Title: Infectious Diseases Immunology
1Infectious DiseasesImmunology
2Health Maintenance
- Maintaining lab animal health requires
- Proper environment.
- Proper food and water.
- Disease prevention program.
- Disease detection program.
- Contingency plan if disease is detected.
3Disease 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.
4Disease 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.
5Disease 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.
6Pathogenic Organisms
- Life forms that have the potential to cause
disease under the proper conditions. - Text classifications
- Bacteria
- Fungi
- Viruses
- Parasites
7Biology 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.
8Viruses
- 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
9DNA Viruses of Mice
- Mousepox (Ectromelia)
- Minute virus of mice
- Cytomegalovirus
- Polyoma virus
- Mouse parvo virus
10DNA viruses of rats
- Polyoma virus (in nude rats)
- Adenovirus
- Kilham rat virus
- Rat parvo virus
11RNA viruses of mice
- Mouse hepatitis virus (MHV)
- Sendai
- Lymphocytic choriomeningitis
- Reovirus
- Hantavirus
- Retroviruses--mouse leukemia virus and mouse
mammary tumor virus
12RNA viruses of rats
- Sialodacryoadenitis virus (SDAV)
- Sendai
- Pneumonia virus of mice
- Hantaan virus
13Bacteria
- 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.
14Bacteria
- Classified by
- Morphology
- Size
- Staining characteristics
- Formation of spores
- Nutrient requirements
- Biochemical reactions
- All are prokaryotes
15Bacterial Morphology
- Cocci (spherical)
- Pairs--Diplococci
- Chains--Streptococci
- Clusters--Staphylococci
- Rods, may be straight or slightly curved
- Spiral shaped
16Bacterial 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
17Fungi
- Many fungi in nature are beneficial
- Used to make
- bread
- beer
- wine
- antibiotics
- A few fungi are pathogenic
- All are eukaryotes
18Beneficial fungus
19Fungi
- Pathogenic species classified into
- Superficial mycoses
- Systemic mycoses
20Superficial mycoses
- Infect superficial tissues skin, hair and nails.
- Commonly called ringworm
- See scaliness and alopecia (hairloss), sometimes
redness
21Systemic 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.
22Parasites
- 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
23Parasites
- 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
24Parasite 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.
25Parasite 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
26Parasite 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
27Protozoan Parasite
- Amoebas
- Flagellates
- Ciliates
- Sporozoa
28Toxoplasma 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
29Toxoplasma gondii
- Trophozoites in lung fluid from an HIV-infected
person - Tissue cyst from a cat
30T. gondii life cycle
31Other protozoa
32Metazoan Parasites
- Trematodes--Flukes
- Cestodes--Tapeworms
- Nematodes
- Arthropods--insects, ticks, mites
33Cestodes--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
34Echinococcus granulosus
35Tapeworm tissue cysts
Cysts in a baboon heart
36Hymenolepis (Rodentolepis) nana
- A tapeworm of rodents and humans
- Has a direct life cycle
37Nematodes--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
38Ascarids
- 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
39Toxacara canis life cycle
40Toxocara canis
41Dirofilaria 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
42Heartworm life cycle
43Acanthocephalans
- Thorny headed worms
- Seen in pigs and nonhuman primates
44Arthropod parasites
- Large group of external parasites that include
- Insects
- Ticks
- Mites
45Arthropod parasites
- In lab animal science most likely to see
- Mites
- Lice
- Fleas
46Mites
- 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
47Sarcoptic 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
48Sarcoptic mange in a dog
49Scabies in a person
50Prevention 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
51Principles 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
52LATG Lecture Series
Immunology
53Historical 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
54Historical Background
- Why did Jenners technique work?
- Smallpox and vaccinia viruses are closely
related, allowing cross-protective immune
responses
55Historical 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
56Historical 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.
57The 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.
58Pathway to Infectious Disease
59Pathway 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)
60Innate 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
61Innate 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)
62The 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
63The 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.
64The 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)
65The 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
66The 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
67Defense 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
68Defense 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
69Defense 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.
70Organs 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
71Antigen 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
72Antigen 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)
73Humoral 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
74Humoral 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
75Immunoglobulins
- 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
76Immunoglobulins
- 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
77Immunoglobulins
- 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
78Immunoglobulins
- 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
79Immunoglobulins
- 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
80Humoral Immune Response
- Primary Immune Response
- Lag Phase
- Log Phase
- Plateau Phase
- Decline Phase
81Humoral 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
82Cell-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
83Types 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
84Types 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
85Types 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
86Transplantation of Organs
- Histocompatiblity of donor and recipient
determines success - Identical twins and inbred animals
87Diseases 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
88Diseases 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
89Diseases 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)