Pathological And Epidemiological Mechanisms Of Disease Flashcards
How does salmonella attach and invade epithelial cells
Depends on fimbrae and flagella
Injects effector proteins resulting in uptake
How does salmonella elicit an immune response
Invasion stimulates cell to provide IL-8
Inflammation and inflammatory diarrhoea
Salmonella remains in vacuole and survives
How does salmonella persist within cells
Growth rate slows Replication Escaping bacteria are ubiquitinated Virulence downregulated Glucose and fatty acids catabolised Transcytosis Move to liver and spread to other organs Find the organ it is shedding from and remove it
Features of campylobacter jejuni
Severe disease in humans
Chickens are carriers
Host needs to be immunologically compromised for infection to occur
How does the body respond to campylobacter
Neutrophils to site of infection
Epithelial cell junctions open to let them out
Campylobacter enters
More inflammation and cycle repeats until epithelium is shed or an adaptive immune response is generated
Doesn’t spread around the body
Why are infections worse in neonate
Few antibodies - only from mother
Poor adaptive immune response
Pathogens subvert the immune response to get in - adaptive immune response in adults slows them down
What causes the greatest mortality in household pets
Cancer 41%
What does neoplasia mean
The pathological process that results is the formation of a neoplasm
What does neoplasia mean
A new growth that occurs over time and is uncoordinated with normal tissue
Consist of neoplastic cells and supporting cells that allow blood vessels in and produce growth factor to allow tumour to grow
What type of disease is cancer
Genetic disease
Changes are genetic mutations that have to be inherited by the next generation of cells
Epigenetic changes
What are epigenetics
The inheritance of patterns of gene activity that do not depend on the nucleotide sequence
What causes cell mutations
Intrinsic factors - DNA replication or repair errors
Extrinsic factors - chemicals, radiation, infectious agents
Need a driver mutation for cancer to occur
What are the hallmarks of cancer
Self sufficient growth Insensitive to anti growth signals Evasion of cell death Unlimited replication Angiogenesis Tissue invasion and metastasis
What are oncogenes
Stimulatory genes that promote self sufficient growth.
How are growth factor receptors involved in tumour growth
They are produced excessively as a result of duplication of growth factor genes in the nucleus
Binding of ligands to the receptors causes massive stimulation for cellular proliferation
What genes are suppressed in cancer cells
Tumour suppressor genes
What is the clonal evolution model
Tumour population is heterogenous
Multiple subclonal populations at different stages of neoplastic transformation
One or more subclones will dominate
Most cells have potential to form new tumours
What is the stem cell model
Stem cells
Unlimited proliferation
Self renewal
Daughter cells formed which follow differential pathways
Only the cancer stem cells can form new tumours
Starting from a single cell explain the basic steps that occur during development of cancer
Cell undergos 6 driver mutations that affect specific genes
Protein expression and function is altered
Cell function and behaviour is altered
Cell proliferates forming more mutant cells
What is the difference between stem cell model and clonal evolution model of cancer
Stem cell model - only stem cells and self renew and proliferate unlimitedly. Daughter cells formed which differentiate
Clonal evolution model- subclonal populations at different stages of transformation. Most of the cells can form new tumours.
Features of cartilage
Light
Flexible
Less vascular and cellular than bone
Bad at repair
What is cortical bone
Rigid outer shell
90% bone is cortical
What is trabecular bone
Occurs at the ends of long bones and in the inner parts of flat bones
Provides strength as provides a complex system of internal supports
Bone marrow occupies space in between trabeculae
What is lamella bone
Parallel or concentric layers of lamellae
Consist of highly organised arrangement of mineralised collagen fibres
Intervertebral discs
What is woven bone
Disorganised collagen fibres
Mechanically weak
1st bone to be made in repair
What is bone covered by
Periosteum - scenes fibrous outer membrane
Endosteum - thin connective tissue lining the marrow
Features of the avian skeleton
Lightweight
Many hollow bones - pneumatic with air sacs for gas exchange instead of marrow
Flexible necks - many cervical vertebrae
Fused collarbone and breastbone (keel)
What is the composition of calcified bone
Organic matrix 20-30%
Inorganic matrix 60-70%
Cells 2-5%
Water 5-10%
What is the organic matrix of bone
Type 1 collagen
Triple helix of polypeptide chains
Cross linked for strength
What is osteogenesis imperfecta
Mutation of collagen causing loss of the triple helix
Poor mineralisation and bone fragility
Collagen poor quality and less than normal
Clinical signs of osteogenesis in dogs
Osteopenia Multiple fractures Bone deformities Pain Pink teeth as thin enamel
Clinical signs of osteogenesis in cats
Bone pain Poor bone mineralisation Stunted Reluctant to move Depression and decreased appetite Poor prognosis
What are the non collagenous properties of bone
Proteoglycans - space filling
Adhesive glycoproteins - RGD containing proteins
Gla protein and osteocalcin - regulate mineralisation
What is bone mineralisation
Calcium phosphate deposited as hydroxyapatite in the gap regions of collagen fibrils
Mediated by osteoblasts and chondrocytes
What are osteoclasts
Cells that reabsorb bone
Macrophage lineage
What are osteoblasts
Synthesise bone
Derived from mesenchymal stem cells
What are osteocytes
Long lived resident bone cell
Mechanoreceptors which can slowly remodel bone
What is the difference between bone modelling and remodelling
Bone remodelling requires the prior resorption of bone by osteoclasts.
Normal bone maintenance instead of change in response to load
What are the steps of bone remodelling
Osteoclasts activation by osteoblasts and osteocyte signalling, cytokines and hormones
Resorption of mineral in acidic lacunae and collagen degraded by proteases
Reversal - osteoclast apoptosis and osteoblasts replace them
Formation of new bone by osteoblasts which produce type 1 collagen matrix onto the resorbed surface
Mineralisation as osteoblasts deposit hydroxyapatite onto the collagen matrix
Osteoblasts become osteocytes and communicate via canaliculi
What are the regulators of bone remodelling
Mechanical load Microdamage Hormones Mineral homeostasis Local regulators Cytokines
Explain calcium homeostasis
Thyroid detects calcium levels too high so releases calcitonin.
Decreased bone resorption and calcium absorption. Calcium excretion through kidneys increases
Parathyroid detects levels too low so secretes PTH to increase bone resorption and calcium absorption. Calcium excretion is decreased. Vit D activated.
How does vitamin d contribute to calcium absorption and release
Causes liver to release calcidiol
This reduces excretion of calcium by kidneys and increase calcium absorption
Kidneys release calcitrol which causes increased calcium release
What systemic hormones regulate bone
Growth hormone - increases bone remodelling
Glucocorticoids- inhibit bone formation
Thyroid hormones - increase bone formation and resorption
Oestrogens - increase bone remodelling
Androgens - increase bone formation
Leptin - reduces bone mass
What are the local regulators of bone remodelling
TGF-B stimulates and inhibits bone resorption and promotes formation
IGFs stimulate osteoblast proliferation
BMPs promote osteoblast differentiation
Receptor Activator NfkB and RANKL allow for direct osteoblast and osteoclast precursor contact
What is intramembranous ossification
Flat bones
No cartilage template
Bone develops directly from fibrous connective tissue membrane
Osteoblasts form a centre of ossification where osteoid is deposited and mineralised
What is endochondral ossification
Long bone formation
Bone collar forms
Cavitation of cartilage where cells start to differentiate
Periosteal invasion of a blood vessel and formation of trabecular bone
Formation of secondary ossification site with an epiphyseal blood vessel
Cartilage remains at articular surface and growth plate
What genes are important for skeletal development
FGF genes - stimulates proliferation and limb outgrowth
Sonic hedgehog - limb development
Indian hedgehog - cartilage development and endochondral ossification
TGFB - signalling
RUNX2 - encodes core binding factor alpha 1 which is essential for differentiation of osteoblasts and conversion of cartilage into bone
What are the phases of bone repair
Reactive phase
Reparative phase
Remodelling phase
What is the reactive phase of bone repair
Vascular and inflammatory phase
Blood clot forms
Fibroblasts and macrophages infiltrate and proliferate to form granulation tissue
How does salmonella persist intracellularly
Evades immune system Provides nutrients Protected replication Persistence Targets epithelial cells and macrophages Entry by invasion or phagocytosis
What is the reparative phase of bone repair
Chondroblasts formed to produce cartilage by fibroblasts in the granulation tissue and periosteal cells in the fracture gap
Osteoblasts formed by periosteal cells distal to fracture which produce woven bone
Fracture gap bridged by soft callus
Endochondral ossification
Woven bone replaced by lamellar bone
Soft callus replaced by trabecular bone
What is the remodelling phase of bone repair
Trabecular bone replaced by cortical bone
Bone remodelled to recover original strength and shape over 3-5years
What are skeletal dysplasia
Abnormalities of cartilage and bone
Can be inherited or spontaneous
Abnormal shape or size of skeleton, disproportion of the long bones, spine and head
What are chondrodysplasias
Disorders of cartilage that cause the skeleton to develop abnormally
Linked to abnormalities in bone length
Achondroplasia and hypochondroplasia are causes of dwarfism
Common in cattle
Normal for dachshunds and bassets - mutation of FGF4
What is spider lamb syndrome
Chondrodysplasia in lambs causing skeletal deformities
FGF3
Long bent limbs and twisted spines
What is osteoporosis
Metabolic bone disease
Gradual lose of bone causing fragility
Low trauma fractures
Pain, deformity and functional impairment
Reported in dogs, horses, cats and chickens
Free range chickens get keel fractures
How might omega 3 prevent osteoporosis
Shifts the balance in favour of bone formation so can prevent bone fragility
What is rickets and osteomalacia
Swellignof joints and bending of the long bones in young
Cartilage not properly calcified as bone
Insufficient vit D, sunlight, phosphorous cause it
What are the causes of metabolic disease in reptiles
Lack of calcium in diet
Not enough UV access so reduced vit D formation
Secondary to diseases of liver, kidney, thyroid, parathyroid and intestine
Incorrect housing temperature
What are the clinical signs of metabolic bone disease in reptiles
Soft shell Bowed legs Arched spine Lumps on leg longbones and spine Rubber jaw Fractures Jerky movement Anorexia Weakness
What is osteoarthritis
Degenerative joint disease
Cartilage destruction
Subchondral bone thickening and growth of osteophytes
No cure
Loss of articular cartilage causes new bone formation at the edges
What is inflammation mediated by
Cells of the innate immune system
What are the phases of normal wound healing
Vascular response
Lag phase
Proliferative phase
Remodelling phase
How is inflammation initiated
Platelet aggregation
Platelets activated by coming into contact with collagen or fibrin from damaged tissue or bacteria
Increase the expression of cell adhesion molecules which bind fibrin and other platelets
What factors are released by platelets
Clotting factors
Cytokines and growth factors
Chemokines
Proteases and inhibitors
Aside from forming a clot what do platelets do
Recruit neutrophils, macrophages and lymphocytes to the site of injury
What is the complement system
Chemical part of innate immune system
Classical pathway - antibody-antigen complexes
Alternative pathway - bacterial proteins
Initiates phagocytosis and cell lysis - the complement is chemotactic for leukocytes
What is the clotting system
Coagulation cascade of proteins and proteases convert fibrinogen to a fibrin clot
Activates platelets to initiate inflammation
Initiated by both intrinsic and extrinsic activation mechanisms
What are neutrophils
Decontaminating phagocytes
Secrete inflammatory cytokines
Release proteases like neutrophil elastase and neutrophil collagenase
Generate reactive oxygen free radicals to kill bacteria
What are macrophages
Highly phagocytic
Release inflammatory cytokines
Then release anti inflammatory cytokines
Release chemokines
Produce aggressive proteases to promote cell infiltration and tissue debridement
What is the action of phagocytic cells
Engulf bacteria to form phagosome
Lysosomes fuse with phagosome to form phagolysosome
Microbe killed by chemicals such as hydrogen peroxide and lactoferin before being released as fragments
What are mast cells
Resident within tissues
Activated by injury, IgE binding or by complement
Degranulate to release histamine and proteases
Synthesise leukotrines and prostaglandins from fatty acids
What does histamine do
Chemotactic Vasodilatory Activated capillary endothelium Causes increase blood vessel permeability Oedema and swelling Pain and itching
What do eosinophils do
Phagocytic granulocytes
Release cytotoxic granular contents to attack large targets
How do monocytes and neutrophils get into tissue
Rolling against blood vessel wall
Shedding of L-selectin - this is margination and pavementing
Adhesion to endothelium
Enters between endothelial cells by diapedesis
Migration into the tissue to phagocytose and destruct C3b coated bacteria
What is the NF-kB pathway
Resides in the cytoplasm in an inactive complex with IkB
NF-kB released from IkB
Goes to nuclease and causes gene transcription
100 NF-kB genes that relate to inflammation, lymphocytes activation and inhibition of apoptosis
What is the activation mechanism of the innate immune response to pathogens
Pathogen associated molecular patterns (PAMPS) bind to toll like receptor
Activation of NF-kB which causes gene transcription in the nucleus
Pro cytokines formed
Danger associated activation patterns (DAMPS) bind to PRR which activates caspase 1
Caspase 1 binds to pro cytokines to form activated cytokines
What is the arachidonic acid pathway
Arachidonic acid metabolism produces pro inflammatory prostaglandins, leukotrines and thromboxanes
In response to pro inflammatory cytokines, TGFb is generated and arachidonic metabolism switches to production of anti inflammatory lipoxins
What is TNFb
Transforming Growth Factor beta
Induces production of IkB
Suppressor of cytokines signalling
What do lipoxins do
Decrease - chemotaxis, transmigration, superoxide generation, inflammatory cytokines, NF-kB, proteases, endothelial cell adhesion
What do resolvins do
Decrease - leukocytes, inflammatory cytokines, NF-kB, hyperalgesia, pain, proteases, leukocyte adhesion
Increase - apoptosis, inhibitory cytokines, chemokine scavengers
How is resolution of inflammation completed
TGFb, lipoxins and resolvins - promote chemokine scavenging
- aid phagocytosis of neutrophils
- limit leukocyte infiltration
- inhibit inflammatory cytokine release
What is the extracellular matrix
Surrounds, supports and regulates cells
With it life would have limited size and function with no mechanical strength or definite shape
Key regulator in inflammation
Contains collagen, elastic proteins, proteoglycans and adhesive glycoproteins
What are adhesive glycoproteins
Cell matrix interactions
Regulate cell attachment, migration and phenotype
Fibroconectin is in all tissue expect basement membrane
Where are elastic fibres found
Ligament
Skin
Blood vessels
Any tissue requiring elasticity
How do cells interact with each other
Cell to cell CAMs (cell adhesion molecules) - cadherins
Cell to matrix CAMs - integrins
What is the structure of cadherins
Extracellular adhesion
Transmembrane domain
Intracellular signalling
What is the structure of integrins
Extracellular binds matrix proteins
Hydrophobic cell membrane anchor
Cytoplasmic cell signalling
What diseases are associated with acute inflammation
Meningitis Tendinitis Tonsillitis Appendicitis Laminitis
What diseases are associated with chronic systemic inflammation
Alzheimer's IBS Nephritis Parkinson's Arthritis Asthma Atherosclerosis Colitis Dermatitis Cancer
What are the markers of inflammation
Glutathione - peptide antioxidant. Marker of oxidative stress
Malondialdehyde- marker of oxidative stress
C-reactive protein- general inflammatory marker released by macrophages and adipocytes. Binds to dead cells to promote innate immunity and formation of complement
Pro inflammatory cytokines
What are the drivers of systemic inflammation
High levels of pro inflammatory cytokines Low levels omega 3 Hyperglycaemia High oestrogen levels Stress Low serotonin Low exercise levels and obesity
What is leukocyte adhesion deficiency
Dysfunctional inflammation
Decrease or absence of B2 integrin found on neutrophils and macrophages
Life threatening bacterial infections, chronic skin infections and delayed healing
Death as a result of sepsis
What is glazmanns thrombasthenia
Absent or defective platelet integrin
Defective platelet aggregation
Prolonged bleeding time and susceptibility to bruising
What effect does stress have on healing
Healing is slower due to increased production of cortisol
What does cortisol do
Modifies T cell responses Impairs fibroblast function Increases vasoconstriction Reduces histamine release Reduces serotonin Down regulates proteases
What is the function of skin
Barrier against injury, chemicals, radiation
Acts as a sensory organ, thermal regulator and determinant of external identity
Features of the epidermis
Stratified epithelium Cornified keratinocytes - dead cells Basal keratinocytes- proliferative cells Melanocytes Langerhans cells
What are keratinocytes
Principle cell of the epidermis
Produces keratin
Maturation is in 4 layers - basal, prickle cell, granular and horny
What are melanocytes and langerhan cells
Melanocytes - in basal layer and produce melanin
Langerhans cells - antigen presenting cells which act as the first stage of the adaptive immune response to pathogens
Structure of the dermis
Separated from epithelium by basement membrane
Collagen type 1, elastic fibres and adhesion glycoproteins
Provides strength, elasticity, thermoregulation and vascular network for the epidermis
Divided into papillary and reticular layers
Mostly fibroblast cells and sensory nerve endings
What is the papillary dermis
Thin collagen fibre bundles
Rich in blood capillaries and nerve endings
What is the reticular dermis
Thick collagen fibres and elastic fibres
Gives skin it’s stretch and elasticity
Contains hair follicles and sweat glands
What is the structure of the hypodermics
Merges with dermis
Loose fatty connective tissue
Collagen fibres anchor it to underlying fascia
Adipocytes act as a store of energy, mechanical cushion and insulation
What are the types of wound healing
Regeneration - complete recovery. Superficial wounds, foetal repair and liver regeneration
Fibroblasia - recovery of function but remains distinct from undamaged tissues
Impaired healing - original function not recovered. Incomplete healing
Fibrosis- too much connective tissue. Function may be impaired
What are the types of repair
Primary - wound edges entirely apposed. Small vessels cut. Little re-epithelialisation needed
Secondary - large wound with separate wound edges. Fills with clot then granulation tissue then scar tissue. Needs extensive re-epithelialisation
What are the phases of wound healing
Vascular response
Lag phase
Proliferative phase
Remodelling phase
What is the vascular response to a wound
Constriction causing ischaemia
Increased stickiness of vessel wall
Increased vascular permeability to allow plasma proteins to leave vessel
Fluid drawn into tissue by presence of proteins in extracellular space
Platelet aggregation, complement activation and clotting
Vasodilation
What is the proliferative stage of wound healing
Fibroblasts and capillaries enter wound and proliferate to high density
Fibrin clot degraded
Provisional extracellular matrix produced in excess in prostaglandins and collagen - granulation tissue
Fibroblasts differentiate into contractile apoptotic myofibroblasts which reduce wound size
Keratinocytes contact type 1 collagen and proliferate until wound is closed, laying down basement membrane - re-epithelialisation
Keratinocytes differentiate to regenerate epidermis
What is the remodelling phase of wound healing
Granulation tissue fills wound and epithelialisation is complete
Capillary growth stopped
Fibroblasts, endothelial cells and macrophages apoptose
Recover normal skin content
Fine fibres replaced with thick fibres
In scar tissue cells are sparse and o melanocytes regenerate
What are the 3 stages of burns
First - damage to epidermis, inflammation and oedema
Second - dermis damage and separation from epidermis
Third - extensive da,age and necrosis of dermis. Graft required
Does not heal normally
What are the 3 stages of frost injuries
First - damage to epidermis
Second - damage to dermis and separation from epidermis. Capillary damage
Third - full depth damage and necrosis of dermis. Blood vessels damaged irreversibly and amputation or debridement may be needed
What do chemical injuries damage
Denaturation of proteins
Necrosis
What wounds have problems healing
Infected by viruses or fungi
Putrid infections
Pyogenic infections - MRSA
Anaerobic infections - clostridia
What is gangrene
Wet - infected wound preventing adequate venous drainage
Dry - no infection but poor blood supply and tissue hypoxic. Occurs in feet from cold, vascular dx or diabetes
What are the 3 types of fibrosis
Hypertrophic scars - tensile force applied during repair increasing matrix deposition
Lymphoedema - excess protein causing fibrotic changes
Keloid scars - proliferation of matrix deposition able to beyond site of injury. Humans only
What is proud flesh
Horses Overgranulation Mechanical loading of skin not supported by underlying tissues Distal limbs Sx
What is a common element in chronic wounds
Tissue ischaemia
What are venous ulcers
Faulty valves in venous return
Ischaemia and repercussion injuries damage skin
What are pressure sores
Poor blood supply and reperfusion
Form on pressure points
Deep necrosis with infection
What are diabetic ulcers
Due to systemic vascular disease, neuropathy, susceptibility to infection and poor remodelling
What are arterial ulcers
Narrowing of arteries, thrombosis and diabetes causes ischaemia
What is the function of stem cells
Repair tissue damage and replace lost cells
Can differentiate into different specialised cell types
What are the potencies of stem cells
Totipotent - form all types of cells and tissues
Pluripotent - can form most cells including those from all germ layers
Multipotent - many different cell types but usually only those derived from a single germ layer
Oligopotent - few cell types
Unipotent - one cell type
What do stem cells do to prevent cell ageing
Add TTAGGG onto the ends of telomeres
What are the types of stem cells
Tissue stem cells - limited to differentiation within that tissue
Embryonic - puri or totipotent
Induced pluripotent stem cells - genetically modified from adult cells
What do haemapoietic stem cells differentiate into and what are their markers
Lymphoid progenitors- B, T and NK cells
Myeloid progenitors - macrophages, neutrophils, eosinophils, basophils, platelets, rbcs
Have CD34 and Sca-1 markers
What do neural stem cells differentiate into and what are their markers
Neurones, oligodendrocytes, astracytes
PSA-NCAM markers
What do mesenchymal stem cells differentiate into and what are their markers
Osteoblasts, chondrocytes, adipocytes
Hypoimmunogenic cells that have no expression of MHC I and II
STRO-1 marker
What do intestinal stem cells differentiate into and what are their markers
Paneth cells, goblet cells, endocrine cells, columnar cells
ASCL2, Smoc2, Lrig1
How are embryonic stem cells derived for medical use
Stem cells taken from blastocyst
Cultured in lab
Differentiation
What are the problems of using embryonic stem cells in medicine
Able to form all types of cells so teratoma formation is possible leading to cancer
Ethical debate
How can you create stem cells for medicine without using an embryo
Take a cell from the body and genetically reprogram it to form iPS cell
Culture in lab
Differentiation
What are the problems with iPS cells
Differentiated iPS may stop being differentiated in situ so risk of teratoma formation
Not known if iPS cells are truly pluripotent
Don’t have the same immune privilege as bone marrow stem cells
Use of viral vectors to transfect genes may introduce oncogenes into iPS
What have stem cells been used for in veterinary
Racehorses treated by stem cells being injected directly into diseased tendons
What is a tendon
Connective tissue connecting muscles to bone
Longitudinal collagen fibres
What is a ligament
Bands or sheets of connective tissue connecting bone
Anatomy of tendons
White
Fibroelastic
Can withstand enormous load
Has a myotendinous junction and a osteotendinous junction
Features of a myotendinous junction
Collagen fibrils of tendon interdigitate with projections of muscle cells and attach to basement membrane
Weak
Muscle cells attach to basement membrane by hemidesmosomes
Features of the osteotendinous junction
Gradual merging
Tendon fibres merge with fibrocartilage then mineralised cartilage then bone
Connective tissue surrounding temdon is continuous with periosteum
Features of the osteoligamentous junction
Ligament fibres merge with fibrocartilage then mineralised cartilage then bone
What is the organisation and structure of tendons
Collagen microfibrils Fibrils Fibres Primary fibre bundles Secondary fibre bundles Tertiary fibre bundles Endotendon surround tertiary fibre bundles Final tendon structure surround by epitenon
What is the blood supply to tendons
Well organised but minimal vascular network
Supplied by bone and vessels in the sheath and epitenon
What are the differences between tendons and ligaments
Tendons are cylindrical and have a separate sheath
Ligaments are sheets and can also be cylindrical.
Tendon fibres run in one directions, ligament fibres dont
Collagenous content of ligaments is lower than tendons
Elastic content is higher in ligaments
Less extensive blood supply in ligaments
Both 60% water
What are the non collagenous components of tendons and ligaments
Elastic fibres made of elastin and fibrilin
Glycosaminoglycans
Proteoglycans
What are the two types of tendon cells and what is their role
Tenoblasts and tenocytes Arranged in rows parallel to collagen fibres Regulate tendon structure and function Remodel extracellular matrix Tissue growth, maintenance and repair Respond to tensile and compressive loads
What are ligament cells called and what is their function
Ligamentocytes
Differ in matrix deposition in response to external stimuli
Why do tendons fail
Usually fail at junctions of muscle and bone
Failure in the middle usually due to chronic tendonosis or acute tendonitis
Fatigue damage - 5% strain
Rupture - 8% strain
Overuse and injury when repeated strain causes accumulated microdamage
Which tendon is usually damaged by horses
Superficial digitor flexor tendon
Core lesion of a blood filled hole in the centre of the tendon caused by tendonosis and made worse by hypoxia and poor repair
Why do ligaments fail
Rupture in the middle when the strain is at a fast rate
Rupture at the bone junction when the strain is a slow rate
Already poor vasculature is disrupted so slow healing
Sprains are traumatic acute injuries
What is extrinsic healing of tendons
Repair cells migrate from outside the repair tissue
What is intrinsic healing in tendons and ligaments
Local migration of fibroblastic cells from surround tissue, epitenon and endotenon
How can tendons and ligaments be replaced
Autografts
Allografts - rejection problem
Permanent prostheses - Fb responses, scar formation and tissue necrosis. No problem with donor site
Tissue engineering - no rejection, quality control before implantation. Difficult to replicate mechanics and micro architectures. Long rehab
What is a Protozoa
Single cell eukaryotic
Nucleus
Sexual reproductive stages
Babesia bigemina or Cryptosporidium
What are metazoans
Parasites
Multicellular eukaryotic organism
Complex lifecycle and sexual reproduction
Worms - haemochus contortus
What is infectious disease
Caused by and agent that can spread between individuals in a population
What is contagious disease
Infectious disease that is contracted by an individual who comes into direct contact with an infected individual
How can contagious disease be transmitted
Sex Mother and offspring Fighting or grooming Nosocomial - contamination of environment Oro-faecal Aerosol
What is vertical disease transmission
An infection passed from one generation to the next in utero
Pseudovertical transmission from mother to offspring in the peri natal period
Features of parvoviruse
Can be contagious
Can be transmitted indirectly via fomites or environmental contamination
Resists desiccation and some disinfectants
How do some parasites have an indirectly infectious lifecycle
They are eaten by another parasite which then finds a host and transfers it over
What is an aerosol
Solid or liquid particles suspended in air
Very tiny particles that can spread far
Most infections target the upper respiratory tract
What affects aerosol spread
Amount of the agent shed
Survival of the agent in the environment - oxygen toxic to some, UV radiation, heat
Weather conditions
Host susceptibility
Features of SARS
2-10 days incubation 7-14 days infectivity Super shedder No sub clinical infection Good aerosol spread Effective spread from physical contact
Features of H1N1
2-3 days incubation 2-5 days infectivity Subclinical infection Very efficient aerosol spread Good physical contact spread
What is foot and mouth disease
Non enveloped RNA virus
Need a large number for infection
Thrives in cool temperatures
Can travel 100km in air
Features of Aujeskies disease virus
Pigs
Herpes virus enveloped DS DNA
Spread between farms up to 14km
Cool damp weather
How do some pathogens spread over long distances
Airborne vector or host
E.g. Migrating waterfowl carry influenza
Name some pathogens that survive in soil or slurry
Enteric pathogens E.coli - survive for months Rotavirus - 6 months Cryptosporidium- 3 months Salmonella - recycling through GI tract of animals so survives in the soil
What are mechanical vectors
Blood feeding insects
Transmit viruses and bacteria via saliva into blood
Does not require any of the parasitic lifestyle to take prt in the vector so some pathogens can have multiple vectors
Signs of inflammation
Heat - increased local blood flow
Swelling- oedema
Redness - vasodilation
Pain - hyperasthesia of nerves
What do neutrophils release
Proteases
Oxidative burst
Cytokines IL8
What are acute phase proteins
Present in plasma, increased synthesis by liver in response to IL1, IL6
Serum Amyloid A - recruits neutrophils, cholesterol transport, induces enzymes for extracellular matrix proteolysis
Fibrinogen - blood clotting
Alpha acid glycoprotein - binds drugs and protein inhibitors
C-reactive protein - binds phosphocholine and assists complement binding and opsonises bacteria
Mannose binding lectin - activates complement
What are the 4 proteolytic cascades
Complement system
Kinin system
Coagulation system
Fribrinolysis system
What are the features of the complement cascade
Mannose binding lectin
Antigen/antibody complexes
Pathogen surfaces
Bind to C1,4,2 or 3b to form C3 convertase
C3 becomes C3a for opsonisation
C5 convertase converts C5 into C5a and C5b
C5a anaphylotoxin
C5b bind C6,7,8,9 to form Membrane attack complex which punches holes in cell membrane
What are the features of the kinin pathway
Recruits and activates neutrophils
Activates monocytes and cytokines release
Release of prostaglandins - pain
What are the features of the blood clotting cascade
Extrinsic pathway -damage to tissue outside the vessel. Tissue thromboplastin.
Intrinsic pathway - damage to vessel. Cascade of clotting factors.
Together these activate X
Prothrombin to thrombin
Thrombin turn fibrinogen to fibrin
Fibrin and Factor VIII form blood clot
What are the features of the fibrinolysis system
Plasminogen reacts with tissue plasminogen activator to form plasmin
Plasmin converted to fibrin
Thrombin activateable fibrinolysis inhibitor creates fibrin degradation products with fibrin
What happens when the endothelium is damaged
Exposed sub endothelial collagen and Von Willebrand factor
Platelets adhere to collagen
Recruits circulating vWf, collagen and factor VIII
What do activated platelets release
Serotonin
VWf
ADP
Thromboxane A2 - vasoconstrictor
How does the adaptive immune response discriminate between self antigens, non threatening food antigens and pathogens
Two component signal
Antigen 3D-B-cell epitope and linear Tcell epitope
PAMP - receptors of the innate immune system
What do PAMPs do?
Toll like receptors on surface of monocytes
Induce signals inside the cell and discriminate between bacteria and viruses
What does C type lectin dectin 1 do
Responds to fungal sugars
Stimulates dendritic cells to mature and produce IL6 and IL23
Causes monocytes to activate respiratory burst, release IL10 and CXCL2
What are damage associated molecular pattern
Released by stressed cells undergoing necrosis that act as endogenous danger signals to promote the inflammatory response
How is a fever caused
Production of interferon and TNFa
They bind to opioid receptors on nerve cells in hypothalamus
COX-2 activated in hypothalamus causing increased PGE2
Altered firing rate of temperature sensitive neutrons in the anterior hypothalamus
Faster they fire the higher the temp
General points about the inflammatory response
Conserved response of living tissue to external threats or damage
Many different stimuli trigger an inflammatory response
Products release from dead or damaged cells also causes inflammation
If some parts of the inflammatory response are unregulated they can cause more tissue damage
First step in healing
What is the main feature of a gram +be cell wall
Peptidoclycan
What enzyme is effective against peptidoglycans
Lysosyme present in tears and milk
What is a feature of gram -vet bacteria
Lipopolysaccharide
How do bacteria activate monocytes
Monocytes bind to the toll like receptors which activate pro inflammatory cytokines
What are the properties of activated macrophages
Enhanced phagocytosis
Enhanced production of reactive oxygen species
Enhanced NO production
Enhanced phagosome lysosome fusion
Increased expression of MHC
Increased production of interferons, cytokines and chenokines
What is the oxidative burst
Neutrophil killing
Hydrogen peroxide produced - Not selective in what it kills
NADP oxidase and myeloperoxidase produced
Features of macrophages
Long lived
Migrate to tissues in blood and lymph
Phagocytic
Adaptive response - antigen presentation
Features of neutrophils
Short lived Stored in circulation and bone marrow Chemotaxis to inflamed sites Phagocytic Oxidative killing
What do tcells do
Recognise short peptides on antigen presenting cells
CD4 make cytokines that activate and control immune response - MHCII
CD8 kill infected cells and make cytokines - MHC1
What does MHCII antigenic presentation do
Activate CD4 helper Tcells which secrete cytokines Direct the immune response Activate NK cells Help expansion of cytotoxic Tcells Help B cell antibody production Essential for immune system
How does IgM antibody kill
By fixing complement
Which antibodies are secreted by B lymphocytes
IgM and IgA
How many IgG isotopes does the horse have
7
Some fix complement
Some enhance phagocytosis by binding FC receptors
What antibacterial actions do antibodies have
Recognise unique surface proteins and polysaccharides
Prevent adhesion and invasion
Opsonise bacteria
Activate complement
Specific antibodies neutralise secreted endotoxins
What bacterial virulence factors inhibit immunity
Capsular polysaccharides block opsonisation
Antiphagocytic M proteins
Protein A binds IgG FC and inhibits opsonisation
Bacterial toxins kill leukocytes
Coagulase converts fibrinogen to fibrin and protects from phagocytosis and complement
How do bacteria escape macrophage killing
Interfere with phagolysosome fusion - Tb Disrupt phagosome membrane and entry into cytoplasm Resists killing Prevent antibody binding Highly variable surface proteins
What is the immune response to viral infection
Interferon NK cells IgM T cells IgG
What is the virus induced inflammatory response in response to tissue damage and viral PAMPs
Epithelium releases interferon b
Fibroblasts release interferon b
Macrophages release interferon a, IL1, IL6
Tcells and NK cells release interferon y
What do interferons do
Alert neighbouring cells via receptors that turn on genes to increase viral resistance
Produce enzymes that degrade RNA or inhibit protein synthesis
Increase expression of MHC
Activate immune cells
Activate NK cells
Mediate fever response and sickness behaviour
What do NK cells do
Monitor cell health and MHC expression
Kill unhealthy cells
Make interferon y and are activated by interferon y
MHC receptors inhibit killing
Some receptors increase killing
Active early in viral infections
Antibody receptors act to enhance killing of infected cells later in the infection cycle
How can viruses avoid destruction by NK cells and IgG antibody attack
They bud into lumen side of mucous membranes
When viruses bud into lumen of cells how are they stopped
IgA antibody secreted by B cells
Transcytosed across epithelium to the lumen
Bind and neutralise virus
Features of MHCI
Expressed on all cells Highest conc on leukocytes Interferon increases expression Inhibits NK cell Presents antigen to CD8 T cells Can only fold with a peptide in the groove Healthy cell has a self peptide
How does MHCI work
Virus infects cell Virus makes protein Protein degraded by proteosome Small peptide translocated into E.R MHCI fold in presence of peptide Folded MHCI transported to cell surface Foreign MHCI/ peptide complex displayed on cell surface
How does MHCII work
Antigen presenting cell Ingestion of virus or cell debris Destruction in lysosome Assembly of MHCII with foreign peptide Presentation of complex on cell surface
Which antibody is associated with parasites
IgE
What are host factors affecting parasite immunity
Age - older more resistance
Immune status
Genetics
What are parasite factors affecting immunity to parasites
Life cycle
Species
Specificity
Immune modulation - evading of immune response
What is the role of IgD in horses
Very early role in making B cells
What is class switching
All B cells start making IgM
Switching occurs when B cells divide
Section of DNA is removed so variable region gene is linked to VDJ heavy chain
Can continue to remove DNA and switch when B cells replicate but can not change back
How to T cells help antibodies change class
Th17 secretes IL17 and IL21 so IgM becomes IgG
Th1 secretes INFy so IgM becomes IgG
Treg secretes TGFb so IgM becomes IgA in gut
Th2 secretes IL4 so IgM becomes IgE
What do macrophages release and what cells do these activate
INFy, IL12 - Th1 and INFy
TGFb, IL6 - Th17
IL10, TGFb - Treg
IL4 - Th2
What are the features of IgE
Half life 72 hours
Binds to Fc on cell surfaces
Basophils have a variety of IgE receptors
Low levels in blood as Usually very localised - specificity needed at site so B cells switch class on arrival
What cells is IgE found on
Mast cells
Also monocytes and dendritic cells
When a parasite binds to IgE on mast cells what is released
Histamine Leukotrines Pro inflammatory cytokines Proteases Eosinophil chemotactic factor
What do mast cells do
Attract and activate eosinophils
What do eosinophils do
Once activated they express IgE and IgG receptors Release IL3' IL5, IL8, leukotrines, PAF Peroxidase Collagenase Major basic protein Eosinophil cationic protein
What does the vaccine for Dictyocaulus Viviparous do
Irradiated L3 larvae
Non patent infection
IgG, IgE, yd T-cells and eosinophils are increased in immunised animals
Immunity is not sterilising
Takes a couple of weeks for an immune response and to build up immune memory
What is the pathology of A. perfoliata
Gross thickening and fibrosis
Erosion of epithelium
Acute inflammatory response IL1, IL6
Infiltration of leukocytes, mast cells, eosinophils
Sub mucosal oedema fibrosis
IgE mast cells migrate to top of epithelium
What are vaccine adjuvants
Substances that enhance the immune response to an antigen
Alum enhances antigen presentation and Th2 response
Freund’s adjuvant - gram -ve Th1 response
Ribi adjuvant - gram +ve
ISCOM - stimulates Th1 and 2, cytotoxic Tcells
What are the most relevant components of the vaccination immune response
Antibodies with memory Tcell and Bcell responses
What do typical antibacterial vaccines contain
Bacterin
Inactivated form of bacterial toxin
Why do many bacterial vaccines require regular boosters
To maintain antibody levels
What are inactivated virus vaccines
Virus grown in culture or embryonated eggs
Virus harvested and inactivated
Protective responses includ serum antibody, B cells and Tcells
Inactivated virus may reduce immunogenicity of vaccine
Seen as safer for pregnant women
What are the examples of inactivated virus vaccines
Rabies
Feline leukaemia
Foot and mouth disease
How is influenza vaccine made
Grow virus in eggs
Extract polymers
Combine with adjuvant
Induces neutralising antibody, Bcell and T cell memory
What are subunit vaccines
Contain certain virus proteins but no nuclei acid
Can extract from cultured virus, synthetic protein, recombinant protein made in lab
Relays on antibody response
What is a live attenuated vaccine
Passage virus in cell culture or eggs and repeat many times
Change its characteristics so it prefers different growing conditions and becomes less virulent in target host
Can still replicate in host but not to a level that causes disease but stimulates a full immune response
How is the bovine respiratory syncytial virus vaccine made
Non structural proteins 1 and 2 block interferon response
Non essential for replication in vivo
Essential for pathogenesis
Deletion mutant can infect calves but non pathogenic- still induces immune response
Features of intranasal vaccination for bovine respiratory syncytial virus
Temperature attenuated so adapted to grow at low temp
Low risk
Instant effect
Stimulates full range of antibody reactions
Good local response including IgA
What does morbidity mean
Proportion of animals that gets sick
What does mortality mean
Proportion of animals that die
What are the phases of disease
Infection
Incubation period
Clinical period
Death/recovery/chronic/carrier
Along side this is the latent and infectious period
What are the phases in a disease outbreak
Infection Spread Exponential sprea Levelling off Dying down
Why does a disease die down
Lack of susceptible animals
Suitable control measures - culling, vaccination, treatment, increased biosecurity
What does disease spread require
Susceptible animals
Infectious agents
Transmission from diseases animals to susceptible animals
What model represents disease spread
SIR
Susceptible
Infected
Removed
Dynamic model - numbers in each class change over time
How can SIR be used to calculate change in numbers in classes
Transition rate = speed that the numbers change
S–b – I – v – R
S(t)+I(t)+R(t)=N is number of animals in pop.
b = contact rate
v= recovery / death rate
Between S and I transition rate is bI
Between I and R transition rate is v
If D is duration of infection v= 1/D
N(b/v)=R0 basic reproduction number or measure of transmission
What does R0<1 mean
Outbreak dies down
What does R0>1 mean
Outbreak becomes epidemic
What does R0=1 mean
Disease becomes endemic
How can transmission (R0) be influenced
Vaccination reduces number of susceptibles - b smaller so R0 smaller
Culling reduces number of infected
- I smaller so R0 smaller
What other models for disease are there
SEIR - Susceptible exposed infectious recovered
MSIR - maternal immunity, susceptible infectious recovered
Carrier state - susceptible infectious recovered carrier
SIS - susceptible infectious susceptible- diseases with non-susceptible recovery
When is SIR not very useful
When there is variability such as seasons
What is epidemiology
Began with the 1854 cholera outbreak in London
Study of the behaviour of disease in populations
The study of distribution and determinants of health related states in populations and use of this study to address health related issues
What are the 5 objectives of epidemiology
Determination of origin of the disease
Investigate and control disease with unknown course
Gain knowledge on disease ecology and natural history
Planning, monitoring and assessment of disease control programmes
Assessment of economic effects - benefit of control programmes
When is it possible to control disease
Amount of disease presence known Risk factors Mode of transmission Workable control measures Monitoring and surveillance to keep an eye of progress
Why do you need to assess the economic effects of disease
Cost of control vs cost of disease
If control costs outweigh the costs of economic loss then the need to control disease is doubtful
What does descriptive epidemiology mean
Observing and recording disease and causal factors
What does analytical epidemiology mean
Analysis using suitable tools and techniques such as statistics and diagnostics
What does experimental epidemiology mean
Observations and analysis in controlled groups of animals
What does theoretical epidemiology mean
Mathematical modelling - representation of disease simulating natural patterns of disease
What is qualitative epidemiology
Natural history of disease
Causal hypothesis testing leading to investigation of causal factors and sources of infection
1st stage of epidemiological investigation
What is quantitative epidemiology
Measurement
Features of an epidemiological survey
Quantitative
Examination of an aggregate of units
Usually a sample of a population
Cross sectional - events at a particular point in time
Longitudinal- events over a period of time
Screening - looking for healthy animals that appear to carry disease
What are the features of epidemiological monitoring and surveillance
Monitoring - routine observations on health, production and environment
Surveillance - collation and interpretation of monitoring data to identify changes in population health status
Features of epidemiological studies
Comparing groups of animals where they have things in common but also are different
Experimental - purposely put together - clinical trials
Observational - naturally occurring disease in the field. Crossectional - animals categorised according to presence of disease and factors. Case-control - compare healthy with diseased group. Cohort - compare groups with and without causal factor and measure prevalence of disease
What are the features of epidemiological modelling
Mathematical modelling using equations
Using biological simulation such as experimental animals simulating pathogenesis of disease
What does Koch say about causality
Present in all cases of disease
Not present in another disease as a non pathogenic organism
Can be isolated and transferred to cause disease in another animal
What are Evan’s rules
Proportion with disease significantly higher in exposed than in not exposed
Exposure to cause more common in those without disease but with constant risk factors
Number of new cases sig. higher in exposed than not exposed
Bell shaped curve of disease following incubation
Spectrum of host responses following exposure
Measurable host response following exposure
Experimental reproduction with greater frequency in exposed
Elimination or modification decreases frequency
Prevention or modification of hosts response decreases disease
How is causality determined
Epidemiology studies association between caus, risk factors and disease
Association needs statistical significance
Studies on groups of animals
Group size determined by level of expected difference between exposed and non exposed
What are the two types of association
Non-statistical - agent can be found in animals both with and without disease
Statistical - noncausal and causal. Causal can be directly or indirectly associated
Eg. A causes b and c but b+c not necessarily associated with each other so connection is non causal
A can cause dehydration via diarrhoea so that association is indirectly causal
What does endemic mean
Disease constantly present in population
Kennel cough
What does epidemic mean
Disease present in much higher than expected numbers
FMD 2001
What does pandemic mean
Widespread epidemic affecting a large proportion of population
HIV
What does sporadic occurrence mean
Happens only irregularly
Rabies
What does prevalence of disease mean
Number of instances of disease in known population
P= no. People with disease / number of individuals in population at risk at that time
What does incidence of disease mean
Number of NEW cases occurring in a known population over a specified period
I = no. New cases in a certain period / sum of length of time all individuals were at risk
Cumulative incidence - number of non diseases cases becoming sick during period
CI = no. Animals becoming sick during period / number of healthy animals present at start of incidence
What is One Health
Worldwide strategy for expanding interdisciplinary collaborations and communications in all aspects of health care for humans, animals and the environment
How is the one health vision achieved
Education
Communication
Clinical care of cross species disease
Cross species disease surveillance and control
Better understanding of cross species transmission
Development and evaluation of new diagnostic methods, medicines and vaccines
Inform and educate political leaders
Why is One Health important
World population increasing so contact with wild animal habitats increases so risk of exposure to new disease
Increasing awareness, knowledge, and understanding of interdependency of health of humans, animals and the environment.
Growing bond with animals
Need protection of food from disease, contamination and acts of terrorism
Contamination of waters by personal care products and pharmaceuticals
Antimicrobial resistance does not distinguish between man and animal
What are the benefits of One Health approach
Improve animal and human health globally with collaboration of all health sciences
Developing centres of education through enhanced collaboration between schools
Increases professional opportunities
Adding to scientific knowledge for innovative programs to improve health
What risk factors create the perfect microbial storm
Adaptation of microbes Global travel and transportation Host susceptibility Intent to do harm Climate change Economic development and land use Human demographics and behaviour A breakdown of both public and animal health infrastructures Poverty Social inequality
Give examples of non communicable conditions and risks crossing species
Among pets, pet owners and their children
Obesity
Exposure to second hand tobacco smoke
Where does One Health enter the practice
Awareness of infectious and non infectious diseases
Info,ration for customers, pet owners and farmers on disease and zoonotic disease risks
Occupational health hazards
Cooperation where applicable
Responsible use of veterinary antimicrobials
Encompasses mental health through human animal bond
Give some examples of vet-human cooperation
Rabies introduction from abroad - vet practice is port of call. Subsequently human world involved
West Nile virus US - jackdaw walked into A&E and dropped dead
How does avian influenza spread
Aquatic birds to poultry, horses and pigs
Poultry also spread to pigs
Pigs spread to humans
What is Ecchinococcus granulosus
Dog tapeworm
Hydatid cyst of ruminants, horses and humans
Sheds segment full of eggs then grows a new one
What is BSE
Nervous disease in cows
Causes vCJD in humans if eat nervous system of cows
What organisations are involved in One Health
WHO
World Organisation for Animal Health
Food and Agriculture Organisation of the United Nations
National governments
National and international medical and veterinary organisations
What do you need to know about infectious diseases
Source
Risk factors for getting disease
How to prevent
What does virulence mean
Degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host
What is disease risk
The likelihood of occurrence and likely magnitude of biological and economic consequences of a disease to animal or human health
What is a risk factor
Characteristic of a host, pathogen, time or environment that influences risk of disease
What is serological epidemiology
Investigation of disease and infection through measurement of variables in serum
Minerals, trace elements, hormones,enzymes, antibodies
Why test for antibodies
Provides evidence of current exposure and previous exposure
Efficient and cheap
Serology can be used to quantify level of antibodies - keep diluting, the longer you can the higher the conc of antibodies in the blood originally
What is the antibody prevalence in an individual
Detectable antibody - animal exposed to antigen
Levels decline without rechallenge - the half life depends on the antibody
Need a cutoff point to determine if an animal is +vet or -ve for an antibody
Two samples taken with a time interval may show rise in serum levels
Features of serological tests and antigen
Tests for determination of types of antigen in serum
-produced by pathogenic microorganisms
- triggers antibody response by host
- specific for species and type of microorganism
Bigger the ability of test to distinguish between variety of species / type the bigger the analytical specificity
How accurate are serological tests
Can cause false positives and negatives
False + - group cross reaction, non specific inhibitors, non specific agglutins
False - - natural or induced tolerance, improper timing, improper test selection, non specific inhibitors, antibiotic induced immunosuppression, incomplete antibody, insensitive tests
What does test sensitivity mean
Number of true positives
What does test specificity mean
Number of true negatives
Why is specificity and sensitivity of serological tests important
Low sensitivity means too many false positives which can cause many animals to be unjustly treated or killed
If specificity too low then too many false negatives and diseased animals stay in the population and don’t receive proper treatment. Increased risk of spread
Why is there a difference between specificity and sensitivity in tests for disease control and clinical disease
Disease control needs to distinguish between positive and negative animals
Clinical disease needs to distinguish between diseased animal and animals with similar conditions
How are sensitivity and specificity calculated
Need information of true status
Have a known test with known result e.g. Post mortem
Derive negative samples from known negative populations e.g. Brucellosis free herds
Express results in a 2x2 table
Ideal test would have 0 false positives or negatives
True positive status / (positive test and false negative test) = sensitivity
True negative status / (false positive test and negative test) = specificity
What is the predictive value
Depends on sensitivity and specificity and prevalence
Gives a proportion or %
Tells us have big the probability is that a test positive animal is truly positive
Probability of a positive test = positive test / (positive + false positive)
Negative = negative test / negative + false negative
Why is specificity and sensitivity important depending on prevalence
High prevalence - low sensitivity not a problem
Low prevalence - tests with higher sensitivity needs to be used
Consequences for costs of control as low predictive value may mean many false positives
What is a likelihood ratio
LR+ is ratio of population of affected individuals that test positive and the proportion f healthy animals that test positive (a/(a+c))/(b/(b+d)) a = positive animals test positive b= negative animals test positive c= positive animals test negative d= negative animals test negative
2x2 table to show not all animals show sign of disease
Infection. Present. Absent
Present. Clinical dx subclinical dx
Absent Sequellae. Healthy
What happens when clinical signs last longer than infectivity
No pathogen present
Determines what diagnostic test to use
What does infectivity mean
Evidence of an infectious agent
What is the attack rate
The proportion of a defined population affected during an epizootic
