Skin Inflammation Flashcards
What cells are found in the skin during inflammation?
Neutrophils, eosinophils, lymphocytes, plasma cells, macrophages and mast cells
What are Langerhans cells?
Dendritic cells the pick up antigens that enter the skin and transport them to lymph nodes where they present the antigen to CD4+ helper T cells
Where are Langerhans cells found?
In the epidermis
Why does skin become red and hot during inflammation?
Increased blood flow and vessel dilatation
Name the five different types of skin inflammation
Mast-cell mediated Antibody-mediated Immune-complex mediated Delayed hypersensitivity Granuloma formation
Outline mast-cell mediated inflammation
An inhaled or ingested pathogen is presented to an APC. The APC presents the antigen to a Th2 cell which then secretes several factors which activates eosinophils to release granules and B cells to produce IgE which will activate mast cells to release their contents too. This leads to vascular leak, broncho-constriction, increased gut motility, inflammation and tissue remodelling.
What is released during mast cell degranulation?
Histamine, leukotrienes, prostaglandin and platelet aggregating factor (PAF)
What substances can trigger mast cell degranulation?
Drugs (aspirin, NSAID), serum factors, insect stings, nuts, shell fish, house dust mites
What are the effects of mast cell degranulation?
Increased vascular permeability, broncho-constriction, increased gut motility, inflammation and tissue remodelling
Outline the main role of histamine on the body (after mast cell degranulation)
Stimulates sensory nerves (causes itching)
Bronchospasm
Arteriole dilatation (causes headache and hypotension)
Smooth muscle contraction (leads to vessel leakage and oedema)
What component of dust mites allow it to act as an allergen to stimulate mast cell degranulation?
Contains Der P1 in faecal pellets which cleaves tight junctions in gut mucosa
What are localised examples of mast cell-mediated inflammation?
Urticaria, asthma and hay fever
What is generalised mast-cell-mediated inflammation known as?
Anaphylaxis: antigen released into the blood stream will bind to the IgE on basophils which will cause a massive release of inflammatory mediators causing bronchospasm and circulatory collapse
What is urticaria?
Skin condition that causes lumps under the skin.
What is cutaneous dermographism?
Where you can gently touch the skin and it will become so inflamed under the touch that you can physically see where the touch has been. This is a characteristic sign of urticaria.
Define acantholysis.
Acantholysis is the loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes, seen in diseases such as pemphigus vulgaris.
What is Pemphigus Vulgaris?
A rare chronic blistering skin disease caused by the formation of antibodies against desmosomes, components of the skin that function to keep certain layers of skin bound to each other. As desmosomes are attacked, the layers of skin separate and the clinical picture resembles a blister
Outline the process of immune-complex mediated vasculitis.
There is deposition of immune complexes in blood vessel walls which initiates complement activation, an influx of inflammatory cells, thrombus formation, and hemorrhagic infarction
What is an early cutaneous manifestation of immune-mediated vasculitis?
Erythema and oedema
Define vasculitis
Inflammation of blood vessel(s)
What is an established cutaneous manifestation of immune-mediated vasculitis?
Palpable purpura
What is an severe cutaneous manifestation of immune-mediated vasculitis?
Ulceration and necrosis
What is purpura?
A rash of purple spots on the skin caused by internal bleeding from small blood vessels.
What antibodies are involved in the pathogenesis of systemic lupus erythematosus?
DNA is the antigen, anti-DNA (auto-antibody)
What antibodies are involved in the pathogenesis of polyarteritis nodosa?
HBsAg (antigen) has Anti-HBs Ab (auto-antibody)
Outline the pathogenesis of allergic contact dermatitis
A delayed hypersensitivity reaction where, firstly, an allergen comes along and triggers the release of IL-2 and IFN-gamma which causes the production of allergen-specific Th1 cells in the lymph node and a macrophage-rich response which can react more quickly to the allergen next time.
What is the function of IL-2 and IFN-gamma produced in response to an allergen in contact allergy dermatitis?
These cytokines promote Th1 responses to secrete IL-2, IL-3, TNF etc and also promote a macrophage-rich response
What products may cause allergic contact dermatitis?
Nickel (such as in cheap jewellery) or paraben in eye cream
What type of inflammatory reaction is allergic contact dermatitis?
Delayed hypersensitivity reaction
Outline the process of granuloma formation using TB as an example
Anitgen is presented and it leads to clonal T cell expansion. These Th1 cells then secrete IL-2, IFN-gamma and TNF which activates macrophages. Some of these macrophages fuse to form Langerhan’s giant cells or foreign body giant cells. Other macrophages transform to become epithelioid macrophages (histiocytes) which then combine with the giant cells to form a granuloma.
What are the causes of grandma formation reactions?
Tuberculosis, sarcoidosis, tattoos etc.
What is the rash associated with cutaneous TB known as?
Lupus vulgaris
Give examples of autoimmune inflammatory skin disorders
Alopecia areata (AA) and vitiligo
