Skin Immunology Flashcards
How is the keratin layer formed?
Terminal differentiation of keratinocytes to corneocytes
Name some structural proteins in keratin layer and epidermis
Filaggrin, Involucrin, keratin
What can activate keratinocytes?
UV and sensitizers (e.g. allergic contact dermatitis)
What do keratinocytes produce?
Antimicrobial peptides (AMPs) that can directly kill pathogens (found at high levels in psoriasis patients). Also cytokines and chemokines
What is the main skin resident immune cell?
Langerhans cells
What type of antigen cells are Langerhans Cells, and what are they characterised by?
Antigen presenting cells, Birbeck granule
What is the function of Langerhans cells?
Act as sentinels in epidermis, process lipid Ag and microbial fragments and present them to effector T cells, help activate T cells
Where are T cells sensitised?
Thymus
What is involved in the interaction in Ag recognition and T cell activation?
T cell receptor (TCR) and Major Histocompatibility Complex (MHC)
What 2 co-receptors enhance Ag recognition and T-cell activation?
CD4/CD8
Describe MHC Class II
Found on APC (B cells, macrophages), Present to TH cells, Present exogenous Ag
Describe MHC Class I
Found on almost all cells, Present Ag to cytotoxic T cells, Present endogenous Ag
What T lymphocytes are found in the epidermis and dermis?
Mainly CD8+T in epidermis, CD4+ and CD8+T in dermis. Also NK cells are found
Which CD4+Th cells are associated with inflammation?
Th1 (psoriasis), Th2 (atopic dermatitis) and Th17 (psoriasis and atopic dermatitis)
What do CD4+ Th1 helper cells do?
Activate macrophages to destroy microorganisms aided by IL2 and IFNgamma
What do CD4+ Th2 helper cells do?
Help B cells to make Ab, with the aid of IL4/5/6
What do CD8+ Cytotoxic T cells do?
Can kill infected cells directly, important protection against viruses and cancer
What is the function of Dermal dendritic cells?
Involved in Ag presenting and secreting cyto/chemokines
What is the function of Plasmacytoid dendritic cells?
Produce IFNalpha, found in diseased skin
Name some skin conditions associated with an inappropriate immune response
Psoriasis, atopic dermatitis, bullous pemphigoid, contact dermatitis, morphea/systemic sclerosis, urticarial, systemic lupus erythematosus, skin infections and tumours
What triggers psoriasis?
Environmental factors in genetically susceptible individuals
What do keratinocytes do under stress in the T cell mediated immunopathogenesis of psoriasis
Release factors that stimulate pDC to produce IFNalpha, release IL-1beta, IL-6 and TNF
Describe the DC response in the immunopathogenesis of psoriasis
Activated by chemical signals, DC migrate to skin draining lymph node to present to and activate T cells TH1/17
Describe what happens to T cells during the immunopathogenesis of psoriasis
They are attracted to dermis by chemokines and secrete IL-17A/17F/22. These stimulate KC proliferation, AMP release and neutrophil-attracting chemokines
What is a key factor development of atopic eczema?
Impairment of skin barrier function. Mutations in fillagrin gene associated with severe/early onset disease, leads to decrease in AMP
What cells are found in the lesions of atopic eczema?
T cells (Th2), DC, KC, macrophages and mast cells (likely attracted by stressed KC)
Name some examples of AI skin conditions
Psoriasis, vitiligo, SLE
What are the routes of exposure in a type 1 allergy?
Skin contact, inhalation, ingestion, injection
What is angioedema?
Localised swelling of subcutaneous tissue or mucous membranes, non pitting
What investigation should be done during anaphylaxis?
Serum mast cell tryptase level
What dosage of adrenaline is given to adults and children in an autoinjector?
300 micro grams adults, 150 children
What are some examples of an endogenous dermatitis?
Atopic eczema, other skin conditions
