Cutaneous Immunology

Question 1

Physical defenses of the skin:

Answer 1

keratinocyte with desmosomal adhesions, impermeable stratum corneum, keratinocyte turnover, antimicrobial peptises and secretion of free FA’s in sebum. All can be modified in an immune response.

Question 2

Describe innate immunity, what is involved, and what stimulates it.

Answer 2

The initial, non-specific immune response where phagocytic cells (neutrophils and macrophages), cells that release inflammatory mediators (mast cells, eosinophils), and NK cells cause local tissue destruction and inflammation from release of cytokines (IL-1, TNF-alpha, IFN-gamma) and mediators of blood flow, fluid accumulation, and recruit other immune cells.

Question 3

Describe adaptive immunity, its actions, and main cells.

Answer 3

An acquired response after a few days to specific antigens. Leads to long-term memory formation to future infection from similar antigens. Cells are B- and T-lymphocytes and the antigen presenting cells stimulate the response.

Question 4

Specialized dendritic cells that reside in the epidermis that phagocytose and process antigens

Answer 4

Langerhans cells

Question 5

Specialized dendritic cells that reside in the dermis that phagocytose and process antigens

Answer 5

Dermal dendritic cells

Question 6

How long after Langerhans or DDC encounter an antigen does it take to migrate and mount an immune response?

Answer 6

7-14 days. Shorter time with subsequent exposure to similar antigens.

Question 7

What do T-cells stimulated by Langerhans cells and dermal dendritic cells express to allow them to migrate into inflammed skin?

Answer 7

Cutaneous lymphocyte antigen

Question 8

What are the cytokines released, immune response type, and pathogens cleared by TH1 cells?

Answer 8

IFN-gamma and TNF direct the cell-mediated immunity to clear viruses, tumors, and intracellular pathogens.

Question 9

TH1 are responsible for what type of allergic reaction seen in allergic contact dermatitis and psoriasis?

Answer 9

Delayed type (Type 4) hypersensitivity

Question 10

What are TH2 cytokines, immune response type, and pathogens cleared?

Answer 10

IL-4, IL-5, IL-10 for humoral immunity via plasma cells and IgE production to clear parasites and extracellular microbes. Seen in atopic dermatitis, urticaria, and other allergic disease.

Question 11

Diseases from autoimmunity in newly discovered TH17 cells?

Answer 11

Crohn’s, ulcerative colitis, and psoriasis.

Question 12

Clinical expression of allergic contact dermatitis

Answer 12

Itchy, red papules and vesicles 24-48 hours after exposure and can worsen up to 4-7 days later. Varies from mild erythema to vesicles and bullae if severe or scale and lichenification if chronic. Shape and distribution give clue to inciting allergen. (Ex: poison ivy= linear rash, nickel jewelry geometric rash)

Question 13

Common skin allergens?

Answer 13

poison ivy, poison oak, nickel, fragrances, preservatives, topical antibiotics.

Question 14

Describe how to do a patch test.

Answer 14

Place suspected allergen on patch, apply to skin for 48 hours, observe for redness and blistering.

Question 15

Molecules that are too small to be recognized independently but capable of stimulating the immune system by binding to native proteins

Answer 15

haptens

Question 16

Pathology of atopic dermatitis

Answer 16

Imbalance in immune system, with TH2 predominance rather than a hypersensitivity. Combination of genetic predisposition (filaggrin mutation), environmental irritants and allergens, and colonization w/ Staph aureus. Associated with atopic triad.

Question 17

Clinical expression of atopic dermatitis

Answer 17

generalized itchy scale and ill-defined erythematous papules and plaques with scale, and crust. Lichenification. Common on face, scalp, and extensors in infants, flexural areas and face in adults.

Question 18

Irritating or scratching skin in areas with psoriasis leading to more psoriasis in otherwise normal skin

Answer 18

Koebner’s phenomenon

Question 19

Clinical expression and pathology of guttate psoriasis

Answer 19

small, round papules and plaques precipitated by a strep infection.

Question 20

Pathology of psoriasis

Answer 20

mediated by TH1 lymphocytes and cytotoxic T cells and others. Histo shows presence of neutrophils in epidermis and lymphocytes signal rapid proliferation leading to thick plaque formation. Control outbreaks by targeting T cell activation or blocking TNF-alpha receptor.

Question 21

Clinical expression of urticaria (hives)

Answer 21

Itchy, annular, edematous, pink papules or plaques known as wheals. Can also present as linear wheals in areas where skin is stroked or scratched (dermatographism). In deep dermis, called angioedema, causing painful swelling in lips or face. Resolves in 24 hours.

Question 22

Pathology of urticaria

Answer 22

Mast cell degranulation and histamine release. Result of Type 1 hypersensitivity reactions. Mast cells coated in IgE respond to antigen, activate, and release histamine, leukotrienes, and prostaglandins.

Question 23

Mast cell stimulators

Answer 23

IgE, nonimmune activators like drugs, or physical stimuli like heat, cold, pressure, vibration, and sunlight.

Question 24

Most common drugs causing drug eruptions

Answer 24

antibiotics, anticonvulsants, and NSAIDS

Question 25

Pathology of exanthematous drug eruptions

Answer 25

delayed type (Type 4) hypersensitivity. LCs phagocytose drug and migrate to lymph nodes to activate lymphocytes that migrate back to the skin for a response. 4-14 days for sensitization.

Question 26

Clinical expression of exanthematous drug eruptions

Answer 26

erythematous papules and macules on trunk and upper extremities and progressively spread outwards. Mildly pruritic, not painful. Called morbilliform and closely resemble rashes of viral infections.

Question 27

Clinical expression of DRESS (drug-eruption with eosinophilia and systemic symptoms)

Answer 27

exanthematous eruption with fever, lymphadenopathy, and facial edema. Onset later (15-40 days) w/ mortality of 5-10%.

Question 28

Clinical expression of urticarial drug eruptions

Answer 28

urticaria from systemic medication. Occur within minutes of exposure to IgE against the drug. A type 1 hypersensitivity.

Question 29

Pathology of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

Answer 29

immune cascade of apoptosis within keratinocytes in epidermis leading to widespread epidermal necrosis 7-21 days after exposure.

Question 30

Clinical expression of SJS/TEN

Answer 30

erythematous, dusky macules coalescing into patches on the head, trunk, and extremities. Hallmarks are: mucosal ulcerations, bullae formation, and sloughing of epidermis to reveal denuded dermis below. Fever and systemic symptoms. PAINFUL! Tx: like burn patients.