Skin inflammation Flashcards
What are the cardinal signs of acute inflammation? What are the causes of these signs?
Heat Redness - both due to increased blood flow and vessels dilatation Swelling - due to accumulation of fluid Pain - due to pressure on nerve endings Loss of function
Which cytokines + tcell mediate neutrophilic inflammation/are microbicidal? What organism(s) do they fight against?
IL-6, TGF-beta, stimulate IL-23, stimulates TH17
Fight against extracellular bacteria and fungi
Which cytokines + tcell mediate monocytic inflammation/intracellular killing? What organism(s) do they fight against?
IFN-gamma, stimulates IL-12, stimulates TH1
Fight against intracellular bacteria, protozoans and viruses
Which cytokines + tcell mediate eosinophilic, basophilic and mast cell inflammation/mucosal clearance? What organism(s) do they fight against?
IL-4 stimulates TH2
Fight against helminths
What type of inflammation causes:
- urticaria
- pemphigus
- vasculitis
- contact allergic dermatitis
- TB + sacroidosis
- Mast cell mediated
- Antibody mediated
- Immune complex mediated
- Delayed hypersensitivity
- Granuloma formation
What type of hypersensitivity is mast cell mediated inflammation?
Type 1
What occurs during mast cell mediated inflammation?
Exposed to allergen
antigen presented by APC to a TH2 cell
two things happen:
1. IL-5 and G-CSF is released from t cell to stimulate eosinophilic degranulation
2. IL-4 and IL-5 from T cell stimulate B cell to produce IgE
This IgE attaches to mast cell which stimulates the release of IL-3 and IL-5
IL-3 and IL-5 also stimulate eosinophilic degranulation
Degranulation of eosinophils + mast cells results in release of histamines, leukotrienes, prostaglandins and platelet aggregating factor
List a few mediators released by mast cells during a type I hypersensitivity reaction and their actions.
- Vasodilation and increased permeability:
- histamine
- PAF
- Leukotriene C4, D4 and E4
- Prostaglandin D2
- Neutral proteases - Smooth muscle spasm:
- Histamine
- PAF
- Leukotriene C4, D4 and E4
- Prostaglandin - Leukocyte extravasation:
- Cytokines (e.g. chemokines and TNF)
- Leukotriene B4
- Chemotactic factors for eosinophils and neutrophils
What are the different effects of histamine on the body?
- Stimulates sensory nerve: itchy flare
- Smooth muscle constriction: vessels leakage and oedema
- Arteriole dilatation: headache and hypotension
- Modulation of immune response via H2 receptors
- Bronchospasm
What is Der P1, and what does it do?
Der P1 = enzymes allergen from faecal pellets of dust mite
It cleaves occludin in tight junctions
Explain mast cell mediated inflammation using Der P1 as an example.
Der P1 is taken up by dendritic cells for antigen presentation and TH2 priming
Der P1-specific IgE binds to mast cells
Der P1 triggers mast cell degranulation
What are the local and generalised effects of mast cell degranulation?
Local: uritcaria, asthma and hayfever
Generalised: occurs when an antigen is released into the blood stream, binds to IgE on basophils –> MASSIVE release of inflammatory mediators and this causes bronchospasm and circulatory collapse, i.e. ANAPHYLAXIS
What is Omalizumab used to treat? What is the MOA of this drug?
Used for resistant urticaria and asthma
Binds to circulating IgE, reducing cell-bound IgE
Also reduces the expression of high-affinity receptors
This reduces tissue infiltration and mediator release which relieves symptoms
What type of hypersensitivity reaction is antibody-mediated inflammation? What type of immunoglobulin(s) is/are involved?
Type II
involves IgG and IgM
List the 4 different mechanisms of antibody-mediated inflammation.
- Complement mediated lysis –> antibody attaches to antigen
- Phagocytosis by extracellular macrophage
- Antibody-dependent cell-mediated cytotoxicity
- Receptor blockage
Explain what occurs in a type II hypersensitivity reaction, using Pemphigus Vulgaris as an example.
In this case the antigen = keratinocyte
IgG antibody-antigen complex binds to the surface of keratinocytes
Autoantibodies break down desmoglein, causing disruption to desmosomes between cells
Causes blistering of the skin
What would a histology slide of pemphigus vulgaris show?
Suprabasal splitting
Acantholysis = loss of cohesion between epidermal keratinocytes
As the keratinocytes are still usually attached to the basement membrane the microscopic slide will often show a characteristic ‘tombstoning’ feature
What are the treatment options for pemphigus vulgaris?
Oral steroids
Immunosuppression by c myophenolate mofetil or azathioprine
rituximab - target CD20 on B cells (inhibit acantholysis)
What type of hypersensitivity reaction is immune complex mediated inflammation? What immunoglobulin(s) is/are sometimes involved?
Type III
IgG
What occurs during immune complex mediated inflammation?
Antibody and antigen form an immune complex
there is production of complements, platelet aggregation (forming microthrombi) and release of lysosomal enzymes from neutrophils
this results in:
- leaky vessel extravasation (= oedema)
- proteases degrading BM
- necrosis of vessel wall due to microthrombi
- deposition of fibrin
What are the early, established and severe manifestations of vasculitis?
Early: erythema and oedema
Established: palpable purpura
Severe: ulceration and necrosis (of skin)
*leukocytoclastic vasculitis is usually drug-induced and pts present with blistering and necrotic skin (histology: fibrin in blood vessel and nuclear dust)
What antigens and antibodies are involved in:
- systemic lupus erythematous
- polyarteritis nodosa
- antigen = DNA
antibody = anti-DNA - antigen = Hep B surface antigen (HBsAg)
antibody = Anti-HBsAg
What type of hypersensitivity reaction is delayed hypersensitivity? Give the most common example of a delayed hypersensitivity reaction.
Type IV
Common example = allergic contact dermatitis
Describe what occurs in a delayed hypersensitivity reaction.
- CD4+ Th1 helper T cell recognised an antigen in a complex with MHC class II on the surface of an APC
- These APCs can be macrophages that secrete IL-12 and stimulate the proliferation of further CD4+ Th1 helper cells
- CD4+ T cells secrete IL-2 and IFN-gamma which:
1. promote Th1 response = secretion of IL-2, IL-3, GM-CSF, IFN-gamma and TNF
2. promote macrophage-rich response - CD8+ T cells kill target cells on contact, whereas macrophages release hydrolytic enzymes and can transform into multinucleated giant cells
**maximal response is 48-72h after exposure
What type of hypersensitivity response is granuloma formation?
Type IV
What occurs during granuloma formation? What causes granuloma formation?
antigen (e.g. mycobacterium TB) causes clonal T-cell expansion
induces secretion of TH1 cytokines = IL-2, IFN-gamma, TNF
stimulates macrophages
macrophages can:
1. fuse = GIANT cell
2. transform = HISTIOCYTE (epithelial macrophage)
Causes: TB, sarcoidosis, foreign body granuloma (tattoo)
What are autoantibodies formed against in:
- alopecia areata
- vitiligo
- Hair follicle
2. Melanocytes
