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BIOS 350
Microbes Benefits to the World
Prokaryotic importance on Earth’s Ecosystems (Good & Bad)
– Produce O2 gas
– Convert N2 gas into Ammonia (NH3) = Nitrogen fixation
– Convert CO2 gas into organic carbon molecules = Carbon
Fixation
All for use by other organisms
Decompose organic material for soil formation and
to recycle nutrients back into the food chain
Bioremediation to degrade toxic pollutants
from environment
Add to greenhouse gases that trap heat in the
atmosphere by producing CO2 and methane (CH4)
< 1% of bacteria are human pathogens = cause disease Prokaryotes live in Communities of interacting populations of organisms Cooperative Interactions Populations both benefit Populations compete for Competitive Interactions resources Interactions between species Symbiosis within a community Examples Microbiota in human digestive tract Fungus secreting antibiotic killing bacteria Mites in human hair follicles Coexistence of vegetative and endospores of Bacillus anthracis Tuberculosis in human lung In 98% of pregnancies the womb is Axenic = free of microbes Start acquiring Microbiome from environment when amniotic membrane ruptures = Normal Microbiota (flora) = all microorganisms colonizing in/on an organism about 39 trillion cells (about 30 trillion human cells) Most normal microbiota acquired in first months of life Within 12 hours newborn has Streptococci, Staphlococci, and Lactobacillus If breastfed, infants intestinal flora are mainly bifidobacterium If bottle fed, mixed population: coliforms, lactobacilli, streptococci, staphylococci Microbiome can change over time Microbes that contact body are: Few hours, days, months Transient (may be pathogens) Resident Remain throughout life Nasal cavity Benefits: Microbial antagonism & competition for resources, digestion, vitamin extraction from food, help regulate immune system Areas of the body with microbes Parts of body that are possibly axenic Lungs, kidneys, liver, spleen, blood stream, nervous system, brain, spinal cord, body fluid E.Coli in intestines 5 Don’t have to memorize Genera > 30 genera, about 500 species of microbes in large
intestine (colon) 99% from < 100 species The solid part of feces is about 30% microbial Don’t have to memorize Genera > 3 million bacteria / cm3 on skin
Microbes are involved in the Global Carbon cycle
Photoautotrophs and chemoautotrophs harness energy from the
sun and from inorganic chemical compounds to produced carbon
containing organic compounds
There is a constant exchange of CO2 between the heterotrophs
(which produce CO2 as a result of respiration or fermentation)
and the autotrophs (which use the CO2 for fixation).
Autotrophs also respire or ferment the organic compounds they
produce
Bacteria and archaea that use methane as their carbon source
are called methanotrophs.
Methane accumulation due to methanogenesis occurs in both
natural anaerobic soil and aquatic environments; methane
accumulation also occurs as a result of animal husbandry
because methanogens are members of the normal microbiota of
ruminants.
Environmental methane accumulation due to methanogenesis is
of consequence because it is a strong greenhouse gas, and
methanotrophs help to reduce atmospheric methane levels.
Bacteria involved in Global Nitrogen
Cycle
Many biological macromolecules,
including proteins and nucleic acids,
contain nitrogen; however, getting
nitrogen into living organisms is
difficult. Prokaryotes play essential
roles in the nitrogen cycle,
transforming nitrogen between various
forms for their own needs, benefiting
other organisms indirectly.
Nitrogen Fixing Bacteria:
Cyanobacteria, Rhizobium,
Azotobacter
Ammonification Bacteria: Bacillus,
Clostridium, Pseudomonas,
Streptomyces
Nitrification Bacteria: Nitrosomonas,
Nitrobacter
Denitrification Bacteria:
Pseudomonas, Clostridium, Bacillus
Sulfur is an essential element for the
macromolecules of living organisms
As part of the amino acids cysteine and methionine, it
is involved in the formation of proteins. It is also
found in several vitamins necessary for the synthesis
of important biological molecules like coenzyme A
Anoxygenic photosynthetic bacteria as well as
chemoautotrophic archaea and bacteria use hydrogen
sulfide as an electron donor, oxidizing it first to
elemental sulfur (S0), then to sulfate (SO42−)
Many bacteria and plants can use sulfate as a sulfur
source
Decomposition dead organisms by fungi and bacteria
remove sulfur groups from amino acids, producing
hydrogen sulfide, returning inorganic sulfur to the
environment
Bioremediation
â—¦ Microbial bioremediation leverages
microbial metabolism to remove
xenobiotics or other pollutants
â—¦ Xenobiotics are compounds
synthesized by humans and introduced
into the environment in much higher
concentrations than would naturally
occur
â—¦ Enhanced bioremediation techniques
involve the addition of nutrients and/or
air to encourage the growth of
pollution-degrading microbes
â—¦ They may also involve the addition of
non-native microbes known for their
ability to degrade contaminants
BIOS 350
CHAPTER 17
INNATE NONSPECIFIC HOST DEFENSES
1
Host Immunity against Pathogens
1st line of defense
Nonspecific: targets wide range of pathogens,
Innate
not a specific one
Nonspecific
Immunity
Innate: humans born with them
Immediate or rapid response
Adaptive
Specific
Immunity
(Unit VI Ch 18)
Acquired through active infection or
vaccination
Specific: against a specific pathogen
Memory: quickly responds to re-exposure of
pathogen
Not perfect – pathogens can still cause disease
Immune response can contribute to signs and symptoms of
disease
Nonspecific Defenses:
Innate Immunity
3
17.1 Physical Defenses
Tight Cell-to-Cell
Junctions act as
physical barrier to
prevent microbes
from reaching deeper
tissue.
Some microbes have
virulence factors to
break these down
The Skin Barrier
â—¦ Keratin:
◦ makes the skin’s surface mechanically tough
and resistant to degradation by bacterial
enzymes
â—¦ Fatty acids:
◦ on the skin’s surface create a dry, salty, and
acidic environment that inhibits the growth of
some microbes and is highly resistant to
breakdown by bacterial enzymes
â—¦ Dead cells of the epidermis:
â—¦ frequently shed, along with any microbes that
may be clinging to them
5
Mucous Membranes
â—¦ Mucous Membranes:
â—¦ Lining the nose, mouth, lungs, and urinary and
digestive tracts
â—¦ Mucus:
â—¦ Covers and protects the more fragile cell layers
beneath it and traps debris and particulate matter,
including microbes
â—¦ Contain antimicrobial peptides.
â—¦ Mucociliary escalator:
â—¦ Found on respiratory tract and oviducts
â—¦ Movement of the cilia propels debris-laden mucus
out and away
â—¦ Peristalsis:
â—¦ Series of muscular contractions in the digestive
tract, moves the sloughed mucus and other
material through the intestines, rectum, and anus,
excreting the material in feces
6
Endothelia
â—¦ Endothelia:
â—¦ The epithelial cells lining the urogenital tract, blood
vessels, lymphatic vessels, and certain other tissues
â—¦ Tightly packed cells provide a particularly effective
frontline barrier against invaders
â—¦ Blood-brain barrier:
â—¦ Protect the central nervous system (CNS), which consists
of the brain and the spinal cord
â—¦ Prevents any transient microbes in the bloodstream from
entering the CNS
7
Mechanical Defenses and Microbiome
â—¦ Mechanical Defenses:
â—¦ Physically remove pathogens from the
body, preventing them from taking up
residence
â—¦ Shedding of skin cells, mucociliary
escalator, and peristalsis
â—¦ Flushing action of urine and tears
â—¦ Microbiome:
â—¦ Occupation of cellular binding sites and
competition for available nutrients
â—¦ Prevent the critical early steps of
pathogen attachment and proliferation
required for the establishment of an
infection
â—¦ Contribute to the chemical defenses of
the innate nonspecific host defenses
8
Chemical Defenses
â—¦ Chemical Defenses:
â—¦ Chemical mediators that inhibit microbial invaders
â—¦ Skin:
â—¦ Sebum:
â—¦ An additonal layer of defense by helping seal off the
pore of the hair follicle
â—¦ Microbiome metabolizes sebum into oleic acid
reducing skin pH
â—¦ Saliva:
â—¦ Lactoperoxidase enzymes react to produce
antibacterial substances
â—¦ Digestive Tract:
â—¦ Tears:
â—¦ Lysozyme
â—¦ Lactoferrin
â—¦ Earwax
â—¦ Antimicrobial
â—¦ Slightly lowered pH
â—¦ Respiratory Tract:
â—¦ Mucus
â—¦ Lysozyme
â—¦ Lactoferrin
â—¦ Lactoperoxidase
â—¦ Mucus
â—¦ Lysozyme
â—¦ Antibacterial peptides
â—¦ Stomach acid
â—¦ Bile
â—¦ Enzymes
â—¦ Urogenital System:
â—¦ Urine slightly acidic pH
â—¦ Vaginal slightly acidic pH
9
Antimicrobial Peptides
â—¦ Antimicrobial Peptides:
â—¦ A special class of nonspecific cell-derived mediators with broad-spectrum antimicrobial
properties
â—¦ Function in a variety of ways
10
Plasma Protein Mediators
â—¦ Plasma:
â—¦ Fluid portion of the blood
â—¦ Acute phase proteins:
â—¦ Primarily produced in the liver and secreted into the blood in response to inflammatory
molecules from the immune system
11
Complement System
â—¦ Complement System:
â—¦ Group of plasma protein
mediators that can act as an
innate nonspecific defense while
also serving to connect innate
and adaptive immunity
â—¦ Group of proteins that circulate
in the blood until activated
â—¦ Three activation pathways:
â—¦ Classical, alternative, lectin
â—¦ Leads to opsonization,
inflammation, chemotaxis, and
cytolysis
12
Cytokines
â—¦ Cytokines:
â—¦ Soluble proteins that act as communication
signals between cells
â—¦ Function in cell proliferation, cell
differentiation, inhibition of cell division,
apoptosis, and chemotaxis
â—¦ Three Classes:
â—¦ Interleukins:
â—¦ Produced by white blood cells and other body
cells
â—¦ Involved in modulating almost every function of
the immune system, their role in the body is not
restricted to immunity
â—¦ Chemokines:
â—¦ Chemotactic factors that recruit leukocytes to
sites of infection, tissue damage, and
inflammation
â—¦ Interferons:
â—¦ Antiviral proteins
â—¦ Stimulate nearby cells to stop production of
mRNA, destroy RNA already produced, and
reduce protein synthesis
13
Chemical Defenses:
Inflammation-Eliciting Mediators
Cytokines binding to Basophil and Mast cells trigger
release of Histamine and Leukotrienes
Cellular Defenses
15
Granulocytes
â—¦ Neutrophils:
Nucleus with three to five lobes
Small lilac colored granules
Destroy bacteria through phagocytosis
Can be stimulated to release toxic molecules into the
surrounding tissue to better clear infectious agents
â—¦ Neutrophil extracellular traps (NETs), which are extruded
meshes of chromatin that are closely associated with
antimicrobial granule proteins and components
â—¦
â—¦
â—¦
â—¦
â—¦ Eosinophils:
â—¦
â—¦
â—¦
â—¦
Nucleus with two to three lobes
Larger granules that stain reddish – orange
Protect against protozoa and helminths
Play a role in allergic reactions
â—¦ Basophils:
â—¦ Two lobed nucleus
â—¦ Larger granules that stain blue or purple
â—¦ Important in allergic reactions and other responses that
involve inflammation
â—¦ Release histamine when stimulated
â—¦ Mast Cells:
â—¦ Function like basophils
â—¦ Unlike basophils, mast cells leave the circulating blood and
are most frequently found residing in tissues
16
Natural Killer Cells
â—¦ Mononuclear lymphocytes
â—¦ Nonspecific mechanisms to recognize
and destroy cells that are abnormal in
some way
â—¦ Cancer cells
â—¦ Virally infected cells
â—¦ Killing chemicals
â—¦ Perforin: a protein that creates pores in
the target cell
â—¦ Granzymes: proteases that enter
through the pores into the target cell’s
cytoplasm, where they trigger a
cascade of protein activation that
leads to apoptosis
17
Monocytes
â—¦ Largest white blood cell
â—¦ Nucleus that lacks lobes
â—¦ Lack granules
â—¦ Phagocytic
â—¦ Leave blood and differentiate into
â—¦ Macrophages and Dendritic Cells
â—¦ Important in phagocytosis and antigen
presentation
18
Pathogen Recognition
â—¦ Phagocytes can recognize
molecular structures that are
common to many groups of
pathogenic microbes
â—¦ Pathogen-associated molecular
patterns (PAMPs)
â—¦ peptidoglycan, found in bacterial cell
walls;
â—¦ flagellin, a protein found in bacterial
flagella;
â—¦ lipopolysaccharide (LPS) from the outer
membrane of gram-negative bacteria;
â—¦ lipopeptides, molecules expressed by
most bacteria; and
â—¦ nucleic acids such as viral DNA or RNA
â—¦ Pattern recognition receptors (PRRs)
also known as Toll Like Receptors (TLRs)
â—¦ On surface of phagocytes
â—¦ Bind PAMPs
19
Phagocytosis
20
Inflammation
â—¦ Signs and Symptoms:
â—¦ Redness, Heat, Pain, and Swelling
â—¦ Allows for recruitment of the cellular
defenses needed to eliminate
pathogens, remove damaged and
dead cells, and initiate repair
mechanisms
â—¦ Acute:
â—¦ Beginning stages
â—¦ Vascular changes
â—¦ Neutrophils dominate
â—¦ Chronic:
â—¦ Ending stages
â—¦ Macrophages dominate
â—¦ Can lead to granuloma formation
21
Extravasation (Diapedesis) of
Leukocytes
â—¦ Leukocytes pass
through the walls of
small capillary blood
vessels within tissues
22
Fever
â—¦ An inflammatory response that extends
beyond the site of infection and affects
the entire body, resulting in an overall
increase in body temperature
â—¦ Pyrogens:
â—¦ chemicals that effectively alter the
“thermostat setting” of the hypothalamus to
elevate body temperature and cause fever
â—¦ Stimulates leukocytes to kill pathogens
â—¦ Inhibits the growth of many pathogens
â—¦ Stimulates release of iron-binding
compounds
â—¦ Too high can be dangerous
23
Inflammation and Fever
Sign something wrong
Benefits
Enhances effects of interferons
Increases metabolism, tissue repair,
immune system function (phagocytes, RBC production)
Inhibits growth of some temperature sensitive microbes
Reduces iron available to microbe
Some recommend not treating fever for otherwise
healthy patients unless it is prolonged or extremely high
Too high a fever causes tissue and
organ damage, possibly death
Superantigens can trigger this
BIOS 350
CHAPTER 18
ADAPTIVE SPECIFIC HOST DEFENSES
1
18.1
Adaptive Immunity is defined by Specificity & Memory:
Specificity
Acts against only 1 molecular shape (Epitope)
(because of monospecific receptors)
Memory
Responds faster & more effectively in later
encounters w/pathogen or toxin
How?
Memory B cells & T Cells are programmed by Primary
Response = first exposure to pathogen or vaccine
Secondary Response = subsequent exposure
HUMORAL Immunity: B Lymphocytes (B cells) mature in bone marrow
Produce Antibodies = Immunoglobulins
CELLULAR Immunity
T Lymphocytes (T cells) mature in
thymus; Direct innate & adaptive
immune responses
Also Cytotoxic T lymphocytes (CTLs)
destroy cells infected with
intracellular pathogens, diseased
cells, or tissue graft cells
Antigens (Ag)
= Immunogens
Pathogen-specific molecules that trigger an
Adaptive Immune response
Foreign (exogenous), Complex, Large
like proteins & glycoproteins
Good Ag
Stimulate Humoral and
Cellular Immunity
Poor Ag
Stimulate Humoral
Immunity only
i.e. Bacterial cell capsules, cell walls,
fimbriae, flagella, pili, extracellular toxins,
exoenzymes
Viral capsids, envelopes, spike proteins
Small, unless bound to carrier molecules
Large, simple, repetitive (carbohydrates like
glycogen), lipids, nucleic acids
Good Antigens
4
Small, surface, 3D regions of Ag that are recognized by
Epitope antibodies and T cells & determine immune response
One Antigen can have many Epitopes
Molecules too small to be antigenic on their own but will
trigger immune response when bound to carrier
Hapten
molecule
i.e. the Poison ivy oil Urushiol
5
and Penicillin
Antibody = Immunoglobulin (Ig) are glycoproteins in blood and tissue fluids
4 protein chains: 2 identical Heavy & 2 identical Light linked by disulfide bonds
Constant & Variable regions of each
Variable regions
form
Fab = Fragment of
antigen-binding
for Epitope
Fc = Fragment of
crystallization
• Binds
complement
• Binds
phagocyte
• Determines Ig
class (IgM, IgG,
IgA, IgE, IgD)
allows
flexibility
è
6
Antibody Classes
(dependent on Fc portion)
Is B-cell Receptor
To kill microbes
or detoxify
1st Ab made in primary & secondary
response
Half-life in blood
23 days
5 days
7
Antibody
Classes
Secretion
= Membrane bound
Anti-parasitic
To kill microbes
or detoxify
Role in Allergies
In mucus traps pathogens
Triggers release of proinflammatory mediators
from basophils and mast
cells
Is B Cell
Receptor
Least abundant
8
Antibody Functions
Complement Activation by IgG, IgM
Microbe lyses & Inflammation triggered
Neutralization
Degranulation
Neutralization by IgG, IgM, IgA
of a toxin by blocking it’s action
of bacteria/virus by blocking adhesion
Agglutination: Abs like IgG, IgM cross-link and aggregate
Ags causing precipitation & increasing chance of phagocytosis
or filtering by spleen and kidneys
9
Antibody Functions
Opsonization
Opsonization: IgG Abs coat microbe to
stimulate phagocytosis because
Neutrophils, Dendritic cells &
Macrophages have receptor for Fc
portion
Antibody-Dependent Cellular Cytotoxicity (ADDC)
IgG Abs coat pathogen è IgG Fc portion binds to receptors on
Natural Killer Lymphocytes (NK Cells)
ADDC
è perforins
and
granzymes kill
pathogen
18.2
MHC I & II = Major Histocompatibility Complexes
Transmembrane glycoproteins that hold epitopes for presentation to T
Lymphocytes
(not RBCs)
MHC I
On all nucleated cells; Present endogenous (made inside
human cell) antigens to CTLs – if abnormal get destroyed
MHC II
on APCs only; Present exogenous (made outside human
11
cell) pathogen antigens to activate T cells
All nucleated cells display pieces of all endogenous proteins
made in cell on MHC I Receptors
If cancerous or virally-infected cell, these displayed epitopes get
recognized by activated Cytotoxic T (Tc) cells and “bad” cell is destroyed
Not done by RBCs
by Golgi
8-12 amino acid pieces
12
Macrophages
& Dendritic
cells
Antigen-Presenting Cells (APCs)
Phagocytes that recognize & attach to pathogens via
nonspecific receptor interactions
i.e. PAMPs, TLRs, opsonins
Ingest, kill pathogens, present the most antigenic or
immunodominant exogenous epitopes
on MHC II receptors to T cells
B Cells
Use their surface receptors, BCR, to
recognize specific pathogens or their
free antigens
Ingest, process, and present
epitopes to T cells on MHC II
receptors
Produce and secrete antibodies
13
18.3
Lymphocytes and Cellular Immunity
T lymphocytes or T cells:
• Target and eliminate cells with intracellular pathogens
• Directs overall Innate & Adaptive immune responses
= CTL
Cluster of Differentiation (CD)
molecules:
cell surface glycoproteins produced by
T lymphocytes that identify and
distinguish their class
14
T Lymphocytes and Cellular Immunity
Formed from Hematopoietic Stem cells in bone marrow and released to
blood stream as Immature T Lymphocytes è
travel to Thymus for final maturation (now called Thymocytes)
Maturation called
Thymic Selection
= 3 step process that eliminates
98% of thymocytes by
Apoptosis = programmed
controlled cell death
15
Thymic Selection
1. Thymocytes with defective
T-cell Receptors (TCRs)
are eliminated
2. Thymocytes that do not
recognize MHC molecules
are eliminated
Immature clones
travel to thymus
3. Thymocytes that react to
normal human (self) antigens
are eliminated (prevents autoimmune
disease)
= Central Tolerance
Mature Naïve T cells are
released to bloodstream &
lymphatic system to lymph
nodes, spleen, tonsils, etc.
16
ç Some
become
T-Cell Receptors
Helper T cells and Cytotoxic T cells
require “activation”
1st step involves
T-Cell Receptor (TCR)
Similar to antibodies
Variable region has antigenbinding site – is epitope-specific
About 25 million T cells with unique
epitope-binding TCRs are required
for antimicrobial protection
Since we only have ~ 25,000
genes, the TCR gene segments
under go Genetic Rearrangements
to get required variety
TCRs can only recognize
17
Proteins
Activation and Differentiation of Helper T Cells by APCs
1. TCR on naïve Helper T
cell recognizes pathogen
epitope presented on
APC MHC II
2. CD4 on naïve
Helper T cell
recognizes APC
MHC II so epitope
alone can’t
activate T cell
3. APC and T cell
secrete cytokines to
activate Helper T cell è
mitosis and
differentiation è
Effector & Memory cells
18
Effector
Cells
Subtypes of Helper T Cells:
depends on Cytokines secreted by APC
Produce Cytokines for Primary immune response
function; short lived
19
Activation and Differentiation of Cytotoxic T cells
= Cytotoxic T Lymphocytes (CTLs) by APCs
1. TCR on naïve CTL
recognizes pathogen
epitope presented on
APC MHC I
2. CD8 on naïve
CTL recognizes
MHC I so epitope
alone can’t
activate T cell
3. APC, TH1, &
CTL cells secrete
cytokines to
activate Cytotoxic
T cell è mitosis
and differentiation
Memory T Cell
for next
exposures to
epitope
Effector
cell
Dendritic cell
CTLs work like Natural
Killer (NK) cells
20
Cell Mediated
Immune Response
Activated
Cytotoxic T cells
(CTLs) induces
apoptosis of virally
infected, diseased
cell, tissue graft
cells
CTLs recognize
these “bad” cells by
their endogenous
epitopes displayed
on MHCI on every
nucleated human
cell
Makes
holes in
membrane
Perforin-Granzyme Cytotoxic
Pathway
Click here for video
CTL
killing
tumor
Superantigens and Unregulated Activation of T Cells
Superantigens
Toxins produced by bacterial and viral pathogens trigger
unregulated and excessive T cell activation
that can be life-threatening
i.e. Staph toxic shock syndrome toxin, enterotoxins
Strep pyrogenic toxins, superantigen, mitogenic exotoxin
Epstein-Barr virus, cytomegalovirus
Superantigen allows APC MHC II receptor with NO EPITOPE to bind to TCR
on naïve Helper T Cell and activate è uncontrolled release of Cytokines =
Cytokine Storm = excessive inflammatory response
Decrease in blood pressure, shock, multi-organ failure, possibly death
No epitope needed for activation if superantigen
present
If normal pathogen epitope not recognized è no activation of naïve Helper T cell
22
18.4
B Lymphocytes and Humoral Immunity: Antibody Secretion
B cells formed from Hematopoietic Stem cells in bone marrow
3 step Maturation process starts in bone marrow
1. B cells with defective B-cell receptors (BCRs) are eliminated
2. B cells with BCRs that recognize self-antigens are eliminated
3. Immature B cells leave bone marrow è spleen for final maturation è
naïve mature B cells è wait for activation
Naïve mature B Cells have up to 100,000
membrane bound IgD and IgM BCR
monomers, each with 2 identical epitope
binding sites
Genetic Rearrangement used to create
millions of these unique BCRs which produce
unique Antibodies after activation
BCRs can recognize free antigens or cell
surface antigens on intact pathogen
(do not need MHC epitope presentation)
BCRs can recognize Proteins,
Polysaccharides, Lipopolysaccharides
T Cell-Independent Activation of B cells: for Non-protein antigens
No not need Helper TH2 cells to become activated
BCRs recognize T-independent antigens with non-protein repetitive epitopes
like polysaccharide capsules, lipopolysaccharide
è allows cross-linkage of multiple BCRs
Once B cell is activated,
it undergoes clonal proliferation and differentiation into Plasma cells
Plasma cells
Lose membrane BCRs and secrete lots of pentameric IgM with
same epitope specificity as original surface BCRs
No Memory B cells made so no response to subsequent exposures
T Cell-Dependent Activation of B cells: for Protein antigens
BCR of naïve mature B
cell may recognize free
antigen or:
Linked Recognition of same epitope
by B cell and activated TH2 cell
Plasma cells produce IgM
first, then Class Switch
T Cell-Dependent Activation of B cells: for Protein antigens
Activation is more complex, stronger primary response, develops memory
1. BCR on naïve mature B cell recognizes free protein antigen
Or BCR recognizes protein antigen on intact pathogen and extracts it
Antigen is phagocytosed, processed, and epitope presented on MHC II
2. Need activated Helper TH2 cell to recognize displayed epitope with its
TCR, and MHC II with its CD4
Linked
Recognition
Coordination between B cells and TH2 cells that both
recognize same epitope
3. After linked recognition, TH2 cells produce & secrete cytokines that activate
B cell è clonal proliferation (rounds of mitosis) & differentiation into:
Memory B
Cells
Quickly respond to subsequent exposure to same protein
epitope
Plasma
Cells
Lose membrane BCRs and initially secrete lots of pentameric
IgM with same epitope specificity as original surface BCRs
Class
Switching
Plasma cells to switch from IgM to IgG, IgA or IgE production
all with same epitope specificity by changing constant region
B Cell Primary and Secondary Responses
Primary Response
~ 10 days: time for all the steps required to produce
Lag Period
functioning plasma cells
IgM levels peak ~ 14 days; IgG levels peak ~ 21 days
Secondary Response: Quicker, longer, and more Abs produced
Lag period only a few days; IgG levels much higher;
Antibodies more effective because higher affinity for their
epitopes; Plasma cells live longer
Active: Patient makes
memory cells
Passive: Patient given
Antibodies
Naturally
acquired
through life
Natural
Passive
Natural
Active
18.5
Vaccines
Classifications
of Adaptive
Immunity
Artificial
Active
Artificially
acquired:
through a
medical
procedure
Artificial
Passive
Given for rabies.
Ebola, or snake
venom
28
Herd Immunity
Reduction in disease prevalence because few individuals in a
population are susceptible to an infectious agent
Vaccination (Immunization) of population creates Herd Immunity
Protects people who can’t mount an effective immune response
29
Vaccines provide Artificial Active Immunity
Inoculation of a patient with attenuated pathogens or
antigens to activate adaptive immunity and protect
Vaccination
against infection
Vaccinations have done more to decrease human disease
than any other medical advancement
Effectiveness measured by
IgG & IgM titer in blood
Measles
Passive immunity
Boosters required if
titer too low
Active
immunity
Polio
30
Classes of Vaccines
CDC Recommended Immunization Schedules
click HERE
31
Exam 4 material
Week 7. Innate and Adaptive Immune Response
1. Recognize the difference between innate nonspecific immunity and
adaptive specific immunity.
Innate nonspecific immunity: An immediate first line of defense that humans are born
with – it does not target a specific pathogen but a wide range of them
Adaptive specific immunity: Immunity from infection or vaccine against a specific
pathogen
2. Identify the three types of nonspecific innate immune defenses.
a. Physical defense
i. Physical
ii. Mechanical
iii. Microbiome
b. Chemical defense
i. Antimicrobial
ii. Plasma protein mediators
iii. Cytokines
iv.
Inflammation-eliciting mediators
c. Cellular Defenses
i. Granulocytes
ii. Agranulocytesre
3. Identify how these physical defenses act as barriers to infection:
a. Cell junctions: acts as a physical barrier to prevent microbes from raching
deeper into the tissue
b. Skin: denies entry to pathogens using keratin (makes skin tough and
resistant), fatty acids (makes skin dry salty and acidic) and dead cells of
epidermis (frequently sheds)
c. Mucous membranes: Mucus covers cell layers and traps debris and
microbes
d. Endothelia: Tightly packed cells provide an effective frontline barrier,
mostly denies access to central nervous system
4. Recognize how these mechanical defenses remove pathogens from the
body:
a. mucociliary escalator: Movement of cilia propels mucus with debris out
and away
b. Peristalsis: moves the sliughed mucus & other material through intestines
and comes out in feces
c. urine flushing: urine flow pushed out pathogens from the bladder area
d. eye blinking: the ‘wiper’ action of the eyelid can remove dust or debris
from entering the eye lid
5. Identify the role of the microbiome in host defense against pathogens.
Microbiomes prevent the critical early steps of pathogen attachment
needed to establish the infection
6. Recognize how these chemical defenses help protect the body from
invading pathogens.
a. Body fluids:
i. Sebum: seals off hair follicle pore then metabolizes it into oleic acid
ii. Oleic acid: reduces skin PH
iii. Lysozyme: digestive tract & tears
iv.
Acid: digestive tract
v. Lactoferrin: tears & resp tract
b. Antimicrobial peptides:
i. Bacteriocins: disrupts membrane in gastrointestinal tract
ii. Defensins: disrupts membrane throughout the body in epithelial
cells, macrophages and neutrophils
iii. Dermicidin: disrupts membrane integrity and ion potentials on the
skin through sweat glands
c. Plasma Acute-Phase proteins:
i. C-reactive protein: coats bacteria preparing for ingestion
ii. Fibrinogen: forms blood clots that trap bacterial pathogens
iii. mannose-binding lectin: activates complement cascade
7. Identify the role of the plasma Complement system and recognize the three
pathways that trigger activation.
Group of proteins that circulate in the blood until activated and leads to
opsonization, inflammation, chemostasis and cytolysis
– Classical pathway
– Alternative pathway
– Mannose-binding lectin pathway
8. Recognize the following outcomes of the plasma Complement system and
identify why each is protective:
a. Opsonization: coats bacteria
b. Chemotaxis:
c. membrane attack complex (MAC)
9. Recognize the role of cytokines in the immune response and differentiate
between:
a. Interleukins: produced by white blood cells and are involved in modulating
almost every function of immune system but their role is not restricted to
immunity
b. Chemokines: recruit leukocytes to site of infection, tissue damage and
inflammation
c. Interferons: antiviral proteins. stimulates nearby cells to stop production of
mRNA and destroys RNA already produced
10. Recognize the role of these inflammation-eliciting mediators:
a. Histamine: promotes vasodilation, bronchoconstriction, smooth muscle
contraction and increased secretion and mucus production
b. Leukotrienes: promotes inflammation, stronger and longer lasting than
histamine
c. Prostaglandins: promite inflammation & fever
d. Bradykinin: increases vasodilation and vascular permeability
11. Identify the cells in the diagram of the cellular defenses hematopoiesis
pedigree and recognize if the cells function:
a. as part of the nonspecific innate defenses.
b. as part of the specific adaptive defenses.
c. as part of both the innate and adaptive defenses.
12. Define hematopoiesis, identify where it occurs, and recognize the following
formed elements it produces and their functions:
a. plasma
b. erythrocytes
c. Platelets
13. Recognize the differences in structure and function of the following
leukocytes:
a. Granulocytes:
i.
Neutrophils: nucleus with 3-5 lobes and small lilac colored
granules, destroy bacteria through phagocytosis
ii. Eosinophils: nucleus with 2-3 lobes, larger granules that stain
reddish/orange
iii. Basophils: 2 lobed nucleus, large granules that stain blue or purple
iv.
mast cells: they leave the blood and are mostly found in in residing
tissues
b. agranulocytes:
i. Monocytes:
ii. Macrophages:
iii. dendritic cells:
14. Identify the role of natural killer cells (NK cells) in immunity, recognize the
cells they target, and identify the process they use to identify and kill
them.
a. Mononuclear lymphocytes:
15. Recognize the stages of phagocytosis and identify the phagocytic cells of
the immune system.
16. Identify the role the following play in pathogen recognition and
phagocytosis:
a. extravasation (diapedesis)
b. transendothelial migration
c. PAMPs
d. PRRs, TLRs
e. phagosome
f. Phagolysosome
17. Recognize the five signs of acute inflammation, and identify its stages and
benefits.
18. Define granulomas and recognize how chronic inflammation produces
them and can be harmful to the body.
19. Identify the relationship between a pyrogen and fever.
20. Recognize the harm and benefits of a fever.
21. Recognize the following attributes of adaptive immunity:
a. specificity
b. Memory
22. Differentiate between humoral and cellular immunity.
23. Define antigen and recognize the characteristics of a good vs. poor
antigen.
24. Differentiate between an epitope and hapten.
25. Recognize the structure of a typical human antibody and identify the
function of each region of the antibody.
26. Identify the five classes of immunoglobulins, recognize the functions of
each one, identify any differences in their structures, and recognize the
relative abundance of each in the body.
27. Recognize the following antigen-antibody interactions:
a. neutralization
b. opsonization
c. agglutination
d. complement activation
e. antibody-dependent cell-mediated cytotoxicity (ADCC)
28. Identify the role of MHC in immunity and differentiate between MHC I and
MHC II molecules.
29. Identify the function of antigen presenting cells (APCs) in immunity.
30. Differentiate between the antigen recognition and presentation of MHC II
molecules associated with macrophages, dendritic cells, and B cells.
31. Identify the origin, development and maturation of T lymphocytes and
associate the process with the following terms:
a. thymocytes
b. thymic selection
c. central tolerance
d. apoptosis
e. mature naïve T cells
32. Recognize what cluster of differentiation (CD) molecules are and identify
the role they play in immunity.
33. Identify the functions of the following T lymphocytes and list the type of
surface CD molecules: they possess
a. helper T cells
b. regulatory T cells
c. Cytotoxic T cells
34. Identify the structure and recognize function of a T-cell receptor (TCR).
35. Identify the process of the activation and differentiation of Helper T cells
and recognize the function of the following subtypes of Helper T cells:
a. TH1
b. TH2
c. Memory Helper T cells
36. Identify the process of the activation and differentiation of Cytotoxic T cells
(CTLs) and recognize the function of the following:
a. activated CTLs
b. perforin
c. granzymes
d. memory CTLs
37. Identify the mechanism and the effects of superantigens when causing a
cytokine storm.
38. Identify the origin and recognize the development of B lymphocytes as they
become naïve mature B cells.
39. Identify the structure and recognize the function of B-cell receptors (BCRs)
indicating how they differ from TCRs.
40. Distinguish between T-dependent antigens and T-independent antigens.
41. Identify the T Cell-Independent activation and differentiation of B cells and
recognize the function of plasma cells.
42. Identify the T Cell-Dependent activation and differentiation of B cells and
recognize the following:
a. linked recognition
b. memory B cells
c. class switching
43. Differentiate between the primary and secondary responses of humoral
immunity.
44. Recognize these classifications of immunity and identify examples of each
of the following:
a. natural active immunity
b. natural passive immunity
c. artificial active immunity
d. artificial passive immunity
e. herd immunity
45. Identify the preparation, advantages, and disadvantages of the following
classes of vaccines:
a. live attenuated vaccines
b. subunit vaccines
c. conjugate vaccines
d. inactivated vaccines
e. toxoid vaccines
Week 8 Benefits to the World
1. Recognize four (4) impactful roles prokaryotes play in ecosystems.
2. Differentiate between cooperative and competitive interactions.
3. Define symbiosis.
4. Recognize the differences between the five (5) symbiotic relationships and
identify an example of each.
5. Define microbiome.
6. Differentiate between resident and transient microbiota, recognize how
they are acquired and identify their positive and negative effects on the
human body.
7. Identify tools of molecular genetics that are derived from microorganisms.
8. Identify the methods used to create recombinant DNA molecules.
9. Identify the methods used to introduce DNA into prokaryotic cells.
10. Recognize the types of genomic libraries and identify their uses.
11. Identify the methods used to introduce DNA into eukaryotic cells.
12. Recognize the mechanisms, risks, and potential benefits of gene therapy.
13. Identify ethical issues involving gene therapy and recognize the regulatory
agencies that provide oversight for clinical trials.
14. Differentiate between somatic-cell and germ-line gene therapy.
15. Recognize the process of CRISPIR-Cas 9 gene editing.
16. Recognize the importance of microorganisms in the biogeochemical cycles
of carbon, nitrogen, and sulfur as well as summarize each process.
17. Define and identify an example of bioremediation.
Exam 3 material below
Week 5 Growth Control and Antimicrobial Drugs
1. Define fomite.
Inanimate objects that can harbor microbes and aid in disease transmission.
Example: doorknob, towels, tabletop surface, toys
2. Identify the 4 levels of biosafety and recognize examples of how microbes
are to be handled at each level.
BSL 1: generally do not cause infection in healthy human adults. This includes
noninfectous bacteria, such as, escherichia coli and Bacillius subtillis, and insect
viruses. Since BSL 1 agents are low risk, few precautions are necessary. Lab
workers may use standard aseptic technique, and wearing PPE.
BSL 2: agents are typically indiginous, they are commonly found in that
geographic area. More precautions are needed including restricted access, PPE,
utilizing autoclave which sterilizes equipment.
BSL 3: These agents have the potential to cause lethal infections by inhalation.
These can be either indiginous or exotic, being derived from a foreign location.
Lab workers must wear a respirator, work in a biological safety cabinet at all
times, hand free sink. These labs are equipped with directional airflow, and
cannot be recirculated.
BSL 4: these agents are the most dangerous and fatal. These agents are exotic
and can easily be transmitted by inhalation, and cause infections that there are
no treatments or vaccines for. In addition of BSL 3, lab workers must change
their clothing entering the lab, full body PPE suit with designated air supply,
HEPA – filtered air supply and exhaust. Lab must be located in a separate
building or isolated portion of a building with its own air supply and exhaust
system.
3. Define these physical and/or chemical microbial control protocols:
On fomite surfaces
On living tissue
a. Sterilization: the complete removal or killing of all vegetative cells,
endospores, and viruses from the targeted item or environment. Surgical
equipment, needles for injections etc. Uses pressurized steam
(autoclave), chemicals, radiation
i.
Sterilant: chemicals that can be used to achieve sterilization
b. Sanitization: Not sterile. Removes enough microbes to achieve levels
deemed safe for public health. Commercial dishwashers, cleaning
restrooms etc.
c. Disinfectant: Not Sterile, heat or chemicals that kill many microbes
d. Aseptic technique: involves a combo of protocols that collectively
maintain sterility thus preventing contamination of the patient with
microbes and infectious agents
e. Sepsis: systemic inflammatory response to an infection that results in high
fever, increased heart and respiratory rates, shock, and possibly death
f. Asepsis: sterility
g. Antisepsis: the process of applying an antiseptic
h. Antiseptic: Not Sterile, antimicrobial chemicals safe for use on living skin
or tissues that lower microbial counts but don’t remove all
i. Degerming: Physical. Microbial numbers are significantly reduced by
gently scrubbing living tissue with a mild chemical to avoid the
transmission of pathogenic microbes. Soap, alcohol swab
4. Identify required microbial control protocols for the following items:
a. critical items: Critical Items must be sterile because they will be used
inside the body, often penetrating sterile tissue of the bloodstream;
examples include surgical instruments, catheters and intravenous fluids.
b. noncritical items: Items that may contract but not penetrate the skin.
Examples are bed linens, furniture, crutches, stethoscopes and blood
pressure cuffs.
c. semicritical items: Gastrointestinal endoscopes and various types of
equipment for respiratory therapies. Examples; they may contact mucous
membranes or nonintact skin but do not penetrate tissues. These items
typically need to be sterilized, but do not require high levels of disinfection.
5. Recognize the difference between –static and –cidal physical and chemical
methods of microbial control.
Physical and chemical methods of microbial control that kill the targeted
microorganism are identified by the suffix -cide or -cidal.
Other methods do not kill organisms but instead, stop or temporarily halt their
growth making their population static; such methods are identified by the suffix
-stat or -static.
6. Identify how the microbial death curve and the decimal reduction time are
used to evaluate microbial control protocols.
The degree of microbial control can be evaluated using the “microbial death
curve” to describe the progress and effectiveness of a particular protocol (your
control method).
When exposed to a particular microbial control protocol, a fixed % of the
microbes within the population will die. This is because the rate of killing remains
constant even when the population size varies, the % killed is more useful
information than the absolute number of microbes killed.
Death curves are often plotted as semi log plots like microbial growth curves
because the reduction in microorganisms is typically logarithmic. The amount of
time it takes for a specific protocol to produce a one order of magnitude decrease
in the number of organisms, or the death of 90% of the population is called
decimal reduction time (DRT) or D-value.
7. Identify the factors that influence the action of antimicrobial agents.
The length of time of exposure is important. The concentration of disinfecting
agent or intensity of exposure is also important
8. Define thermal death point and thermal death time and recognize the
significance of these numbers.
Thermal death point: (TDP) of a microorganism is the lowest temperature
where all microbes are killed in 10 min exposure.
Thermal death time: (TDT is the length of the time needed to kill all
microorganisms in a sample at a given temperature
9. Differentiate between moist and dry heat sterilization, identify which one is
more efficient, and recognize the reason why.
Moist heat is much more effective than dry heat because boiling water heats up tissues
and inanimate objects faster than dry hot air does. Moist heat penetrates cells better
than dry heat
Example: sticking your hand into an oven preheated to 325°F would take time to burn
your skin; Putting your hand into water that was 200°F would burn your hand
instantaneously.
10. For these heat control methods, 1) identify the time and temperature used,
2) recognize if it is sporicidal (does it kill resistant bacterial spores?), 3)
identify common uses, and 4) recognize limitations.
These are physical methods. Heat can kill by altering cell membranes and
denaturing their proteins.
a. boiling water : One of the oldest methods of moist-heat control, killing
vegetative cells and some viruses
i.
T/T: 100°C at sea level.
ii. Sporicidal: No, boiling is less effective at killing endospores
iii.
Common use: Cooking
iv. Limitations: Not as effective at higher altitudes. Not used anymore
in lab or clinical setting
b. Autoclave: denatures proteins and alters membranes
i. T/T: 121°C for 15 min pressurized steam kills microbes
ii. Sporicidal:
iii.
iv.
Common use: used for heat stable medical/laboratory equipment
and kill spores that boiling water could not kill
Limitations: does not destroy all prions
; this; Incineration:
v.
vi.
vii.
viii.
T/T:
Sporicidal:
Common use:
Limitations:
exposure to flame; destroy by burning; used in flaming loop and
microincinerator
c. Oven:
i. T/T:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
Dry heat. Can sterilize things but it takes longer. 170 degrees celsius for
two hours
d. Pasteurization:
i. T/T:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
HTST is 72°C for 15 minutes; this dentures proteins and alters
membranes; this is used to prevent food spoilage of milk, honey, and other
ingestible liquids
e. high-temperature short-time pasteurization (HTST):
i. T/T: 72°C for 15 minutes
ii. Sporicidal:
iii. Common use: dairy products
iv.
Limitations:
exposes milk to a temp of 72 degrees celsius for 15 seconds, this lowers
bacterial numbers while preserving the quality of milk.
f. ultra-high-temperature pasteurization (UHT) : the milk is exposed to a
temp of 138 degrees celsius for 2 or more seconds. Used for foods that
are not refrigerated.
11. For these cold control methods, identify the temperature used, recognize
how it works, identify whether it is sporicidal (does it kill resistent bacterial
spores?), recognize common uses, and identify limitations
These are physical methods. Slows microbial growth and preserves food and
laboratory products
a. Refrigeration :
i. T/T:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
used in home kitchens or the lab to maintain temps between 0-7 degrees
celsius. This temp range inhibits microbial metabolism, slowing the growth
of microorganisms significantly and helping preserve refrigerated products
such as food or medical supplies.
b. Freezing :
i. T/T:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
Freezing below -2 degrees celcius may stop microbial growth and even kill
susceptible organisms. Bacterial cultures and medical specimens
requiring long-term storage or transport are often frozen at
ultra-low-temperatures of -70 degrees celsius or lower. These ultra low
temperatures can be achieved by storing specimens on dry ice in an ultra
low freezer or in special liquid nitrogen tanks.
12. For these pressure control methods, identify the methods used, recognize
whether it is sporicidal (does it kill resistant bacterial spores?), identify
common uses, and recognize limitations:
These are physical methods.
a. Pascalization:
i.
Methods used:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
in the food industry, high pressure processing (aka pascalization) is used
to kill bacteria, yeast, molds, parasites, and viruses in foods while
maintaining food quality and extending shelf life.
b. hyperbaric oxygen therapy:
i.
Methods used:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
it is sometimes used to treat infections. In this form, a patient breathes
pure oxygen at a pressure higher than normal atmospheric pressure,
typically between 1 and 3 atm. This is done by placing the patient in a
hyperbaric oxygen therapy that helps increase oxygen through a breathing
tube. This helps to increase oxygen saturation, enhances the body’s
immune response by increasing the activities of neutrophils and
macrophages, white blood cells that fight infections.
13. For these desiccation control methods, identify the methods used,
recognize whether it is sporicidal (does it kill resistent bacterial spores?),
identify common uses, and recognize limitations:
These are physical methods.
a. Evaporation i.
Methods used: driving out the water, a necessary component for all
cells (including microbes), through drying (dessicating) out the
environment.
ii. Sporicidal: No
iii. Common uses: Used to preserve foods
iv.
Limitations: May control microbial growth, but does not kill all of it.
b. Lyophilization i.
Methods used: food is rapidly frozen and placed under a vacuum
so that water is lost by sublimation. Freezing while drying
ii. Sporicidal:
iii. Common use: used for food preservation and allows food to be
stored at room temperature
iv.
Limitations:
c. osmotic pressure:
i.
Methods used:
ii. Sporicidal:
iii. Common use:
iv.
Limitations:
adding sugars and salts around the environment to drive the water out of
the cell and thus cause plasmolysis.
14. Define these radiation control methods and identify examples, recognize
their strength, identify how they kill, recognize whether they are sporicidal
(does it kill resistent bacterial spores?), and identify common uses:
These are physical methods.
a. ionizing radiation i.
Examples: X-rays, gamma rays, and high-energy electron beams
ii. Strength: more powerful than non-ionizing radiation
iii.
Mode of action: Radiation penetrates microbes and damages DNA,
ionizes water to make ROS
iv. Sporicidal:
v.
Common use:
ionization affects the DNA of microbes and causes mutations that
eventually lead to death. used to sterilize things that cannot be autoclaved
such as plastic petri dishes, plastic inoculating loops, gloves , IV tubing
and other latex or plastic items. over all sterilizes items that are sensitive
to high heat (tissue, drugs).
b. nonionizing radiation – is commonly used for disinfection and uses less
energy than ionizing radiation. It does not penetrate cells or packaging.
UV light is one example. creates thymine dimers in cell DNA, where DNA
polymerase can not always create complementary nucleotides and thus
kills the microbes. used for consumers and laboratory personnel to control
microbial growth. used in water purification in homes and germicidal lamps
are used in surgical suites, biological safety cabinets and transfer hoods.
emits 260 nm.
15. For these physical control methods, identify the methods used, recognize
whether it sterilizes, identify if it is sporicidal (does it kill resistant bacterial
spores?), and recognize common uses:
These are physical methods. Usually a bit more disruptive.
a. Sonication – The use of high-frequency ultrasound waves to disrupt cell
structures. The waves cause rapid changes in pressure within the
intracellular liquid. This leads to cavitation and formation of bubbles that
eventually lead to collapse or lyse of the cell. Useful for laboratory settings
to lyse cells of their contents for research. Used outside the laboratory for
cleaning surgical instruments, lenses and other objects such as music
instruments.
b. air HEPA filtration – filtration of physically separating microbes from
samples found in the air. have pores small enough to catch bacteria cells,
endospores, and many viruses as air is passed through the filter. used in a
wide variety of environments from cars, airplanes, and in the home. also
used in hospitals in certain instances of burn units, operating rooms, or
isolation units.
c. liquid membrane filtration – used to remove microbes from liquid
samples. used to remove bacteria have an effective pore size of 0.2 µm,
smaller than the average size of a bacterium (1 µm). used for removing
microbes from heat sensitive medium such antibiotic solutions and vitamin
solutions.
16. For each chemical control group listed, identify the mode of action,
recognize whether it is sporicidal (does it kill resistent bacterial spores?),
identify its common uses and recognize limitations.
These are Chemical methods.
a. Phenolics: bisphenol hexachlorophene and triclosan i. Mode of action: Inhibit microbial growth by denaturing proteins and
disrupting membranes
ii. Sporicidal: No
iii. Common use: In antiseptic mouthwashes
iv.
Limitations: Long-term exposure could be harmful (ex, triclosan)
found in antiseptic mouthwashes and throat lozenges. consists of a
benzene ring with an –OH group, tends to be stable, persistent on
surfaces, and less toxic than phenol. inhibit microbial growth by denaturing
proteins and disrupting membranes. Lysol. The bisphenol
hexachlorophene, a disinfectant, is the active ingredient in pHisoHex, a
topical cleansing detergent widely used for handwashing in hospital
settings. Initially used in toothpastes, triclosan has also been used in hand
soaps and impregnated into a wide variety of other products, including
cutting boards, knives, shower curtains, clothing, and concrete, to make
them antimicrobial, banned by FDA
b. Heavy Metals: mercury, silver, copper, and zinc – Heavy metals kill
microbes by binding to proteins, thus inhibiting enzymatic activity. are
oligodynamic, meaning that very small concentrations show significant
antimicrobial activity. Ions of heavy metals bind to sulfur-containing amino
acids strongly and bioaccumulate within cells, allowing these metals to
reach high localized concentrations. causes proteins to denature. Topical
antiseptics such as mercurochrome, which contains mercury in low
concentrations, and merthiolate, a tincture (a solution of mercury dissolved
in alcohol) were once commonly used. Silver used as an antiseptic,
drinking water was stored in silver jugs, treating wounds and burns,
newborn eye care, used with antibiotics. Copper sulfate is a common
algicide used to control algal growth in swimming pools and fish tanks.
Copper linings in incubators help reduce contamination of cell cultures.
Copper coatings are also becoming popular for frequently handled objects
such as doorknobs in health-care facilities in an attempt to reduce the
spread of microbes. Nickel and zinc coatings are now being used in a
similar way. Zinc oxide is found in a variety of products, including topical
antiseptic creams such as calamine lotion, diaper ointments, baby powder,
and dandruff shampoos.
c. Halogens: iodine, chlorine, and fluorine – Iodine works by oxidizing
cellular components, including sulfur-containing amino acids, nucleotides,
and fatty acids, and destabilizing the macromolecules that contain these
molecules, used as a topical tincture, but it may cause staining or skin
irritation. Chlorine gas is commonly used in municipal drinking water and
wastewater treatment plants, with the resulting hypochlorous acid
producing the actual antimicrobial effect. Sodium hypochlorite is the
chemical component of common household bleach, and it is also used for
a wide variety of disinfecting purposes. Chloramines and other cholorine
compounds may be used for disinfection of drinking water. Some may
irritate the skin, nose, or eyes of some individuals, and they may not
completely eliminate certain hardy organisms from contaminated drinking
water (boil water instead). Fluoride is the main active ingredient of
toothpaste and is also commonly added to tap water to help communities
maintain oral health, a bacteriostatic.
d. Alcohols: ethyl alcohol and isopropyl alcohol – commonly used as
disinfectants and antiseptics. They work by rapidly denaturing proteins,
which inhibits cell metabolism, and by disrupting membranes, which leads
to cell lysis. used at concentrations of about 70% aqueous solution.
Alcohols tend to be bactericidal and fungicidal, but may also be viricidal for
enveloped viruses only. not sporicidal, but do inhibit the processes of
sporulation and germination.
e. Surfactants: soaps, quaternary ammonium detergents (quats) – They
can interact with nonpolar oils and grease to create emulsions in water,
loosening and lifting away dirt and microbes from surfaces and skin.
Soaps do not kill or inhibit microbial growth and so are not considered
antiseptics or disinfectants. However, proper use of soaps mechanically
carries away microorganisms, effectively degerming a surface. quats have
the ability to insert into the bacterial phospholipid bilayer and disrupt
membrane integrity. tend to be bactericidal by disrupting membranes.
They are also active against fungi, protozoans, and enveloped viruses, but
endospores are unaffected. may be used as antiseptics or to disinfect
surfaces. Mixtures of quats are also commonly found in household
cleaners and disinfectants (lysol, mouthwash, skin antiseptics).
f. Bisbiguanides: chlorhexidine and alexidine – are cationic (positively
charged) molecules known for their antiseptic properties. Chlorhexidine
disrupts cell membranes and is bacteriostatic at lower concentrations or
bactericidal at higher concentrations, in which it actually causes the cells’
cytoplasmic contents to congeal. It also has activity against enveloped
viruses. It has broad-spectrum activity against yeasts, gram-positive
bacteria, and gram-negative bacteria, is not sporicidal.used in the clinical
setting as a surgical scrub and for other handwashing needs for medical
personnel, as well as for topical antisepsis for patients before surgery or
needle injection.
g. Alkylating agents: formaldehyde & formalin; Glutaraldehyde,
o-phthalaldehyde (OPA), and ethylene oxide – a group of strong
disinfecting chemicals that act by replacing a hydrogen atom within a
molecule with an alkyl group (CnH2n+1), thereby inactivating enzymes
and nucleic acids. Formaldehyde is a strong, broad-spectrum disinfectant
and biocide that has the ability to kill bacteria, viruses, fungi, and
endospores, leading to sterilization at low temperatures. Formaldehyde
(CH2OH) is very irritating to living tissues and is also carcinogenic;
therefore, it is not used as an antiseptic.Glutaraldehyde is structurally
similar to formaldehyde but has two reactive aldehyde groups, allowing it
to act more quickly than formaldehyde. o-Phthalaldehyde is thought to
work similarly to glutaraldehyde and formaldehyde, but is much less
irritating to skin and nasal passages, produces a minimal odor, does not
require processing before use, and is more effective against mycobacteria.
Ethylene oxide is a type of alkylating agent that is used for gaseous
sterilization. It is highly penetrating and can sterilize items within plastic
bags such as catheters, disposable items in laboratories and clinical
settings (like packaged Petri dishes), and other pieces of equipment. it is
carcinogenic, like the other alkylating agents, and is also highly explosive.
h. Peroxygens: hydrogen peroxide, peracetic acid, benzoyl peroxide, ozone
gas – strong oxidizing agents that can be used as disinfectants or
antiseptics. Hydrogen peroxide solutions are inexpensive skin antiseptics
that break down into water and oxygen gas, both of which are
environmentally safe. This decomposition is accelerated in the presence
of light, so hydrogen peroxide solutions typically are sold in brown or
opaque bottles. One disadvantage of using hydrogen peroxide as an
antiseptic is that it also causes damage to skin that may delay healing or
lead to scarring. Hydrogen peroxide works by producing free radicals that
damage cellular macromolecules. Hydrogen peroxide has broad-spectrum
activity, working against gram-positive and gram-negative bacteria (with
slightly greater efficacy against gram-positive bacteria), fungi, viruses, and
endospores. To kill endospores, the length of exposure or concentration of
solutions of hydrogen peroxide must be increased. Gaseous hydrogen
peroxide has greater efficacy and can be used as a sterilant for rooms or
equipment. Peracetic acid can be used as a liquid or plasma sterilant
insofar as it readily kills endospores, is more effective than hydrogen
peroxide even at rather low concentrations, and is immune to inactivation
by catalases and peroxidases. Benzoyl peroxide is a peroxygen that is
used in acne medication solutions. ozone gas is a peroxygen with
disinfectant qualities and is used to clean air or water supplies.
i. Supercritical Carbon dioxide (scCO2) – Supercritical carbon dioxide works
by penetrating cells and forming carbonic acid, thereby lowering the cell
pH considerably. This technique is effective against vegetative cells and is
also used in combination with peracetic acid to kill endospores. non
reactive, nontoxic, and nonflammable properties of carbon dioxide, and
this protocol is effective at low temperatures. preserves the object’s
integrity and is commonly used for treating foods (including spices and
juices) and medical devices such as endoscopes. It is also gaining
popularity for disinfecting tissues such as skin, bones, tendons, and
ligaments prior to transplantation. scCO2 can also be used for pest control
because it can kill insect eggs and larvae within products.
j. Enzymes: Lysozyme and Prionzyme – lysozyme breaks down the
peptidoglycan walls of bacteria. cell wall weakens and lysis. works well
against gram positive bacteria. Prionzyme breaks down prions in
microbes.
17. Identify how these chemical preservatives work, recognize their common
uses, and identify their limitations.
a. sorbic acid
b. propionic acid
c. benzoic acid
d. sulfur dioxide
e. Nitrites
f. Natamycin
g. Nisin
18. Identify how these methods are used to evaluate the effectiveness of
disinfectants and antiseptics:
a. disk-diffusion method: A technique for testing rapidly growing pathogens
b. use-dilution test: Tests how well a disinfectant works on a bacteria that is
already dried on a non-porous object
c. in-use test: Tests specimens before and after they disinfecting agent is
applied
19. Define these terms:
a. Chemotherapy – any use of chemicals or drugs to treat disease
b. antimicrobial drugs – target infectious microorganisms, work by
destroying or interfering with microbial structures and enzymes, kill
microbial cells or inhibit their growth
20. Recognize how these scientists played a role in the development of
antimicrobial drugs:
a. Paul Ehrlich – set out to discover or synthesize chemical compounds
capable of killing infectious microbes without harming patients; compound
606 target the bacterium Treponema pallidum (cause of syphilis);
screened a wide variety of compounds for the discovery of new
antimicrobial agents
b. Alexander Fleming – discovered penicillin, first natural antibiotic, penicillin
is made from mold, is antibacterial
c. Selman Waksman – led a research team that discovered several
antimicrobials (actinomycin, streptomycin, and neomycin); actinomycetes
source more than half of all natural antibiotics and serve as a reservoir for
novel antimicrobial agent discoveries
d. Gerhard Domagk – discovered the antibacterial activity of a synthetic dye
(prontosil) that could treat streptococcal and staphylococcal infections in
mice; worked with sulfanilamide, the active breakdown product of prontosil
in the body, it was the first synthetic antimicrobial, was the foundation for
family of sulfa drugs
e. Dorothy Hodgkin – determined structure of penicillin, now scientists can
modify and create semisynthetic penicillins
21. Define these terms:
a. synthetic antimicrobial
b. natural antibiotic
c. semisynthetic antimicrobial
22. Identify the clinical considerations in prescribing antimicrobial drugs.
23. Define these terms:
a. narrow-spectrum antimicrobial
b. broad-spectrum antimicrobial
24. Recognize the risk associated with using broad-spectrum antimicrobials
and identify how this could lead to a superinfection.
25. Define dosage and identify the factors that contribute to ensuring optimum
therapeutic drug levels.
26. Identify the various routes of administration for antimicrobial drugs
recognizing the plasma concentration as a function of time.
27. Recognize the difference between synergistic and antagonistic drug
interactions.
28. Define the term selective toxicity and recognize why most antimicrobial
agents are antibacterial drugs.
29. Define the term mode of action. – the way in which a drug affects microbes
at the cellular level
30. Identify six (6) modes of action of antimicrobial drugs and recognize their
cellular targets.
31. For these antimicrobial drugs, identify the mode of action and recognize
the microbes they are used against:
a. Beta-lactams
b. vancomycin
c. bacitracin
d. aminoglycosides
e. tetracyclines
f. macrolides
g. polymixins
h. rifamycin
i. fluoroquinolones
j. Antimetabolites
32. Identify why the treatment of fungal, protozoan, and helminth infections is
difficult.
33. For these antimicrobial drugs, identify the mode of action and recognize
the microbes they are used against:
a. Imidazoles – antifungal, disrupts cell membrane
b. Polyenes – antifungal, disrupts cell membrane with pores
c. Polyoxins – antifungal, targets chitin synthesis for fungal cell walls
d. Artemisinin – antiprotozoal, targets metabolic pathway of cells to produce
reactive oxygen species that are damaging to the cell, used for malaria
e. Nitroimidazoles – antiprotozoal, interfere with DNA replication by
breaking DNA strand
f. Quinolones – antiprotozoal, targets metabolic pathway by interfering with
heme detoxification, used for malaria
g. Benzimidazoles – antihelminthic, prevents microtubules formation and
thus mitosis and the cell cycle
h. Ivermectin – antihelminthic, blocks neuronal transmission causing
starvation, paralysis and death of worm
i. Praziquantel – antihelminthic, causes calcium influx resulting in intense
spasms and paralysis of worm
34. Identify why selective toxicity with regard to viral infection is almost
impossible to achieve. Unlike the complex structure of fungi, protozoa, and
helminths, viral structure is simple, consisting of nucleic acid, a protein coat, viral
enzymes, and, sometimes, a lipid envelope. Furthermore, viruses are obligate
intracellular pathogens that use the host’s cellular machinery to replicate. These
characteristics make it difficult to develop drugs with selective toxicity against
viruses.
35. Identify the mechanism of action and recognize the viruses inhibited with
these drugs:
a. Acyclovir – a synthetic analog of the nucleoside guanosine. It is activated
by the herpes simplex viral enzyme thymidine kinase and, when added to
a growing DNA strand during replication, causes chain termination. used
for the treatment of herpes virus infections.
b. Olsetamivir (Tamiflu) – target influenza viruses by blocking the activity of
influenza virus neuraminidase, preventing the release of the virus from
infected cells. Administered orally.
c. AZT – competitive nucleoside analog inhibitor for HIV infection.
d. Etravirine – non-nucleoside noncompetitive inhibitor that binds reverse
transcriptase and causes an inactivating conformational change. HIV
e. Ritonavir – protease inhibitor that blocks the processing of viral proteins
and prevents viral maturation. HIV
f. Enfuviritide – a fusion inhibitor which prevents the binding of HIV to the
host cell coreceptor (chemokine receptor type 5 [CCR5]) and the merging
of the viral envelope with the host cell membrane, respectively.
36. Define Drug Resistance and identify the factors that contribute to it.
37. Identify two genomic changes that can cause drug resistance.
38. Identify how exposure to an antimicrobial drug can lead to drug resistant
populations.
39. Recognize these drug resistance mechanisms of action:
a. Drug modification or inactivation – Resistance genes may code for
enzymes that chemically modify an antimicrobial, thereby inactivating it, or
destroy an antimicrobial through hydrolysis.
b. Cellular uptake prevention or efflux – Microbes may develop resistance
mechanisms that involve inhibiting the accumulation of an antimicrobial
drug, which then prevents the drug from reaching its cellular target. This
can involve changes in outer membrane lipid composition, porin channel
selectivity, and/or porin channel concentrations. Additionally, many
gram-positive and gram-negative pathogenic bacteria produce efflux
pumps that actively transport an antimicrobial drug out of the cell and
prevent the accumulation of drug to a level that would be antibacterial.
c. Target modification – Because antimicrobial drugs have very specific
targets, structural changes to those targets can prevent drug binding,
rendering the drug ineffective. Change active site or give it low affinity for
binding drug
d. Target overproduction – the microbe may overproduce the target enzyme
such that there is a sufficient amount of antimicrobial-free enzyme to carry
out the proper enzymatic reaction.
e. Target mimicry – involves the production of proteins that prevent drugs
from binding to their bacterial cellular targets.
f. Enzymatic bypass – the bacterial cell may develop a bypass that
circumvents the need for the functional target enzyme.
40. Identify the difference between:
a. multiple drug resistant microbes (MDRs) – known as “superbugs” and
carry one or more resistance mechanism(s), making them resistant to
multiple antimicrobials.
b. Cross-resistance – a single resistance mechanism confers resistance to
multiple antimicrobial drugs.
41. Recognize the testing of antimicrobial effectiveness with these procedures:
a. Kirby-Bauer Disk Diffusion Susceptibility test (include term zone of
inhibition)
b. Minimum Inhibitory Concentration (MIC)
c. Minimum Bactericidal Concentration (MBC)
d. Macrobroth dilution test
e. Etests
42. Identify the current strategies for antimicrobial discovery.
Week 6 Pathogenicity and Disease Tracking
1. Define and identify the difference between:
a. infection (colonization of a host by a microbe) and disease (a condition
in which normal body structure and function are damaged):
Infections are often the first step and can lead to disease, though not
always.
b. signs (objective and measurable observation that can be made by
another person; ex. high blood pressure) and symptoms (subjective
feelings and experiences by the patient; ex. headaches):
Symptoms can’t be objectively measured or clincally confirmed- they are
felt by the person!
2. Define:
a. Syndrome – A specific group of signs and symptoms characteristic of a
particular disease
b. asymptomatic or subclinical – diseases that do not present any
noticeable signs or symptoms.
c. zoonotic disease – a disease that is transmitted from an animal to a
human.
3. Identify the difference between these diseases:
a. infectious and noninfectious – An infectious disease is any disease
caused by the direct effect of a pathogen. A pathogen may be cellular
(bacteria, parasites, and fungi) or acellular (viruses, viroids, and prions).
Noninfectious diseases are diseases that people are born with or can
develop such as genetics, immune dysfunction, sickle cell anemia.
b. communicable, contagious, and noncommunicable – Communicable
can be spread from person to person through direct and indirect
mechanisms. Contagious diseases are easily spread from person to
person. Non communicable diseases are not spread from person to
person. ex tetanus, legionnaires disease. people can get it from objects
from endospores but can not spread it to another person.
c. iatrogenic and nosocomial – Iatrogenic diseases are contracted from
medical procedures such as wound treatments, catheterization or surgery
if the wound becomes contaminated, infections from the actual procedure
itself. Nosocomial diseases are acquired in hospital settings. Sick patients
bring numerous pathogens into hospitals and these pathogens can be
transmitted easily via improperly sterilized medical equipment, bed sheets,
call buttons, door handles, or by clinicians, nurses, or therapists who do
not wash their hands before touching a patient. Many hospital patients
have weakened immune systems, making them more susceptible to
infections.
4. Identify and recognize the characteristics of the five periods of disease.
5. Identify the duration of the illness period for the following diseases:
a. acute disease – pathologic changes occur over a relatively short time
(e.g., hours, days, or a few weeks) and involve a rapid onset of disease
conditions. Common flu.
b. chronic diseases – pathologic changes can occur over longer time spans
(e.g., months, years, or a lifetime). Hepatitis B.
c. latent diseases – the causal pathogen goes dormant for extended
periods of time with no active replication. Chickenpox to shingles.
6. Identify the four steps of Koch’s postulates.
Koch’s Postulates
(1) The suspected pathogen must be found in every case of disease and not
be found in healthy individuals.
(2) The suspected pathogen can be isolated and grown in pure culture.
(3) A healthy test subject infected with the suspected pathogen must develop
the same signs and symptoms of disease as seen in postulate 1.
(4) The pathogen must be re-isolated from the new host and must be identical
to the pathogen from postulate 2.
7. Recognize how virulence is related to pathogenicity.
The ability of a microbial agent to cause disease is called
pathogenicity, and the degree to which an organism is pathogenic is called
virulence. Virulence is a continuum. On one end of the spectrum are organisms
that are avirulent (not harmful, possibly asymptomatic) and on the other are
organisms that are highly virulent (severe illness).
8. Identify the difference between median infectious dose (ID50) and median
lethal dose (LD50).
Two important indicators of virulence are the median infectious
dose (ID50) and the median lethal dose (LD50), both of which are typically
determined experimentally using animal models. The ID50 is the number of
pathogen cells or virions required to cause active infection in 50% of inoculated
animals. The LD50 is the number of pathogenic cells, virions, or amount of toxin
required to kill 50% of infected animals.
9. Identify the characteristic of the following types of pathogens:
a. Primary – can cause disease in a host regardless of the host’s resident
microbiota or immune system.
b. Opportunistic – can only cause disease in situations that compromise the
host’s defenses, such as the body’s protective barriers, immune system,
or normal microbiota.
10. Identify the following stages of pathogenesis and recognize the process by
which they occur:
a. Exposure – An encounter with a potential pathogen, aka contact
b. adhesion – refers to the capability of pathogenic microbes to attach to the
cells of the body using adhesion factors at the portal of entry
c. invasion – involves the dissemination/spread of a pathogen throughout
local tissues or the body. Pathogens may produce exoenzymes or toxins,
which serve as virulence factors that allow them to colonize and damage
host tissues as they spread deeper into the body. Pathogens may also
produce virulence factors that protect them against immune system
defenses.
d. Infection – successful multiplication of the pathogen leads to infection.
Can be described as local, focal, or systemic. microorganisms begin to
colonize at the attacked area.
11. Identify the body’s portals of entry and recognize their importance to the
infection process.
12. Differentiate between these types of infections:
a. Local – is confined to a small area of the body, typically near the portal of
entry.
b. Focal – a localized pathogen, or the toxins it produces, can spread to a
secondary location.
c. Systemic – when an infection becomes disseminated throughout the
body
d. primary/secondary – Sometimes a primary infection, the initial infection
caused by one pathogen, can lead to a secondary infection by another
pathogen. Opportunistic pathogens!
13. Identify the body’s portals of exit and recognize how their secretions and
excretions help transmit pathogens.
Some examples of portals of exit are through the mouth, nose, anus, urethra, etc.
The secretions help transmit the pathogens because it serves as a carrier. The
mouth has saliva, the nose has mucus, the urethral secretions are urine, and
coming into contact with these secretions exposes one to the possible pathogens
a person may carry.
14. Recognize how septicemia can lead to shock and death.
15. Recognize the importance of virulence factors.
16. Identify the role the following exoenzymes play in host cell invasion:
a. Hyaluronidase – degrades the glycoside hyaluronan (hyaluronic acid),
which acts as an intercellular cement between adjacent cells in connective
tissue. This allows the pathogen to pass through the tissue layers at the
portal of entry and disseminate elsewhere in the body
b. Proteases – Degrades collagen in connective tissue to promote spread,
protein-digesting enzymes, collagenase allows the pathogen to penetrate
and spread through the host tissue by digesting this connective tissue
protein.
17. Define toxin.
biological poison that assists in a pathogen’s ability to invade and
cause damage to tissues
18. Identify the endotoxin and recognize how our body responds to it.
19. Recognize the differences between endotoxins and exotoxins.
20. Identify how the following exotoxins increase invasion of and damage to
host tissues.
a. cholera enterotoxin
b. botulinum neurotoxin
c. tetanus neurotoxin
d. diphtheria exotoxin
e. streptolysin
f. phospholipases
g. superantigens
21. Recognize the role the following play in host immune system evasion:
a. capsules
b. M protein
c. coagulase
d. antigenic variation
e. proteases
f. mycolic acid
g. kinases
22. Identify how these contribute to Influenza viral virulence:
a. adhesions
b. antigenic drift
This is when a pathogen changes slightly over time, to where it appears slightly different
to one’s immune system. As a result of it looking different the human immune system
does not recognize this virus and thus does not attack as soon as it’s noticed. It is in this
way that some infections and viruses persist in many populations.
c. antigenic shift
This is when the genes of one virus combine with the genes of another to create a new
strain that the body does not recognize. It is because of this that vaccines are taken
annually, because diseases themselves do not stay the same, therefore the treatments
and preventive measures shouldn’t stay the same either.
23. Identify the virulence factors used by the following eukaryotic pathogens:
a. fungi
b. protozoa
c. helminths
24. Define the following terms associated with the patterns of disease
distribution:
a. epidemiology
b. morbidity
c. mortality
d. incidence
e. prevalence
f. etiological agent
g. endemic
h. sporadic
i. epidemic
j.
pandemic
25. Recognize the difference between common source vs. propagated spread
of infectious disease.
26. Define each of the following terms and recognize its role in pathogen
transmission:
a. reservoir
b. passive carrier
c. active carrier
d. asymptomatic carrier
27. Recognize each of these modes of transmission:
a. direct contact:
Vertical: from mother to baby
Horizontal: from person to person contact; coughing, sneezing, hugging, etc,
aerosol droplet
b. indirect contact: fomite
Coming into contact with an inanimate object that has been contaminated by an infected
person
c. vehicle: airborne, waterborne, foodborne
d. vector: mechanical, biological
28. Recognize the significance of healthcare-associated (nosocomial)
infections (HAIs).
29. Identify the role of the Centers for Disease Control and Prevention (CDC) in
the U.S.
30. Identify the role of the World Health Organization (WHO).
31. Identify the difference between emerging and reemerging infection
diseases.

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