Immunology Flashcards
What factors contribute to skin’s immunological function?
Structure - keratin layer, stratification
Cells - immune cells and keratinocytes
Cytokines, chemokines, antimicrobial peptides
Genetics
What is hypersensitivity?
Immune response that causes collateral damage to self by exaggeration of normal immune mechanism
What is autoimmunity?
Reaction to host tissue
How do keratinocytes contribute to the immune response?
Activated by UV, sensitisers
Sense pathogens via cell surface receptors
Produce anti-microbial peptides that can kill pathogens
Produce cytokines and chemokines
How do keratinocytes contribute to the immune response?
Dendritic cell (APC) Process lipid antigens and microbial fragments and present them to effector T cells in order to activate them
Where in the skin are CD4+ and 8+ T cells found?
CD8+ are in the epidermis and the dermis
CD4+ are in the dermis
Which CD4+ helper T cells are associated with which conditions?
Th1 - psoriasis
Th2 - atopic dermatitis
Th17 - both
What is the difference in action between Th1 and Th2 CD4+ T cells?
Th1 - activate macrophages to destroy microorganisms and release IL2, IFN gamma
Th2 - help B cells to make antibodies and release IL4, IL5 and IL6
What is a plasmacytoid dendritic cell?
One that produces IFN alpha
Found in diseased skin
What is a dermal dendritic cell?
One involved in antigen presenting and secreting cytokines and chemokines
What are other examples of cells in the dermis that contribute to the immune response?
Macrophages
Neutrophils
Mast cells
What are the effectors of IgE-mediated immune response?
Mast cells
Which mediators do mast cells release?
Pre-formed: tryptase, chemise, TNF, histamine
Synthesised: interleukins, TNF, interferons, prostaglandins
What chromosome is the MHC associated with?
6
What is the function of class I MHC?
Found on almost all cells
Presents antigens to cytotoxic T cells
Present endogenous antigens
What is the function of class II MHC?
Found on antigen presenting cells
Present to T helper cells
Present exogenous antigens
What is the basic function fo MHC?
Control the immune response through recognition of self and non-self
What are examples of skin conditions associated with inappropriate immune response and inflammation
Psoriasis
Atopic eczema
What is the underlying pathology of psoriasis?
Altered tissue structure and function due to inflammation
What are the symptoms of psoriasis?
Erythematous, itchy plaques on the extensors of the skin and the scalp
Nail signs
Arthritis and joint disease
How is the immune system involved in psoriasis?
Keratinocytes release factors the stimulate production of IFN alpha and release interleukins and TNF
TH1 and TH17 activated
CD8+ cells activated
Dermofibroblasts release epidermal growth factors
Which skin conditions are autoimmune?
Psoriasis
Vitiligo
SLE
What is allergy?
An immune response to a normally harmless substance
What is type 1 hypersensitivity?
Allergy
What is the timescale of a type 1 hypersensitivity reaction?
Immediate (minutes to 2 hours)
What are the routes of exposure for type 1 hypersensitivity, and examples of alleges for each?
Skin contact (nuts)
Inhalation (pollen)
Ingestion (latex)
Injection (bee sting, medication)
What is the pathophysiology of type 1 hypersensitivity?
Antigen binds to APC, which present to T cells
Th2 cells release interleukins
B cells are activated and release IgE, mast cells are activated
Mast cells degranulate and release mediators
What are the symptoms of a type 1 hypersensitivity reaction?
Urticaria
Angioedema
Wheezing
Anaphylaxis
What is urticaria?
Very itchy patches or erythema
Hives, wheals
What is angioedema?
Localised swelling of subcutaneous tissue or mucus membranes
What is anaphylaxis?
Severe, life threatening generalised or systemic hypersensitivity reaction
In what ways does anaphylaxis affect the airways, breathing and circulation?
Airways - pharyngeal or laryngeal oedema
Breathing - bronchospasm with tachypnoea
Circulation - hypotension, tachycardia
What are the investigations that can be done for type 1 hypersensitivity?
- Specific IgE
- Skin prick test
- Challenge test
Serum mast cell try-tase level during anaphylaxis to confirm true anaphylaxis
What is that management for type 1 hypersensitivity?
Allergen avoidance Antihistamines (first line) Corticosteroids (second line) Adrenaline autoinjector (in anaphylaxis) Sodium chromoglycate
What is the pathophysiology of type 2 hypersensitivity?
IgG and IgM mediated
Cytotoxic
Antibodies directed against cell surface antigens mediated cell destruction via complement activation
What are examples of type 2 hypersensitivity reactions with skin manifestations?
Blood transfusion reactions
Autoimmune haemolytic anaemia
What is the pathophysiology of type 3 hypersensitivity?
Immune complex mediated
Antigen-antibody complexes deposited in various tissues induce complement activation and inflammatory response mediated by neutrophils
What are examples of type 2 hypersensitivity reactions with skin manifestations?
Serum sickness
Necrotising vasculitis
Rheumatoid arthritis
SLE
What is the timescale for type 4 hypersensitivity?
Delayed - after 24-48 hours
What are some examples of type 4 hypersensitivity reactions with skin manifestations?
Contact dermatitis
Tubercular lesions
Skin graft reactions
What is the pathophysiology of type 4 hypersensitivity?
APCs present take up antigen and present to T cells
Activated T cells cause apoptosis of keratinocytes and production of cytokines and chemokines
Cytokines activate macrophages which mediate direct cellular damage
What are examples of acute connect dermatitis allergens?
Direct skin contact - preservatives in cosmetics
Airbourne contact - fragrances
Injection - tattoo
What is the clinical presentation of acute contact dermatitis?
Reaction in the area of skin in contact with allergen
What is the investigation of acute contact dermatitis?
Patch testing
What is irritant contact dermatitis?
Non-immunological process - not an allergy
Caused by contact with agents that abrade, irritate and traumatise the skin directly
What are examples of common irritant contact dermatitis?
Nappy rash
Lip lick dermatitis
