Podcast
Questions and Answers
What is the primary cause of allergic contact dermatitis (ACD)?
What is the primary cause of allergic contact dermatitis (ACD)?
What is the primary mechanism that leads to the elicitation phase of contact dermatitis after initial hapten exposure?
What is the primary mechanism that leads to the elicitation phase of contact dermatitis after initial hapten exposure?
Which of the following statements accurately describes the treatment of ACD?
Which of the following statements accurately describes the treatment of ACD?
Which factor contributes to the difficulty in identifying allergens in occupational ACD cases?
Which factor contributes to the difficulty in identifying allergens in occupational ACD cases?
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Which of the following cytokines is implicated in the activation of the inflammasome during contact dermatitis responses?
Which of the following cytokines is implicated in the activation of the inflammasome during contact dermatitis responses?
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Which SNP has been reported in association with allergic contact dermatitis in recent studies?
Which SNP has been reported in association with allergic contact dermatitis in recent studies?
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Which immune cells have been shown to compensate for the loss of Langerhans cells in contact hypersensitivity responses?
Which immune cells have been shown to compensate for the loss of Langerhans cells in contact hypersensitivity responses?
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What role does Pellino-1 play in the context of allergic contact dermatitis?
What role does Pellino-1 play in the context of allergic contact dermatitis?
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What role do TRMs (tissue-resident memory T cells) play in the context of contact allergy?
What role do TRMs (tissue-resident memory T cells) play in the context of contact allergy?
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What is a primary distinction between central memory T cells and TRMs in terms of their responses?
What is a primary distinction between central memory T cells and TRMs in terms of their responses?
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Study Notes
Allergic Contact Dermatitis (ACD)
- A common inflammatory skin condition triggered by repeated exposure to haptens (low-molecular-weight chemicals/metals).
- Haptens interact with endogenous proteins to form immunogenic antigens.
- ACD can be acute (e.g., after urushiol exposure) or chronic (e.g., occupational exposure to metals like nickel or chromium).
- Treatment focuses on avoiding re-exposure to the allergen and using corticosteroids (topical or systemic).
Identifying the Offending Allergen
- Identifying the offending allergen can be challenging, especially in occupational ACD cases.
- Individual susceptibility and familial predisposition to ACD have been observed, but evidence for strong genetic susceptibility is weak.
- HLA haplotype associations and gene polymorphisms (like ACE, TNFA, IL16) have been suggested, but results are inconsistent and/or cohort sizes were too small.
- Recent GWAS studies have shown associations between SNPs in Netrin-4 and Pellino-1 with nickel allergy in Korean populations.
Rodent Models of ACD (Hapten-Induced Contact Hypersensitivity)
- Rodent models (hapten-induced contact hypersensitivity) are widely used to study the mechanisms of ACD.
- In experiments, haptens are applied to shaved mouse skin, initiating the sensitization phase.
- The innate immune system is activated, leading to APC activation and subsequent T cell activation.
- Subsequent exposure to the hapten causes a T cell-mediated dermatitis response,quantified by measuring ear swelling.
Initial Hapten Exposure and Innate Immune Responses in ACD
- Initial contact with haptens triggers inflammasome and/or toll-like receptor (TLR) signaling pathways, key parts of innate immunity.
- Examples: urushiol stimulates skin cell release of ATP, DAMPs, ROS, and hyaluronic acid, activating inflammasomes and chemokine/cytokine release (IL-1β, IL-18, TNF-α).
- Nickel (Ni2+) can trigger CHS in human TLR4-expressing mice, but not in control mice.
- Ni2+ binds to human TLR4, stimulating interferon, IL-1β, and IL-18 production. Other metals like Cr2+ stimulate innate immunity via TLRs and inflammasomes.
Roles of Different Cell Types in ACD
- Langerhans cells (LCs) were long thought to be critical APCs in contact hypersensitivity.
- However, evidence isn't conclusive. Results from mouse studies with LC depletion are varied.
- Dermal dendritic cells (DDCs) may compensate for LC loss and are implicated in CHS responses.
- Other antigen-presenting cells (APCs) potentially play roles depending on the allergen.
T-Cell Responses in ACD
- Antigen-bearing dendritic cells migrate to lymph nodes to initiate T cell expansion and memory T cell development.
- CD8+ T cells are primary mediators of skin inflammation.
- CD4+ T cell activation is important for optimal CD8+ T cell responses.
- CD8+ T cells can populate lesional, post-lesional, and distant skin sites as resident memory T cells (TRMs).
- TRMs mediate rapid contact hypersensitivity responses, while central memory T cells cause delayed responses.
- Regulatory T cells are important for inflammation resolution in contact hypersensitivity.
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Description
Test your knowledge on Allergic Contact Dermatitis (ACD), its triggers, and treatment options. Learn about the role of haptens and the challenges in identifying allergens in occupational settings. Discover the genetic associations that may influence susceptibility to ACD.
