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Infectious Diseases Immunology. LATG: Chapters 10-11. Health Maintenance. Maintaining lab animal health requires Proper environment. Proper food and water. Disease prevention program. Disease detection program. Contingency plan if disease is detected. Disease Prevention.

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Infectious Diseases Immunology

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infectious diseases immunology

Infectious DiseasesImmunology

LATG: Chapters 10-11

health maintenance
Health Maintenance
  • Maintaining lab animal health requires
    • Proper environment.
    • Proper food and water.
    • Disease prevention program.
    • Disease detection program.
    • Contingency plan if disease is detected.
disease prevention
Disease Prevention
  • Type of program depends upon species.
  • Rodents--primarily review of vendor data and procedures in place to prevent introduction and spread of disease.
  • Nonrodents--As for rodents but may also have other facets such as vaccinations, dewormings etc.
disease detection
Disease Detection
  • Like NORAD, PADDS (Pfizer Animal Disease Detection System) relies on
  • Early warning system--technicians who check animals daily.
  • Early response--veterinary technicians who evaluate reported problems.
  • Final response--delivered after evaluation and consultation with veterinarian and PI.
disease detection5
Disease Detection
  • A rodent sentinel program is in place to screen for potential viral, bacterial and parasitic contaminants.
  • In the rare instance of an actual infection steps are taken to evaluate the extent of the infection and eliminate it.
pathogenic organisms
Pathogenic Organisms
  • Life forms that have the potential to cause disease under the proper conditions.
  • Text classifications
    • Bacteria
    • Fungi
    • Viruses
    • Parasites
biology influencing organisms
Biology Influencing Organisms
  • In laboratory animal science we are also very concerned with biology influencing organisms.
  • These organisms may or may not cause clinical disease.
  • Biological systems can be influenced even by subclinical infections.
  • Small particles made up of nucleic acid and a protein capsule.
  • Viruses may also be covered by an envelope
  • Many viruses can infect laboratory animals, most do not cause clinical disease.
  • Viruses are divided into two main classes.
    • DNA viruses
    • RNA viruses
dna viruses of mice
DNA Viruses of Mice
  • Mousepox (Ectromelia)
  • Minute virus of mice
  • Cytomegalovirus
  • Polyoma virus
  • Mouse parvo virus
dna viruses of rats
DNA viruses of rats
  • Polyoma virus (in nude rats)
  • Adenovirus
  • Kilham rat virus
  • Rat parvo virus
rna viruses of mice
RNA viruses of mice
  • Mouse hepatitis virus (MHV)
  • Sendai
  • Lymphocytic choriomeningitis
  • Reovirus
  • Hantavirus
  • Retroviruses--mouse leukemia virus and mouse mammary tumor virus
rna viruses of rats
RNA viruses of rats
  • Sialodacryoadenitis virus (SDAV)
  • Sendai
  • Pneumonia virus of mice
  • Hantaan virus
  • Many bacteria in nature are beneficial.
  • In nearly all mammals there are more bacterial cells than mammalian cells
  • Consist of a cell membrane, a cell wall and cytoplasm.
  • Classified by
    • Morphology
    • Size
    • Staining characteristics
    • Formation of spores
    • Nutrient requirements
    • Biochemical reactions
  • All are prokaryotes
bacterial morphology
Bacterial Morphology
  • Cocci (spherical)
    • Pairs--Diplococci
    • Chains--Streptococci
    • Clusters--Staphylococci
  • Rods, may be straight or slightly curved
  • Spiral shaped
bacterial staining characteristics
Bacterial Staining Characteristics
  • Classified into Gram negative and Gram positive groups
  • Gram positive--dark blue/violet stain, due to a thick cell wall
  • Gram negative--red stain, due to a thin cell wall with high lipid content
  • Many fungi in nature are beneficial
  • Used to make
    • bread
    • beer
    • wine
    • antibiotics
  • A few fungi are pathogenic
  • All are eukaryotes
beneficial fungus
Beneficial fungus
  • Saccharomyces cervisae
  • Pathogenic species classified into
    • Superficial mycoses
    • Systemic mycoses
superficial mycoses
Superficial mycoses
  • Infect superficial tissues; skin, hair and nails.
  • Commonly called “ringworm”
  • See scaliness and alopecia (hairloss), sometimes redness
systemic mycoses
Systemic mycoses
  • Infect deep tissues; lung, bone, CNS, GI tract.
  • Often associated with certain geographic areas
    • Lower Sonoran desert--Coccidioides immitis
    • Central and southeastern US--Blastomyces spp.
  • Large group of single cell (protozoans) and multi-cell (metazoans) animals which must coexist on another animal during some part of their life cycle
  • A parasite must also have the potential for causing disease in the host
  • Websites of interest
  • Parasites and Parasitological Resources
  • Identification and Diagnosis of Parasites of Public Health Concern
parasite lifecycles
Parasite Lifecycles
  • “If you know the enemy and know yourself, you need not fear the result of a hundred battles.” Sun-tzu, “The Art of War”
  • Knowing the life cycle of a parasite is the key to knowing how to prevent and treat infestation.
parasite lifecycles25
Parasite Lifecycles
  • Life cycles can be direct or indirect.
    • Direct--parasite eggs/larva can infect definitive host
    • Indirect--parasite needs to pass through an intermediate host prior to infecting the definitive host
parasite hosts
Parasite Hosts
  • Definitive host--the species of animal responsible for housing the reproductive stage of the parasite
  • Intermediate host--the species of animal responsible for housing any of the non-reproductive stages of the parasite
  • Disease can occur in both types of host
protozoan parasite
Protozoan Parasite
  • Amoebas
  • Flagellates
  • Ciliates
  • Sporozoa
toxoplasma gondii
Toxoplasma gondii
  • A sporozoan parasite
  • Definitive host--cat
  • Intermediate host--almost any other mammal or bird
  • Causes self-limiting diarrhea in cats
  • May cause severe disease in immunosuppressed intermediate host
toxoplasma gondii29
Toxoplasma gondii
  • Trophozoites in lung fluid from an HIV-infected person
  • Tissue cyst from a cat
other protozoa
Other protozoa
  • Giardia
  • Trypanosome
metazoan parasites
Metazoan Parasites
  • Trematodes--Flukes
  • Cestodes--Tapeworms
  • Nematodes
  • Arthropods--insects, ticks, mites
cestodes tapeworms
  • Parasites which inhabit the GI tract of the definitive host
  • May cause lesions in many different tissues in the intermediate host
  • Do not have their own digestive system
  • Life cycle often indirect but may also be direct
tapeworm tissue cysts
Tapeworm tissue cysts

Cysts in a baboon heart

hymenolepis rodentolepis nana
Hymenolepis (Rodentolepis) nana
  • A tapeworm of rodents and humans
  • Has a direct life cycle
nematodes the roundworms
Nematodes--The “Roundworms”
  • Worms that are round in cross-section
  • Body structure contains a GI tract as well as reproductive organs
  • Both direct and indirect life cycles
  • May live in many tissues in both the intermediate and definitive hosts
  • Common intestinal parasite of dogs, cats, swine and humans
  • Also called roundworms
  • Both direct and indirect life cycles
  • Infections in humans can result in visceral larval migrans or ocular larval migrans
dirofilaria immitis heartworm
Dirofilaria immitis Heartworm
  • A nematode parasite that lives in the right side of the heart in dogs and occasionally cats
  • Life cycle of this parasite requires passage through mosquitoes
  • Infection can cause heart failure
  • Thorny headed worms
  • Seen in pigs and nonhuman primates
arthropod parasites
Arthropod parasites
  • Large group of external parasites that include
    • Insects
    • Ticks
    • Mites
arthropod parasites45
Arthropod parasites
  • In lab animal science most likely to see
    • Mites
    • Lice
    • Fleas
  • Parasites in the arachnid family
  • Have eight legs in the adult stage
  • Live on the skin, sometimes deep in the hair follicle
  • May be zoonotic
sarcoptic mange mite
Sarcoptic mange mite
  • Sarcoptes scabiei with multiple subspecies
  • Infest a multitude of species
  • Infestation is also called “scabies”
  • Can cause intense pruritis
  • Infestation is worse if animal is immunosuppressed
prevention of infectious disease
Prevention of Infectious Disease
  • In all cases it’s easier to prevent diseases than to treat them
  • Principles of prevention are simple and usually more cost-effective than treatment
principles of prevention
Principles of Prevention
  • Purchase disease free animals
  • Ship them correctly
  • Receive them correctly
  • Use proper practices to keep them disease free
  • Have detection methods in place
  • Have a plan for therapy if needed
historical background
Historical Background
  • In 1790’s, Edward Jenner observes that milkmaids who had contracted cowpox (vaccinia virus) were immune to smallpox
    • In 1797, Jenner inoculates a boy with material from a cowpox lesion, then intentionally infects him with smallpox
    • Luckily for the inoculated boy, Jenner’s reasoning was correct and the boy was immune
historical background54
Historical Background
  • Why did Jenner’s technique work?
    • Smallpox and vaccinia viruses are closely related, allowing cross-protective immune responses
historical background55
Historical Background
  • In 1870’s , Louis Pasteur accidentally discovers the concept of an attenuated vaccine while studying fowl cholera
    • Chickens infected with an old culture of fowl cholera bacteria, Pasteurella multocida, became sick but survived and became immune to lethal challenge with virulent bacteria
    • Attenuation = loss of virulence
historical background56
Historical Background
  • Pasteur extended the attenuation concept to other infectious diseases.
    • Sheep vaccinated with heat-treated anthrax bacillus were protected against challenge with live anthrax
    • Administers an attenuated rabies virus vaccine to a boy who had been bitten by a rabid dog.
the immune system
The Immune System
  • Immunity = ability to resist diseases caused by foreign infectious (contagious) agents.
    • Bacteria (e.g. streptococcus, E. coli)
    • Viruses (e.g. influenza, HIV, polio)
    • Parasites (e.g. protozoan and helminthic)
    • Prions (e.g. “mad cow disease”, scrapie)
    • Fungi (crytococcus, candida)
  • Some evidence for protection from proliferative diseases caused by cancer cells
  • Also involved with allergy, transplantation, autoimmunity, immunodeficiency, etc.
pathway to infectious disease59
Pathway to Infectious Disease
  • ExposureInfectionDiseaseDeath
  • Host Immunity - operates at two basic levels to restrict progression to disease and death. These are termed innate and adaptive immunity.
  • ExposureInfection (innate)
  • ExposureInfectionDisease (adaptive)
  • ExposureInfectionDiseaseDeath (adaptive)
innate vs adaptive immunity
Innate vs. Adaptive Immunity
  • Innate
    • “nonspecific” and nonadaptive
    • Basic resistance mechanisms that an individual is born with (requires no prior experience)
    • First line of defense against invading pathogens
    • Acts within minutes to hours
    • Broadly recognizes certain features shared by various classes of microorganisms
      • bacterial cell walls
      • double-stranded RNA of some viruses
innate vs adaptive immunity61
Innate vs. Adaptive Immunity
  • Adaptive
    • Specifically recognize and selectively eliminate invading pathogens
    • Requires several days to a week for optimal induction the first time a pathogen is encountered (sometimes not fast enough!)
    • Backs-up the innate response against specific infectious agents, parasitic infections and neoplastic (cancer) transformations.
    • Mediated by lymphocytes (B and T cells) and antigen presenting cells (macrophages, dendritic cells and B cells)
the innate immune response
The Innate Immune Response
  • Anatomic (External) Barriers
    • Skin (mechanical barrier)
    • Mucous membranes (normal flora competes; mucus traps microorganisms and cilia propels them out of the body)
  • Physiological Barriers
    • Temperature (e.g. fever)
    • Low pH of stomach, skin
    • Chemical mediators (lysozyme, interferons, complement, fatty acids)
    • Species specific physiological differences
the innate immune response63
The Innate Immune Response
  • Phagocytic Barriers
    • Phagocytic cells such as macrophages , neutrophils, Natural Killer cells engulf and destroy pathogens
  • Inflammatory Barriers
    • Vasodilation, increased vascular permeability
    • Production of inflammatory mediators such as C-reactive protein, histamine, kinins
  • Species, sex, nutrition, fatigue, age, and genetic constitution are influencing factors.
the adaptive immune response
The Adaptive Immune Response
  • Specificity
    • Capacity to distinguish among various molecules (antigens) produced by pathogens
    • Mediated by antigen recognition molecules - antibodies, T cell receptor, MHC
  • Diversity
    • Capacity to react with an almost limitless variety of antigens (>109 different antibodies can be produced)
the adaptive immune response65
The Adaptive Immune Response
  • Memory
    • Ability to “remember” a previous encounter with an antigen
    • “Secondary” response is typically induced more quickly and is considerably more vigorous than the “primary” response
    • Immunological memory can be exploited by vaccination
  • Self/nonself recognition
    • Ability to respond to and eliminate foreign antigens without bringing harm to one’s own tissues
the adaptive immune response66
The Adaptive Immune Response
  • Humoral immune response
    • the production and secretion of soluble antibody molecules that neutralize and/or destroy infectious agents
  • Cell-mediated immune response
    • the generation of active lymphocytes that work at close range to destroy infectious agents, parasites or other cells
defense cells of the adaptive immune system
Defense Cells of the Adaptive Immune System
  • B Lymphocytes (B Cells)
    • Provide antibody-mediated immunity
    • Originate in the bone marrow in higher vertebrates and the bursa of Fabricius in birds
    • Develop into plasma cells that produce and secrete antibody
defense cells of the adaptive immune system68
Defense Cells of the Adaptive Immune System
  • T Lymphocytes (T Cells)
    • Develop in the thymus
    • Provide cell-mediated immunity
    • Serve as helper or regulator cells to B cells
    • Release lymphokines or cytokines that activate macrophages
  • Macrophages
    • Attack and destroy viral-infected cells and cancer cells
    • inhibit certain white blood cells from migrating away from areas in which they are needed
defense cells of the adaptive immune system69
Defense Cells of the Adaptive Immune System
  • Lymphocytes circulate from the bloodstream through the spleen, the lymph nodes, the thoracic duct and back into the bloodstream.
organs of the immune system
Organs of the Immune System
  • Primary Lymphoid Organs
    • Thymus
    • Bone Marrow
  • Secondary or Peripheral Lymphoid Organs
    • Lymph Nodes (tissue)
    • Spleen (blood)
    • Gut-associated lymphoid tissue (Peyer’s patches)
    • Tonsils
antigen processing for the adaptive immune response
Antigen Processing for the Adaptive Immune Response
  • Recognition
    • self or nonself
    • requires interactions between a signal molecule and a receptor molecule
  • Processing
    • transmission of the received signal from the receptor to other molecules and cells
    • mediated by cytokines
  • Response
antigen processing for the adaptive immune response72
Antigen Processing for the Adaptive Immune Response
  • Response
    • Organism responds with active immunity against nonself antigens
    • Humoral and/or cellular immunity depends on:
      • antigen’s chemical structure
      • living or dead organism
      • concentration
      • route of inoculation
    • Second response to the same antigen is quicker and stronger than the first (Anamnestic Response)
humoral immune response
Humoral Immune Response
  • Antibodies (Abs)
    • Also known as Immunoglobulins (Ig)
    • Produced by B lymphocytes
    • May be membrane bound or found in serum, the fluid portion of blood
    • Bind to specific sites on antigens or infectious organisms
    • IgA, IgM, IgG, IgE, IgD
humoral immune response74
Humoral Immune Response
  • Antibodies
    • Symmetrical molecule, 2 heavy and 2 light chains
    • Composed of polypeptides (protein) and carbohydrates
    • Antigen combining or binding site reacts with antigen
    • Antibodies + Complement - lyse (cause to break apart) bacteria and infected cells
  • IgG
    • Most abundant serum Ab
    • Only Ig that crosses placenta, conferring immunity to the fetus
    • Also transferred in the colostrum (first milk) after birth
    • Associated with secondary anamnestic response
  • IgM
    • Second most abundant Ig
    • First Ig produced by fetus
    • First produced in primary immune response to an antigen
    • IgM titer (concentration) drops as IgG rises
    • May be on membrane of B cells
  • IgA
    • Found in mucus secretions of the intestines, lungs, nose and urogenital tract
    • Also found in tears, bile, saliva and milk (colostrum)
    • Helps protect body surfaces from invasion by bacteria and viruses
    • Common Mucosal Immune System
  • IgE
    • Found in very low concentrations
    • Levels increase during parasitic infections and other allergic reactions
    • Attaches to mast cells and basophils which release chemicals like histamine that produce inflammation and cause tissue damage
    • Over response with IgE associated with hypersensitivity reactions such as hay fever, food and skin sensitivities, other allergies and asthma
  • IgD
    • Not much known
    • Sometimes found with IgM on membranes of B cells
    • may be involved in the recognition process and in the activation of B cells
humoral immune response80
Humoral Immune Response
  • Primary Immune Response
    • Lag Phase
    • Log Phase
    • Plateau Phase
    • Decline Phase
humoral immune response81
Humoral Immune Response
  • Secondary or Anamnestic Immune Response
    • Response to the same antigen is more rapid and the antibody levels rise higher and last longer than in Primary response
    • Peaks 2-3 weeks later
    • Gradual decline over weeks or months
    • Additional boosters result in stronger anamnestic responses
cell mediated immune response
Cell-mediated Immune Response
  • Mediated by long-lived T cells originating in the thymus
  • T cells stimulated by an antigen divide into memory cells and killer cells (cytotoxic T lymphocytes, CTL’s)
  • Lymphocyte blastogenesis - the production of new lymphocytes
types of immunization
Types of Immunization
  • Passive Immunization
    • Transfer of Abs from an immune animal to a nonimmune animal
    • Develops immediately after transfer
    • Temporary immunity, Ab degrades over several weeks
    • Examples - Abs in colostrum, Abs crossing placenta, antiserum injections
types of immunization84
Types of Immunization
  • Active Acquired Immunity
    • Produced by an animal in its own body in response to exposure to a foreign antigen
    • Develops slowly after exposure to antigen
    • Longer, stronger protection than Passive Immunization, especially with periodic re-exposure
    • Memory
types of immunization85
Types of Immunization
  • Vaccines
    • Live, attenuated whole organism vaccines stimulate the best immune response but have the risk of disease transmission (oral polio, measles, rabies, vaccinia)
    • Dead organism vaccines are more stable in storage, have no risk of disease and suppress contaminating organisms
    • Adjuvants mixed with vaccines enhance the immune response by prolonging the presence of antigen in the tissue
transplantation of organs
Transplantation of Organs
  • Histocompatiblity of donor and recipient determines success
  • Identical twins and inbred animals
diseases of the immune system
Diseases of the Immune System
  • Autoimmune Disease
    • An organism’s immune system mistakenly recognizes self as nonself
    • Immune response attacks its own tissues
    • Autoimmune hemolytic anemia - red blood cells destroyed leading to severe anemia
    • Multiple Sclerosis - myelin sheath protecting nerves
diseases of the immune system88
Diseases of the Immune System
  • Immunodeficiency Disease
    • Primary immunodeficiency disease
      • innate error of metabolism or inherited genetic disease
      • Athymic nude mouse - lack T cells
    • Secondary immunodeficiency disease
      • more common than primary immunodeficiency disease
      • Caused by infectious disease, cancer, aging, poor nutrition, immune suppressing drugs
      • FeLV, HIV
diseases of the immune system89
Diseases of the Immune System
  • Chronic Immune Complex Disease
    • Chronic infections produce a prolonged elevation of soluble antigens in the blood
    • Immune complex formed between antigen and bound antibody and deposited in tissues, particularly the kidneys (immune complex glomerulonephritis)