BMS Test 1 Flashcards
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.
HPV is a viral carcinogen (high risk type most common on mucosal surfaces). What does it tend to do?
turn off tumor suppressor genes (TP53 esp.)
what is the most common cause of hair loss? what is the most common cause of diffuse hair loss?
androgenic alopecia (AGA)
telogen effluvium - diffuse
chronic inflammation commonly from ulcers or burns almost all result in what type of cancer?
Squamous cell carcinoma (more aggressive).
note also inflammatory skin/mucosal conditions
Alopecia areata (AA) ?
autoimmune hair loss in children, well demaracated patches
cytotoxic CD8 T cells target hair follicles
onychomycosis vs psoriasis nails
Onychomycosis: fungal, hyperkeratosis, separation, thickening and crumbling NO pitting
psoriasis: pitting due to hyperkeratosis, leukonychia, nail separation, vulnerable to fungal infections
when does varicella herpes zoster (chicken pox) reactiavte to shingles?
when T cell mediated immunity falls
when does most transmission occur for herpes simplex virus? differentiate between type 1 and 2
primary infection because its asymptomatic
HSV1 - warts
HSV2 - genital
How do superantigens (toxins produced by staph aureus) work?
activate T cells in a nonspecific and exaggerated way, binding to immmune proteins and causing massive response
Toxic shock (TSST-1)
- high fever, hypotension, rash, organ failure
Protein A is expressed on the surface of S. aureus, what does it do?
blocks antibody -mediated phagocytosis by neutrophils and macrophages
why are recurrent infections common with staph?
adaptive immune responses are not fully capable of stopping staph
some types of staph aureus can make exfoliative toxins, what are tehse and what do they do
ETs are serine proteases that bind to cell-adhesion molecule desmoglein-1 -> blistering skin disorder
what is M-protein
GAS (group A strep) has M-protein that is a mutlifunctional protein -> inhibits immune defences. Invades by binding fibronectin and CD46 on keratinocytes
