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Beyond Midterms


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Define 'Specificity'.
-refers to the fact that an immune response is able to contain one microbial pathogen

-is rarely effective against a second microbe

*think about key is specific to lock*
Define Universality.
-refers to the fact that the immune system can react to the whole unicerse of macromolecular foreign substances.

-the immune sys can attack virtually all microbes

*Hardware store has all keys to all locks*
Define inducibility
-refers to the fact that immune responses take time to develope
What are the 3 basic characteristics of immune responses?
1) specificity
2) universality
3) inducibility
What are 'Innate Defense Mechanisms'?
-these mechanisms are present and very often effective at the time of infection.
-think of these as the foot soldiers while immune mechs are the tanks and shit

**Innate defense mechanisms are CONSTITUTIVE while immune responses are INDUCIBLE**
What are the 3 defensive systems in vertebrates?
1) The surface of the body (ie: skin)

2) Innate defences by cells and molecules in the blood

3) Immune system that comes into action if the first 2 systems fail
What are the 3 characteristics of innate defence?
1) immediate protection upon infection
2) relatively non-specific
3) constitutive (ie: no warm up period, available immediately)
What are the 4 main process of innate defence?
1)Inflammation: histamine from mast cells cause this

2)Phagocytosis: eats foreign cells. Important ones in blood are neutophils and monocytes (AKA macrophages)

3)Processes initiated by complement: consists of a series of interacting proteins. Cascading effect like dominoes
-Complement components are involved as inflammatory mediators
-C3b binds to surface of bacteria making it 'marked'
-cells attack the C3b marked bacteria and kill it

4)Interferon production: important in defence against viral infections by its action of interfering with viral replication.
-3 kinds: alpha, beta, gamma
What is meant when we say that immune system expresses MEMORY?
-increases the temp of immune response b/c it knows what it has to do

*memory is SPECIFIC*
Define Attenuating pathogens.
-makes pathogens less virulent, important for vaccines
What's the difference between vaccination and immunization?
-vaccination involves inoculating a person

-immunization involves making someone immune to something
How do vaccinations work?
-inoculate person with attenuated bacteria
-attenuated bacteria causes disease-like symptoms but not to full degree
-immune system makes antibodies against these symptoms, so...
-if real disease comes around, body is ready
What is serum?
-the cell free, yellowish liquid medium, cetrifuged from blood from an immune animal that contains antibodies

-serum can be used to immunize other animals
1)protective molecules that bind specifically to antigens
-job of anitbodies is to bind to antigen and call upon various mechanisms to attack the antigen to which they are bound

2)the 'bad-boys'
What is agglutination?
-the presence of precipitation due to interactions between antibodies and antigens

-the interactions are highly specific
What are the 3 effector mechanisms activated by antibody molecules?
1)Activation of Complement: anitbodies can 'tagteam' antigens

2)Enhancement of Phagocytosis: can actually make macrophages more efficient. Antibodies that do this are called OPSONNINS

3)Triggers Accute Inflammation: some antibodies (cytophilic anitbodies) have mast cells attached to them. So when these antibodies go to work, they bring mast cells with them that release histamine on site, causing inflammation and allergies
What's the difference between passive and active immunization?
-passive immunization doesn't cause any symptoms (ie: transferring serum)

-active immunization causes minor symptoms (ie: flu shots)
What is humoral immunity?
-has soluble antibodies present in the immune serum

-effects can be transferred to unimmunised animals by the transfer of serum from immune animals
What is cell mediated immunity?
-the immunization of animals by transfer of specific cells
What is the difference between humoral and cell mediated immunity?
*Both are arms of the immune system and used to fight foreign invaders*

Humoral immunity: is transfered via serum(responsible for allergic state)
-directed at bacterial infections and extracellular viruses (in fluids), but can also resopnd to individual proteins introduced into the organism

Cell mediated: immunity is transferred via cells (responsible for hypersensitivity)
-destroys host cells infected by viruses and also destroys some parasites in foreing tissues
What is 'immediate/delayed type hypersensitivity'?
-immediate causes inflammation within minutes of antigen injection

-delayed takes b/w 24 and 72hrs to kick in
Why doesn't the immune system attack the bodies 'normal' organisms?
-immune system is SELF-NONSELF DISCRIMINATING (it's smart enough to know what to attack and what not to)
What are autoimmune diseases?
-disease which turns off the self-nonself discrimination so that the immune ends up eating the bodies 'normal' macrophages and shit
What are the 4 major classes of antibodies?
What are allergens?
-antigens that cause an allergic response
-if person has IgE antibodies, and are exposed to alergens, than they will have symptoms of inflammation at the site of allergan/antibody interaction
What is autoimmunity?
-immunity to self antigens
-sometimes induced by immunising foreign antigens that cross react with self antigens (ie: immunizing rabbits with turkey thyroglobulin causes an antibody rabbit thyroglobulin)
-this can be explained by both antigen bridge model and by the MHC restricted model of B-T cell collaboration(pg.41)
Why isn't organ transplantation 100% successful?
-the transplanted organ may be recognized as a foreign invader and the immune system would REJECT it

-steps may be taken so that the immune sys doesn't see it as foreign, but these aren't easy
Why isn't the immune sys effective against cancer cells?
-cancer cells camoflage themselves as 'normal' cells
-therefore immune doesn't recognize them and therefore they don't get attacked
What are antibodies composed of?
-2 identical light chains
-2 identical heavy chains
-shaped like a 'Y'
-pairs of heavy & light chains make up the arm of the 'Y'
-VARIABLE REGION is near the tips of the 'Y' arms(by antigen binding sites)
-CONSTANT REGION is near the base of the 'Y' arms
-has 2 antigen binding sites
How are antibodies classified?
-classified based on the nature of the constant domains of the heavy chain of the anyibody
What is a lattice formation?
-the chained formation due to the fact that:

1)all antibodies can bind to more than one molecule of antigen and...

2)most antigen molecules can bind to more than one antibody

*precipitin reaction is due to lattice formation*
What is responsible for making all of the different types of antibodies?
-since antibodies are proteins and since DNA is responsible for making proteins, the answer is DNA
What is the Clonal Selection Theory?
-a theory that deals with the nature of the processes that lead to the generation of so many different antibody molecules

*has 3 basic elements*
What are the 3 basic elements of the clonal selection theory?
1)Selection: There are shitloads of antibodies sitting around, some inactive because they haven't found their 'mate' yet. But once the antigen shows up, the antibody is selected and it gets to work

2)The Cells Able To Respond To Antigen Are Clonal: -cells have the antibody on their surface
-if the antibody takes the bait, the cell now has it's info and when the cell divides, it can code for the antibody.
-Parent cell called 'precursor cell', daughter cell called 'clone'

3)Self-Nonself Discriminatory:
-they won't attack themselves
What are Major Histocompatibility Complex (MHC) Molecules?
-they are another class of molecules that performs a cental role inrecognition of antigens

*there are 2 kinds*
What are the 2 kinds of MHC molecules?
1) Class I:
-found on the surface of all cells of the body
-Purpose: is to represent the intracellular proteins within the cell so that the immune system recognizes the cell as 'self' and doesn't attack it, or can ID the cell as defective so the immune system attacks it.
-Done so by: attaching protein segments from cell into the groove and then hanging out on the cell membrane, (like waving a flag). If the proteins are 'normal' no prob, vice versa

2) Class II:
-found mainly on phagocytic cell(hunters)
-Purpose: similar to Class I, but instead shows to the immune system what it ate
What are B cells?
-developed in the 'B'one marrow
-makes antibodies; therefor is key factor in humoral immune responses
-precursor cells for antibody production which are generated in the bone marrow
-binds the antigen itself

*a major class of cell that carries out and regulates immune responses*
What are T cells?
-are generated in the 'T'hymus
-key factors in cellular immune responses
-they mark abnormal cells
-they don't bind the antigen themselves, but bind to peptides dervied from the antigen that are themselves bound to MHC molecules

*a major class of cell that carries out and regulates immune responses*
What are the 4 elements of the immune system?
1)Antibodies: eg. lattice formation

2)Precursor Cells and Clonal Selection Theory: eg. 3 elements of clonal theory

3)Major Histocompatibility Complex(MHC) Molecules: puts 'markers' on the cell

4)Antigen-Specific B and T Cells: cells that carry out and regulates immune responses
If the immune system is exposed to an antigen during development, it 'learns' to regard this antigen as 'self' in the sense that it will not mount an immune reponse against the antigen even when the individual is continually exposed to the antig

but read pg.21-31 in handout and pg.175 for a better understanding... Bretscher is an idiot
1)Precursor Cells
2)Clone Cells
1)Cells that have the ability to make ONE antibody, specifically for an antigen
-does so by presenting antibody on surface to trap an antigen
-once caught and info is retrieved, precursor cells start mass producing so that each daughter cell can make antibodies

2)Daughter cells of precursor cell dividing. Each clone cell can make specific antibodies
What is immunogenic?
-a substance that can induce antibody production is said to be immunogenic
What are haptens?
-haptens are small molecules that bind to large immunogenic molecules which in turn cause a antigenic response

*if the molecule is too small(ie: the hapten), it would be unproductive for the immune system to respond to it (pg175), but when bound, antibodies will be produced and they will attack the hapten when freed from the larger molecule*
What is presented as evidence against the direct antigen binding model?
-macromolecular haptens exist
-antibodies require 2 cell types to obtain an antibody response
1)Bone Marrow cells (B-cell)
2)Thymus cells (T-cell)

-the significance of cellular cooperation:
"B cell can be induced by antigen only if a second cell, the helper T cell, also binds to the antigen"
What's the difference between B cells and T cells?
B cells:
-produces immuglobins that bind to bacteria, viruses, or large molecules identified as foreign and target them for destruction
-has class II MHC antigens on their surface

T cells:
-recognize infected cells or parasites
-are antigen specific
-there are T cells specific for foreign material, but not to self
-derives helper T cells [T(h)]

T(h) cells:
-produce soluble signaling proteins called cytokines
-B cell needs T(h) cell, both bound to the antigen, in order to produce antibody against foreign antigens
What is the antigen bridge model?
-the hypothesis for the nature of the interaction between B and T(h) cells, required in order to induce antibody formation
What is the "MCH-restricted B cell/
T(h) helper cell interaction model?
*more in depth and complete than the antigen bridge model*
-states that antigens must be endocytosed by the B cell
-once inside, antigen is broken down to peptide fragments
-B cell has class II MHC on surface and displays the peptide fragment of antigen
-such complexes of peptide and MCH molecules could be recognised by specific T(h) cells
-then these 2 go about making antibodies
What are cytokines?
-they either pos or neg regulate the growth and differentiation of other cells, including other T cells, to which they are delivered
-can cause 'macrophage activation' (prevents viral multiplication, pisses macrophages off)
What is antigen specific inactivation?
-when an antigen interacts with a B cell in the absence of a T cell, the B cell dies and DOESN'T make antibodies in the process
What is an epitope?
-the area on an antigen molecule complementary to an antibody molecule
-ie, the binding point
What is crossreactivity?
-occurs when separate but related 'organisms' (ie: mouse serum albumin and rat serum albumin) produce a precipitin reaction
-this is because those related
'organisms' have epitopes in common
Is the class of immunity induced dependant on the host?
What is humoral immune deviation?
-when the humoral immune system kicks in first and inhibits the cell mediated system from kicking in
-the response appears to be locked into a humoral mode
What is cell-mediated immune deviation?
-when the cell mediated immune system kicks in first and inhibits the humoral system from kicking in
-the response appears to be locked into a cell mediated mode
Whats the purpose of clones of T cells?
-lymphocytes with a given function is very rare, therefore making it hard to analyze
-stimulating single precursor cells that have a particular growth hormone for T cells, called IL2, causes mass reproduction
-such clones of T cells are very useful as representatives of individual cells
What cytokines do T(h2)make?
-IL4: increases IgG and IfE responses

-IL10: favors the induction of humoral responses
What cytokines do T(h1) make?
-IL2: growth factor

-IFNgamma: causes macrophage activation (pisses them off so they work more visciously)

Cells without B7 on their surface cannot induce T cells efficiently.
The induction of CD4+ T-helper cells requires... interaction of the phagocytic cell bearing the peptide and the precursor cell of the activated CD4+ T cell
-the association of a peptide fragment with MHC molecules before a T cell can recognize a peptide
What is commensalism?
-microbe benefits
-host unaffected
What is parasitism?
-microbe benefits
-host is harmed
What is mutualism?
-both benefit
Define pathogen.
-a microbe which, through its' interactoin with a host, causes harm or damage to the host
1)when a microbe becomes established and begins to grow on an “external” host surface

2)when a microbe penetrates a body surface, enters and multiplies within the body tissue (and may or may not trigger the host’s immune response)

3)any condition in which there is damage to, or a noticeable impairment, of body function
What are some general functions of normal flora?
1)production of essential nutrients (intestinal flora)

2)defense against infection (lowers pH on skin)

3)As a source of potentially pathogenic bacteria (when good bacteria go bad)

4)As a reservoir of genetic information
How would you manipulate or alter the normal flora?
-long term antibiotic use disrupts intestinal flora

-bone marrow transplant patients
What are probiotics? How do they work?
-living microorganisms administered to a human host in an attempt to improve health
- Competitive exclusion → growth on host tissues prevents pathogenic organisms from attaching
- Use up the nutrients required by other bacteria
- Stimulate intestinal & urogenital cells to secrete protective mucus
- Produce compounds which are toxic to other microbes
- Stimulate immune system so it reacts better to foreign agents
What are the possible outcomes of host/microbe interactions?
What is the reservoir for microbes?
-The natural habitat of a microbe (supports growth, survival) and the site which acts as the source of infection
What are the mechanisms of transmission of disease?
1)Direct Contact
-physical person to person contact
-2 hosts in very close proximity

2)Indirect Contact
-via 'vehicles' (ie: foodborne, waterborne, airborne, etc.)
-via 'fomites' (inanimate objects ie: doorknobs)
-via 'vectors' (living animals or insects)
What are some ways of contolling the spread of disease?
1)Control the reservoir (ie. control at the source)

2)Control transmission

3)Control the susceptible populatoin

4)Establish a 'Disease Control Network'
3)virulence factor
1)the ability of a microbe to cause disease

2)quantitative measure of the degree of pathogenicity, as indicated by mortality rate, disease severity, etc.

3)a microbial component that is required for, or contributes to , pathogenicity
What are the 5 steps needed to be a successful bacterial pathogen?
1. Transmission to, and entry into, a suitable host
2. Avoid being removed after entry (Attachment)
3. Migrate to a site able to support growth (Invasion)(Endocytose and excocytose through cell)
4. Multiply at the preferred site & evade host’s defenses(obtain nutrients from host, evade host defenses)
5. Exit the host and transfer to a new host so cycle repeats
Key Points:
- This is a staged (progressive)process and each stage must be completed before the next stage begins
- Specific bacterial virulence factors are required at each stage
- In most cases, symptomatic disease is not evident in the host until the later stages (ie. steps 3 - 5)
How do bacterial pathogens cause damage to the host?
1. As a result of the immune response to the pathogen
- inflammation
- excessive activation of complement
- by-products of phagocytic cell attack on bacteria

2. As a direct result of the pathogen’s actions
- metabolic waste products (acids, gas) damage host tissue
- replication inside host cells
(host cell lysis)
- action of tissue degrading enzymes (eg. Collagenase)
- “ toxins” produced and released by the bacteria
What are the 2 types of bacterial toxins?
1) Endotoxins (Gram neg. bacteria only)
• Lipid A portion of lipopolysaccharide
• Non-protein (not destroyed by heat)
• Located in outer membrane of bacteria
(released when bacteria die & lyse)
• LPS from all gram neg species has
exactly the same biological effect:
⇒causes immune system to over-produce cytokines

2)Exotoxins (both gram neg. and gram pos. bacteria)
• Extracellular proteins secreted by bacteria
• Most (not all) are destroyed by heat
• Soluble → can be carried by blood and act at sites away from site of original infection
• Usually toxic in very low doses
(eg. lethal adult dose of tetanus toxin is ≈ 130 micrograms)
• Many different types & modes of action (but all act on euc. cells)
- classified as “neurotoxins”,
“cytotoxins”, “enterotoxins”
depending on mode of action and type of target cell
What are the general mechanisms of exotoxin action?
⬢ Inhibit protein synthesis (cytotoxins)
⬢ Inhibit function of nerve synapses (neurotoxins)
⬢ Cause electrolyte and fluid loss from intestinal cells (enterotoxins)
What are the 2 examples used for respiratory transmitted diseases?
1)Myobacterium tuberculosis
-acid fast bacillus
-slow growing
-humans are only reservoir
-2 forms: Primary and Secondary TB
*(discussed later)

2)Streptococcus pyogenes
-gram +'ve, coccus
-humans are only reservoir
-transmission via inhalation of respiratory droplets

**Symptoms discussed later**
What are the symptoms of Mycobacterium tunberculosis?
-weight loss
-night sweats
-bloody cough
What are the symptoms of Streptococcus pyogenes?
-sore throat
-visible on tonsils (grayish-white color)
How does one become infected with streptococcus pyogenes?
1)Airborne transmission
-from a host with active disease
-from a host who has recovered without treatment

2)Strep enters throat & attaches to epithelial cells
→ Protein F
- surface protein
- binds to fibronectin on epithelial cells

3)Strep colonizes and grows in throat:
→ Evades phagocytosis by:
- capsule
- surface “Protein M” (degrades
complement C3b)
- surface “Protein G” (blocks IgG - phago. interaction)
→ Secretes hemolysin & other degradative enzymes
- releases nutrients from red
cells, kills phagocytes
- degrade DNA, dissolve blood clots

4)Symptoms appear:
→ red, sore throat with pus (from action of secreted enzymes)
→ inflammatory response (redness, swelling of lymph nodes)
- activation of complement by
Strep peptidoglycan
- by-products of phagocytic attack
on Strep
What are some complications after a Streptococcus pyogenes infection?
1) Scarlet Fever
• Strep throat symptoms + skin rash
• Caused by certain strains of Strep
which produce “Erythrogenic Toxin”
- exotoxin encoded by lysogenic phage
- toxin carried via blood through
- damages small blood vessels
→ pink rash, “strawberry tongue”
→ inflammation
• Less severe today than in 1800’s
(less potent toxin??)

2) Glomerulonephritis
• Fever, high blood pressure, blood in urine occurring during recovery stage of untreated Strep throat (but only caused by some strains of Strep - why??)
• Accumulation of immune complexes (anti-Strep antibodies + Strep antigens) in glomeruli (blood vessels) of kidneys

3) Rheumatic Fever
• Inflammation of joints, heart valves occurring 3 - 4 weeks after
self-limited Strep throat infection (only by some Strep strains)
→ scarring of heart valves, possible
later heart failure
• Autoimmune disease (?) - Antibodies formed against Strep cross-react with antigens found in heart, joint tissues
• Rare in North America, but leading cause of heart disease in developing world (espec. in kids)

4)Necrotizing fasciitis
• Caused by strains with greater virulence than pharyngitis strains
→ NF strains secrete additional
enzymes which degrade connective
→ Tissue separates, sloughs off and
allows Strep to invade into deeper
• Require prior entry of Strep into skin via cuts before invasion occurs
(ie. not respiratory spread)
What is Primary tuberculosis?
-a first time tuberculosis infection
→ Inhalation of respiratory aerosols from an infected host
→ M.tb. settle in lungs and are phagocytosed by macrophage
→ M.tb. survive and multiply inside macrophage (how??)
→ ≈ 3 weeks later → T-cells proliferate and activate macrophage
→ Activated macrophage kill M.tb. or form walled off lesions which
enclose M.tb. and prevent further spread ( = “Tubercles”)

• In 90% of primary cases
→ tubercles calcify (although live
M.tb. can remain)
→ may be visible on chest X-rays
→ person often remains healthy and
• In 10% of primary cases (espec. kids, immunocompromised, etc)
→ cellular immunity fails (no /
delayed macrophage activation)
→ M.tb. spreads to many other organs
(= “Disseminated TB”)
→ by-products of macrophage attack
causes tissue damage
- M.tb.- filled necrotic cavities
in lungs, other organs
- bloody sputum containing M.tb.
- coughing promotes further
transmission of M.tb.
→ up to 50% fatality if untreated
What is secondary tuberculosis?
• Reactivation of dormant M.tb. from tubercles
→ tubercles “liquify” and M.tb.
escape into lungs
→ inflammation causes cough reflex
→ macrophage attracted ->progressive
tissue destruction due to
hypersensitivity reaction
→ fever, weight loss, night sweats
(due to release of cytokines from
• May occur years after primary infection
eg. 2 - 20% lifetime risk of reactivation in a healthy person

• Immune system suppression increases risk of reactivation
eg. 5 - 10% per year risk of reactivation in HIV+ person
How is TB diagosed?
1) Acid-fast stain of sputum
(difficult if low #’s of bacteria)

2) Lab culture of M.tb. from sputum
(slow → may take weeks)

3) Tuberculin skin test (Mantoux test)
→ inject non-infectious protein
extract of M.tb. under skin
→ look of reddening at injection
site due to immune reaction
(indicates prior exposure only -
not necessarily active disease)
What is the vaccine for TB?
- “BCG” vaccine (live Mycobacterium bovis)

- Limited effectiveness; usually given only in high prevalence areas

- Results in a positive skin test (invalidates later use of skin test)
How is TB treated?
Pre - 1950’s:
Long-term care in sanitoriums (provide rest, good nutrition, etc. → boost immune system)

Various anti-mycobacterial agents used in combination:
-Isoniazid - blocks mycolic acid
-Rifampin - blocks transcription

-9 to 12 month continuous treatment necessary (to penetrate tubercles and kill slow growing / dormant M.tb.)

Problems - lack of patient compliance
(introduction of “Directly Observed Therapy”)
- emergence of multi-antibiotic resistance strains of M.tb.
Why is TB a great public health concern?
⬢ Leading cause of death due to a single microbial species, yet
the disease is preventable and treatable

⬢ Global increase in incidence of TB and multi-resistant M.tb.

⬢ Highly infectious nature of M.tb.
- est. minimum infectious dose is 10
- more contagious in children vs.
What is the rate of occurence of TB?
• Canada ≈ 2000 new cases per year
• World wide ≈ 8 million new cases per year (3 million deaths)
• Est. that 1.5 - 2 billion people are infected with M.tb.
• Occurrence varies greatly with geographic location
eg. - Canada ≈ 6.5 new cases per
100,000 people
- Southeast Asia ≈ 250 new cases
per 100,000
What causes gastrointestinal infections?
-enteric bacteria
What's the difference between food poisonings and food infections?
I. Food Poisonings
→ Bacteria grow in foods and release
→ Toxin consumed with food and
causes illness
- Consumption of live bacteria not required
- Symptoms occur in 4 - 6 hours because toxin pre-exists

II. Food Infections
→ Bacteria are present in foods and
ingested with food
→ Bacteria enter gut → grow in gut
→ cause illness
- Consumption of live bacteria required
- Symptoms in 18 - 24 hours because bacterial growth required
What are the symptoms of Staphylococcus aureus (Food Poisonin)?
If Ingested:
-vomiting & diarrhea

If it enters through a lesion:
**involves additional exotoxins which enable invasion, etc**
-swelling, redness and warmth at site of the lesion
-fever with shaking chills
-lower back pain

**they are gram positive coccus in grapelike clusters**
How does one become infected with Staphylococcus aureaus? What are the symptoms? How can you prevent it?
-direct contact

If contaminated food left at room temperature:
→ Staph grows & releases enterotoxin (exotoxin) into food
• Enterotoxin has no taste or odor
• Boiling for 30 min kills Staph, but does not destroy toxin
⇒ enterotoxin enters gut when food
→ acts on gut epithelial cells
(prevents adsorption of
water, leading to diarrhea)
→ stimulates nerve receptors in
gut (nausea, vomiting)
• Rapid symptoms (2 - 6 hours) because toxin is pre-formed (actual presence of Staph in gut is not necessary)
• Recovery without treatment after toxin has cleared gut (18 hrs)
• Prevention:
- proper refrigeration limits
Staph growth in food
- known carriers should take
are in food handling
What are the symptoms of Escheria coli O157:H7 (food infection)
-poor appetite
-spotty rash
-fever and diarrhea, lasts about a week
-bloody diarrhea
What is Escherichia coli O157:H7?
-form of food infection
• E. coli O157:H7 = “enterohemorragic” strain of E. coli
*“O157” - refers to type of LPS “O”
side chain (eg. 157th type)
*“H7” - type of flagella antigen

• Reservoir is intestinal tract of cattle

• Infection sources:
- beef contaminated with feces during slaughter and processing
- drinking water contaminated with cattle feces
- other environmental sources (fruit, veg. ?)
What does E.coli do to you?
→ attach to gut wall with pili → multiply, but do not invade

→ secrete an exotoxin (“Verotoxin”)
- kills gut epithelial cells (blocks
protein synthesis)
-bloody diarrhea from breakdown of
but blood (tissue barrier)
What is Hemolytic Uremic Syndrome (HUS)?
-a complication of E.coli if the verotoxin enters the blood

-If verotoxin enters blood
→ lysis of red blood cells
→ kidney damage

-Possibly fatal (especially in kids) due to kidney failure
What's the difference between
E.coli O157 and E.coli K12?
-E. coli O157 and E. coli K12 are different strains of the same species

-O157 is a pathogen and K12 is a non-pathogenic lab strain

What makes one strain a pathogen and the other not??
-Chromosome sequencing allows comparison of O157 to K12:
- both have ≈ 4.1 million bases of
- O157 has 1387 genes not found in
- K12 has 528 genes not found in O157
- the novel O157 genes encode known
virulence factors(pili, toxins)
but also unknown functions

Conclude: continuous, on-going genetic evolution
- genetic exchange (into E. coli
from other species?) + loss &
replacement of some genes
- speculate that O157 / K12 split
occurred < 50 years ago
What is Vibrio cholerae?
Waterborne transmission, causes cholera

• Transmission via fecal - oral route:
Ingestion by humans->Bacter in
feces->Fecal pollution of water
• Gram negative curved rod
• Enters small intestine via
contaminated water (or foods
washed in contam. water)
• Large # of bacteria (≈ 108) needed
to cause disease (most die in acidic
• Attach to intestinal wall via pili +
adhesion proteins (no invasion)
→ produce cholera exotoxin during
What are the symptoms of Vibrio Cholera?
-Severe diarrhea (up to 20 L. fluid / day)
(“rice water stools” = mucus + H2O +
live Vibrio)
-Shock, vomiting, dehydration
(→ increased blood viscosity)

-Death unless fluids replaced (“oral
rehydration therapy”)

-Vibrio in feces = source of new
infections if sewage un-treated
What is Helicobacter pylori?
-causes stomach ulsers

•Present in 90% of people with
duodenal & gastric ulcers
•Est. that 25% of North Americans are
infected with H. pylori
→ most are asymptomatic
→ approx. 10% develop ulcers or
gastric inflammation
→ possible increased risk for
developing stomach cancer
•Gram negative, curved or spiral rod
•Identified in 1983 from gastric
•Transmission route & reservoir are??
→ possible animal reservoir (cats?)
→ fecal - oral spread ?
→ found in dental plaque ?
What are the 6 steps of pathogenesis for H.pylori?
1) H. pylori colonizes mucus layer lining stomach

2) Produces urease enzyme:
Urea->Ammonia + CO2, ammonia
neutralizes stomach acidity;
allows H. pylori to survive

3) H. pylori penetrates mucus and attaches to stomach epithelial cells

4) Causes inflammation (influx of phagocytes + other immune cells)

5) Localized destruction of epithelial & mucus-producing cells
→ from by-products of inflammatory
→ from “cytotoxin” (exotoxin)
produced by H. pylori

6) Exposure of stomach lining to acids, leads to ulcers
How do you treat ulcers?
(assumed that stomach acidity was only cause)
- bland diet, drugs (eg. Tagamet → reduces stomach acidity)
-Ulcers return if therapy stopped (95% relapse within 2 years)

(assumes that H. pylori is major cause)
- antibiotics + Pepto Bismol (inhibits growth of gram neg.)
-Eliminates bacteria; therefore little / no recurrence of ulcers

Result: More effective treatment at much lower costs
What is the top ten list of STD's?
1. Papilomavirus (genital warts)
2. Chlamydia (urethritis)
3. Candida (yeast infection)
4. Trichomonas (urethritis)
5. Herpes Simplex Virus (genital
6. Neisseria gonorrhoeae
8. Treponema pallidum (syphilis)
9. Hepatitis B virus
10. Gardnerella (vaginitis)
What are the symptoms of Neisseria gonorrhoeae?
-mild vaginal inflammation, burning sensation upon urination
-often unrecognized (and therefore untreated)
-potential for “carriers” (30% of cases)

-urethral canal inflammation, painful urination, discharge of pus
-more easily recognized & treated (10% of cases are carriers)

• 1% of primary N. gon. infections result in entry of bacteria into blood
→ spread to other organs (disseminated gonorrhea)
⇒ joint inflammation (arthritis)
⇒ skin rash + pustular lesions
⇒ possible heart, liver infections
What is Neissaria gonorrhoeae?
-an STD
-Gram negative coccus in pairs
-Survives < 2 hrs on dry, inanimate
-Reservoir and only host = humans
-Very common: 700,000 cases / yr. USA;
4000 cases / yr. Canada
(65% of cases in 15 - 25 age group)
What does pathogenesis of N. gon include?
• Point of entry is vagina (female)
or urethral canal (male)
• < 1000 bacteria can start infection
(30 - 50% chance of disease after
single sexual contact)

1)N. gon attach to epithelial cells
of genital tract
- pili & outer membrane proteins

2)Invades epithelial cells and enters
into sub-epithelial tissues
→ influx of phagocytes
→ release of endotoxin (LPS)
→ inflammatory response

3)Tissue damage (from phagocytic attack) allows release of free bacteria
into genital secretions ⇒ re-transmission
What are important viruluence factors in N. Gonorrhoeae? 4 of them
1)Pili, membrane proteins (attachment)
eg. mutants lacking pili are completely avirulent

2)IgA protease (enzyme which degrades secretory IgA of host)

3)“Serum-resistance” factors (proteins that interfere with action of
complement → allow survival in human blood)

4)Iron scavenging membrane proteins
->enable N. gon. to use iron
sources found in human blood

Note: No Exotoxins identified
What are some complications from N. gonorrhoeae infections?
→ Usually arise only if gonorrhea left untreated

• Urethral scarring, infertility (male)
• Bacteria ascend into uterus and fallopian tubes (female)
→ inflammation, fever, abdominal
pain (“Pelvic Inflammatory
→ scarring of fallopian tubes
• Possible transmission of N. gon. to infant during birth (vaginal births only)
→ eye infection, blindness
→ give antibiotic drops immediately
after birth
How do you diagnose and control N. gonorrhoeae?
- Gram stain of genital discharges
(look for gram neg. cocci)

- Must be confirmed by culture

- Almost all strains are resistant to
penicillin, tetracycline, erythromycin

- No immunity from prior infection
→ immunity req. antibodies to pili
→ N. gon. “switches” between
different types of pili to avoid
immune recognition

- No vaccine (yet)
What are 4 characteristics to
Host-Pathogen Interactions?
1) Note representative examples of pathogenic bacteria
→ many other bacteria follow similar
pattern of pathogenesis

2) Note the step-wise or staged nature of the infection process
ie. entry → → → exit

3) Note that blocking one step or stage will prevent later stages
→ try to develop vaccines &
therapies that block at earliest
stage possible

4) Note types / roles of virulence factors in pathogenesis
(ie. what do bacteria need in order to complete each stage?)

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