Infectious Diseases Immunology - PowerPoint PPT Presentation

Infectious DiseasesImmunology

LATG: Chapters 10-11

• Maintaining lab animal health requires
• Proper environment.
• Proper food and water.
• Disease prevention program.
• Disease detection program.
• Contingency plan if disease is detected.

• 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.

• 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.

• 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.

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

• 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

• Mousepox (Ectromelia)
• Minute virus of mice
• Cytomegalovirus
• Polyoma virus
• Mouse parvo virus

• Polyoma virus (in nude rats)
• Adenovirus
• Kilham rat virus
• Rat parvo virus

• Mouse hepatitis virus (MHV)
• Sendai
• Lymphocytic choriomeningitis
• Reovirus
• Hantavirus
• Retroviruses--mouse leukemia virus and mouse mammary tumor virus

• 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

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

• 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

• Saccharomyces cervisae

• Pathogenic species classified into
• Superficial mycoses
• Systemic mycoses

• Infect superficial tissues; skin, hair and nails.
• Commonly called “ringworm”
• See scaliness and alopecia (hairloss), sometimes redness

• 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
• http://www.biosci.ohio-state.edu/~parasite/home.html
• Identification and Diagnosis of Parasites of Public Health Concern
• http://www.dpd.cdc.gov/DPDx/Default.htm

• “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.

• 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

• 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

• Amoebas
• Flagellates
• Ciliates
• Sporozoa

• 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

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

• Giardia
• Trypanosome

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

• 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

Cysts in a baboon heart

• A tapeworm of rodents and humans
• Has a direct life cycle

• 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

• Adults
• Egg

• 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

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

• 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

• 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

• 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

• 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

LATG Lecture Series

Immunology

• 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

• Why did Jenner’s technique work?
• Smallpox and vaccinia viruses are closely related, allowing cross-protective immune responses

• 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

• 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.

• 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.

• 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
• “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

• 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)

• 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

• 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.

• 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)

• 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

• 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

• 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

• 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

• Lymphocytes circulate from the bloodstream through the spleen, the lymph nodes, the thoracic duct and back into the bloodstream.

• Primary Lymphoid Organs
• Thymus
• Bone Marrow
• Secondary or Peripheral Lymphoid Organs
• Lymph Nodes (tissue)
• Spleen (blood)
• Gut-associated lymphoid tissue (Peyer’s patches)
• Tonsils

• 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

• 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)

• 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

• 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

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

• 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

• 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

• 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

• 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

• 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

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

• 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

• 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

• 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)