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Lesson 9: after completing this lesson students should be able to:
Understand the concepts and terms concerning Specialized Host Defenses
 The third line of defense of a host involves lymphocytes and the Lymphatic System
 Understand that the 3rd line of defense is a Specific resistance that is acquired
 Is an immune response done by lymphocytes
Understand the nature of Antigens:
 a protein or large polysccharide is "more antigenic" than lipids and nucleic acids, need a
molecular weight of 10,000 or greater. Yet, small molecules can be antigenic if
combined w/ a large molecule. Surface molecules of a microbe serve as antigens.
 Know antigenic determinants/epitopes
Understand the concepts and terms concerning Lymphocytes
 know agranulocytes vs granulocytes
 Lymphocytes: B cells and T cells, NK (Natural Killer) cells
T Cells
 start in an adult in the bone marrow & migrate to the thymus
 immature T-cell lymphocytes divide rapidly, and only those with the ability to recognize
foreign antigens survive
 teen-age mature T-cells emerge from the thymus
 T-cells are the cell-mediated arm of the immune system
 they are effective against bacteria and viruses in cells, & rejection of foreign tissue and
cancer. They are not good against bacteria free in the body.
B Cells
 Know where B-cells originate and migrate to
 Know the B-cell receptors or BCR.
 ~500,000 copies of 1 B-cell receptor/cell. Because there are 1X109 B-cells each w/ a
different receptor, we can mount an immune response to nearly anything.
 When exposed to an antigen, B-cells undergo clonal selection & differentiation.
Differentiated cells become memory cells and plasma cells that produce antibodies
 B-cells are the humoral (fluid) arm of the immune system because antibodies are in the
bodies fluids (blood, plasma, and mucous).
Understand the concepts concerning The Results of Antibody Binding
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When an antibody binds to an antigen, these results may happen:
neutralization – very important w/ toxins
opsonization - enhancing phagocytosis
agglutination - enhances phagocytosis, reduces infectious units, hinders spreading, and
precipitates the antigen. IgM is the best at this.
complement activation - a complement protein (C1) binds to the antibody
inflammation - antibodies provide a spot for complement to start inflammation
antibody-dependent cell mediated cytotoxicity – discussed in context of
natural killer cells
Understand the concepts and terms concerning Antibodies:
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shaped like a Y, have 4 polypeptide chains, and two binding sites
the Fab or variable region. know what it does
other end called Fc or constant region know what it does
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The structure of antibody molecules:
five different types of constant regions, five classes of antibodies or immunoglobulin
molecules.
constant region of antibody has the same sequence of amino acids
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IgG – is a small monomer w/ many actions. It can do nearly everything that an antibody can
(except for acting like IgE and IgD).
IgM – athe largest antibody, is a pentamer, w/ a J-chain holding them together. It has 10
bidning sites. It can do most things IgG can do and is the first antibody produced in an
immune response.
IgA – is monomer and dimer. Know how and why this is and where it is found
IgE – is a monomer that will bind to basophils and mast cells. Know its actions:
IgD –is a monomer and is B cell receptor. Know its actions:
Understand that a B-cell and its clones will first produce IgD, then IgM, and lastly IgG which
all have the same variable region which allows their antibodies to bind to the same thing!
Understand the concepts and terms concerning Immunity:
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Immunity can be naturally acquired or artificially acquired
Immunity can be active or passive
Naturally acquired active immunity
Naturally acquired passive immunity
In humans, this occurs between a mother and her child involving IgG and IgA
Artificially acquired active immunity (by vaccination)
Artificially acquired passive immunity
antibodies are administered not a vaccine. This one is short-lived
Understand the concepts and terms concerning Cell Mediated Immunity:
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occurs by T-cells:
o react specifically to one epitope
o Understand how T-cell receptors (TCRs) get stimulated
o when a T-cell is stimulated, it undergoes clonal selection & differentiation
o memory cells and active (mature) T-cells develop from this.
Know the Action of each Type of T-cells and its cell surface molecules
Cytotoxic T cells (TC)
o kill cells by either putting a pore in the membrane (perforin), or cause
apoptosis (programmed cell death)
o CD 8 is a surface molecule on cytotoxic T-cells
Helper T cells (TH)
o help other immune cells by producing cytokines.
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Understand the role of Antigen Presentation Cells
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CD 4 is a surface molecule on helper T-cells
Type 1 helper T-cells
produce cytokines that activate and/or stimulate cytotoxic T-cells
Type 2 helper T-cells
produce cytokines that activate and/or stimulate B-cells
Understand the concepts and terms concerning the Types of Antigens:
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T-dependent antigen
need the assistance of helper T cells. Know why.
T-independent antigens can stimulate directly the B-cells. Know why.
Lesson 10: Immunization and Hypersensitivities: after completing this lesson
students should be able to:
Understand the concepts and terms concerning Immunization:
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Know that Edward Jenner started immunization w/ the 1st vaccine.
He used another virus, cowpox to protect against smallpox.
No one understood why his vaccine worked, but you need to know!
The next vaccine was not produced for nearly 100 years by Louis Pasteur.
His experiments allowed people to understand vaccines and make others.
Understand the concepts and terms concerning Immunity and Vaccines
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There are 3 types of vaccines:
1. Attenuated live vaccines
2. Inactivated (killed) vaccines
3. Toxoid vaccines
Understand the concepts of Attenuated live vaccines
 The virulence is removed or reduced, but it is alive so it may cause mild disease and may
mutate back to virulence (oral polio: best studied).
 gives a strong response, requires one or few doses, lifelong.
 provides herd immunity (protecting the herd).
 Examples, the attenuated oral polio vaccine (Sabin), cowpox, Yellow fever.
Understand the concepts of Inactivated (killed) vaccines
 The microbe has been killed, or may only be molecules or fragments of the microbe.
 They require several boosters, immunity is usually long but not lifelong.
 Only a humoral immune response
 Examples, inactivated polio (Salk) shots, flu shots, rabies shots
Understand the concepts of Toxoid vaccines
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They do not fight the pathogen, but rather its toxin. They are modified toxins that are not
toxic though they may cause inflammation. Their immunity is not strong or long lasting,
requires several boosters in childhood, and every 10 years or less.
Only a humoral response is made
Examples, tetanus and diphtheria vaccines.
Understand the concepts of Hypersensitivity:
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The immune system prevents disease, but it can cause disease. If it does, it is called a
hypersensitivity or an allergy. They are the same, though an allergy is often less severe.
Hypersensitivity is to too much of an immune response, or one at the wrong time or both.
Are B-cell or T-cell mediated
o B-cells account for 3 of the 4 types of hypersensitivities
o are relatively rapid compared to T-cell hypersensitivities
T-cell hypersensitivities
o accounts only for Type IV hypersensitivity
o is usually 24-72 hours.
Understand the concepts of the Types of hypersensitivities:
Type I: Anaphalactic Response
1. First exposure a patient’s system is exposed to the antigen (Sensitization)
o B-cells get stimulated to produce antibodies to the antigen, including IgE
o IgE coats Mast Cells and Basophiles, now the patient is primed to act
2. Second and Later Exposures to the Antigen cause the problem
o IgE is on Mast cells/Basophiles and ready to bind to the antigen
o Once IgE binds to the antigen, the Mast cell releases histamine/heparin/ and other
inflammatory chemicals
o Get a rapid inflammatory response that we call a hypersensitivity
3. The Response
o if local, is not usually a problem. We call it an allergy, like hay fever giving
someone a runny noise and itchy eyes.
o if systemic, it can be life threatening. The bronchial smooth muscles contract,
the blood vessels dilate, restricting the airway which may cause death.
o Epinephrine may be administered to relax the muscles
Type II: Cytotoxic Hypersensitivity Response
 In this case, the host is exposed to something (usually cells) that carry an antigen and
antibodies are produced which react to these antigens.
 The host destroys the antigen usually w/ compliment, but may be phagocytosis.
 Is responsible for many autoimmune diseases, such as destroying RBC upon a
mismatched blood transfusion, and Rh incompatibility.
 You should know the specifics of Rh incompatibility.
 Unlike other B-cell mediated hypersensitivities, this one takes longer, 5-12 hr
Type III: Immune Complex Hypersensitivity
 Is often mediated by IgG but can be other small antibodies (all my examples use IgA).
 The small antibodies bind to a small antigen forming forming a complex that is small
enough to circulate in the blood or lymph.
 IgM complexes usually do not do this; in fact, they may precipitate out of the blood.
 These small complexes get wedged in small places such as capillaries, joints, etc.
 The complexes attracts complement, phagocytes, and other inflammatory agents, and this
causes inflammation which causes damage to the patient.
 All my examples use IgA and are a hypersensitivity pneumonitis caused by dust or mold
breathed in. IgA complexes to the dust or mold causing inflammation in the lung. When
the patient has this, their lungs swell up and they have difficulty breathing.
Type IV: Cell-Mediated Hypersensitivity
 This one is mediated by T-cells, no antibodies are involved.
 It also takes longer, from between 24-72 hours, more time is need for Tc to become
activated, move to, and attack their antigen.
 The antigen that causes the problem usually comes into the body from outside, such as w/
poison ivy. But tissue or organ transplants are other examples.
 The antigen stimulates Tc cells which go on to kill the cell that the antigen is attached to
(or the cells of an organ transplant).
 An example is a case of poison ivy or oak
Understand the concepts of AutoImmune Diseases:
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The immune systems creates B and T cells that react to many antigens. Normally in early
childhood, any B or T-cell that reacts to a molecule of the self is pruned (removed).
If the immune system does produce antibodies or Tc cells against molecules (antigens) of the
host, it is an autoimmune disease where the immune system attacks the host.
Most develop with no predisposing factor, though viral infections sometimes may play a role.
They are more likely to occur in the elderly and in woman and you should know why.
Understand that there are two types of autoimmune diseases:
1. Single Tissue diseases
o autoimmune hemolytic anemia – where a patient’s immune system attacks their RBC
o immunological attack on islets of Langerhans can result in type I diabetes
o multiple sclerosis (MS) where the immune system attacks myelin sheaths of neurons
2. Systemic Autoimmune Diseases
o Lupus (systemic lupus erythematosus) -Tc and antibodies produced against many
antigens of the host. The patient can have many symptoms, depending on what is
attacked. Autoantibodies are made against the patient’s own DNA, and the DNA
antibody complexes in the blood damage the kidneys.
o Rheumatoid arthritis – where the patient’s immune system attacks against collagen,
causing inflammation in the joints.
Understand the concepts of Congenital Immunodeficiency Diseases
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Inherited defects have been found in all the bodies lines of defense, they include:
phagocytes that are unable to kill ingested bacteria
IgA deficiency – is the most common, these children have multiple gastrointestinal infections
IgG or IgM defiency –these children are more likely to have bacterial infections.
severe B cell deficiency -cannot make any antibodies, usually have recurring bacterial infections.
They are usually ok w/ viral and eukaryotic infections. Until relatively recently, they died.
T-cell deficiencies -children who lack a thymus and therefore have no functioning T-cells. These
children are resistant to most bacteria, but usually die before reaching adulthood from viral
infections.
Severe combined immunodeficiency disease (Bubble Boy Disease), these children have no
functioning B or T-cells. They have to live in a sterile bubble or they will die.
Genetic engineering of people has begun! Some of these children have been genetically
engineered to the specifications desired by their parents! Be able to give an example.
Lesson 11: Viruses: after completing students should be able to:
Understand the following terms and concepts concerning Viruses:
 are intracellular parasites
 use the machinery of their host cell to reproduce by making viral proteins and viral nucleic acid
 viral proteins and viral nucleic acid makeup naked viruses
 enveloped viruses have an envelope, viral nucleic acid, and viral proteins.
 There are viruses to every kingdom
 Viruses are around 100nm and smaller in diameter
 size & shape of viruses vary
Understand Viral Morphology
 Morphology includes viral shape and components
 3 basic shapes:
1. helical (Tobacco Mosaic Virus)
2. polyhedral (Poliovirus)
3. complex (nearly any shape, i.e. Ebola, Bacteriophage T4, rabies)
 Viral Components
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Nucleic acid:
o double stranded (dsRNA or dsDNA)
o or single stranded (ssRNA or ssDNA)
o if single stranded, need to discuss which strand:
 ssRNA (+) strand (as mRNA)
 or (-) strand (complimenatry)
 Capsid: is the viral protein. It surrounds the nucleic acid.
 Envelope: only in some viruses, called enveloped viruses
o Used in attachment to the host and is range specific
o Most viruses are specific for infecting certain species or even certain cells
o The envelope contains viral surface proteins or glycoproteins
that bind to certain receptors (proteins/glycoproteins) on cells
HIV binds to CD4 receptor
Spikes: on enveloped viruses, useful in attachment.
o Rabies virus
Enzymes may be found in some viruses:
o Reverse transcriptase in retroviruses.
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Understand the terms and concepts concerning Viral Classification:
1. Viruses vary a lot in many regards this variation is used to classify viruses:
2. Viral names are unusual as they have no Latin names, only English.
3. They are not classified into superkingdoms, kingdoms, phylums, and classes
4. Only a few are classified by their order (most do not have an order)
5. They are classified by their families, genera, species, and strains.
6. Why they are not classified into higher groups is because we are not sure of their
evolutionary relationships as they have so little nucleic acid that evolves quickly.
7. A virus’s evolutionary past is not as important to how it is evolving with its host cells.
8. Note, we classify viruses into the kingdom they infect (animal and plant viruses)
Understand the terms and concepts concerning Bacteriophages:
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bacteriophages or phages are viruses which infect eubacteria.
T4 is the most studied/well known virus
It looks like the lunar lander and has tail fibers for attaching and penetrating the cell wall.
Bacteriophage Lambda is similar except it lacks the tail fibers.
Bacteriophages have tail structures that are lacking in animal viruses because animal viruses
do not need an elaborate structure to infect their cells.
Understand the terms and concepts concerning the Lytic Life Cycle:
 Viruses can have a few life cyes (how they live).
 T4 and Lambda have a lytic life cycle.
 In the lytic life cycle, the virus infects a cell and the protein coat stays on the outside of the
cells. The sheath injects the viral DNA into the cell. The first thing a lytic virus does is to
degrade the host chromosome. This ensures the virus controls the cell.
 New viral DNA and proteins are made and are assembled into virions.
 The virus then causes cell lyses to release the virions.
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You can follow the lytic cycle over time
Burst time - time from attachment to the cell bursting
Burst size - number of new virions
Understand the terms and concepts concerning Viral Life Cycles:
 Some only have a lytic life cycle (i.e., T4).
 But other viruses have other life cycles:
1. lysogeny (Lambda has this)
2. budding or persistent infections (HIV)
3. latency (Varicella-Zoster, HIV).
 Some viruses can have more than one life cycle;
o Lambda has lysogeny and the lytic life cycle
o HIV has the budding and latent life cycles
Understand the terms and concepts concerning Bacteriophage Lysogeny
 Lambda – has both a lytic and a lysogenic life cycle.
 In lysogny, the viral DNA integrates into the host chromosome, it is called a prophage but is
viral DNA. The lytic genes are repressed by the lysogenic gene. The only time the prophage
replicates is when the host cell replicates its DNA.
 For unknown reasons, the lysogenic gene gives up control, the prophage is exised from the
host chromosome, and the lytic genes are expressed.
 When this happens, the lytic life cycle begins which will kill the cell.
Understand the concepts concerning Bacteriophages & Human Health:
 Bacteriophages do not infect animals, so their affect on human health is not direct.
 But, bacteriophages can bring new phenotypes to eubacterial cells, including encoding for
virulence factors. Recall that Corynebacteria diphtherium only makes the diptheria toxin
when it carries a lysogenic prophage of a virus which encodes for the toxin.
 Bacteriophages are also responsible for transduction that can bring new phenotypes to
eubacterial cell, including antibiotic resistance.
 In the 1920's and 30's, bacteriophage therapy was commonly used to treat disease. It was
discontinued in the 1940’s because it was not very effective and antibiotics became available.
They are used in a few hospitals in the country to treat infections which are resistant to all
known drugs, such as some strains of MRSA.
Understand the concepts of Budding & Persistent Infections of Animal Viruses:
 Some animal viruses also infect cells and integrate into the host chromosome. If they do,
animal viruses become permanently integrated. They are called a proviruses.
 Such animal viruses can replicate, but they usually bud out of the cell (or leave by exocytosis)
and do not kill the cell. They bud out of the cell, ER, or nuclear membrane.
 All enveloped viruses bud out of cells, that is how they get their envelope.
 Some naked viruses do something similar, they integrate into the chromosome, replicate,
and then leave the cell by exocytosis. Such naked viruses are called Persistent Infections.
 Animal viruses w/ the Budding and Persistent Infection life cycles do not kill cells. The
immune system does most of the killing to these infected cells.
Understand the concepts concerning Animal Virus Latency
 Sometimes animal viruses become dormant and enter the latent life cycle.
 Some of these integrate into the host chromosome, but not all of them.
 Chickenpox (Varicella-Zoster) is an example. A child gets the chickenpox, and the virus
goes latent in nerve cells. About 15% develop shingles years later. When this happens, the
virus leaves latency and reenters the budding life cycle.
 herpes simplex virus-1 that causes cold sores is another example.
Understand the concepts concerning Animal Viruses
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differ from bacterial viruses in a number of respects, one difference, they have no tails for
attaching to cells, instead using protein/glycoproteins in spikes, capsid, or envelopes.
bacteriophages have to replicate in the cytoplasm, but animal viruses do not
DNA animal virus generally replicate in the nucleus, while RNA animal viruses generally
replicate in the cytoplasm. RNA retroviruses are an exception, they replicate in the nucleus.
Understand the concepts concerning Retroviruses
 HIV is an example.
 They are unique because the have the enzyme Reverse transcriptase. This enzyme copies the
viral RNA to make DNA, this DNA then integrates into the host chromosome.
 Once the viral DNA is transcribed, it makes viral RNA (as its genome) and viral protein
which assemble into virions. The new viruses then bud out of the cell w/o killing it. If the
cell dies, it is usually from the host’s immune system.
Understand the terms and concepts concerning Prions
 Examples: Mad cow disease and scrapie.
 Prions are not viruses or cells, it is thought that they are caused by proteins. It is thought that
there are two forms of the protein, PrP, differing in protein folding.
 Plaques in brains, hence the name "spongiform."
 In the 1990s, an epidemic of Bovine spongiform encephalopathy (mad cow disease)
 The disease spread because the British ground up cow brains, added it to grain, and fed it to
cows. During the mad cow epidemic, there was a higher incidence of prion disease in people
in Britain; this disease is called Creutzfeldt-Jakob. At the same time, there were a lot of cats
which came down w/ prion disease. Although unproven, it is thought the British people and
cats came down w/ prion disease from eating tainted beef.
Understand the concepts concerning Viroids
 Are infectious RNA molecules, they are not known to infect animal cells, but cause disease in
plants, such as stunted potatoes.
Lesson 12: Pathogenic Viruses: after completing this lesson students
should be able to:
Understand the following terms and concepts concerning Viruses and Disease:
 Many viruses cause human disease, including 7 families of DNA Viruses & 15 families of
RNA Viruses.
 Treating viruses has been elusive. There is not, has never been, and for the foreseeable future
will not be any therapy to cure a viral disease; prevention is possible with vaccines.
Understand the terms and concepts concerning DNA Viruses:
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1. Pox family:
Are dsDNA virus with an envelope
Smallpox is the most important member of family, playing important roles in history
Edward Jenner created the first vaccine against smallpox by using cowpox
Smallpox was in 1980 the first and only disease that has ever been eradicated
The U.N. began trying to eradicate polio
There were two strains of smallpox
1. variola major –severe mortality
2. variola minor -less severe
Both produced high fevers, prostration, and pox lesions that left severe scars.
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There are a number of other viruses in the pox family that humans can get, such as cowpox and
monkeypox, but there is only one, molluscum contagiosum that is a human virus.
The later is not a severe disease and is most commonly spread by contact among children or
sexually active adolescents.
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2. Herpes Family of Viruses:
dsDNA virus with an envelope.
New Name
Common Name
Disease and notes
Human herpesvirus 1
herpes simplex virus-1
cold sores, whitlow, ocular herpes (~90%)
Human herpesvirus 2
herpes simplex virus-2
genital lesions, whitlow, neonatal herpes
Human herpesvirus 3
Varicella-Zoster
chickenpox and shingles (was ~90%)
Human herpesvirus 4
Epstein-Barr Virus,
EBV
most asymptomatic, mono, Burkitt's lymphoma, etc. (~90%)
Human herpesvirus 5
Cytomegalovirus, CMV
most asymptomatic but may be severe in fetuses, newborns
and immunocompromised (US ~50, some 90%)
Human herpesvirus 6
Roseolovirus
illness & skin rash in children, maybe a role in MS, ~100%
Human herpesvirus 7
Roseolovirus
illness & skin rash in children, usually later than HHV 6. (>90%)
Human herpesvirus 8
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3. The Family Papillomavirus
causes Kaposi's sarcoma, a blood vessel cancer seen in the
skin (very low %)
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dsDNA naked virus.
Papillomaviruses cause benign growths called warts, 40 varieties cause warts in man
They are transmitted by direct contact or by fomites
Seed warts on the fingers especially common in boys
Plantar warts on the sole of the feet are common among athletes
Genital warts are the most common sexually transmitted disease in USA. It increases one's (and
one's partner's) risk of many forms of cancer. Females giving a normal birth, it increases the risk
that the child will get cancer of the larynx.
4. Adenovirus Family
are dsDNA naked viruses.
Around 30 different adenoviruses cause the cold.
Also can cause eye infections called pinkeye and diarrhea in children.
Understand the following terms and concepts concerning RNA Viruses:
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1. Family Picornaviridae
(+) strand ssRNA naked viruses, this family is very diverse
> 100 varieties of picornaviruses cause colds (rhinoviruses)
Highly contagious, a single virion can cause a cold. Are respiratory infections, but the most
common means of transmission is by hand with subsequent inoculation of the eyes.
Several varieties are transmitted by the fecal-oral route (enteroviruses) including:
o Polio
o Coxsackie A and B viruses
Some varieties of Coxsackie A cause oral lesions
Other varieties of Coxsackie A cause colds that are transmitted fecal to oral
One variety of Coxsackie A causes hand-foot-and-mouth disease
A variety of Coxsackie B causes myocardial & pericardial infections resembling a heart attack
Some Coxsackie B viruses infect the pancreas and may cause diabetes
Other picornaviruses include:
o Hepatitis A that is transmitted fecal to oral.
2. Families Togaviridae and Flaviviridae (Togaviruses and Flaviviruses)
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Are (+)ss RNA viruses that are enveloped
Most are transmitted by arthropod vectors (mosquitoes, ticks, flies, etc.) and are called
arboviruses. The vectors and the animals they bite are reservoirs. These viruses can have very
broad host ranges (humans, birds, mosquitoes)
Most cause mild flu-like symptoms 3-7 days post infection with the virus entering the blood so
that the vector can become infected, but this is not persistent in humans
Occasionally, virus spreads to other tissues which can cause severe disease, examples:
o Eastern equine encephalitis
o Western equine encephalitis
o Venezuelan equine encephalitis
o West Nile virus (severe cases cause encephalitis)
o Dengue fever
o Yellow fever
Yellow fever is the most severe disease, w/ a mortality rate up to 20%. It was in the USA before
mosquito control and the development of a vaccine eradicated it.
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Rubella
Rubella or the German measles is a togavirus, but is transmitted by the respiratory route, not by
arthropod vectors
is usually not serious, especially in kids, adults may develop encephalitis or orchitis
it can cause severe birth defects when a pregnant mother becomes infected
before the vaccine, it was the leading cause of birth defects in the USA
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Hepatitis C
is a flavivirus but is not transmitted by arthropods vectors, but by needles, blood, and sex
usually it is asymptomatic but may lead to severe liver damage
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3. Family Coronavirus
Are (+)ss RNA viruses that are enveloped
Second most common cause of Colds, behind rhinoviruses & ahead of adenoviruses
SARS is an example
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4. Family Paramyxoviridae
Are (-) strand ssRNA viruses containing an envelope.
The paramyxoviruses include many childhood illnesses including:
o The measles (red measles)
 one of the more contagious and serious childhood diseases
 diagnosed especially against rubella from Koplik's Spots
o Mumps
 usually not serious, especially in kids
 vaccine in combination w/ measles and rubella (MMR)
o Croup (kroop) and parainfluenza (respiratory infections).
 strain 4 is associated w/ mild upper respiratory infection.
 strains 1 & 2 cause Croup, a severe lower respiratory infection w/ inflammation
that may restrict the airway and causes a "seal bark"
5. Family Orthomyxoviridae
Are (-) strand ssRNA viruses containing an envelope
The swine flu pandemic of 1918-1919
Influenza or the flu is caused by two species of orthomyxoviruses
o Influenza types A
o Influenza type B
Infects and grows in a variety of species, including pigs and birds
The envelope has spikes containing hemagglutinin (HA) or neuraminidase (NA) which are the
major antigens on the virus. The flu genome is highly changeable, especially HA and NA
Mutations allow the HA and NA genes to change slightly
o This is called antigenic drift
o Because of antigenic drift, flu shots are good for only ~ 3 years
When two differing viruses exchange genes, this may make major changes in the virus
o this is called antigenic shift
o When antigenic shift occurs, people's immune systems have no immunity to the new
virus and pandemics usually occur
o This happens about every 10 yrs.
Unlike other viruses, in one envelope there are 8 capsids
o Each capsid has a different RNA molecule, splitting the genome into 8 pieces
o This unusual packaging helps the virus exchange genes allowing antigenic shift
Lesson 13: Pathogenic Gram+ Bacteria: after completing this lesson
students should be able to:
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Understand the terms and concepts concerning Mycobacterial disease:
cell walls w/ mycolic acid, a long lipid chain of 60-90 carbons
mycolic acid give Mycobacterium these properties:
o a slow growth rate
o protection from lysis upon phagocytosis by macrophages
o growth w/i WBC
o resistance to drying, can survive for months
o resistance to detergents, many antibiotics, and to Gram staining
o acid fast staining properties
~75 species known but only 3 cause disease in man:
o M. tuberculosis causing the diseases of tuberculosis (TB),
o M. leprae, leprosy
o M. avium-intacellulare, opportunistic infections in AIDS patients
Understand the following terms and concepts of Mycobacterium tuberculosis:
The cord factor
TB is a master at evading host defenses; disease progresses as:
1. Infection can start anywhere, but most often in the lungs
2. Mycobacterium attracts macrophages which engulf the bacteria in phagosomes
3. But the bacteria prevent fusion of the lysosome and phagosome.
4. The bacilli grow inside, eventually killing the macrophage, releasing bacteria and attracting
more macrophages to the area. The cycle repeats.
5. The macrophages begin to form a tubercle, other cells encase the tubercle in collagen
6. After a few weeks, the tubercle forms a caseous center from cell death
7. The disease may remain dormant at this stage for decades
8. The host and bacteria enter a stalemate
Most of the time, the immune system is able to stop disease progression but is unable to rid the
body of disease. Understand why. Such patients are carriers with a dormant disease
Sometimes, the immune system is able to break the stalemate
o killing all the Mycobacterium
o forming calcified lesions on X rays
Sometimes, the bacterium is able to rupture the tubercle, reestablishing an active infection.
If macrophages carry the pathogen via blood or lymph, the disease may spread
o disseminated TB, old name was consumption
o the patient suffers weight loss, coughing up blood, and a loss of vigor, as the bacteria
grows throughout the body.
M. tuberculosis is not very virulent, yet, if untreated, disseminated TB has a high mortality rate
Understand the Diagnosis and Treatment of TB:
There is a skin test
If sensitized to TB, a raised red hypersensitivity reaction occurs. The test cannot distinguish
between those who have been exposed but are uninfected, carriers, & those with active disease
Diagnosis involves staining sputum smears with acid fast stains
Treatment includes streptomycin, rifampin, isoniazid and pyrazinamide for many months
Understand why drug resistant strains are developing
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A vaccine is available but is not used much in the US
Understand why evolution matters in regard to TB infections
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Understand the concepts of Staphyloccoccal Infections:
Staph are cocci that grow in clusters like grapes
Two species commonly cause staph infections:
o Staphyloccocus aureus
o Staphyloccocus epidermidis
S. epidermidis is part of the normal human skin biota, is an opportunistic pathogen in a wound or
an immunocompromised patient
Staphyloccocus aureus is a true pathogen
Understand the concept of Staphyloccocus aureus as a pathogen
It is often found on the skin or nasal passages and is easily transmitted between individuals by
direct contact or by fomites. It is transmitted among athletes or hospital patients.
The bacterium has three features that make it virulent:
o structures to evade phagocytosis
o enzymes
o toxins
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Structures to Evade Phagocytosis:
o protein A inactivates antibodies in two ways:
 inhibit its acting as an opsonin
 inhibit its compliment binding
o A polysaccharide slime layer (or a capsule)
 inhibits chemotaxis and phagocytosis by WBC
 (and aids bacterial attachment to medical devices).
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Enzymes that increase virulence
o coagulase bound and unbound
o Clotting walls the bacteria off, but hides it from the immune system
o Staphylokinase that dissolves the clot
o Hyaluronidase allowing the basteria to spread
o Beta (β)-lactamase (penicillinase) to inactivate penicillin
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Understand the of Toxins of S. aureus
S. aureus produces a number of proteins that are toxins
Five cytolytic toxins:
o α,β,Γ,Δ, and leukocidin
o lyse cells cells providing some protection against phagocytosis
2 Exfoliative toxins
o dissolve desmosomes, which hold adjoining epidermal cells together
o causing the patient’s skin to slough (sluff) off
Toxic-shock-syndrome toxin causing Toxic shock syndrome
5 Enterotoxins (designated A-E) that cause food poisoning
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Understand the concepts of Staphyloccoccal Enterotoxicosis:
S. aureus food poisoning is one of the more common
Is an intoxication and not a food poisoning
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S. aureus is quite resistant to drying, high osmostic pressure and heat lamps
The enterotoxin is even more stable, surviving up to 30 minutes of boiling.
The toxin is NOT destroyed if the food is reheated
It grows well in foods with high osmotic pressure from sugar or salt including:
o custards, cream pies, potato salad, processed meat, and ham
A typical outbreak of Staphylococcal food poisoning goes something like this:
o The food is cooked, killing off bacteria
o A worker contaminates the food with S. aureus
o The food is at room temperature too long or cools too slowly
o Enough Staph grows to release the toxins
o The toxins are eaten as the food has no unusual taste or appearance
o It is a preformed toxin, there is no waiting for illness
o Illness does not last long as the toxins are cleared from the body
o Symptoms usually within one to six hours and usually last 24 hours or less
Understand that S. aureus causes several Cutaneous Diseases (skin diseases):
Scalded skin syndrome
o Caused by an Exfoliative toxin released by S. aureus
o Has a reddening of much of the skin
o Large blisters form that contain clear fluids but no bacteria or WBC
o The skin epidermis peels off in sheets as if dipped in boiling water
o Serious secondary infection may occur in denuded areas.
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Impetigo
o is a skin disease
o pyogenic (pus-filled) vesicles that eventually crust over
o contains bacteria and WBC
o 80% by S. aureus, the rest by streptoccocci.
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Folliculitis, Boils and Carbuncles
o Folliculitis is an infection of a hair follicle
o in an eyelid, it is called a sty
o When spreads deeper, it is a boil or furuncle, is a more painful and larger disease
o When several boils coalesce, they form a carbuncle, having a fever and chills
o If it invades further, it becomes a systemic disease
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Understand the concept of Systemic Diseases of S. aureus
Bacteremia
o When a species of bacteria invades the blood. S. aureus invades the blood from a
spreading lesser infection. It may travel to other sites causing a usually serious disease
elsewhere. The names & symptoms of these diseases are many, such as pneumonia.
Toxic Shock Syndrome
o usually caused by a localized infection
o produce the systemic Toxic-shock-syndrome toxin.
o is fatal in ~5% of patients
o causes blood pressure to fall, red skin that peels in sheets, fever
o occurs in both males and females, but in 1980, was an epidemic among women
o Super-absorbent tampons was the cause
Readings: After completing the READINGS students should be able to:
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Know the Gram Positive families of bacteria and the diseases they cause:
Streptococci group A (Streptococcus pyogenes): strep throat (pharynigitis), scarlet fever,
impetigo (most are staph), toxic shock syndrome (most are staph), necrotizing fasciitis
(flesh-eating strep), rheumatic fever, etc.)
Streptococci group B: neonatal diseases, normal biota of lower Gi and lower
genitourinary tracts
Streptococci group viridans: normal biota of mouth, throat, Gi and genitourinary tracts.
Cause cavities, and as an opportunistic may cause bacteremia, meniningitis, and
endocarditis.
Streptococci pneumoniae: pneumonia, sinusitis, otitis (ear), bacteremia, meniningitis,
and endocarditis.
Enterococcus: normal biota of GI, may cause nosocomial infections and endocarditis.
Bacillus anthracis causes gastrointestinal, cutaneous, or lung disease
Clostridium species cause: food poisoning, gas gangrene, explosive diarrhea,
pseudomembranous colitis, botulism, and tetanus.
Listeria monocytogenes: severe opportunistic infections in pregnant women, newborns,
elderly, and immunocompromised.
Corynebacterium diphtheriae -diptheria.
Propionibacterium acnes -acne, nosocomial infections fr/ medical devices.
Nocardia and Actinomyces - opportunistic infections.
Staphylococcus epidermidis –causes infectiond in puncture wounds
S. aureus -toxic shock syndrome, bacteremia, folliculitis, boils, carbuncles, impetigo,
scalded skin syndrome, and enterotoxicosis (food poisoning).
Multidrug resistant Staphylococcus aureus (MRSA) is an emerging and nosocomial
threat.
Mycobacterium tuberculosis causes TB
Mycobacterium leprae causes leprosy
Mycobacterium avium-intracellulare causes opportunistic infections in AIDS patients
Lesson 14: Pathogenic Gram- Bacteria: after completing this lesson
students should be able to:
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Understand the concept of Endotoxins
From Gram negative (-) cell walls
symptoms: fever, vasodilation, shock, and disseminated intravascular coagulation (disseminated
blood clots)
Understand the concept and terms concerning the Enterics (family Enterobacteriaceae):
Large family, ~250 species, many are opportunistic, some are pure pathogens, are everywhere,
cause a large percentage of nosocomial infections, are coccobacilli or bacilli
we use their antigens to distinguish between strains and species, including:
o a core polysaccharide,called the common antigen
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o the "O polysaccharide" that varies by species
o lipid A (which can cause serious disease)
o some species also have K and H antigens
o i.e, E. coli O157:H7 has antigens O157 & H7 & is potentially deadly
Enterics are split into 3 groups:
o coliforms
o noncoliforms
o true pathogens
Coliforms
o Coliforms are opportunistic rods
o found everywhere, especially in the gut
o Most follow the fecal-oral route of transmission
o E. coli is the most important coliform
o E. coli causes a number of diseases
 bacteremia
 urinary tract infections
 neonatal meningitis
 gastroenteritis.
 Gastroenteritis is the most common disease, prevalent in children in third world
countries and is often associated w/ a toxin.
 Gastroenteritis symptoms: watery diarrhea, cramps, nausea, and vomiting.
 Causes most of the urinary tract infections in the U.S.
 Nearly 1/3 of women in their lifetime
 it can spread up to the bladder once
 if spreads to the kidneys, it is a serious disease involving fever, pain, profuse
perspiration, and vomiting.
 the antigens O157, O111, H8, and H7 are virulent
o Klebsiella pneumoniae causes pneumonia, bacteremia, meningitis, wound and urinary
tract infections.
o Serratia, Enterobacter, Hafnia, and Citrobacter are all opportunistic pathogens
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NonColiforms:
o The noncoliforms are opportunistic pathogens, mostly involving catheters
o Proteus mirabilis is the most important noncoliform
 it has the unusual property of swarming
 found in half of all long term catheter patients
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True Enteric Pathogens
o include three genera: Salmonella, Shigella, and Yersinia
o Except for Yersinia, most follow the fecal oral route
o
Salmonella
 causes salmonellosis (nonbloody diarrhea, fever, headache, muscle pain, nausea,
vomiting, abdominal cramps)
 causes typhoid fever (gastroenteritis, increasing fever, headache, muscle pains,
malaise, appetite loss for a week or more).
 is more sever and longer lasting than salmonellosis
 Some patients are asymptomatic carriers; Typhoid Mary
o
Shigella
 causes a severe dysentery called shigellosis:
 abdominal cramps, fever, diarrhea, and bloody stools.
 colonizes the small intestine
 uses host actin fibers to propel itself into neighboring cells to avoid the immune
system
 is easily killed by phagocytes
 the mortality can be as high as 20%
o
Yersinia
 Yersinia enterocolitica and pseudotuberculosis follow the fecal to oral route of
transmission
 Yersinia pestis is transmitted either by flea bites or by respiration of aerosols
o
Yersinia pestis has two forms of the disease:
 bubonic plague
 pneumonic plague
o
bubonic plague
 spread by starving fleas, infected patients get buboes
 if it gets in the blood, it becomes disseminated and may grow widely
 if it grows subcutaneously, it kills tissue inviting secondary infection by
Clostridium causing gangrene.
 the dark color of the dead skin gives it its second name, the "Black Death"
pneumonic plague
 in the lungs, either from dissemination of the blood or by respiratory infection it
is called pneumonic plague
 develops rapidly, starts with a fever, pulmonary distress follows w/i a day.
 It is fatal if not treated rapidly
 Pneumonic plague can spread from person to person, but is unlikely because it
grows deep in the lungs
 Cats tend to spread it because it grows high in their respiratory system
o
Understand the concept and terms concerning the Family Bartonella
 this family only causes serious disease in man
 The most serious disease, bartonellosis
 spread by flies in S. America.
 fever, severe anemia, headache, skin infections and is often fatal.
 trench fever (also called 5-day fever)
 spread by human lice
 was common in the trenches of WWI
 Cultural connection: trench fever helped inspire JRR Tolkien!
o
Bartonella henselae is much more common in the USA
 Children and immune suppressed individuals are at greater risk, ~22,000 children
in the USA/yr become infected
 It has never been successfully cultured in the lab
 prolonged fever, malaise, swelling at the site of infection and local lymph nodes
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If untreated, disease often lasts for several months, it occasionally worsens into a
serious disease. Is treated with antibiotics, but the diseases often relapses.
The cause is the bite or scratch cats. Its name: cat scratch fever
Understand the concept and terms concerning the Pseudomonas Family:
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Pseudomonas are ubiquitous Gram- bacilli that are not particular about their growth environment
found in most moist environments including mop water, flower vases, and dilute detergents
Pseudomonas aeruginosa is the most important
Pseudomonas aeruginosa has many virulence factors:
o fimbriae and adhesins for attaching to eukaryotic cells
o a capsule for attaching and blocking phagocytosis
o the endotoxin Lipid A
o exotoxins A and S
 inhibit protein synthesis in eukaryotic cells
o the enzyme elastase
 degrades elastic fibers, complement proteins, IgA and IgG
o the blue-green pigment pyocyanin
 forms oxygen radicles that damage host tissue
 Pseudomonas aeruginosa rarely makes healthy people sick
o it needs to breach the skin or mucous membranes
o it can cause opportunistic infections in compromised patients nearly anywhere
 respiratory, urinary tract, and ear infections
o It is very common in burn patients (2/3),
o it thrives in the warm moist environment of a burn
o skin infections often have a blue-green pus
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Understand the concepts of Pseudomonas, Cystic Fibrosis and Biofilms:
cystic fibrosis is an inherited disorder
P. aeruginosa infections in the lungs of cystic fibrosis patients are common
can be life threatening
cystic fibrosis patients have lots of mucus in their lungs, providing a suitable environment for the
bacteria to grow. As the bacteria grow, it stimulates the lungs to produce more mucous. Is a
positive feedback loop that exacerbates the patients condition & if not corrected leads to death.
The bacteria form a biofilm
Biofilms are less susceptible to antibiotics and other antibacterial agents
Biofilms are microcolonies of bacteria surrounded by a gooey extracellular matrix
Understand quorum sensing and gene expression in biofilms
Biofilms have a number of properties that aid bacterial survival:
 Channels through the biofilm
 Oxygen and nutrient concentrations that vary within the biofilm
 Cells at differing metabolic states
 Cells buried within the biofilm may survive concentrations of antibiotics and disinfectants that
kill free-living bacteria
 The surviving cells can reestablish the biofilm
 Biofilms can generating novel phenotypes, such as resistance to hydrogen peroxide
 Can be more resistant to some antimicrobial agents
Understand that Biofilms contribute to diseases caused by many organisms:
o Legionnaire's disease
o periodontal disease
o and some ear infections are just a few examples
o The Center for Disease Control estimates that biofilms account for ~two-thirds of bacterial
infections
Readings: After completing the READINGS students should be able to:
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Know the Gram Positive families of bacteria and the diseases they cause:
Neisseria gonorrhoeae causes gonorrhea, a STD, and pelvic inflammatory disease
Neisseria meningitidis causes meningitis
Proteus causes urinary tract infections
Proteus, Morganella, Providencia, and Edwardsiella cause nosocomial infections
Yersinia pestis causes bubonic and pneumonic plague
Haemophilus influenzae causes meningitis,epiglottitis, and arthritis
Haemophilus ducreyi is a STD
Brucella causes brucellosis (undulant fever)
Bordetella pertussis causes pertussis (whooping cough)
Francisella tularensis causes tularemia (rabbit fever or tick fever)
Legionella causes Legionnaires’ disease (legionellosis)
Coxiella burnetii causes Q fever
Lesson 15: Other Bacteria: after completing this lesson students should
be able to:
Understand the concepts and terms concerning the Mycoplasmas:
 The first Bergey's Manual of Sytematic Bacteriology placed prokaryotes in 4 divisions:
1. Gram positives
2. Gram negatives
3. Archeabacteria
4. Mycoplasmas
 After looking at the DNA, placed Mycoplasmas w/ the Gram positives
 Are wall-less bacteria, w/o ETC, Krebs cycle, are parasites that colonize osmotically
protected areas. Are highly pleomorphic and look like fungi ("myco" means fungus)
 Understand why Mycoplasma are grouped w/ Gram positives but stain Gram negative
 Are smallest free-living cells, 0.1-0.8 micrometers
Understand the concepts and terms concerning Mycoplasma pneumoniae
 "walking pneumonia."
 Cause cilia to stop beating
 Mucous builds up, causing an unproductive cough
 Symptoms: sore throat, headache, fever and malaise
o Early symptoms resemble the flu
o Later symptoms resemble pneumonia
 Can occur year round, atypical of other seasonal pneumonia
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Also not as severe as other pneumonia, why it is called walking pneumonia
Nasal secretions spread Mycoplasma
Understand the concepts and terms concerning Ureaplasma
 Ureaplasma similar in most respects to Mycoplasma and are parasites of other organisms
 Same family as Mycoplasma
 Ureaplasma hydrolyze urea into ammonia
Understand the concepts of these STD’s:
 Ureaplasma urealyticum is the most common
 genitourinary tract found in ~ 70% of all sexually active Americans
 Mycoplasma hominis infects ~15% of sexually active Americans
 M. genitalium is a third less common STD
 Most patients/Americans are asymptomatic
 But the STD weaken the body's defenses and put holes in the epithelial barrier
 An infection may spread up the urethra
 M. genitalium and U. urealyticum mostly cause inflammation of the urethra
 M. hominis may cause kidney inflammation, postpartum fever, and pelvic inflammatory
disease. Pelvic inflammatory disease only occurs in women.
Understand the concepts and terms concerning Rickettsia
 are small Gram- obligate intracellular parasites
 transmitted by biting or blood sucking arthropods
 Rickettsia rickettsii causes Rocky Mountain Spotted Fever
 transmitted by ticks
 Symptoms: spotted rash, malaise, fever, muscle pain, vomiting, and encephalitis
 Fatal in ~5% of treated cases
 It damages the blood vessels, resulting in low blood pressure
 Quick treatment is required
 Prevention is the best policy
Understand the concepts and terms concerning Spirochetes
 Gram- tightly coiled bacteria
 Have a flagella inside of an axial filament: endoflagella
 Have a unique corkscrew movement
 Parasitic spirochetes burrow through tissue
 Treponema pallidum pallidum of most importance
 Several strains or subspecies, hence 3 names
 The other subspecies cause disease mostly in impoverished children in the third world
Understand the concepts of Treponema pallidum pallidum
 Syphilis, a STD
 is transmitted mostly by sex, but also blood products, and from mother to fetus
 Untreated, Syphilis has 4 stages:
 Primary syphilis
o a chancre is seen 0-21 days post infection, though often not observed in women
o is extremely infectious
o disappears in 3-6 weeks
o in 1/3 of the cases, host rids itself of disease
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In 2/3, Secondary syphilis occurs
o is disseminated disease
o sore throat, mild fever, malaise, muscle pain, and a widespread skin rash
o painless and itchless
o contagious
The Latent Phase
o is clinically inactive and may remain so for 30+ yrs
o bacteria are present
o mothers may pass it to their fetus
Tertiary Syphilis –occurs in 1/3
o the immune system reacts violently, causing the symptoms
o symptoms vary widely and may include:
o dementia, blindness, paralysis, heart failure, and lesions called gummas
Understand the concepts of the other Treponema pallidum diseases:
 Other Treponema pallidum subspecies cause 3 diseases:
1. bejel
2. pinta
3. yaws
 Mostly found in impoverished children, they are NOT STD
 Spread by direct contact, except for bejel, which is also spread by fomites
 Bejel is unusual in that it is spread by fomites, largely eating utensils
o often involves oral lessions
 Pinta and yaws are spread by contact
 Both are skin diseases often with crusty sores
 Pinta gets its name because the skin may look like the Pinta horse
Readings: After completing the READINGS students should be able to:
Know the families of bacteria in Bauman Ch. 21 and the diseases they cause:
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Rickettsia rickettsii causes Rocky Moutnain Spotted Fever
Rickettsia prowazekii causes epidemic typhus
Rickettsia typhi causes endemic typhus
Orientia tsutsugamushi causes scrub typhus
Chlamydia trachomatis causes the most reported bacterial STD in USA
o most men have buboes, fever, chills, anorexia, and muscle pain
o most women are asymptomatic
o Chlamydia trachomatis can infect the genitals, eyes, or respiratory tract
o Can cause blindness in eye infections
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Treponema pallidum pallidum causes syphilis, a STD
Treponema pallidum endemicum causes bejel
Treponema pallidum pertenue causes yaws
Treponema pallidum carateum causes pinta
Borrelia burgdoferi causes Lyme disease
Borrelia causes louse-borne relapsing fever and tick- borne relapsing fever
Vibrio cholerae causes cholera
Other Vibrio species cause gastroenteritis and blood poisoning
Helicobacter pylori lives in the stomach and causes ulcers