Micro Exam 3 Flashcards
4 Variables that dictate the most appropriate antimicrobial strategy
- Type of microbe
- Number of microbes
- Risk of infection
- Object being sterilized/disinfected
Process by which all living cells, sores, and viruses on an object are destroyed
Sterilization
The killing, or removal, of disease-producing organisms from inanimate surfaces
Disinfection
Killing or removal of most pathogens from living tissues
Antisepsis
Reduces the microbial population to safe levels and usually involves cleaning
Sanitation
Antimicrobial chemical agents that kill microbes
Cidal agents
Antimicrobial chemicals that inhibit or control microbial growth
Static agents
Can antimicrobial agents also kill nonpathogenic microbes?
Yes
In the presence of antimicrobial agents, microbes are killed:
At an exponential rate
The time it takes to kill 90% of the population
Efficacy of disinfecting and sterilizing agents are measured using this
Decimal reduction time (D-value)
Sterilization by using high pressure (15psi) and high temperature (121C)
Pressured steam sterilization
Biohazards waste is destroyed by burning
Incineration
Heat sterilization for moisture-sensitive items
Dry oven
100C, kills most organisms and viruses, but not spores or hyperthermophiles
Boiling
The heating of food at a temperature and time combination that kills pathogens
Pasteurization
4-8C, is used for food preservation because most pathogens are mesophilic
Refrigeration
Cultures mixed 1:1 with glycerol can be stored for long term at low temperatures -70C
Freezing
Cultures are quickly frozen at very low temperatures in a vacuum, the LOWEST microbial presence here
Freeze drying (lyophilization)
Is using cold physical agents static or cidal?
Static because the microbes are not killed, the growth is just stopped
Sterilization where solutions are passed through filters with tiny pores
Filtration
Food is bombarded with high energy radiation
Irradiation
Microbial sensitivity to irradiation is relative to the genome size. Larger genomes =
More sensitive, more likely for mistakes to happen
4 factors that influence the efficacy of a disinfectant
- The presence of organic matter
- The kinds of organisms present
- Corrosiveness
- Stability, odor, and surface tension
Test that measures how well a disinfectant kills microbes dried onto a surface
Use-dilution test
Objects that cannot be heat sterilized are best sterilized by this process by gamma irradiation or antimicrobial gases such as ethylene oxide
Gas sterilization
Any chemical used to treat disease
Chemotherapeutic agent
Any chemical that kills or inhibits microbes
Antimicrobials
Chemical compounds that are synthesized by one microbe to selectively kill other microbes. They are a natural antimicrobial, chemotherapeutic agent
Antibiotics
Drugs that kill bacterial cells
Bactericidal drugs
Drugs that slow or inhibit bacterial growth
Bacteriostatic drugs
Antibiotics that target one or limited groups of bacteria
Narrow spectrum
Antibiotics that target large groups of bacteria
Broad spectrum
Why don’t we use broad spectrum antibiotics for every bacterial infection?
Can lead to disruption of the host microbiota
What specific factors do health care providers need to consider when administering an antimicrobial drug?
-Tissue distribution
-Excretion
-Metabolism
Effect where one drug inhibits the function of another
Antagonistic effects
Effect where two drugs work better together than their additive effects
Synergistic effects
What is the selective toxicity of a drug? How is this measured?
The ability of a drug to be harmful against bad microbes while not harming the body. Measured via therapeutic index. You want a high TI to maximize killing bad microbes while minimizing toxicity
The concentration of drug needed to completely inhibit bacterial growth in culture
MIC (Minimum inhibitory concentration) You want a low MIC
Tests a bacterial culture for susceptibility to 12 antibiotics on one plate
Disk diffusion assay
Reduces the productivity of an enzyme by (usually) forming a weak bond to an enzyme
Metabolic Inhibitor
DNA polymerase inhibitors act on DNA polymerase, so that chromosomal DNA cannot be replicated, resulting in bacterial death.
DNA replication inhibitor
Regulation of transcription in response to environmental changes and in the virus-host relationship
RNA polymerase inhibitor
A compound that stops or slows the growth or proliferation of cells
Protein synthesis inhibitor
Antibiotics targeting this should selectively kill bacteria because it does not exist in eukaryotes
Peptidoglycan
In growing cells, this type of drug causes the cell walls to fall apart and burst the cell from internal pressure
Cell wall inhibitors
3 common targets for antivirals
- Attachment or entry
- Nucleic acid synthesis
- Maturation and release
Fungal and protozoal infections are difficult to treat because they are…
Eukaryotes like us
Many of these drugs target metabolic functions, can be used by releasing free radicals that damage the parasite
Antiprotozoal agents
Many of these drugs target the unique ergosterol membrane or DNA synthesis
Antifungal agents
3 general bacterial mechanisms to resistant antibiotics
- Prevent intracellular accumulation
- Prevent antibiotic binding to target
- Dislodge the antibiotic
Drug resistance that is due to the inherent characteristics of that organism. Mycobacterium: Waxy mycelia acid cell wall. Gram-negative: 2 Membranes
Innate (Intrinsic) Resistance
Acquired resistance in this process where resistance genes readily occurs between related and unrelated bacteria. Responsible for the generation of multi-drug resistant bacteria
Horizontal gene transfer
Acquired resistance in this process where they occur at a low rate, but quick generation time and exponential growth provides many genetic variants that can persist under selective pressure (natural selection)
Mutations
Multi-drug resistant bacteria are caused by…
Horizontal gene transfer
How does horizontal gene transfer affect antibiotic resistance of otherwise-susceptible bacteria when antibiotics are misused? Why is antibiotic misuse lead to resistance?
HGT allows for resistance to be transferred. Susceptible bacteria die but resistant ones live and multiply
The total community of microbes associated with an organism
Microbiome
7 body parts that harbor microbes
-Nose
-Skin
-Vagina
-Ear
-Small intestine
-Oropharynx
-Large intestine
3 body parts meant to be sterile
-Eye
-Urethra
-Stomach
The number of microorganisms that typically inhabit an environment
Bioburden
4 most prominent microbial ecosystems in the human body
-Skin
-Oral and nasal cavities
-Genitourinary tract
-Intestine
The place with the highest bioburden
Intestine
Why do anaerobes outnumber aerobes in all tissues?
The intestinal microbiome is fully anaerobic and has a neutral pH. Only anaerobes and facultative anaerobes can survive there
How does skin limit microbial growth? In other words, what conditions do bacteria have to endure to thrive on our skin?
Skin has multiple mechanisms to keep growth under control:
-Acidic (pH 4-6)
-High salt
-Low moisture content
-Enzymes like lysozyme (sweat)
An imbalance in microbiome composition that can lead to adverse effects
Dysbiosis
How do eyes keep a low bio burden even though they are exposed to the outside environment?
Tears contain lysozymes which eyes are constantly bathed in to wash away germs
How does saliva limit microbial growth?
Contains antimicrobial compounds like H2O2 and lysozymes
Washes the mouth, making the environment difficult to adhere to
What are the aerobic and anaerobic surfaces in the human mouth?
Anaerobic- Spaces between teeth
Aerobic- Surface of teeth
Where are the aerobic and anaerobic surfaces in the human oronasopharynx?
Anaerobic- The small pits along the tonsil surface (crypts)
Aerobic- The top of the mouth/behind the nose and in the center of the back of the throat
Mechanism in lungs where the ciliated mucous lining of the bronchioles, trachea, and bronchi sweep foreign particles up and out of the lungs
Mucociliart escalator
What does the upper respiratory tract use to keep most microorganisms in the nasopharynx?
Cilia
How does the stomach inhibit microbial growth? Where do bacteria colonize in the stomach?
Keeps pH very low (2) to inhibit growth. Colonize in the mucus lining
What microbiome has the most abundance and diversity than all other microbiomes?
Intestinal microbiome
What are the benefits of the intestinal microbiome?
Vitamins and hormones are produced by microbes and absorbed by our cells
Nerves in the GI tract that connect to the CNS
Microbiome-gut-brain axis
Normal bacteria and pathogens compete for the same spot, so normal bacteria produce this to fight off the pathogens
Antimicrobial compounds
What 3 outcomes can result from severe intestinal dysbiosis?
-Deadly infections
-Inflammatyory bowel diseases (Crohn’s)
-Bacteremia and organ infection
How does the female genitalia inhibit bacterial growth?
Female genital tract is slightly acidic. Most dominant vaginal microbiome is acid-tolerant
Part in the genitourinary tract that should be sterile
Kidneys
3 Parts in the genitourinary tract that have their own microbiomes
-Bladder
-Urethra
-Vagina
2 results of genitourinary tract dysbiosis
-UTI
-Yeast infection
What are some human behaviors that dramatically alter our microbiota composition?
-Clean water
-Cesarean deliveries
-Preterm antibiotics
-Smaller family size
-Reduced breast-feeding
Proposes that dramatic changes in human behavior have influenced the makeup of out microbiota
Hygiene hypothesis
Food or supplements that provide plant fibers that can be digested by beneficial bacteria. (fruits, vegetables, whole grains)
Prebiotics
Food or nutritional supplements that contain live organisms to promote colonization by beneficial bacteria (most commonly lactobacillus and bifidobacterium)
Probiotics
Transfer of the microbiome of a healthy person to a person with severe intestinal disease
Fecal microbiota transplant (FMT)
May be a possible alternative to antibiotics in targeting pathogenic bacteria
Phage therapies
3 physical barriers
-Epithelial
-Blood-brain
-Maternofetal (placental)
What holds the 3 barriers together?
Tight junctions
Multiprotein adhesion complexes that hold cells together
Tight junctions
What is the purpose of physical barriers and how do we get nutrients past them?
Tight junctions are strictly regulated and control what passes through, they keep microbes out
What is the most regulated physical barrier?
Blood-brain barrier
What can pass through the blood-brain barrier?
Only oxygen, CO2, and alcohol. Glucose and other nutrients need carrier systems
The fetus is considered ________ because of the placental barrier
Germ-free
True or false: Fetal and maternal bloodstreams never mix
True
An example of a virus that can cross the placental barrier and infect the fetus
Ziika
Summary of the immune system
Distinguishes self from non-self. Sense and react to foreign antigens that have some sort of way to be identified
The system of nonspecific mechanisms that the body uses for protecting against pathogens (Immediately activated-mechanisms already in place. Not specific about what they target)
Innate immunity
Immune responses activated by a specific antigen and mediated by B cells and T cells (adaptive responses take a week or so to develop. Highly specific to a given pathogen)
Adaptive immunity
All immune cells are made via this process
Hematapoiesis
The formation of blood cellular components
Hematapoiesis
Red blood cells and platelets
Erythrocytes
B cells, T cells, and natural killer cells
Lymphoid cells
Mast cell, Eosinophil, basophil, neutrophil, monocyte, macrophage, dendritic cell
Myeloid cells
Cell type that is always in tissues
Mast cell
Cell types that are mostly in blood
Eosinophil, basophil, neutrophil
Cell type that is always in the blood
Monocyte
Cell types that are mostly in tissues
Macrophage and dendritic cell
Innate white blood cells that can phagocytose and kill microbes
Neutrophils
2 Innate white blood cells that secrete antimicrobial compounds
Eosinophils and basophils
Innate white blood cells only found in tissues and secrete antimicrobial compounds
Mast cells
Innate white blood cells that differentiate into macrophages or dendritic cells
Monocytes
Circulate in the blood, engulf foreign material (phagocytosis), enter tissues and differentiate to macrophages or dendritic cells (more aggressive endocytosis)
Monocytes
Phagocytic and dispersed in tissues, likely make first contact with invading pathogens
Macrophages
Antigens from engulfed pathogens are presented to the adaptive immune system
Antigen presentation
Phagocytose, process, and present small antigens on their surface, can take up small soluble antigens from the surroundings in addition to phagocytosis. An important component to bridge innate and adaptive immunity
Dendritic cells
Monocytes that stay behind and protect
Macrophage
Monocytes that go and get help
Dendritic cell
4 steps of phagocytosis
- Bacterium binds to the surface of phagocytic cell. Antibody or complement can aid in binding.
- Phagocyte pseudopods extend and engulf the organism.
- Invagination of phagocyte membrane traps the organism.
- A lysosome fuses and deposits enzymes into the phagosome. Enzymes cleave macromolecules and generate reactive oxygen, destroying the organism.
2 results for a microbe after phagocytosis
- Into extracellular space
- Antigen presented on the membrane
Cells that can engulf bacteria through phagocytosis
Phagocytes
Cells that activate the adaptive immune system
Antigen-presenting cells (APCs)
The group of organs, vessels, and tissues that complement the immune and circulatory systems
Lymphatic system
Organs where immune cells originate and mature
Primary organs
Organs where immune cells encounter antigen
Secondary organs
Where T and B cells spend most of their lives, waiting to be presented antigen
Lymph nodes
Interstitial fluids and which blood cells
Lymph
How is lymph drained?
Lymphatic vessels through movement
Where are T cells formed?
Thymus
Where are B cells formed?
Bone marrow
Antimicrobial enzyme that targets peptidoglycan
Lysozyme
Antimicrobial enzyme that produces toxic superoxide radicals
Lactoperoxidase
Antimicrobial enzymes that are positively charges small molecules, target membranes
Defensins
5 Cardinal signs that mark inflammation (HERPA)
-Heat
-Edema (swelling)
-Redness
-Pain
-Altered function or movement
Movement of white blood cells from the blood stream into the tissues (produces signs of inflammation)
Extravasation
What are the dominant cells that flood the site of infection?
Neutrophils
Inflammatory response
- Resident macrophages engulf and digest invading organisms
- Endothelial tight junctions loosen, and cytokines promote expression of adhesion molecules on endothelial cells
- Damaged tissue cells express bradykinin, which directly promotes vasodilation (loosen capillaries)
- Bradykinins also promote prostaglandin secretion from endothelial cells, which signals to nerve cells to send a pain input to the brain.
- Once microbe is cleared, neutrophils, cytokines, and chemokine are removed and the tissue can heal.
Signaling peptides that communicate with other immune cells
Cytokines
Increase vascular permeability (vasodilation)
Vasoactive factors
Signaling peptides that guide immune cells towards the site of infection (chemotaxis along the concentration gradient)
Chemokines
What kind of inflammation will lead to permanent damage?
Chronic
Inflammation that causes cell damage as a worthwhile cost to clear out the pathogen
Acute
Inflammation that occurs when the foreign body persists in the tissues (TB)
Chronic
What do macrophages probe the environment with to determine if the cell they are in contact with is self or non-self?
Pseudopods
What surrounds a bacterial to make it too slippery to grab?
Capsule
Arm-like projections for bacteria that are too slippery
Psuedopods
How does phagocytosis actually kill microbes?
By fusing the phagosome with the lysosome
How do some microbes take advantage of phagocytosis?
They use it to enter the cell cytoplasm
Ticking time bombs packed with pro-inflammatory molecules. Healing cannot take place when these molecules are present
Neutrophils
Process that kills neutrophils, clean way to remove them
Apoptosis
Cells that kill defective host cells, only lymphocyte in immune system. Don’t directly kill microbes, they kill the cells that allow for microbial replication
Natural killer cells
When will NK cell force the cell to undergo apoptosis?
When infected of defective cells express less MCH-I
“Self” molecule that is a receptor that all host cells express
MCH-I
NK cells kill first by inserting pore-forming protein called:
Perforin
Next, NK cells release cytotoxic proteins like _____________ that enter the cell and initiate apoptosis
Granzyme
Patterns include those found in strongly immunogenic molecules like lipopolysaccharide, peptidoglycan, lipoteichoic acid, etc. Occur only in microbes, and are critical components of the microbial cell (virus), so they will not change
PAMPS/MAMPs
Patterns that our immune cells know where our cells might leak out when damaged
DAMPs
What sensed DAMPs and PAMPs?
Pattern-recognition receptors (PRRs)
Primary example of PRRs
Toll-like receptors (TLRs)
PRR activation leads to the cell producing _____________ that alert neighboring cells and immune cells the type of infection taking place
Cytokines
TLRs on _______________ will sense PAMPs in the extracellular environment (bacteria, yeast, protists)
Cell membrane
TLRs on ____________ will sense PAMPs taken up by endocytosis related to viruses and intracellular bacteria
Endosomal membranes
Cytokines that cells express during infection to warn other cells to establish an antiviral state
Interferons
A systemic inflammatory response to infection that can lead to multi-organ failure and death
Sepsis
Main cause of sepsis
Bacterial infections
These cause fever by influencing the hypothalamus to “turn up the thermostat”
Pyrogens
A family of proteins present in the blood that react to bacterial membranes
Complement
2 consequences of complements
1) they can coat the bacterial cell and make them easier to be eaten by phagocytes (opsonization)
2) they add up to form a structure called the membrane attack complex that forms pores in the membrane.
All of our own cells have surface proteins that inactivate complement. Do bacteria have these proteins?
No
What does severed combined immunodeficiency (SCID) lead to?
The death of T cells during development, preventing B cells from functioning. Leads to susceptibility to all pathogens, especially viruses
Any molecule that will elicit an immune response when introduced into a person
Antigens
An antigen that can elicit the production of antibodies
Immunogen
Each antigen can have one or more of these that themselves can elicit an immune response
Epitopes
What cells do APCs present to?
Macrophages and dendritic cells present antigens to T cells
Which cells bind free antigen from the lymph?
Free-floating antigens from the microbe bind to B-cell receptors
Type of adaptive immunity that is mediated by antibodies that are secreted by plasma cells and activated by B cells
Humoral immunity
Type of adaptive immunity that is mediated by cytotoxic T cells
Cell-mediated immunity
These cells are central to activating both humoral and cell-mediated immunity
Helper T cells
How are helper T cells activated?
Bind to B cells that have taken up free-floating antigens in the lymph
B cells also form ________ cells, which can be quickly activated in the next infection
Memory
2 distance signals B cells need to activate
- Antigen binding to the B cell antigen receptor
- Tfh cell interaction with the B cell
B cells activate, rapidly diving and forming ________ cells that secrete antibody
Plasma
Help identify alien things in the body. Y-shaped protein that circulates in the bloodstream to bind to matched antigens on an infecting pathogen
Antibodies
These enter the bloodstream, then tissues to directly kill infected cells
Cytotoxic T lymphocytes (CTLs)
2 signals that CTLs need to activate
- Binding to an APC presenting an antigen it recognizes
- Cytokines secreted by a similarly-activated Th cell
Where to T and B cells go?
T cells to site of infection, B cells to bone marrow
Measures how well an antigen elicits an immune response
Antigenicity/immunogenicity
Most antigenic molecule
Proteins (can be manipulated most)
This principle governs how effective vaccines are against different pathogens.
Antigenic specificity
An antibody expressed on the cell membrane
B cell receptor (BCRs)
How do BCR differentiate between B cells?
Our bodies produce millions of B cells and each naive B cell has a BCR specific to a different antigen
B cell that has gone through selection in the bone marrow and is ensured to not react to self antigens
Mature B cell
Are all B cells in the lymph node mature?
Yes
Why do naive B cells not secrete antibody?
Because they have not seen antigen yet (antigen activates them
Naive B cells exist as _________ within the lymph node
Clones
The theory that specific antigen receptors exist on lymphocytes before they are presented with an antigen due to random mutations during initial maturation and proliferation
Clonal selection
A small number of precursor cells that recognize a specific antigen proliferate into expanded clones, differentiate and acquire various effector and memory phenotypes, which promote effective immune responses
Clonal expansion
Once a clone has expanded, what does it differentiate to?
Memory B cells or plasma cells
Do memory B cells or plasma cells release antibodies?
Plasma cells
2 regions of antibodies
Fab (antigen-binding) and Fc (constant)
Process where antibodies bind to bacteria, and the Fc portion of the antibodies binds to receptors on the macrophage surface
Opsonization
How do complement proteins attack bacterial cell membranes?
Assemble into the membrane attack complex to poke holes in the membrane and cause the cell to lyse
Isotype that is most abundant in blood/tissues, most associated with protective immunity
IgG
Isotype where the monomer is the BCR, and the secreted form is a huge, five-antibody pentameter
IgM
Isotype where it exists as a dimer, secreted into mucousal surfaces, and protects against pathogens in the mucosa
IgA
Isotype that causes allergy
IgE
Isotype that is primarily found on the surface of B lymphocytes where it functions as a receptor for antigen
IgD
Two isotopes that are found in all naive B cells
IgM and IgD
All activated B cells use this process to decide their isotype
Isotype switching
Which isotype is secreted first?
IgM
Which isotype is secreted for most of the response?
IgG
Primary response vs. secondary response
Primary- Specific to the antigen, but has relatively weaker affinity
Secondary- Memory B cells continually divide, and make up 40% of the circulating B cell population. Upon reinfection, memory B cells quickly expand and differentiate to more memory cells and plasma cells
