The Skin Immune System and When It Goes Wrong: Psoriasis

Question 1

What is innate Immunity? and what does it consist of?

Answer 1

non-specific local reaction to danger

• Epidermal barrier
• epidermal induction of local, non-specific immune responses
• blood derived cells
• cytokines
• epidermal reaction

Question 2

How is the eidermal barrier involved with the innate immune system?

Answer 2

the skin forms a barrier to invasion through production of many proteins including Filagrin. There are also Constituitively expressed Ani-Microbial peptides (AMP) like Defensins at the barrier

Question 3

WHat are non-specific immune responses and how does the epidermis undeuce them in an innate immune response?

Answer 3

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 pocess. Tese include TNFalpha and IL-1 and cytokines that attract blood-derived cells

Question 4

How are blood derived cells involved in the innate immune response?

Answer 4

blood derived cells are resident in the skin but can also increase in number with chemokine attraction. These include:

Dendritic cells

macrophages

mast cells

neutrophils (can be recruited to skin)

Question 5

What cytokines are involved in the innate immune response and what produces them?

Answer 5

IL-23 and TNF by Dendritic cells

**these cytokines induce the production of**

IL-17A and F by T cell, mast cells, and neutrophils

IL20, IL22 by T cells and macrophages

***these are all increased by the presence of IFNy produced by helper T cells

Question 6

What happens to the epidermis during an innate immune reaction?

Answer 6

the epidermis thickens, increases barrier proteins, and markedly increased the number of AMPs to fight off infection

Question 7

What is adaptive immunity?

Answer 7

T cell activation adn B cell production of antibody with specificty. much less significant in bacterial infections of the skin.

Question 8

Who gets psoriasis?

Answer 8

• most common inflammatory disease in adults 3% of pop.
• any age
• men=women
• there is a genetic disposition, but 50% of pts. don’t have first degree relative with condition
  *

Question 9

What does having psoriasis increase your risk of having?

Answer 9

inflammatory arthritis, diabetes, coronary artery disease, and lymphoma, depression

Question 10

What are the clinical and histological presentations of psoriasis

Answer 10

all related to epidermal abnormalities

• thickened skin: keratinocytes are reproducing rapidly, migration to stratum corneum is 3-7 days instead of 28
• scale: keratinocytes do not mature normally and don’t shed properly. abnormal proteins like keratin 16 are produced
• redness: blood vessels are nearer to the surface, proliferate and dilate

Question 11

What used to be thought about psoriasis

Answer 11

• previously thought to only include skin
• with the use of cyclosporine for organ transplants psoriasis would improve
• 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

Question 12

WHat is the current model of psoriasis?

Answer 12

• internal or external stimulus initiated local immune response in skin
• keratinocytes produce TNFa and IL1
• dermal dendritic cells produce IL23
• IL23 activates T cell, mast cells, and neutrophils to produce IL-17 and IL-22
• Keratinocytes respond by expressing STAT-3 and changing into psoriatic cells
• genes associated with psoriasis include those that code for TNF and IL-23 responses
• targeted treatments are being developed to block IL-17, IL-23 and TNF

Question 13

What is the difference between therapy targeted at IL-17 and IL-23?

Answer 13

IL-23=log term repsonse

IL_17=fastest response