Cutaneous Immunology Flashcards
Cutaneous physical defenses
- relatively impermeable stratum corneum
- continuous keratinization and dequamation
- antimicrobial peptides and secretions of free fatty acids through sebum
Innate immunity
inherently programmed cells that destroy invading microbes before they establish infection
- non-specific and quick
- no long term memory
- mediated by phagocytic cells (neutrophils + macs)
- release inflamm mediators (mast cells + eosinophils) and also other cells like NK cells
- activated cells cause local tissue destruction and release cytokines (IL-1, TNF-a, IFN-y) for increased blood flow and fluid accum and recruit other immune cells
Adaptive immunity
acquired response against specific antigens
- takes several days after initial stimulus
- subsequent exposures have faster and stronger response
- long-lived memory
- modulates response by altering cytokines released and cells recruited
- B-T lymphocytes and APCs (antigen presenting cells)
Langerhans cells (LCs)
specialized dendritic cells (APC) that reside in epidermis
- phagocytose and process antigens
- encounter antigen –> migrate to regional lymph node to present antigen to T cells (form Cutaneous Lymphocyte Antigen cell-surface marker)
- if antigen specific T cell present, APC stimulate 2nd signal to activate T cell –> T cell proliferate/differentiate
Dermal dendritic cells (DDCs)
Langerhan cells in the dermis
TH1 cells
release IFN-y and TNF to stim cell-mediated immunity
- activate macrophages, dendritic cells, neutrophils and cytotoxic T cells
- clears viruses, tumors, intracellular pathogens
- Type IV (delayed) hypersensitivity
TH2 cells
release IL-4, IL-5 and IL-10 to stim humoral immunity
- activate eosinophils and plasma cells for IgE production
- clears parasites and extracell microbes
- atopic dermatitis, urticaria + allergenic diseases
TH17 cells
implicated in development of autoimmune diseases like Crohn’s disease, ulcerative colitis and psoriasis
Allergic Contact Dermatitis (ACD)
adaptive cutaneous immune system producing exaggerated inflammatory response
- immune system creates local inflamm to destroy allergen
- AKA Type IV/delayed hypersensitivity
- itchy red papules and vesicles appear 24-48 hrs post exposure and worsen for 4-7 days
- mild erythema and scale to vesicles and bullae if severe acute or scale and lichenification if chronic
- allergens are usually haptens, which diffuse into epidermis and is phyagocytosed by LCs –> lymph node –> T cells –> TH1 reaction, clonal proliferation and migration of clones to skin (first time takes about 7-14 days, rexposure 24-48hrs)
- first exposure often doesn’t produce response
Haptens
molecules too small to be recognized independently but capable of stimulating immune system after binding to native proteins
Atopic Dermatitis
Eczema
- looks almost identical to ACD but due to TH2 dominance
- imbalance of immune system (assoc. with asthma and allergic rhinitis)
- genetic predisposition (filaggrin mutation), envi irritants/allergens (enters barrier disruption to initiate TH2 with positive feedback loop, impaired TH1), s. aureus
- generalized itchy skin and ill-defined erythematous papules and plaques with scale and crust (lichenification)
- Infants : affects face, scalp, extensor extremities
- Adults : affects face, flexural areas (antecubital/popliteal)
Psoriasis
increased keratinization causing thickening epidermis
- erythematous, well-demarcated plaques with thick silvery-white scale resembling mineral mica
- some itching but less severe than in dermatitis
- extensor surfaces, trunk, extremities and genitals, nails
- associated with destructive arthritis (psoriatic arthritis)
- predominantly mediated by TH1 lymphocytes
- lymphocytes release cytokines to signal epidermis to proliferate rapidly causing thick plaques with scale
- controlled with chemotherapy targeting T cells or blocking TNF-a receptor
- TH17 involvement
Koebner phenomenon
irritating or scratching of skin leads to outbreaks of psoriasis
Guttate psoriasis
small round papules and plaques precipitated by strep infection
Pustular psoriasis
numerous pustules localized to palms and soles
Urticaria
Hives
- itchy, annular, edematous, pink papules/plaques (wheals)
- also can be linear wheals (dermatographism)
- deep in dermis = angioedema, causes painful swelling and often affects lips and face
- evanescence (lasts less than 24 hrs before resolving)
- type I (immediate) hypersensitivity
- Mast cells coated with IgE –> activation causes release of histamine, leukotrienes and prostaglandin
- histamine causes dilation of blood vessels and expansion of gap between endothelial cells –> fluid transudates to form localied edema
- histamine also works on nerves to cause itching
- fluid drained by lymphatics and substances broken down
Mast cell degranulation
- IgE Ab activation against allergen (Type 1 hypersensitivity)
- drugs (opiates, ethanol)
- physical stimuli (heat, cold, pressure, vibration, sunlight)
Drug eruptions
Range from limited small fixed plaque to widespread blistering and sloughing of skin
-most commonly antibiotics, anticonvulsants and NSAIDs
Exanthematous (morbilliform) drug eruptions
> 90% all drug eruptions (measle-like)
- drug metabolites cause delayed (type IV) hypersensitivity
- LCs phagocytose drug –> lymph node –> TH1 activation –> migration to skin
- takes 4-14 days after initiation of medication
- begin as erythematous macules/papules on trunk and upper extremities
- spreads outward to become confluent
- mildly itchy but not painful/isn’t morbid
- neither clinical appearance nor pathology can differentiate a viral exanthem from drug rxn nor identify drug responsible
DRESS
drug eruption with eosinophilia and systemic symptoms
- characterized by exanthematous eruption with fever, lymphadenopathy and facial edema
- 15-40 days after drug with 5-10% mortality (fulminant hepatitis)
Urticarial drug eruptions
subset of urticaria due to systemic medications
- 2nd most common cutaneous drug eruption
- occur within minutes of exposure when patient has IgEs
- immediate hypersensitivity (Type I)
- potential to be life threatening from airway compromise by angioedema or from widespread vasodilation and severe hypotension from anaphylaxis
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)
immune system activates cascade of apoptosis, causing widespread epidermal necrosis
- 7-21 days after exposure
- characterized by erythematous and dusky macules coalescing into patches on head, trunk and extremities
- mucosal ulcerations, bullae formation, sloughing of epidermis in sheets –> reveals dermis
- fever, systemic symptoms
- painful skin lesions + mortality complications
