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Ability to live in a .......... is a MAJOR virulence factor
Phagocyte / They are obligate intracellular pathogens live in them, cannot be detected by antibodies
Beta cells differentiate into....
plasma and memory cells, plasma B cells produce antibodies
What does IgG stand for?
Immunoglobulin G, most common antibody,
The variable region of IgG (antibody) is.....
Antigen specific, the properties of the antibodies and what antigen they will attack are found in this region
Infection
Growth of an orgranism on or within a host
Pathogenicity
Ability of an organism to cause disease
Opportunistic PAthogen
Causes disease only in the absence of normal host resistance mechanisms
Virulence
Measure of the pathogenicity of the organism
Measuring virulence: ID50
Infectious dose that is seen 50% of the time. The amount of an agent required to infect exactly half of the tested hosts
Measuring virulence: LD50
Infectious dose that is fatal 50% of the time. The amount of agent required to kill exactly hald of the tested hosts
Exception to LD50
Highly virulent pathogens show little differene in the number of cells required to kill 100% of the population compared to just 50%
Stages of virulence in order
Exposure: to pathogen
Adherence: binding to host
Invasion: entering host
Colonization and growth: production of virulence factors
Path 1: toxicity: toxin effects
Path 2: invasiveness: further growth
all lead to -> disease
Attentuation
The decrease or loss of virulence
Toxicity
Organism causes disease by use of toxin meant to inhibit or kill host cell. Toxins can travel to cites within hosts not inhabited by pathogen.
Invasiveness
Ability of a pathogen to grow in host tissue at densities that inhibit host function. CAn cause damage w/o producing toxin
Toxicity vs Invasiveness
toxicity: phage producing toxins that cause the damage, the organism itself may not be actually causing issues but its products are
Invasiveness: Organism is actually inside of the host, living and growing. The direct growth of this organism can cause disease.
True or False: Pathogens utilize only Toxicity or invasiveness to cause pathogenicity
False, Many bacteriums use a combination of toxins, invasiveness, and other virulence factors to enhance pathogenicity
Activation of Beta cells leads to....
Clonal Expansion
Memory B cells allow rapid and strong production of antibodies after ...... exposure to antigen
Second
Primary Response to a pathogen has mostly ..... the second exposure mostly has...
IgM -> memory cells generated , IgG (due to memory cells) -> memory cells develop into plasma cells
How antibodies help: Agglutination
Sticking bacteria in one big clump, one phagocyte can clear them out
How antibodies help: Opsonization
Coating antigen with antibody = easy grip by phagocytes (lube it up)
How antibodies help: Neutralization
Blocks adhesion of bacteria and viruses to mucus = prevent binding receptors/no active binding
How antibodies help: Inflammation
Disruptuon of cell by complement, reactive protein that attracts phagocytic and immune cells
Activation of the Complement
Antibody binds to cell and punches hole in cell wall
Membrane Attack Complex (MAC)
What actually makes a hole in the activation of the compliment
Clonal Deletion
Removes self-reactive T-cells and antibodies, clearing out cells that would hurt you
Strep Throat
a case of molecular mimicry, 50% viral and 50% Streptococcus pyrogenes, if strep is due to pyrogenes -> you must NOT let the immune system clear it. The same antibodies that attack the bacterium will attack your heart valve too
What does cross reactive mean
Attacks pathogens and body
Allergies
People with allergies produce IgE
Being too clean especially as a kid is bad because it can result in more allergies, bone marrow thansplant can resolve allergies. THEY ARE A MATTER OF CROSS LINKED ANTIBODY MOLECULES
True or false: pregnant women should not clean out littler boxes
True, There are chemicals in cat pee that hurt the fetus. Toxoplasmosis -> messes up the placenta
Booster Shots increase...
IgG in the system up until the second exposure
Lady Mary Montegue (1689 - 1762)
Learned about practice of virulation to prevent smallpox.
Edward Jenner
Coined word vaccination
Epitope
Portion of a protein that elicits B-cells to make antibodies, usually 8-10 AA in length
What happens if clonal deletion does not occur?
Can result in autoimmune diseases, if non self if mistakenly deleted / it can result in a "hole"
IgE
binds to mast cells, dimerizes them and that signals mast cells to release histamine. Important in getting rid of helminths (worms and parasites)
Treatments for Allerigies
Antihistamines: block histamine receptors
Thymus processing eliminates....
98-99% of T lymphocytes
Poison Ivy
Delayed type hypersenstivity reaction
History of immunization
Smallpox, virulation came from Lady Montegue and proven by Edward Jenner. Weakened form of a pathogen can be used to raise a protective immune response w/o causeing disease. Vaccination = vacca -> cow
Specific immunity: Natural exposure: Active
Normal experience is how you develop immunity
Specific immunity: natural exposure: passive
From parents (womb, breast feeding)
Specific immunity: artificial: Active
Vaccines (antibodies injected into you)
Specific Immunity: artificial: passive
Transplants (blood, marrow)
Tetanus
Clostridium tetani, toxin causes muscles to contract. Require booster shot 10/yr to help prevent.
Cryptosporidium parvum
Protozoan, single eukaryote, THE MOST IMPORTANT WATER BORN PATHOGEN IN THE DEVELOPED WORLD, resistant to chloring treatment
What is a reservoir in relation to a pathogen?
It's the way in which you would find it in nature, could be humans, animals, water, etc.
Carriers
People who carry pathogen but do not have disease
Staph aureus is a .... repitaory infection and Streptococcus penumonie is a .... resporatory infection
Upper / Lower
Types of exposure
Direct contact, vectors, soil, H20, food
Pasteur proved that ....... give things like good wine and bread
Good organisms like yeast
PAsteurization
Heating to destroy all undesirable organisms w/o destroying the product
Loxiella burnetelli
Q fever, #1 food borne pathogen, lots of pathogens are found on row or undercooked meat
Stanley Falkow (1934-)
Father of molecular microbial pathogenesis, genes and proteins must be involved in pathogenesis
Adherence
Diseases have to stick to host tissues before they can invade them -> capsules prevent phagocytosis -> sticky and hard to break
Adherence is usually a..... and ...... fit
Lock and Key
UPEC
Ueropathogenic E. coli
UTI
Urinary tract Infection, Capsule, flagella, biofilm , anf fimbrae
......... protein binds to .................. host glycoproteins on epithelial cells of the .........
FimH / mannosylated / bladder
What can we take to prevent adherence of UTI's?
Mannose, so the FimH just binds to that instead of the bladder walls, basically just a decoy
Invasion
Pathogens produce enzymes that enhance virulence by breaking down or altering host tissue to provide access to nutrients
Protecing the Pathogen
Interfering with normal host defense mechanisms.
Iron
Bacteria have to work hard to get iron in the environment. Iron is present in very tiny amounts. Bacteria and fungi synthezise and secrete iron chelaters.
Siderophores
Iron bearer
Gram negative bacteria versus humans
Gram - want more iron whereas humans work to keep iron low
Transferin
Iron binding protein, moves iron in and out of cells, keep serum levels low
If you have a mouse infected with 100000 pathogens and one with just 100 pathogens (this is their LD50), what happens if you give them an iron injection?
Their LD50s decrease by a 100x change. So only 1000 will cause the disease in the first and only 1 will cause the disease in the second.
TonB system of E coli
A novel type of ACTIVE transport across the unenergized outer membrane. TonB is a virulence factor for UPEC. New target for antibiotics.
What happens if you block the TonB system? Why don't gram + have a tonB system?
The gram - are not effective able to interact with FepA (infectious factor) and that will eventually kill the cell. Gram + have one membrane, so they don't need TonB
Toxins
Exotoxins (action at a distance) - cytolitic, AB, superantigen
Endotoxins: part of bacterium
Exotoxins
Proteins released from the pathogen cell as it grows
3 Major types of EXOtoxins
Cytolitic, AB (2 subunit), superantigen
Cytolitic Toxins
Work by DEGRADING cytoplasmic membrane cytoplasmic membrane integrity, causing host cell lysis and death.
Cytolitic toxins that lyse red blood cells are called
Hemolysins, ex is Staphylococcal alpha-toxin
AB Toxins 2 subunits
A + B subunits, work by binding to host cell receptors via subunit B and transferring damaging agent, A, across cell membrane Ex: Clostridium botulinium
Mediucal uses for botulism toxin
Relaxes overactive muscles. Botox
tetanus Toxin medical uses
Excites nonactive muscles
Botulism
soil bacterium, easy way to contract is from not properly canned foods, spored germinate in anerobic environment
Superantigens (SAGS)
Pouring gasoline on the immune response fire, cause acute-system-wide inflammation that damages tissues and organs ex: s. aureus
John Snow (1813)
Father of epidemiology Found that cholera is spread through water. Cholera was a pandemic at the time and now.
Cholera enterotoxin is encoded on a temperate bacteriophage
Toxin co-regulated pillus is found on a "pathogenicity-island". Both toxin and pillus are virulance factors.
PAthogenicity ISland
REgions of a chromosome that harbor lots of different virulence genes. These virulence genes are surrounded by removable IS sequences that make them transposable elements.
Endotoxin
Lipopolysaccharide portion of cell envelope of the gram - bacteria elicits an imflammatory response. GENERALLY LESS TOXIC THAN EXOTOXINS
Vaccines prevent bacterial....
Capsule formation
Most tuberculosis infections are....
Latent/dormant, they hide in the system and then they come out when characteristics are right. Stays walled off in the lungs
Humans have evolved lipocalins, which are
A human made proteins that bind and deactivate the enterochelin formed by bacteria that tries to steal iron.
E.coli, to combat lipocalins, now produce....
Strains of enterochelins decorated with glucose that the body can't recognize.
Cytokine storm
attack self tissue, can be prevented with clonal deletion
Potable
safe to drink, not accessible in third world countries. Most who drink water become carriers/
A cholera outbreak in Haiti was due to...
Un workers who were carriers
Herd Immunity
The ability of the group to resist disease. When the herd has immunity, infection can only be transmitted to the susceptible.
CoEvolution of host and pathogen (Rabbit in austraila example)
Takes a lot of time. First the rabbits are highly susceptible. then they start becoming resistant. That leads to the virulence of the phage to decrease too. Myxoma is the disease in rabbit population.
What happens if there is no herd immunity?
Anyone who is susceptible will become infected
Ro is...
The number of people that one person with the disease can infect.
If Ro = 50 for X and Ro = 2 for Y, which is more infectious?
Ro = 50
Animal REservioirs
Zoonoses
Smallpox Eradiacation
No Carrier State: humans are only reservoir, an infected person always shows symptoms
Transmission is exclusively human -> human. Vaccine was extremely effective.
Enterotoxins
Variety of exotoxins active in the gut
Cytotoxic T-cells can recognize........
Host cells with pathogens inside