Skin Pathology 4 Flashcards
IMMUNE MEDIATED DISORDERS. -Outline how host defences may result in tissue damage and explain the role of Th1 and Th2 cells. -Define hypersensitivity and detail the key features of the four main types. -Define anaphylaxis and outline how it can occur. -Explain, with examples, the process of Type 1 hypersensitivity and describe the main features of insect bite hypersensitivity in animals. -Explain the current understanding of the aetiopathogenesis of atopic dermatitis and describe the m
HYPERSENSITIVITY TYPES
TYPE I- food allergy, anaphylaxis, atopic skin disease, insect bite hypersensitivity.
TYPE II- introduction to autoimmune disease.
TYPE III- vaccine reaction, cutaneous vasculitis.
TYPE IV- TB test, allergic contact dermatitis, tuberculosis.
IMMUNE MEDIATED DISEASE
A broad, ‘umbrella’ term that encompasses various disorders in which tissue damage is due to immune responses.
“Defence responses can cause tissue damage”- excessive inflammation, due to uncontrolled proinflammatory cytokine/chemokine production from innate immune cells and Th1 cells.
-Eosinophilia and allergic reactions- uncontrolled Th2 cell responses.
-Killing of host cells by CD8+ cytotoxic T cells and NK cells.
HYPERSENSITIVITY REACTIONS
One type of immune mediated disorder.
An exaggerated or inappropriate immune response to a mild pathogen or innocuous substance (allergen).
TYPE I- Immediate, anaphylactic.
TYPE II- Antibody dependent (IgG), cytotoxic.
TYPE III- Immune complex mediated.
TYPE IV- Cell mediated, delayed.
TYPE I HYPERSENSITIVITY
Exposure to allergen
- > antigen presenting cell presents allergen to naive T cell
- > Th2 effector cell
- > B cells produce ANTIGEN SPECIFIC IgE
- > IgE binds to mast cell membranes via high affinity receptors
- Re-expousure to allergen results in RAPID MAST CELL DENGRANULATION, stimulated by cross linking of bound IgE.
- Rapid release of preformed mediators, including histamine and prostaglandins.
- Results in severe, generalised systemic reaction (anaphylaxis), OR a milder, local reaction.
eg. Food allergy- classic trigger of anaphylaxis in humans and animals.
ANAPHYLAXIS
“Immediate systemic reaction caused by rapid, IgE mediated immune release of potent mediators from tissue mast cells and peripheral basophils”.
“A serious allergic reaction that is rapid in onset and may cause death”
Involves a variety of tissues- skin, mucosal tissue (respiratory, GI). The extent to which each tissue is involved depends on species etc.
ANAPHYLAXIS- TRIGGERS
Foods, medications, venoms, unidentified (<30% human cases, more in animals).
Not all reactions directly involve IgE.
Some triggers DIRECTLY stimulate mast cells- no previous exposure is required eg. VENOMS.
MAST CELL ACTIVATION AND DEGRANULATION
Initiated by cross linking of sensitised IgE bound to membrane Fc receptors.
Immediate response mediated by preformed stored mediators- histamine etc.
-Late phase reaction mediated by cytokines and phospholipid derivatives- leukotrienes.
TYPE I HYPERSENSITIVITY- EXAMPLES IN ANIMALS
-Atopic dermatitis
-Insect bite hypersensitivity- fleas, culicoides midges (sweet itch)
-Drug eruptions
-Food allergy.
Between them, atopic dermatitis and flea bite hypersensitivity account for the majority of cases of skin disease in dogs and cats.
ATOPIC DERMATITIS (AD)
A multifactorial, multifaceted disease, involving complex interactions between GENETIC and ENVIRONMENTAL factors.
Mutations in the gene that codes for profilaggrin- FLG- are considered the most important risk factor for AD in humans (eczema), but this is not the only factor- not all eczema patients have the mutation, and not all those with the mutation develop eczema.
FEATURES OF SKIN IN AD PATIENTS
(Human)- lesional and non lesional skin has:
- Decreased filaggrin expression and decreased NMF (Natural Moisturising Factor), due to loss of function mutations in FLG gene.
- More limited and discontinuous lipid later due to decreased synthesis of lipid lamellae.
- Enhanced protease activity(endogenous and exogenous eg. from parasites, bacteria)- alters rate of desquamation
- Altered expression of antimicrobial peptides
- Greater numbers of antigen presenting cells (APCs) bound with IgE
- Th2 cell responses predominate (genetic predisposition)- IL4 promotes Th1 to Th2 switching.
- IL13 induces immunoglobulin class switching, to IgE.
CANINE ATOPY
TYPE I HYPERSENSITIVITY REACTION TO ENVIRONMENTAL ALLERGENS.
Common- house dust mites.
Predisposition seems to be inherited- Westies, Cairns, Scotties, Boxers etc. Not a simple inheritance.
PRURITIC DERMATITIS AND OTITIS (sometimes conjunctivitis)- often affects face, feet and ventrum. Characteristic clinical features.
Histology- variable, often minimal. Early biopsies often show no signs, signs in later biopsies are often from cell trauma.
ATOPIC DERMATITIS
Includes canine atopy.
Superficial dermatitis, interstitial oedema, acute inflammation, often see mast cell-rich infiltrate.
Secondary skin changes/lesions are often seen (consider chronicity of condition)
Formerly called ‘Allergic Inhalant Dermatitis’, but it is now well established that allergens can be absorbed via the skin as well as via inhalalation.
An abnormal skin barrier contributes to the pathogenesis of canine atopic dermatitis- variations in filaggrin expression (mutations in FLG excluded as a major cause in Westies), disorganised lipid lamellae, altered balance of antimicrobial peptides.
INSECT BITE HYPERSENSITIVITY
Allergic dermatitis, can be acute or, more often, chronic.
Common in horses, dogs, cats, humans.
Triggers- fleas, biting midges, blackflies, mosquitoes.
TYPE I HYPERSENSITIVITY, therefore classed as an atopic disorder in horses and humans.
Considered separate to atopy in cats and dogs.
Horses- ELA (Equine Leukocyte Antigen), a component of MHC II, is a risk factor- if present, will predispose the animal to hypersensitivity.
Lesion distribution reflects insect eg. Culicoides midges bite at the mane and tail.
eg. Fleas often bite around the tail head
eg. Mosquitoes often bite around the head.
Reaction can be localised- focal necrosis beneath exudate crust- or more dramatic- eosinophilic furunculosis with much oedema.
Reaction is often characterised by EOSINOPHILS.
FLEA BITE HYPERSENSITIVITY
aka. Flea allergy dermatitis. TYPE I HYPERSENSITIVITY (can be type IV- delayed. Will not respond to antihistamines; use steroids to treat)
- Common; no breed predilection.
- May be seasonal- Summer and Autumn
- PRURITIC PAPULAR DERMATITIS eg. miliary eczema (cats)
- Often affects dorsal lumbosacral area (tail head), neck, inner thighs, abdomen. Hair loss seen from self trauma due to pruritis.
- Histology- may include eosinophils in dermal infiltrate and/or intraepidermal eosinophilic abscesses.
TYPE IV HYPERSENSITIVITY
CELL MEDIATED immune response.
DELAYED TYPE HYPERSENSITIVITY (DTH) reactions involves the same processes as cell mediated immunity to microbial infection.
-Balance swings from protection to tissue damage if the stimulus is great or unusually persistent.
-Sensitised T cell population develops after initial contact with antigen, via APCs.
-Reexposure -> lymphocyte activation -> cytokine release -> macrophage infiltration.
-Tissue damage is due to- ACTIVATED MACROPHAGES- release proinflammatory cytokines- and CYTOTOXIC T CELLS- directly cytotoxic.
eg. Tuberculin test- a response is seen if the animal has already been exposed to TB antibodies (ie. it is infected); this has allowed priming of T cells.
Some reactions to insect bites or stings are similar.
