BMS Test 1 Flashcards
(37 cards)
What epidermal barrier protein is associated with a loss of function mutation in AD?
Filaggrin
Where is the filaggrin gene located?
Chromosome 1q21
What happens with the downregulation of cornified envelope genes?
Key structural proteins like keratin, filaggrin, and loricrin are essential for skin barrier integrity. Reduced expression weakens the stratum corneum, increasing vulnerability to allergens, irritants, and pathogens.
What are the effects of reduced ceramide levels in atopic dermatitis?
Diminished ceramides lead to impaired barrier function and increased transepidermal water loss (TEWL), contributing to dryness and irritation.
What is the impact of increased endogenous proteolytic enzyme activity in atopic dermatitis?
Proteases become overactive, especially under elevated skin pH, accelerating the breakdown of structural proteins and lipids in the epidermis.
What does enhanced transepidermal water loss (TEWL) indicate?
TEWL reflects the compromised barrier’s inability to retain moisture, exacerbating dryness, inflammation, and pruritus.
How do soap and detergents affect the skin barrier?
They increase skin pH, making it more alkaline, which enhances protease activity and degrades proteins and lipids, creating a cycle of barrier breakdown, increased TEWL, and inflammation.
What are the signs of T helper 2 (Th2) immune activation in AD comorbidities?
High levels of IgE, eosinophilia, predisposition toward allergic comorbidities, and psychosocial impact.
What are some features of filaggrin deficiency common in AD patients?
Ichthyosis vulgaris, keratosis pilaris, and hyperlinear palms.
How do you know it’s subacute or chronic eczema?
Dry scaly plaques, excoriation from itching and lithification, less erythema compared to acute.
How do you know it’s acute eczema?
Erythematous papulovesicular, crusting or exudation from pruritis.
What is the hallmark symptom of atopic dermatitis (AD) aka atopic eczema?
Itch.
Why is eczema not a one treatment for all?
Because filaggrin mutations and other mutations affecting skin barrier only occur in a minority of AD patients and also occur in healthy people. Suggesting that factors other than skin barrier gene mutations are required for development of AD.
what are the 3 major types of Innate lymphoid cells (ILCs)?
NK, resident, NKT
What are the cytokines secreted by ILC1?
TNF-a (pro inflammatory)
IFN-y (activates macrophages)
What are the cytokines secreted by ILC2?
IL-4 (basophils along wiht IL13)
IL-5 (eosinphils - cause inflammation and tissue damage)
IL-13 (basophils - allergy symptoms like itching and red)
What are the cytokines secreted by ILC3?
IL- 22 (maintains barrier function and tissue repair)
- inflammatory skin disease
IL-17 (neutrophils)
- autoimmune tissue inflammation
What stimulates ILC1?
IL-12
IL - 2 (also stimulates ILC2)
What stimulates ILC2?
Alarmins (early warning cytokines)
- IL-25
- IL-33
- TSLP
What stimulates ILC3?
IL-23
What conditions are associated with ILC1, 2 and 3?
ILC1 - allergic contact dermatitis
intracellular pathogens, tissue inflammation
ILC2 - atopic dermatitis
- allergies
ILC3 - psoriasis
extracellular bacteria or fungi in barrier tissues, autoimmune tissue inflammation
what do cytotoxic T cells (adaptive) and NK cells (innate) both do in anti viral defense
release perfornin (pores) and granzymes (apoptosis)
PAMPs (pathogen associated molecular patterns) trigger innate or adaptive?
innate via PRR like TLRs
Why are keratinocytes considered directors of immune response?
Have TLRs and RIGS
can release cytokines, alarmins, and chemokines upon infection.
