major immunological role in skin?
- Blood derived cells are resident in the skin but can also increase in number with chemokine attraction
- __DENDRITIC CELLS
- MACROPHAGES
- MAST CELLS
- NEUTOPHILS
- (also T cells)
What major cytokines interact to promote specific reactions in the skin?
- Dendritic cells produce
- INTERLEUKIN-23 (impacts other blood borne cells such as T cells, neutrophils, and basophils)
- TNF
- IL23 and TNF from DCs induce the production of
- INTERLEUKIN 17 A and F by T cells, mast cells, and neutrophils
- IL-20 and 22 by T cells and macrophages
- These are all increased by the presence of INTERFERON GAMMA produced by T helper cells
What is the epidermal reaction to activation of the innate immune system?
The epidermis thickens, increases barrier proteins, and markedly _increases the number of AMP_s/recruitment of new cells to fight off infection
Describe the role of adaptive immunity in the skin immune response
- T cell activation and B cell production of antibody with specificity
- Much less significant in bacterial infections of the skin than innate immunity
Describe psoriasis (prevalence, comorbidities)
- most common inflammatory disease in adults with approximately 3% of the US population with the condition.
- Can happen at any age, involves men and women equally
- Genetic predisposition. However, about 50% of patients do not have a first degree relative with the condition.
- Increases risk of inflammatory arthritis, diabetes, coronary artery disease (increased risk of MI), and lymphoma.
- Has been found in Egyptian mummies and was likely described in Leviticus with the first report of phototherapy.
Describe the Clinical and Histological presentation of psoriasis
- All related to the epidermal abnormalities
- Skin is thickened (keratinocytes are reproducing too rapidly… Migration to the stratum corneum is 3-7 days as opposed to the normal 28 days)
- Scale (keratinocytes do not mature normally and do not shed properly… Abnormal proteins are produced like keratin 16)
- _Redness (_Blood vessels are nearer to the surface, proliferate, and dilate)
Describe the developing understanding the pathophysiology of psoriasis
- **bedside to bench
- For years thought to be a disease exclusively of the skin.
- With the use of cyclosporine for organ transplants, psoriasis would improve -> T cell model of psoriasis.
- Use of anti-TNF therapy (infliximab and etanercept) were of benefit but there was no good explanation of how the immunological activity changed the skin.
- STAT-3 mouse models caused a murine type of psoriasis.
- The IL-23/IL-17 system put it all together.
Describe the current basic model for psoriasis
**the normal response to infection in overdrive
(Some internal or external stimulus initiates an immune response locally in the skin.)
What do keratinocytes and DCs produce in psoriasis?
- Keratinocytes produce TNFalpha and IL-1.
- Dermal dendritic cells produce IL-23 (activates T cells, mast cells, and neutrophils to produce IL-17 and IL-22)
** Genes associated with psoriasis include those that code for TNF and IL-23 responses.
How do keratinocytes change in psoriasis?
Keratinocytes respond by expressing STAT-3 and changing into psoriatic cells.
What are targeted treatments aimed at in the psoriasis MOA?
- Targeted treatments are being developed to block IL-17, IL-23, along with TNF.
- Different targets give different response characteristics
- IL-23 agents have longer term responses
- IL-17 agents give the fastest responses
What is contraindicated in psoriasis patients?
Oral corticosteroids (prednisone); although the patient will initially get better, stopping treatment will make the patient very sick
What are some possible treatments for psoriasis?
- topical therapies (corticosteroids, vitamin A/D)
- phototherapies (UVB lasers, psoralen + UVA)
- systemic therapies
- methotrexate
- cyclosporine
- retinoids
Contrast the histology of psoriatic and normal skin
Psoriasis on the right;
- perikarytosis (retention of nuclei in the stratum corneum)
- very thick skin
- dilation of blood vessels
- immune cells present
Topical corticosteroids are in what family of steroids?
Glucocorticoids
**overall anti-inflammatory effect
Describe the classes of topical corticosteroids
Class I-VII, with class I being the most potent
Describe the vehicles used for topical corticosteroids
**Dermatologists mostly prefer ointment formulation (allows for better penetration of the active ingredient through the stratum corneum, effectively increasing the efficacy)
Describe atopic dermatitis
- the most common chronic inflammatory skin disease
- Onset in infancy is typical, but delayed onset in adulthood may be seen
- TRIAD with allergic rhinoconjunctivitis and asthma
- Mutations in the profilaggrin gene (also responsible for ichthyosis vulgaris!)
- infection with S. aureus is common and can aggravate AD by stimulating the inflammatory cascade
Describe Seborrheic dermatitis
- a mild inflammatory condition with a variable presentation based on age
- In infants, involvement of the scalp with greasy, yellow scale (“cradle cap”) is common
- Infantile seborrheic dermatitis is self-limited, with most infant having resolution by several months of age
- In adolescents and adults, seborrheic dermatitis occurs in areas of high sebum production
Describe the clinical symptoms of lichen planus
- small, polygonal-shaped, violaceous, flat-topped papules which are typically pruritic
- Planus= “purple, polygonal, pruritic, planar (flat) papules and plaques”
- Fine white lines, called “Wickham’s’ striae”, may be seen over the surface of the papules
- buccal mucosa, wrists and forearms, tops of hands, and shins are common sites
