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Infectious Diseases Immunology

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Title: Infectious Diseases Immunology


1
Infectious DiseasesImmunology
  • LATG Chapters 10-11

2
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.

3
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.

4
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.

5
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.

6
Pathogenic Organisms
  • Life forms that have the potential to cause
    disease under the proper conditions.
  • Text classifications
  • Bacteria
  • Fungi
  • Viruses
  • Parasites

7
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.

8
Viruses
  • 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

9
DNA Viruses of Mice
  • Mousepox (Ectromelia)
  • Minute virus of mice
  • Cytomegalovirus
  • Polyoma virus
  • Mouse parvo virus

10
DNA viruses of rats
  • Polyoma virus (in nude rats)
  • Adenovirus
  • Kilham rat virus
  • Rat parvo virus

11
RNA viruses of mice
  • Mouse hepatitis virus (MHV)
  • Sendai
  • Lymphocytic choriomeningitis
  • Reovirus
  • Hantavirus
  • Retroviruses--mouse leukemia virus and mouse
    mammary tumor virus

12
RNA viruses of rats
  • Sialodacryoadenitis virus (SDAV)
  • Sendai
  • Pneumonia virus of mice
  • Hantaan virus

13
Bacteria
  • 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.

14
Bacteria
  • Classified by
  • Morphology
  • Size
  • Staining characteristics
  • Formation of spores
  • Nutrient requirements
  • Biochemical reactions
  • All are prokaryotes

15
Bacterial Morphology
  • Cocci (spherical)
  • Pairs--Diplococci
  • Chains--Streptococci
  • Clusters--Staphylococci
  • Rods, may be straight or slightly curved
  • Spiral shaped

16
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

17
Fungi
  • Many fungi in nature are beneficial
  • Used to make
  • bread
  • beer
  • wine
  • antibiotics
  • A few fungi are pathogenic
  • All are eukaryotes

18
Beneficial fungus
  • Saccharomyces cervisae

19
Fungi
  • Pathogenic species classified into
  • Superficial mycoses
  • Systemic mycoses

20
Superficial mycoses
  • Infect superficial tissues skin, hair and nails.
  • Commonly called ringworm
  • See scaliness and alopecia (hairloss), sometimes
    redness

21
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.

22
Parasites
  • 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

23
Parasites
  • Websites of interest
  • Parasites and Parasitological Resources
  • http//www.biosci.ohio-state.edu/parasite/home.ht
    ml
  • Identification and Diagnosis of Parasites of
    Public Health Concern
  • http//www.dpd.cdc.gov/DPDx/Default.htm

24
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.

25
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

26
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

27
Protozoan Parasite
  • Amoebas
  • Flagellates
  • Ciliates
  • Sporozoa

28
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

29
Toxoplasma gondii
  • Trophozoites in lung fluid from an HIV-infected
    person
  • Tissue cyst from a cat

30
T. gondii life cycle
31
Other protozoa
  • Giardia
  • Trypanosome

32
Metazoan Parasites
  • Trematodes--Flukes
  • Cestodes--Tapeworms
  • Nematodes
  • Arthropods--insects, ticks, mites

33
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

34
Echinococcus granulosus
35
Tapeworm tissue cysts
Cysts in a baboon heart
36
Hymenolepis (Rodentolepis) nana
  • A tapeworm of rodents and humans
  • Has a direct life cycle

37
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

38
Ascarids
  • 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

39
Toxacara canis life cycle
40
Toxocara canis
  • Adults
  • Egg

41
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

42
Heartworm life cycle
43
Acanthocephalans
  • Thorny headed worms
  • Seen in pigs and nonhuman primates

44
Arthropod parasites
  • Large group of external parasites that include
  • Insects
  • Ticks
  • Mites

45
Arthropod parasites
  • In lab animal science most likely to see
  • Mites
  • Lice
  • Fleas

46
Mites
  • 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

47
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

48
Sarcoptic mange in a dog
49
Scabies in a person
50
Prevention of Infectious Disease
  • In all cases its easier to prevent diseases than
    to treat them
  • Principles of prevention are simple and usually
    more cost-effective than treatment

51
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

52
LATG Lecture Series
Immunology
53
Historical Background
  • In 1790s, 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, Jenners
    reasoning was correct and the boy was immune

54
Historical Background
  • Why did Jenners technique work?
  • Smallpox and vaccinia viruses are closely
    related, allowing cross-protective immune
    responses

55
Historical Background
  • In 1870s , 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

56
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.

57
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.

58
Pathway to Infectious Disease
59
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)

60
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

61
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)

62
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

63
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.

64
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 (gt109 different antibodies
    can be produced)

65
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 ones own
    tissues

66
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

67
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

68
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

69
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.

70
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 (Peyers patches)
  • Tonsils

71
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

72
Antigen Processing for the Adaptive Immune
Response
  • Response
  • Organism responds with active immunity against
    nonself antigens
  • Humoral and/or cellular immunity depends on
  • antigens 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)

73
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

74
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

75
Immunoglobulins
  • 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

76
Immunoglobulins
  • 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

77
Immunoglobulins
  • 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

78
Immunoglobulins
  • 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

79
Immunoglobulins
  • 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

80
Humoral Immune Response
  • Primary Immune Response
  • Lag Phase
  • Log Phase
  • Plateau Phase
  • Decline Phase

81
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

82
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, CTLs)
  • Lymphocyte blastogenesis - the production of new
    lymphocytes

83
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

84
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

85
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

86
Transplantation of Organs
  • Histocompatiblity of donor and recipient
    determines success
  • Identical twins and inbred animals

87
Diseases of the Immune System
  • Autoimmune Disease
  • An organisms 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

88
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

89
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)
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