Skin and the Immune System

Question 1

The cutaneous immune system is composed of the […] and the […]

Answer 1

Epidermis and dermis

Question 2

What is the role of keratinocytes in immune function of the skin?

Answer 2

• They provide a permeability barrier at the stratum lucidum/granulosum layer
• They produce defensins (insert into microbial membranes) and cathelicidins (direct toxicity to microbes)
• Expression of PRRs (TLRs and NLRs) that can stimulate an innate immune response

Question 3

Langerhans cells

• Found in what layer of the skin?
• When do they develop?
• What type of cell are they?

Answer 3

• Epidermis –> Stratum spinosum
• Early in fetal development
• Specialized dendritic cell / macrophage

Question 4

Dermal dendritic cells are derived from […] progenitors

Answer 4

Bone marrow myeloid

Question 5

What do langerhans cells and dermal dendritic cells have in common?

Answer 5

• They both express TLRs
• Both migrate to lymph nodes to stimulate immune response

Question 6

What immune cells are present in the epidermis?

Answer 6

Keratinocytes and langerhans cells

Question 7

What immune cells are present in the dermis?

Answer 7

Dendritic cells

Resident macrophages

Mast cells

Question 8

Mast cells

• What cells do these arise from?
• What receptor do they express?
• What do they contain in their cytoplasm?

Answer 8

• Bone marrow myeloid cells
• Receptor for IgE
• Granules with histamine and inflammatory mediators

Question 9

Type 1 hypersensitivity is also called […] and is activated by […] cells

Answer 9

Immediate type hypersensitivity

Mast

Question 10

Describe the process of type 1 hypersensitivity.

Answer 10

Question 11

What are the 2 phases of type 1 hypersensitivity (allergy) response upon repeat exposure to allergen?

Answer 11

Question 12

What cells are responsible for causing the allergic reaction seen with type 1 hypersensitivity?

Answer 12

Mast cells

• Resident in tissue, numerous in connective tissue under epithelia
• Release histamine, cytokines, enzymes

Basophils

• Migrate from blood
• Express IgE receptors
• Release histamines, cytokines, enzymes

Eosinophils

• Migrate from blood
• Release toxic microbial substances

Question 13

What is the name for the classic dermatologic finding of type 1 hypersensitivity?

Answer 13

Urticaria (aka hives)

Question 14

What is urticaria?

What 2 dermatologic features are characteristic of this condition?

Answer 14

Question 15

What is atopy?

Answer 15

The genetic predisposition to produce IgE in response to allergen. These individuals have higher serum IgE and more Th2 CD4+ cells than general population. It is unclear why.

Question 16

People who develop allergy typically have family members with allergy.

True/false

Answer 16

True

Question 17

What role does the environment play in allergy development?

Answer 17

• Allergies are more common in developed countries
• Hygiene hypothesis - early life exposures to infection and mcirobes decreases likelihood of allergic response later to non-pathogenic subtances like pollen

Question 18

Another name for type 2 hypersensitivity is […]

Answer 18

Antibody-mediated

Question 19

Type 2 hypersensitivity is a diseas caused by […] against […]

Answer 19

Antibodies

Self

Question 20

How can antibodies become self reactive?

Answer 20

Antibodies may be specific for normal cell antigens or foreign antigens that look very similar to self antigens, so the antibodies that are supposed to recognize foreign antigen can actually recognize self via “cross reaction”

Question 21

What are the 3 main mechanisms of antibody-mediated injury in type 2 hypersensitivity?

Answer 21

Inflammation

Opsonization and phagocytosis / complement activation

Cellular dysfunction (antibodies directed against cell surface receptors impair or dysregulate function without causing cell injury or inflammation)

Question 22

Pemphigus Vulgaris

• This is an example of what type of hypersensitivity reaction?
• What type of condition is this?
• What is that pathophysiology?
• What is the clinical presentation?

Answer 22

NOTE: for question 2 - Autoimmune disease of skin due to presence of IgG against desmogleins which are part of desmosomes (not tight junctions) in keratinocytes

Question 23

Another name for type 3 hypersensitivity is […]

Answer 23

Immune complex

Question 24

Describe the mechanism of hypersensitivity in type 3 hypersensitivity.

Answer 24

Antibodies bind to antigen (can be foreign or self antigen) and travel systemically where they tend to deposit at sites of high pressure and elicity injury at this distant site.

Question 25

What causes injury in type 3 hypersensitivity?

Answer 25

Mechanisms of injury are similar to type 2, just at a site that is distant from where antigen originated from.

Question 26

Cutaneous Polyarthritis Nodosum

• What type of hypersensitivity is this?
• This is a type of what condition?
• What features are seen in histological sections from patients with this disease?
• What are the mechanisms of injury?
• What other 2 things is this condition is associated with?

Answer 26

• Type 3
• Medium vessel vasculitis
• Deposition of C3 and Ig in vessel walls
• Vessel inflammation (vasculitis) and vessel injury; tender subcutaneous nodules; fever; arthralgia; myalgia
• Certain meds (antibiotics, birth control) and infections (HBV, Group A Strep)

Question 27

Another name for type 4 sensitivity is […]

Answer 27

T-cell mediated, Delayed Type

Question 28

What is the mechanism of hypersensitivity for type 4?

Answer 28

Question 29

Contact dermatitis

• What type of hypersensitivity is this?
• In my own life, I’ve experienced this when I was bitten by bed bugs. What caused me to have the reaction that I did?

Answer 29

• Type 4
• Proteins in the bed bug saliva penetrated my skin and were taken up by APCs in my skin. These APCs then activated CD4+ T-cells to become Th1 cells which then traveled to the area of the bite in the skin. Here the Th1 cells released INF gamma which produced inflammation. Mast cells were also stimulated to release granules causing itching and redness. CD8+ cells also could have induced cell death as seen with the blistering skin lesions I had.