Immunology Flashcards
Name factors that contribute to skin as an immunological system
- structure; keratin layer (stratum corneum), stratification
- cell types; immune system cells and keratinocytes
- cytokines, chemokines, eicosanoids, antimicrobial peptides; chemical signals / molecules that influence cell behaviour or help target pathogens
- genetics
Describe the keratin layer
- tough, lipid rich, physical barrier
- formed by terminal differentiation of keratinocytes to corneocytes
- also known as the stratum corneum
Name important structural proteins in the keratin layer and epidermis
- filaggrin
- involucrin
- keratin
Describe the keratinocytes in the epidermis
- structural and functional cells of the epidermis
- sense pathogens via cell surface receptors and help mediate an immune response
- produce antimicrobial peptides that can directly kill pathogens
- produce cytokines and chemokines
What have been found at high levels in patients with psoriasis?
Antimicrobial peptides (AMPs)
Describe the langerhans cells in the epidermis
- a type of dendritic cell that intersperse with keratinocytes in the epidermis
- the main skin resident immune cells
- they are antigen presenting cells, characterised by the birbeck granule
- act as sentinels in the epidermiis
What is involucrin?
A structural protein that also helps to form the so called cornified envelope in the outer dermis. Helps to from structural cohesive to shield from microbes
Describe the T cells in the epidermis and dermis
- healthy skin contains a large number of t lymphocytes in both the epidermis and dermis
- mainly cd8 t cells in the epidermis
- cd4 and cd8 ells are in the dermis
- other subsets of T cells eg natural killer cells are also found
TH1 cells are associated with which condition?
Psoriasis
TH2 cells are associated with which condition?
Atopic dermatitis
TH17 cells are associated with which condition?
Psoriasis and atopic dermatitis
Describe dendritic cells in the dermis
- dermal DC; involved in Ag presenting and secreting cyto and chemokines
- plasmacytoid DC; produce INFalpha, found in diseased skin
- APCs; transmit information to T and B cells
- secrete cyto / chemokines during the inflammatory response
Name some skin conditions associated with inappropriate immune response / inflammation
- psoriasis
- atopic dermatitis
- bullous pemphigoid
- contact dermatitis
- morphea / systemic sclerosis
- urticaria
- systemic lupus erythematosus
- skin infections
- skin tumours
Name the four types of immunological hypersensitivity
- immediate reactions mediated by IgE and mast cells
- cytotoxic reactions mediated by IgG and IgM antibodies and complement
- arthus reaction / immune complex mediated disease
- delayed / cell mediated reactions, involving lymphocytes and lymphokines
What two types of hypersensitivity are seen in the skin?
Type 1 and type 4
Describe the process of type 1 hypersensitivity
- IgE antibody in cell surface passively sensitises the cell
- antigen binds directly to antibody and activates cell membrane
- release of histamine, heparin, other chemotactic factors (ECF, NCF), PAF, leukotrienes and prostaglandins
Name some cutaneous examples of type 1 hypersensitivity
- urticaria
- angio oedema
- anaphylaxis
Describe urticaria
- red wheals develop
- resembling in nettle rash, caused by dilated blood vessels and leakage of fluid into surrounding tissue
Describe angio-oedema
- a deeper cutaneous reaction than urticaria
- causing swelling of sub-cutaneous tissues, including mucous membranes eg lips
Describe anaphylaxis
- life threatening generalised reaction, with urticaria a/o angio-oedema, laryngeal (throat) swelling, bronchospasm (narrowed airways in lungs), hypotension or shock (drop in blood pressure)
Name some cutaneous examples of type 4 hypersensitivity
- allergic contact dermatitis
- photo allergy (delayed reaction to sun exposure)
- skin response to bacteria, fungi, viruses
- abnormal delayed response in atopic eczema
- all require initial sensitisation with antigen (allergen) and once sensitised any area of skin contact will react
Describe contact hand dermatitis
- small blisters (vesicles) and erosion due to delayed hypersensitivity to rubber chemicals
Name some factors that will increase the potential of topical steroids to cause side effects
- duration of therapy
- steroid potency used
- extent of application
- occlusion eg skin folds, gloves etc
- thin skin; elderly, children, face, genitalia
- inflamed skin
Describe the systemic side effects of steroids
- syppression of HPA axis, by increasing negative feedback
- cushings (rare)
- growth retardation (extremely rare)
Describe reversible steroid effects
- poor wound healing
- unstable pustular psoriasis
- modification of existing disease
- pigmentary changes
- tinea incognito
- tachyphylaxis
- steroid folliculitis
- steroid rosacea
- peri-oral dermatitis
- contact allergy
What is tinea incognito?
A fungal infection masked by inappropriate use of topical steroid
What is steroid folliculitis?
Pustules in hair follicles
Describe permanent effects of steroids
- poor wound healing
- hirsutism
- glaucoma, cataract
- atrophy (thinned epidermis) and multiple telangiectasia (dilated superficial blood vessels)
- atrophy, bruising
- striae (stretch marks)
How can the potential risks of steroids be reduced?
- do not use topical steroids where they wont work; diagnosis not made, infection, urticaria, rosacea, acne etc
- use the least potent preparation that is effective
- short term higher potency and reduce use
- know the quantities required for appropriate use
Describe the quantities of steroid for appropriate use
- 1 fingertip unit = 500mg, enough for 1 application to both palms
- 1 standard tube of cream or ointment usually 30g
Why are children more at risk of increased steroid side effects?
Due to a larger surface area to volume ratio
Topical steroids may cause suppression of the pituitary-adrenal axis, why is it important to know if a patient has developed this?
- our bodies production of glucocorticoids varies and increases markedly during stressful events
- this feedback system does not work if enough exogenous steroid (oral or topical) is taken as this increases negative feedback
- the normal response to stress is then lost and additional exogenous steroid may need to be given to cover the episode
