Midterm 1 Flashcards
Interaction of Host and Infectious agent(s); Non-specific Defenses; Acquired Immunity
Prions
“slow viruses” - protein folding problem. Spongiform encephalitis.
Kuru,Creutzfeldt-Jakob, scrapie in sheep, bovine spongiform encephalopathy (BSE) in
cattle.
single proteins but have the capacity to wreck havoc on brain cells of an individual. Prions have many similarities with viruses which is what confuses people.
Prions are pathogens discovered by Stanley Prusiner. These are infectious agents that cause many neurodegenerative diseases such as transmissible spongiform encephalopathy. Surprisingly, prions are made up of harmless proteins that are found in mammals and birds. But these proteins are in abnormal form and once they enter human brain, they are capable of severe brain infections. Normally these prions are ingested but they also get formed through mutation of a gene that contains this protein. One thing that seperates them from viruses is that they lack nucleic acids (RNA and DNA).
As soon as prions find their way into brain, they cause normal proteins to turn into abnormal ones. They soon multiply causing severe infection. Holes appear inside the brain that can only be treated by incineration.
Viruses
genetic material (RNA or DNA, never both), protein, lipid.
Commandeer host metabolic machinery to replicate.
Polio, small pox, chicken pox, herpes, AIDS
(HIV), measles.
Viruses are made up of proteins and nucleic acid and lipids. These nucleic acids (RNA and DNA) contain the genetic code that helps these viruses to grow and reproduce once they find their way into a living organism. The nucleic acid remains covered in a protective covering called capsid. Before invading a living thing, viruses are in extracellular form and are known as virions. These virons, once they find a host cell transform into an intracellular form when the capsid gets removed and only nucleic acid remains. Viruses take help of the building materials of the host to grow and reproduce.
Bacteria -prokarotes (before nucleus) -
lack internal organelles. Single cells.
About 30 genera cause disease. Strep., Staph, TB, gonorrhea, RMSF, etc.
Eukaryotes (true nucleus)
Fungi
- saprophytes - single cell or multicellular or one to the other: yeast to
mycelial phases. Athlete’s foot, “yeast” infections. Not all bad, some make beer
and wine!
Eukaryotes (true nucleus):
Animals
protozoa - single cell animals. Malaria, Montezuma’s revenge,
Giardia.
- Multicellular - flat worms (tapeworm); round worms (schistosomiasis).
Study of the Host (Us) responses to infection:
Non-specific:
tears, skin, flow of liquids out, phagocytes
Study of the Host (Us) responses to infection:
Specific:
Immunity = Immunology
Humoral (blood) = antibody; protein molecules that bind to foreign material
and inactivate it.
Cellular (cell-mediated immunity) = cells interact with foreign material to
kill also control immune response. CD4+, CD8+, etc.
Humoral (blood) =
antibody; protein molecules that bind to foreign material
and inactivate it.
Cellular (cell-mediated immunity)
cells interact with foreign material to
kill also control immune response. CD4+, CD8+, etc.
History of Medical Micro
longterm or short term & eg
is very long from organism’s point of view. “Germs”
(Hollywood term) have been around for millennia.
Bacteria - Tuberculosis in 5,000 yr old mummies. TB, a disease of the lung, is also
known as consumption, the white plague, or wasting disease.
Many diseases described by the ancients are hard to nail down. e.g. leprosy (Bible)
was probably a fungal disease, not leprosy. Others are dead certain.
Black Plague:
Yersinea pestis.
The great black death. Bubonic and pneumonic
plague. Changed history. The first pandemic occurred in 500 AD, altered the
Roman Empire. The 2nd pandemic occurred in 1250 - 1350 AD. Knocked Europe
out of the dark ages. 25% of the population killed.
Bubonic plague -
spread by bite of rat flea. Swollen lymph nodes, black (buboes).
Spreads to entire body, especially lungs, leading to a characteristic wheezing
snuffle. Ugly red/black spots occur on the skin as blood leaks into skin. The victim
becomes very morose and turns blue/black from lack of oxygen, becomes prostrate,
70% die within 7 days.
Pneumonic plague -
spread by aerosol droplets from patient with lung infection.
Droplets are inhaled, they infect lung. Ninety percent of the people with pneumonic
plague die within 24 hours. Physicians came to treat and clergy came to give last
rites - they died from pneumonic plague before the patient did. Wiped out the
educated classes and resulted in physicians refusing to make house calls (ha, ha!).
brought small pox to he New World
1500 - Cortez brought small pox to he New World. The first Indian epidemic
occurred in 1520, reaching the Rio Grande in 1527. Estimates of Aztec deaths range udd, RC, El Med Micro, page 3
from 20-50% of the population. The Indian population had never seen this disease
(no premunition). The officers Amherst and Bouquet were the first to use small pox
as a biological warfare agent during the French/Indian wars (circa 1760). It appears
that the US government used small pox to subdue native Americans in the 1800s.
1650 - Antonie van Leeuewenhock invented
1650 - Antonie van Leeuewenhock invented compound microscope and saw
“animicules”.
1798 - Edward Jenner
1798 - True Vaccination.xxxxx described immunization with cow pox
(vaccinia) to prevent small pox (variola).
1854 Snow
1854 - Contagion - Snow recognized cholera was spread from the Broad Street
pump in England
Robert Koch and Louis Pasteur
Two rivals, much as Germany and France. Both
National Heros. Pasteur was flamboyant, lots of press, serendipity. Koch Teutonic,
meticulous.
Koch -
Koch - pure culture technique, solid media. First used potato slices to grow TB,
then gelatin, but too many bacteria liquify gelatin so he used an extract of the sea
weed Agar agar, to solidify media. He developed staining techniques and studied
TB, anthrax and cholera, to name but a few of his accomplishments.
Pasteur -
Pasteur - “Father of Microbiology” - developed attenuated vaccines for anthrax and
chicken cholera. He produced the first viral vaccine for rabies (saved boy, became
guard for Pasteur Institute in Paris - killed in line of duty). Amazing dude.
Hx
1890’s - Eli Metchnicoff - Russian who developed cellular immunity studies
Thanatology.
1900 - Bacillus Calmette-Guérin - TB vaccine.
1904 - Plague spreading worldwide.
1930s - Vaccines for tetanus, diphtheria.
1943 - Chain and Fleming - penicillin - antibiotic age began.
1950s - Salk polio vaccine, then Sabin.
1960s -70s - viral vaccines - measles, mumps, etc.
1980s - Microbiological Revolution: Immunology, recombinant DNA
technology (molecular biology). AIDS
1990s - Chicken pox vaccine. Cancer (genes), transgenic mice, gene therapy,
transplantation, new drugs (AZT, ddl, protease inhibitors), new antibiotics, etc.
Absolute explosion of knowledge. Decade of STDs. Use of bacterial or fungal
products e.g. streptokinase, coagulase, Protein A and G (even shark immune
molecule to fight cancer). Cloned products: Factor 5 - hemophiliacs; Interferon
- anti-cancer; Insulin; vitamins; Cyclosporin - fungal transplantation drug.
2000- Era of genetic miracles. Gardasil - HPV vaccine
Extremely relevant today:
Extremely relevant today: Most common infectious disease? Dental caries; Judd, RC, El Med Micro, page 4
athlete’s foot; ascariasis. Most common life threatening? Tuberculosis and malaria.
Second most common? Schistosomiasis.
Current disease problems:
Staphylococcus aureus - first completely drug resistant bacteria.
Escherichia coli 0157:H7 - enterohemorrhagic diarrhea.
Streptococcus pyogenes - “flesh-eating” bacterium.
Bordetella pertussis - whooping cough. Recent outbreaks in Idaho, MT.
Salmonella typhimurium - milk-born outbreaks in Illinois, Wisconsin and
Minnesota. Associated with fowl.
Giardia lamblia - giardiasis - western MT streams.
Brucella abortis - disease in bison leaving in Yellowstone Park.
Mycobacterium tuberculosis (and related species) - tuberculosis - AIDS
epidemic has spawned a TB epidemic.
Vibrio cholerae - cholera - Rwanda, Peru, Brazil, India.
Pasteurella pestis - plague - India. Potential bio-terror agent.
Borrelia burgdorferi - Lyme Disease.
Bacillus anthracis - zoonose and a bio-terror agent.
Sinomber virus - “hanta-like virus” - respiratory disease.
Human immunodeficiency virus - AIDS.
Ebola virus
Encephalitis viruses
Bovine spongiform encephalopathy (BSE) - prion. Mad cow disease.
Norwalk-like viruses; Rotaviruses
Severe Acute Respiratory Syndrome (SARS)
Asian bird influenza
Human papilloma virus (HPV); a new vaccine - Gardasil.
Influenza HIN 1
Infection v disease
Infection is not necessarily disease; disease is damage to the host mediated by the
infectious agent; pathology is the disease (i.e. damage) caused by the infectious
agent; virulence is a quantitative measure of the ability of an infectious agent to
cause disease. Pathogenic - potentially disease-causing.
Disease can be due to a toxin (poison); damage to cells or host tissues; nutrient
depravation, blockage of vessels etc.
Prions; Viruses; Prokaryotes (bacteria); Eukaryotes
protists - single cell;
multicellular. Among the Eukaryotes are fungi and animals. Plants generally are not
infectious agents.
Carbon, nitrogen, oxygen, phosphorous, hydrogen,
sulfur. Trace elements are also required such as iron, zinc, calcium, etc.
Carbon, nitrogen, oxygen, phosphorous, hydrogen,
sulfur. Trace elements are also required such as iron, zinc, calcium, etc.
Molecules of life:
nucleic acids:
ribonucleic acid (RNA) and deoxyribonucleic acid(DNA) - adenine, guanine, cytosine, thymidine, and uracil (replaces adenine in RNA) + ribose (RNA) or deoxyribose (DNA); genetic material and involved in translating the genetic code into protein.
Molecules of life:
proteins -
- strings of amino acids (22) peptide bonds; primary structure - the amino
acid sequence; secondary structure - the interaction of the amino acids in the string;
tertiary structure - the important stuff, the folding of the protein to assume its
functional structure - temperature, acid/base, electrolytes and other
considerations can effect tertiary structure; quaternary structure - interaction of
two or more proteins to form a functional structure (insulin A and B chains).
Structural, enzymes, toxins, antibodies, hormones.
Molecules of life:
carbohydrates -
sugars - hydrogen and oxygen in the same ratio as water. Structural,
energy conversion.
Molecules of life:
lipids - fats
long chains for carbon. If double bonded = unsaturated; single bonds
= saturated. Glycolipids, fatty acids, sterols. Membranes, structural, hormones,
energy.
Glycoproteins, lipoproteins (proteolipids), etc.
Infectious Agents:
Prions; Viroids
Viruses
Bacteria (prokaryotes)
Eukaryotes: fungi, protista, animal
viruses
Viruses: are they alive? Philosophical question.
Life is often defined as: 1) the ability to metabolize (grow); 2) reproduce; 3)
respond to the environment. Viruses can’t really do any of these independently.
Therefore, viruses are not “organisms” whereas bacteria and eukaryotes are. I refer
to viruses as infectious agents. Viruses cause many common diseases such as head
colds, influenza, intestinal diseases, etc.
Viruses range in size from 0.02p.m diameter, averaging 0.1 |im. They lack sufficient
metabolic machinery to replicate and grow. Virus enters host cell, releasing its
nucleic acid, some “early” enzymes such as polymerases, then shuts down host
replication and forces the host cell to produce proteins directed by the virus. Some
viruses integrate their nucleic acid into the hosts genome and can be passes from
parent to offspring. “Late” proteins are produced involved in the structure of the
virus and packaging of the replicated viral nucleic acids into the viral “head”. Virus
either ruptures cell or buds out. It may pick up some host membrane that acts as a
envelope.
Basic Viral Structure: See “Introduction to Viruses notes” notes, page 46.
RNA vs DNA; single strand vs double strand; + strand vs - strand. Capsid.
Bacteria (prokaryotes)
Bacteria are small (l-40p,m in diameter, averaging 5p.m),
single cell organisms generally capable of free living. Most bacteria are good.
Involved in remineralization, food (cheese, yogurt, sour cream, black tea, coffee,
etc.). Only about 30 genera cause disease and only a few are dependent on humans.
Most are accidental infections. Unbelievable distribution in nature, living with air
(aerobic), without air (anaerobic). Some metabolize sulfur, producing sulfuric acid,
others live at 70°C. Others live in up to 20% salt - that would pickle you! Some’
photosynthesize others live deep in frozen glaciers in Antarctica
Circular chromosome of DNA; transcribe mRNA; translate to protein. Many have plasmids - self replicating genetic elements. Most have restriction/modification systems. Some can resist drying (endospores). They multiply by binary fission.
Classification of bacteria
a nomenclature vs a taxonomy, e.g. bacteria can’t be distinguished
based on structure. Biochemical distinctions. Enzymes, genetic content. Five major
structural types: coccus, bacillus, vibrio, spirochete, pleomorphic. Two major
groupings: Gram +; Gram -. see “Bacterial Disease”, page 63 . Other stains, acid
fast, silver, etc.
Some have capsules of protein or carbohydrate (meningococcus; pneumococcus),
some have flagella - motility; Fimbria/pili - adherence, sex.
Basic Bacterial Structure: see “Bacterial Diseases” page 63.
Gram +; Gram -; various shapes; LPS; cell walls; toxins; spores
5 major structural types of bacteria
coccus, bacillus, vibrio, spirochete, pleomorphicf
Eukaryotes:
Fungi: asexual (budding) reproduction - ascospores; conidiospores; arthrospores
or by sexual reproduction.
Zygomycetes, ascomycetes, basidiomycetes, deuteromyctes
Yeast vs mycelial
Protista: Single cell organisms of plant, animal, fungi and algae
Animal: Malaria; giardia; Entamoeba; Leishmania; etc. Multiply by sexual
reproduction.
relationships between infectious agents and humans
- Couldn’t care less - Free living. Most organisms by far.
- Commensal - “sharing a table”. No damage.
- Symbiotic (mutualism) - both gain…Normal flora.
- Parasitic - it harms you.
May or may not cause disease. For disease there must be a PATHOLOGICAL
CHANGE in the host. - Saprophytic - live on dead and decaying material.
Factors of organisms that influence disease
For infectious agents to succeed they must:
- Get from host to host - TRANSMISSION.
- Correct portal of entry.
- Find correct “niche”
Get from host to host - TRANSMISSION. We are mortal so bugs must get from
you to me to someone else. Examples are NOT COMPLETE.
DIRECT CONTACT - Staph, herpes, athlete’s foot
SEXUAL or VENEREAL transmission - HIV, HPV, gonorrhea,
chlamydia, syphilis
RESPIRATORY - Strep, influenza
FECAL/ORAL - salmonella, giardia, cholera, polio
WATER; FOOD
FOOD - botulism, salmonella, various food infectious agents
FOMITE - inanimate objects (drinking fountain, forks, etc.) - some of the
above
VECTORS - living agents that transmit disease. Black plague, Rocky MT
spotted fever
Horizontal transmission - among a population.
Vertical transmission - parent to offspring.
- Correct portal of entry
Mouth, nose, cut, ear, etc
- Find correct “niche”
0 2- aerobic, anaerobic. Gangrene, tetanus vs strep.
Correct pH - acid/base. Stomach low (pH 2) gut high (pH 9). Tissue pH 7.4.
Correct nutrients.
Overcome other organisms (e.g. normal flora). Tetracycline/yogurt.
Overcome host defenses.
Do infectious agents live extra or intra cellularly?
Most bacteria, fungi and some parasites live extracellularly. Some live
intracellularly (TB, Chlamydia, malaria). All viruses are obligate intracellular
infectious agents. Some organisms can live in or out of cells
PATHOGEN
potentially disease-causing
VIRULENCE
quantitative measure
of disease.
Infection vs disease, e.g. Normal flora vs a pathology
Infection is the process of gaining entry and growing. Disease is a detrimental
change in host tissues or structures caused by the infecting agent. That detrimental
change is called PATHOLOGY.
We contact pathogenic (potentially disease-causing) agents all the time!
what are the 4 outcomes when We contact pathogenic (potentially disease-causing) agents?
- Most common - we control and destroy with no symptoms. Our Immune
Systems protect us. - We get sick and then recover, destroying the agent.
- We control it but we become carriers - Typhoid Mary.
- It kills us.
Exogenous v Endogenous
from without
from within
Types of INFECTIONS:
Local - remains at one site. A zit.
Focal - spreads to other sites from a point source. Tetanus.
Systemic - throughout body. Plague.
Primary - disease results from invading agent.
Secondary - disease caused by other agent(s) as a result of debility due to
disease or therapy. Cortisone, chemotherapy, AIDS.
Mixed - two or more agents involved. Staph/strep + tetanus.
Inapparent or subclinical - most common. You have an immune response but
never any symptoms.
Local infection
Local - remains at one site. A zit.
Focal infection
Focal - spreads to other sites from a point source. Tetanus.
Systemic infection
throughout body. Plague.
Primary v secondary infection
Primary - disease results from invading agent.
Secondary - disease caused by other agent(s) as a result of debility due to
disease or therapy. Cortisone, chemotherapy, AIDS.
Mixed infection-
two or more agents involved. Staph/strep + tetanus.
Inapparent or subclinical -
You have an immune response but
never any symptoms.
-EMIAS
what are they?
examples?
- “bugs” in the blood.
BACTEREMIA - transitory state where bacteria are in the blood moving to another spot.
SEPTICEMIA - blood is the infected tissue.
PYEMIA - pyogenic bacteria in blood (staph/strep).
TOXEMIA - poison in blood. Tetanus, etc.
VIREM1A - virus in blood.
PARASITEMIA - parasite in blood. Malaria.
Whether a pathogen causes disease depends on the relationship between the agent and the host. Very complex.
Factors of the agent:
- Ability to invade - enzymes (hyaluronidase, proteases, lipases, neuraminidase, nucleases).
- Capsules - polysaccharide or protein. Antiphagocytic.
-
Toxins - poisons.
- -Exotoxins - usually poisonous proteins (tetanus, botulism, diphtheria). Exotoxins are often described by the organ or tissue affected: e.g. enterotoxin -gut poison; neurotoxin - brain of CNS toxin, etc.
- -Endotoxin - lipopolysaccharide (LPS) of Gram negative bacteria. Fever, shock, intravascular coagulation.
- Motility - flagella, cilia.
- Adherence - fimbria(ae)/pilus(i), receptors on viruses and parasites, etc.
- Antigenic variation - ability to change surface at high rate, confusing our IR
Whether a pathogen causes disease depends on the relationship between the agent and the host. Very complex.
Factors of the Host that affect our resistance to disease:
- Premunition - physiological ability to resist infection due to generations of contact.
- Age - very young (immature immune system); very old (deteriorating immune system).
- Genetic ability to resist diseases - Correct immune response genes (strepsusceptible).
- Nutrition.
- Occupation - Health care workers (HIV, hepatitis, etc.). Ranchers (brucella, leptospirosis). Abattoir workers, prostitutes, etc.
- Other diseases - diabetes, cancer, infectious diseases.
Non-specific Resistance
The “First Line of Defense”:
Physical/Chemical Barriers
Physical/Chemical Barriers
Portals of entry
- Skin surface - integument, Largest organ of body. Fatty acids, salinity, pH 5, normal flora. Abrasion, cuts, bites (insects/rabies).
- Mucous Membranes - all the orifices of our body are lined with mucous - viscous fluid, sticky with neuraminic acid.
- Ears - ear wax.
- Nasopharynx - mucous, expectoration, nose hair, flow out, etc.
- Oropharynx - mucous, expectoration, lysozyme, lytic enzymes.
- Respiratory tract - many get in few cause disease. Mucous, cilia, flow out.
- Eye - mucous, tears, lysozyme.
- Gut - low stomach pH (Helicobacter), intestine high pH. Lytic enzymes, bile salts, peristalsis normal flora.
- Urogenital tract - flushing with urine, flow out, low pH of vagina (pH 4-5), normal flora (pill).
Physical/Chemical Barriers
Chemicals:
Acid, bases, bile salts, enzymes (lysozyme, proteases, lipases, nucleases, etc.).
Acid: a low “pH” - meaning lots of free H+ ions around; Base: a high pH -meaning lots of OH- ions around.
pH 7.0 means there is an equal number of H+ ions and OH- ions (neutral). Most of our tissues are about pH 7.4 (very, very slightly basic).
The “First Line of Defense”: Physical/Chemical Barriers
Mechanical Flow
flow of tears, saliva, urine, blood is all OUT! Washes organisms away
The “First Line of Defense”: Physical/Chemical Barriers
Normal Flora:
Organisms that live with us. Cover up sites, produce antimicrobial agents, etc
The “Second Line of Defense”:
Elements of the blood and lymph, Reticuloendothelial System (RES), a system of phagocytes and inflammation.
Blood:
plasma
serum
Blood - great stuff. Its an organ. -50% cells, - 5 0 fluid
Fluid portion of blood is called plasma. If the clotting factors have been removed,
serum.
Plasma exits blood to bathe tissues with 0 2
and nutrients. If too much, swelling
(edema). Fluid is returned to blood by lymphatic system.
Plasma has lots of good stuff in it. Toxic peptides (short proteins), complement,
antibody, interferon, etc.