7 - Skin Immune System and Inflammatory Disorders Flashcards
What is cutaneous immunity?
Cutaneous immune system encompasses both the physical means to keep pathogens out and responses centered in the skin when pathogens get in.
Describe the innate immunity of the skin?
- Physical barrier
- Epidermal production of protective proteins
- Local cytokine production
- Blood derived cells
Describe the first barrier of the skin?
Physical barrier, including the stratum corneum. Barrier proteins like filaggrin block microbes from penetrating the skin.
Normal skin flora are competitive for spots to bind to skin.
Describe the second barrier of the skin?
The microbe encounters constituitively expressed anti-microbial proteins in the stratum corneum.
Defensins are the most common proteins.
What is the third barrier of the skin?
After the stratum corneum, the microbe separates tight junctions and activates toll-like receptors, inducing an imune reaction.
New AMPs are produced and blood borne immuen cells are activated.
What blood-borne cells are the most active in the skin? What are other blood derived cells that are resident in the skin?
Keratinocytes.
Also: dendritic cells, macrophages, and mast cells.
PMNs can also be recruited to the skin.
Describe the immune activation of the skin? What cytokines are secreted?
Epidermis reasponds to activation of protease receptors and TLRs by making cytokines to active immune response: TNF, IL-1, and chemokines for recruitment.
Due to chemokine attraction: DCs, macrophages, mast cells, and PMNs can be recruited.
Once recruited, what do dendritic cells do?
Produce IL-23 and TNF.
These induce the production of IL-17A and F by T cells, mast cells, and PMNS and IL-20 and 22 by T cells and macrophages.
These are all increased by the presence of IFN gamma by helper T cells.
What is the function of IL-23?
Impacts many blood borne cells including T cells, PMNs, and basophils.
Multiple cytokines are produced with the most intersting being the IL-20 family, most importantly IL-17.
What is the function of IL-17?
Induces further thanges in the epidermis, including thickening and induced AMP production, and promotes increased recruitment of new cells.
What occurs when an orannism gets into the epidermis?
It causes proliferation of IL1 and TNF.
This induces cytokine IL-23 to activate T cells to make IL-17, 20, and 19. These cause further changes in the epidermis that allow it to fight off infection.
How common is psoriasis? Who gets it? What is it caused by?
Most common inflammatory skin disease in adults: about 3% of the population, equally occuring in men and women.
Significant genetic predisposition, though 50% of patients do not report a family hx.
What are the different locations of the body that can be affected by psoriasis?
Really anywhere (limited or extensive)
Palmar-plantar psoriasis
Scalp psoriasis
Psoriatic nails
What is this an image of? When can it occur?
Pustular psoriasis: sterile pustules all over or in certain areas.
Seen when patients with psoriasis are given corticosteroids. Even though the steroids initially help while the patient is on them, stopping them causes this.
Take home: DO NOT give prednisone to pts with psoriasis
What is this an image of? What other issue can arise because of this?
Erythrodermic psoriasis.
Pts can have heart failure because all of the blood is going to the skin.
What are common symptoms reported by patients with psoriasis?
Most common symptoms: pain
About 70% report itch.
Psoriasis patients are NOT otherwise healthy.
Patients with severe psoriasis have a significantly increased risk of what medical condition compared to patients with mild or no psoriasis?
Myocardial infarction.
The attributable risk of MI or stroke is about 6.2% over 10 years; about equivalent to very high cholesterol.
Patients with >___% of their body surfaces covered in psoriasis are more likely to _____. What is a common goal of treatment?
>10% ; More likely to die.
Common goal of treatment is to get below 10% body coverage.
What are other psoriasis co-morbid diseases?
- Psoriatic arthritis
- Depression (thought to be unrelated to how they feel about their skin)
- Diabetes mellitus
- Crohn’s disease
- Economic instability
Severe arthritis is correlated to what socioeconomic factors?
Severe psoriasis is correlated to lower income.
Unemployment also correlates to psoriasis severity.
What are some of the common reasons that patients with psoriasis do not seek care?
- Give up
- Cost
- Other
- Too much hassle
- Takes too much time
- Access to specialist
- Too far away
What are three general treatment options for psoriasis? What are examples in each category?
- Topical therapies: topical corticosteroids, topical vitA and D derivatives
- Phototherapies: UVB diffuse and excimer laser, psoralen + UVA
- Systemic therapies: methotrexate, cyclosporine, retinoids
How does psoriasis compare to normal skin? How long does it take for the bottom later to get to the top?
It’s thicker and the skin just doesnt fall off well like it should. Also see dilation of blood vessels.
It takes 3-7 days to get from the bottom latre to the top (instead of the normal 28 days)
The clinical presentation of psoriasis stems from changes in resident cell populations in the skin. What are these three changes?
- Scale: abnormal keratinocyte maturation and abnormal keratin expression (keratin 16) - scales don’t fall off.
- Thickness: rapid keratinocyte proliferation - increase in cell cycle markers (Ki-67).
- Redness: cutaneous vascular proliferation and dilation.