ENI - Immunology Flashcards
Describe the processes behind bacterial pyoderma
- Staphylococcus intermedia most common
- Can be superficial (epidermis and hair follicles) or deep (dermis/deep dermis)
- Pus in skin
- Bacterial cause
- Pustules not always obvious
- Neutrophils lead to pyogenic efect
- Cytokines recruit neutrophils, engulf bacteria end up with chronic disease
Describe the lymph of the skin
- Afferent lymph deep to epidermis
- Gives rise to cells surveying tissue e.g. T lymphocytes and other dendritic cells
- Allows mobile populations of cells as well as static
Where are mast cells located?
At all points of interface with environment
Describe the actions of Langerhans cells
- Epidermis
- Phagocytose pathogens
- Act as exceptional APCs
- Precursors of dermal dendritic cells
- Migrate into dermis during maturation, become dermal dendritic cell
- Make was as APC to initiate and maintain immune responses
Describe macrophages of the dermis
- Phagocytose and kill pathogens
- Good APCs
What are the different types of hypersensitivity reactions?
- Type I: immediate, IgE
- Type II: IgG
- Type III: IgG/immune complex
- Type IV: T cell
Describe Type I hypersensitivity
- Immediate (30 mins)
- Mast cel degranulation
- IgE mediated
- IgE bound to receptors on mast cells and basophils (Fc Epsilon RI)
- Degranulation via antigen contact with antigen specific IgE on mast cell/basophil
- Leukocyte stimulation/migration
- Esp. eosinophils
Give examples of type I hypersensitivity
- Allergy
- Asthma
Describe type II hypersensitivity
- IgG mediated
- Antibody-dependent cell mediated cytotoxicity
- 5-10h
- Ab recognises self antigen on host cell or tissue
- Or recognises small molecule bound to cell or tissue
- Cell opsonised and phagocytosed by innate immune cells
- Or innate immune cells engage antibody produced cell toxins e.g. NK cell killing
Describe an example of type II hypersensitivity
- Pemphigus vulgaris
- Dogs and cats most common
- Phagocytes destroy epithelium = epidermal lesions
Describe type III hypersensitivity
- Immune complexes, soluble antigen, deposits on vessel wals (e.g. joints, kidney) = inflammatory reaction and destruction of tissue
- Complexes escape normal clearance
- Antigen solube, not attached to organ involved
- May be from exogenous source e.g pathogen
- Or endogenous
- Complexes deposit in tissue to allow receptors on mast cells to bind
Give an example of a localised Type III reaction
- Arthus reaction
- Vasculitis in skin e.g. to injected antigen
Describe tissue destruction in type II hypersentitivity
- Bound to tissue
- Mast cell binds to antigen
- Leads to degranulation
- Vasodilation
- Increased recruitment of neutrophils
- Leads to tissue destruction
- e.g. Discoid lupus (chronic skin condition)
Describe type IV hypersensitivity
- T cell mediated
- Delayed (24-72h)
- Dendritic and primed T cells
- T cells recruit and activate mononuclear cells e.g. monocytes and tissue macrophages
- Inflammation at site of DC/T cell interaction occurs not at draining lymph node
- Accumulation of T cells and bacteria
- Granuloma formation
Compare primary and secondary skin infection
- Primary: pathogen is direct cause
- Secondary: infection results from underlying disease e.g. allergic disease leading pruritus and thus skin damage through which infection can occur
Give examples of immune medaited skin diseases
- Flea allergy dermatitis (FAD) and Atopic dermatitis (AD)
- Pemphigus, discoid lupus-
Describe pemphigus
- Blistering autoimmune disease
- Auto-antibodies to desmoglein
- Antibodies unglue cells (acantholysis), leading to bliserting
- Treated with oral steroids
Describe discoid lupus erythematosus
- Mainly chronic skin condition
- Inflamed skin patches
- Scaling and crusty
- Lighter centre area
- Autoimmune disease - antibodies attacking healthy cells
How is type IV hypersensitivity used in TB testing?
- Single intradermal comparatice cervical tuberculin test
- If positive will react to injection of M bovis antigen as T cells already primed
- Measure skin thickness to establish granuloma formation
- Indicates previous infection
What are atopic dermatitis and flea allergic dermaititis examples of?
- Type I allergic reactions
- Immune mediated, with IgE hypersensitivity
Describe flea allergic dermatitis
- Pruritic condition of dogs and cats
- Most common skin disease
- Reaction to flea saliva peptides
- Produce histamines in response
- Erythema, papules, pustule, crusts
- Sensitised animals intermittently exposed to fleas have increased reaction
- Lessened reaction if constantly exposed
- Mainy Type I, many also show type IV
Describe type I hypersensitivity in FAD
- Mast cells and IgE in skin
- Migration of eosinophils into skin
- Basophils sensitive to allergens in flea saliva
Describe atopic dermatitis
- Pruritic skin disease
- Cause often undiagnosed
- IgE
- Atopy is genetic tendency to develop allergic disease
- WHWT and boston terries more susceptible
- Occurs when in contact with allergen e.g. house dust mite, capet fibres etc
- Th2 response: cytokines, eosinophils and mast cells etc in tissue
- Th1 cytokines in chronic lesions
- Tolerance associated with anti-inflammatory cytokines TGF-beta and IL-10 rather than switch from Th2 to Th1
Outline treatments for FAD and AD
- Anti-inflammatories
- Glucocorticoids often with antibiotics
- Removal of fleas in FAD
- Avoidance of possible allergens
Describe the structure of Gram +ve
- One cell membrane
- Thick cell wall
- Stain able to get stuck
Describe the structure of Gram -ve
- 2 cell membranes
- Thin cell wall
- Stain cannot get in
Describe the structure of acid fast bacteria and explain their stainign properties
- Mycolic acids in cell walls
- Peptidoglycan layer linked to arabinogalactan, furhter linked to high molecular weight mycolic acids
- Resist decolourisation by acid-alcohol, remain stained red colour of first stain in acid fast staining
Describe the structure of mycoplasma and explain their staining properties
- Do have cell membrane but no cell wall
- Hence do not stain Gram +ve
- No distinct structural morphology
Describe the microscopic appearance of Streptococci
- Long chains of cocci
- Gram +ve
- Acid fast
Describe the microscopic appearance of Staphylococci
- Bunches of cocci
- Gram +ve
Describe the microscopic appearance of Diplococci
- Join up as pairs
- Cocci
- Gram -ve
Describe the microscopic appearance of E. coli
- Rod shaped
- Can be motile with flagella
Describe the microscopic appearance of Malassezia
- Yeast appearance
- Snowmen
Describe the microscopic appearance of Actinomyces
- Rod shaped, but clump to appear hyphal
- Gram +ve
- Non-acid fast genera of Actinomycetes
Describe the microscopic appearance of filamentous fungi
Hyphae containing multiple nuclei
Describe the microscopic appearance of Clostridium
- Rod shaped
- Endospores bottle shaped
- Gram +ve
- Endospores stained by malachite green
List some causes of skin disease
- Parasitic
- Bacterial
- Viral
- Fungal
- Neoplastic
- Nutritional
- toxic
- Physical
- Congenital
- Combination of above
How does the keratin layer of skin protect against colonisation?
- Not live cells
- Dry, inhospitable
- pH poor for bacteria
- Shedding also sheds bacteria
What feature of hair follicles allows them to be more easily colonised?
- Secretions from glands
- Bacteria prefer to be bathed in serous fluid as contains nutrients beneficial to them
Describe the normal skin flora
- Sin and hair not sterile
- Have normal resident flora incl bacteria and yeasts
- Aid exlusion of pathogens but may also contribute to disease
Give some examples of normal skin microflora
- Bacteria: Micrococcus spp, Staphylococcus, Propionobacterium acnes, Bacilus, Clostridium (Gram +ve all)
- Yeasts: Malassezia
Outline how disease may occur in the skin
- When virulent pathogens overwhelm defences
- When resident flora are disadvantaged by local conditions
- Opportunistic infection by commensals e.g. through trauma
What is the effect of elevated temperature with humidity on bacterial population?
Substantial increases in aerobic and anaerobic bacterial populations
What factors influence the colonising ability of microorganisms?
- Temperature and humidity of skin
- Occluded areas
- Exposure to UV light
- Diet impacting skin turnover
- Hormonal changes altering gland activity and keratinisation
- pH, salinity, nature of lipids
- Defences present e.g. antimicrobial peptides (defensins) in sweat
What are the colonisation niches based on?
- Local secretions
- Local pH
- Contamination from local structure, mouth, prepuce and anus
- Moisture etc
List normal skin bacteria of the dog
- Micrococcus spp.
- Coagulase -ve Staphylococci
- S. epidermidis, S. xylosus
- beta-haemolytic Streptococci
- Clostridium spp
- Propionobacterium acnes
- Acinetobacter spp.
List normal hair bacteria of the dog
- Bacillus spp
- Micrococcus spp
- Gram -ve aerobes
- Staphylococcus pseudintermedius
List normal hair follicle bacteria of the dog
- Micrococcus spp
- Propionbacterium acnes
- Staphylococcus pseudintermedius
- Bacillus spp
List transient skin bacteria of the dog
- Staphylococcus pseudintermedius, S. aureus
- E. coli
- Proteus mirabilis
- Cornyebacterium spp.
- Bacillus
- Pseudomonas
List normal skin bacteria of cats
- Micrococcus spp.
- Staphylococcus siimulans
- beta-haemolytic streptococci
- S. aureus
- S. pseudintermedius
- Acinetobacter spp
List transient skin bacteria of cats
- beta-haemolytic streptococi
- E. coli
- Proteus mirabilis
- Pseudomonas spp
- Alcaligenes spp,
- Bacillus spp.
- Staphylococcus spp.
Describe Staphylococcus species as skin commensals
- Gram +ve, pairs, tetrads or clusters, catalase positive
- At least 30 species
- Opportunistic pathogens
- Colonies white, opaque
- Some coagulase -ve are pigmented
- Facultatitve anaerobes
Describe Staphylococcus pathogenicity
- Pyogenic
- Minor trauma can predispose to disease
- Number of virulence factors
- Include: coagulase, lipases, elastase, proteinA inhibiting opsonisation, range of toxins
Describe Malassezia
- Commensal and opportunistic pathogen of cats and dogs
- M. pachydermatitis
- Breed dispositions
- Common concurrent infection with Staph pseudintermedius
What dog breeds are pre-disposed to higher levels of Malassezia?
- Basset
- Dachshunds
- Cocker spaniels
- West highland white terriers
- genetic predispostion not sex linked
What factors contribute to infection with Malassezia?
- Hypersensitivity disorders
- Keratinisation defects
Hot, humid weather
Describe Pseudomonas
- Rod, Gram -ve, one or more polar flagella, aerobic, non-spore forming
- Catalase and oxidase +ve
- Readily found in environment
- Wide range of opportunistic infections
- Capsules of slime, sticky biofilms
What species of Pseudomonas is most associated with opportunistic infections?
Pseudomonas aeruginosa
Define resident microorganism
Can replicate on skin and can persist
Define nomad microorganism
Organisms that colonise and reproduce on skin for short periods of time, do not stay long as are poorly adapted
Define transient microorganism
Cannot replicate so only stay for shor periods
List some non-immune defence mechanisms of the skin
- Physical barrier
- Desquamation
- Poor conditions (dry, low pH)
- Competition by normal flora
List some innate immune factors of the skin
- Keratin layer
- Antimicrobial peptides
- Protective substances such as mucus
- Soluble complement proteins
- Phagocytic cells
- Intraepithelial lymphocytes and NK cells
- Mast cells
- Cytokines and chemokines
- Inflammation
List mechanisms by which microbes can avoid host defences
- Antigenic variation
- Inhibition of antigen processing
- Inhibiting of complement activation
- Resistance to phagocytosis
- Inactivation of reactive oxygen species
- Escape from phagolysosome following being engulfed
- Production of cytokine receptor homologues
Describe the overactivation by some Staphylococci and superantigens
- Stimulation by superantigens e.g. Staphylococci spp
- Superantigens over activate T-lymphocyte, bypassing normal process
- Activation by binding MHC and lymphocytes, not through protein binding cleft
- Can lead to cytokine production and inflammatory response
- Uncontrolled immune response contibuting to pathology
- Single protein by bacteria stimulating hypersensitivity reaction leading to responses in skin allowing further colonisation
List factors impacting on cutaneous environment
- Moisture/humidity
- Damage
- Normal tissue maintenance
- Washing
- Behaviour
- Health
- Physical breaches of barrier
List the factors predisposing to proliferation of commensals
- Hypersensitivity
- Systemic disease
- Damage/compromise of defence
Compare colonisation and infection
- Colonisation amy occur without infection e.g. commensals
- Infection will always require colonisation
Give the most common skin infections for dogs, cats, cattle, pigs, sheep, horse
- Dog: Staphyloccus pseudintermedius
- Cat: subcutaneous abscesses (bites)
- Cattle: dermatophytosis (ringworm)
- Pig: greasy pig disease (Staphylococcus hyicus)
- Sheep: sheep scab (parasite)
- Horse: mud fever (Dermatophilus)
Give examples of viral skin infections
- Distemper
- Papilloma virus
How can mastitis be described as a skin disease?
- Surface colonisation of teats
- But also internal udder infection
name the causative agent of Dermatophilosis
Dermatophilus congolensis
- Actinomycete
Describe the structure of Dermatophilus congolensis
- Gram +ve filamentous bacterium
- Non-acid fast
- Facultative anaerobe
- Motile zoospore activated to form mycelium
- 2 forms: filamentous hyphae and motile zoospores
Describe infection with Dermatophilus congolensis
- Wide host range
- Causes exudative dermatitis with scab formation
- Cattle goats and horses: cutaneous streptothrichosis
- Horses: mud fever
- Sheep: lumpy wool
Describe the pathogenesis of Dermatophilus congolensis
- Zoospore attracted to sites on skin
- Germinate
- Produce hyphae that penetrate into living epidermis
- Spread from focal point in all directions
- Penetration causes acute inflammatory reaction
- Acute or chronic infections
- Acute: filamentous invasionceases 2-3 weeks, lesions heal spontaneously
- Chronic: affected follicles and scabs are sites from which intermittent invasions of non-infected hair follicles and epidermis occur
Compare superficial, intermediate and deep mycological infection
- Superficial: hair, skin, calws, limited to surface epidermis and outer layers of hair and claws
- Intermediate: infections of dermis and subcutaneous tissues
- Deep: subcutaneous and systemic infections
List factors critical to establishment of mycological infection
- Exposure to organisms
- Critical mass/time of infective material
- Ineffective grooming
- Warm, humid environment
- Pre-existing skin conditions
- Poor immune status
Give the anamorphic genera of Dermatophytes
- Microsporum
- Trichopyton
- Epidermophyton
Gives esxamples of yeasts and yeast-like organisms that can infect skin
- Candida
- Malassezia
- Trichosporon
Outline the pathogenicity of mycologicl infection
- Grow on skin
- Secrete enzymes
- Break down cells
- Use products of breakdown for own growth
Describe dermatophytes
- ~40 species
- Septate, filamentous fungi
- Initial infection, slow growing, radial, penetrate skin then grow out
- 3 anamorphic genera
- Grow exclusively in non-living tissue of skin, nails and hair (keratinised areas only)
How are dermatophytes differentiated?
Features of their conidia
Describe the appearance of Trichophyton dermatophytes
- Macroconidia up to 50um long
- Thin smooth walls
- Microconidia ~4um
Describe the appearance of Epidermophyton dermatophytes
- Macroconidia up to 15um
- Thin smooth walls
- Microconidia absent
Describe the appearance of Microsporum dermatophytes
- Macroconidia up to 125um long
- Thick rough walls
- Microconidia ~4-7um
Describe cattle ringworm
- Mostly Trichopyton verrucosum
- Less common T. mentagrophytes
- Common in young stock, adults also affected
- Close animal contact is risk factor
- Affects animal and hide value
Describe reservoirs for cattle ringworm
- Spores can survive many months
- Contaminated environment
- Soil
- Infected animals
- Fomites
- Asymptomatic canine adn feline carriers
Describe the pathology of cattle ringworm
- Incubation period 1 week
- Fungus invades anagen hairs
- By digestion of keratin
- Hyphal growth only as far as keratinisation of hair takes place
- Hair breaks = alopeca
- Inflammatory response
Describe deep mycoses
- Infections invading deep into skin, many produce skin lesions secondary to systemic infections
- Direct inoculations, ingestion or inhalation of spores
- Can be divided into subcutaneous and systemic infections
Give an example of a deep mycosis
- Cryptococcus neoformans in cats
- Cats with FIV increased risk
- Anamorphic yeast producing capsules
Describe bovine papilloma virus
- Warts
- Infectious disease of young cattle
- Contact and minor abrasions
- Usually self limiting
- 5 strains, each different preferred infection site
List key diagnostic techniques in dermatology
- Examination of coat with lens
- Flea combing
- acetate tape prep
- Cytology
- richogram
- Skin scrapings
- Wood lamp examination
- Fungal culture dermatophytes
- Mckenzie toothbrush culture
- bacterial culture and susceptibility testing
- Skin biopsies
Describe fungal culture for dermatophytes
- Select broken hairs or those along edge of alopecic lesions
- Toothbrush collection where pooly defined lesion
- Common medium: dermatophyte test medium (DTM)
Describe Wood’s lamp examination
- For Dermatophytes
- 50% of strains produce metabolites following hair invasion that fluoresce an apple-green colour when illuminated by lamp
- Inexpensive
- But poor sensitivity
Describe trichograms for examination of Dermatophytes
- Microscopic examination of plucked hair
- Aim to get bulb and not fracture shaft
- Immersed in mineral oil, coverslip, examine at X40
Describe skin scrapes for examination of Dermatophytes
- Scalpel blade coated with mineral oil scraped along skin
- Materal then placed on slide, coverslip, examine at X40 or X100
What stain is commonly used for fungal examination?
Lactophenol cotton blue
