Devbio Notes 2018-2019

• DEVELOPMENTAL IMMUNOLOGY
• The body’s capability to react to antigens depends on:
1. person's age,
2. antigen type,
3. maternal factors
4. area where the antigen is presented
• Neonates are said to be in a state of physiological immunodeficiency, because both their innate
and adaptive immunological responses are greatly suppressed.
• Once born, a child’s immune system responds favorably to protein antigens while not as well
to glycoproteins and polysaccharides
• In fact, many of the infections acquired by neonates are caused by low virulence organisms:
Staphylococcus Pseudomonas
• In neonates, opsonic activity and the ability to activate the complement cascade is very limited.
For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult.
• Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as
well as diminished up-regulation of integrin and selectin receptors, which limit the ability
of neutrophils to interact with adhesion molecules in the endothelium.
• Their monocytes are slow and have a reduced ATP production, which also limits the newborn's
phagocytic activity. Although, the number of total lymphocytes is significantly higher than in
adults, the cellular and humoral immunity is also impaired.
• Antigen-presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of
a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-
12, and IFN-g which limits their capacity to activate the humoral response as well as the
phagocytic activity of macrophage. B cells develop early during gestation but are not fully active.
• Maternal factors also play a role in the body’s immune response
• At birth, most of the immunoglobulin present is maternal IgG. Because IgM, IgD, IgE and IgA
don’t cross the placenta, they are almost undetectable at birth.
• Some IgA is provided by breast milk. These passively-acquired antibodies can protect the
newborn for up to 18 months, but their response is usually short-lived and of low affinity.
• These antibodies can also produce a negative response. If a child is exposed to the antibody for
a particular antigen before being exposed to the antigen itself then the child will produce a
dampened response.
• Passively acquired maternal antibodies can suppress the antibody response to active
immunization.
• Similarly the response of T-cells to vaccination differs in children compared to adults, and
vaccines that induce Th1 responses in adults do not readily elicit these same responses in
neonates.
• Between six and nine months after birth, a child’s immune system begins to respond more
strongly to glycoproteins, but there is usually no marked improvement in their response
to polysaccharides until they are at least one year old. This can be the reason for distinct time
frames found in vaccination schedules.
• During adolescence, the human body undergoes various physical, physiological and
immunological changes triggered and mediated by hormones, of which the most significant in
females is 17-β-oestradiol (an oestrogen) and, in males, is testosterone.
• Oestradiol usually begins to act around the age of 10 and testosterone some months
later. There is evidence that these steroids not only act directly on the primary and secondary
sexual characteristics but also have an effect on the development and regulation of the immune
system
• There is also some evidence that cell surface receptors on B cells and macrophages may detect
sex hormones in the system.
• The female sex hormone 17-β-oestradiol has been shown to regulate the level of immunological
response, while some male androgens such as testosterone seem to suppress the stress
response to infection. Other androgens, however, such as DHEA, increase immune response.
• The male sex hormones seem to have more control of the immune system during puberty and
post-puberty than during the rest of a male's adult life.
• Physical changes during puberty such as thymic involution also affect immunological response.
• CLASSICAL IMMUNOLOGY
• Classical immunology ties in with the fields of epidemiology and medicine.
• It studies the relationship between the body systems, pathogens, and immunity.
• Immunology alone is the study of response of an organism to antigenic challenge and its
recognition of what is self and what is not.
• It deals with the defense mechanisms including all physical, chemical and biological properties
of the organism that help it to combat its susceptibility to foreign organisms, material, etc.
• Classical immunology deals with the relationship between the body systems, pathogens, and
immunity.
• The earliest written mention of immunity can be traced back to the plague of Athens in 430
BCE.
• Thucydides noted that people who had recovered from a previous bout of the disease could
nurse the sick without contracting the illness a second time.
• Many other ancient societies have references to this phenomenon, but it was not until the
19th and 20th centuries before the concept developed into scientific theory.
• Studying the immune system
• The immune system is studied as per its molecular and cellular components. Their function
and interaction form the core of study of immunology as we know today.
• The immune system is divided into those which are static, or innate to the organism, and
those which are responsive, or adaptive to a potential pathogen or foreign substance.
• To maintain the integrity of our organism, it is essential to distinguish between self and non-
self.
• Early in evolution, simple multicellular organisms developed a defense system activated by

sensing typical molecules and chemical structures associated with pathogens.
• This system is evolved to its present day immunology.
• This innate, prefabricated, one-size-fits-all immune system is immediately available. It stops

the pathogens and keeps an infection in check for a few days.
• After the first defense is overwhelmed the adaptive immune system kicks in.
• The humoral response is a response of antibodies produced by the body to antigens.
• Antibodies are specific proteins released from a certain class of immune cells (B lymphocytes).
• Antigens are proteins or chemicals or even living organisms that elicit generations of
antibodies, hence they are called “Anti”body “Gen”erators.
• Immunology is the study of these two biological entities.
• Once exposed to antigens the body mounts a cellular response.
• This can kill infected cells in its own right and also controls the level of antibody response.
• The whole system is a highly balanced one and there are disorders of both under-active as
well as over-active immune system.
• Both activities are highly interdependent.
• In this century immunology has spread its frontiers with much research being performed in
the more specialized niches of immunology.
• This includes the immunological function of cells, organs and systems not normally associated
with the immune system along with studies of classical models of immunity.
Clinical Immunology – is the study of diseases caused by disorders of the immune system (failure and
malignant growth of the cellular elements of the system). It also involves diseases of other systems,
where reactions play a part in the pathology and clinical features.
The diseases caused by disorders of the immune system fall into two broad categories:
1) Immunodeficiency, in which parts of the immune system fail to provide an adequate response.
2) Autoimmunity, in which the immune system attacks its own host’s body.
Other immune system disorders include various hypersensitivities (such as in asthma and other
allergies) that respond inappropriately to otherwise harmless compounds.
The most well-known disease that affects the immune system itself is AIDS, an immunodeficiency
characterized by the suppression of CD4+ (“helper”) T cells, dendritic cells and macrophages by the
Human Immunodeficiency Virus (HIV).
Clinical Immunologists also study ways to prevent the immune system’s attempts to destroy allografts
(transplant rejection)
The Mount Sinai Hospital has been involved in immunology since early in the 20th century, when
immunology was in its infancy. A crucial clinical test called the Schick test was invented by Dr. Béla
Schick, a Mount Sinai physician from 1923 to 1936. It is used to determine whether or not a person is
susceptible to diphtheria. Dr. Schick and Dr. Clemens von Pirquet first coined the term “allergy” as a
clinical diagnosis.
In 1930, Dr. Joseph Harkavy and his colleagues at Mount Sinai identified a new chemical substance that
is released during severe allergic reactions. The substance is what immunologists now call SRS-A, or
slow-reacting substance of anaphylaxis. Dr. Harkavy was also the first to link cigarette and cigar smoking
to allergies and cardiovascular disease.
The Division of Allergy and Clinical Immunology was found in 1978.
1) From Edward Jenner’s pioneering work in the 18th Century that would ultimately lead to vaccination
in its modern form (an innovation that has likely saved more lives than any other medical advance).
2) To the many scientific breakthroughs in the 19th and 20th centuries that would lead to, amongst other
things, safe organ transplantation, the identification of blood groups, and the now ubiquitous use of
antibodies.
• History of Biotechnology
• Stages of Biotech
 Ancient
 Classical
 Modern
• Ancient Biotech
 Begins with early civilization
 Developments in ag and food production
 Few records exist
• Ancient Biotech
 Archeologists research
 Ancient carvings and sketches sources of information
• Classical Biotech
 Follows ancient
 Makes wide spread use of methods from ancient, especially fermentation
 Methods adapted to industrial production
 Produce large quantities of food products and other materials in short amount of time
 Meet demands of increasing population
 Many methods developed through classical biotech are widely used today.
• Modern Biotech
 Manipulation of genetic material within organisms
 Based on genetics and the use of microscopy, biochemical methods, related sciences and
technologies
• Modern Biotech
 Often known as genetic engineering
 Roots involved the investigation of genes
• Ancient Biotech
 Not known when biotech began exactly
 Focused on having food and other human needs
• Ancient Biotech
 Useful plants brought from the wild, planted near caves where people lived
 As food was available, ability to store and preserve emerged
• Ancient
 Food preservation most likely came from unplanned events such as a fire or freeze
• Domestication
 15,000 years ago, large animals were hard to capture
 People only had meat when they found a dead animal
 Came up with ways of capturing fish and small animals
• Domestication
 Food supplies often seasonal
 Winter food supplies may get quite low
 Domestication is seen by scientists as the beginning of biotech
• Domestication
 Adaptation of organisms so they can be cultured
 Most likely began 11,000 – 12,000 years ago in the middle east
• Domestication
 Involved the collecting of seed from useful plants and growing crude crops from that seed
 Involved the knowledge that the seed had to properly mature
• Domestication
 Proper planting
 Need for water, light and other conditions for plant growth
 Earliest plants likely grains and other seeds used for food
• Domestication
 Raising animals in captivity began about the same time in history
 Easier to have an animal close by that to hunt and capture a wild one
• Domestication
 Learned that animals need food and water
 Learned about simple breeding
 How to raise young
• Domestication
 Cattle, goats and sheep were the first domesticated food animals
• Domestication
 About 10,000 years ago, people had learned enough about plants and animals to grow their own
food
 The beginning of farming.
• Food
 Domestication resulted in food supplies being greater in certain times of the year
 Products were gathered and stored
• Food
 Some foods rotted
 Others changed form and continued to be good to eat
 Foods stored in a cool cave did not spoil as quickly
• Food
 Foods heated by fire also did not spoil as quickly
 Immersing in sour liquids prevented food decay

• Food preservation
 Using processes that prevent or slow spoilage
 Heating, cooling, keeps microorganisms (mo’s) from growing
• Food preservation
 Stored in bags of leather or jars of clay
 Fermentation occurs if certain mo’s are present
 Creates an acid condition that slows or prevents spoilage
• Cheese
 One of the first food products made through biotechnology
 Began some 4,000 years ago
 Nomadic tribes in Asia
• Cheese
 Strains of bacteria were added to milk
 Caused acid to form
 Resulting in sour milk
• Cheese
 Enzyme called “rennet” was added
 Rennet comes from the lining of the stomachs of calves
• Cheese
 Rennet is genetically engineered today
 Not all cheese is made from produced rennet
• Yeast
 Long used in food preparation and preservation
 Bread baking
 Yeast produces a gas in the dough causing the dough to rise

• Yeast
 Fermented products
 Vinegar
 Require the use of yeast in at least one stage of production
• Yeast
 Species of fungi
 Some are useful
 Some may cause diseases
• Vinegar
 Ancient product used to preserve food
 Juices and extracts from fruits and grains can be fermented
• Fermentation
 Process in which yeast enzymes chemically change compounds into alcohol
 In making vinegar the first product of fermentation is alcohol
• Fermentation
 Alcohol is converted to acetic acid by additional microbe activity
 Acid gives vinegar a sour taste
 Vinegar prevents growth of some bacteria
• Vinegar
 Keeps foods from spoiling
 Used in pickling
 Biblical references to wine indicate the use of fermentation some 3,000 years ago
• Fermentation control
 In ancient times, likely happened by accident
 Advancements occurred in the 1800’s and early 1900’s

• Fermenters
 Used to advance fermentation process
 Specially designed chamber that promotes fermentation
• Fermenters
 Allowed better control, especially with vinegar
 New products such as glycerol, acetone, and citric acid resulted
• Development
 Of yeasts that were predictable and readily available led to modern baking industry
• Antibiotics
 Use of fermentation hastened the development of antibiotics
 A drug used to combat bacterial infections
• Antibiotics
 Penicillin
 Developed in the late1920’s
 Introduced in the 1940’s
 First drug produced by microbes
• Antibiotics
 Many kinds available today
 Limitations in their use keep disease producing organisms from developing immunity to
antibiotics
• Antibiotics
 Use antibiotics only when needed.
 Overuse may make the antibiotic ineffective when really needed later
• Antibiotics
 Some disease organisms are now resistant to certain antibiotics
 Used in both human and vet medicine

• Modern Biotech
 Deals with manipulating genetic info
 Microscopy and advanced computer technology are used
 In-depth knowledge of science
• Modern Biotech
 Based on genetics research from the mid 1800’s
• Genetics
 Study of heredity
 Most work has focused on animal and plant genetics
 Genes – determiners of heredity
• Genes
 Carry the genetic code
 Understanding genetic structure essential for genetic engineering
• Heredity
 How traits are passed from parents to offspring
 Members of the same species pass the characteristics of that species
• Heredity
 Differences exist within each species.
 Differences are known as variability
• Heredity &variability
 Are used in modern biotechnology
• Modern Biotech
 Use of biotech to produce new life forms
 Emerged in mid 1900’s
 Made possible by rDNA technology

• rDNA
 Recombinant DNA Process
 Genetic material is moved from one organism to another
 Materials involved are quite small
• rDNA
 Challenging and often controversial
 Many have opposing or negative views of biotechnolgy
• People in Biotech
 Zacharias Janssen
 Discovered the principle of the compound microscope in 1590
 Dutch eye glass maker
• Anton Van Leeuwenhoek
 Developed single lens microscope in 1670’s
 First to observe tiny organisms and document observations
• Anton V.L.
 Work led to modern microscopes
 Electron microscope developed in 1931 by group of German scientists
• Gregor Mendel
 Formulated basic laws of heredity during mid 1800’s
 Austrian Botanist and monk
 Experimented with peas
• Mendel
 Studied inheritance of seven pairs of traits
 Bred and crossbred thousands of plants
 Determined that some traits were dominant and other recessive

• Mendel
 Findings were published in 1866
 Largely ignored for 34 years
• Johan Friedrich Miescher
 Swiss Biologist
 Isolated nuclei of white blood cells in 1869
 Led to identification of nucleic acid by Walter Flemming
• Walter Sutton
 Determined in 1903 that chromosomes carried units of heredity identified by Mendel
 Named “genes” in 1909 by Wilhelm Johannsen, Danish Botanist
• Thomas Hunt Morgan
 Studied genetics of fruit flies
 Early 1900’s
 Experimented with eye color
 His work contributed to the knowledge of X and Y chromosomes
• Thomas Hunt Morgan
 Nobel Peace Prize in 1933 for research in gene theory
• Ernst Ruska
 Build the first electron microscope in 1932
 German electrical engineer
 Microscope offered 400X magnification
• Alexander Fleming
 Discovered penicillin in 1928
 First antibiotic drug used in treating human disease
 Observed growth of molds (Penicillium genus) in a dish that also contracted bacteria
 Bacteria close to the molds were dead
 Extracting and purifying the molds took a decade of research
 Penicillin first used in 1941
 Penicillin credited with saving many lives during WWII when wounded soldiers developed
infections.
• Rosalind Elsie Franklin
 Research in France and England in mid 1900’s
 Led to discovery of structure of DNA
 Her early research was used to produce an atomic bomb
• Rosalind Franklin
 Set up X ray diffraction lab
 Photographs of DNA showed that it could have a double helix structure
• Rosalind Franklin
 Some questions surround the theft of her work in 1952
 Including x ray photographs
• Watson and Crick
 James Watson
 Francis Crick
 Collaborated to produce the first model of DNA structure in 1953
• Watson and Crick
 Described DNA dimensions and spacing of base pairs
 Had major impact on genetic engineering carried out today
• Watson
 Born in the US
 Crick – born in England
 Collaborative research at Cambridge University in England
• Norman E. Borlaug
 Developed wheat varieties producing high yields
 Research in Mexico
 Semi dwarf varieties
 Developed wheat variety that would grow in climates where other varieties would not
• Borlaug
 Nobel Peace Prize in 1971
 Credited with helping relieve widespread hunger in some nations
• Mary Clare King
 Research into nature of DNA during late 1900’s
 Determined that 99% of human DNA is identical to chimpanzee
• Mary Clare King
 1975 found similar gene pools between humans and chimpanzee made it possible to research
hereditary causes of breast cancer
• Ian Wilmut
 Cloning of a sheep named Dolly in 1997
 Produced from tissue of an adult sheep
 Previous cloning efforts had been from early embryos
• Research
 Use of systematic methods to answer questions.
 Problems may be basic or applied
• Basic
 Require generating new info to gain understanding
 Applied – involve use of knowledge already acquired.

• Research
 Supplies facts that can be used to improve a process or product
 Settings range from elaborate labs to field plots
• Field Plot
 Small area of land that is used to test questions or hypothesis
 Belief is that same result would be obtained if carried out on larger scale
• Field Plots
 Often tested several times
 Known as replication
• Research
 Done by agencies, universities, private companies, individuals
 Biotech research in ag is carried out by ag experiment stations and large corporations
• Development
 Creation of new products or methods based on findings of research
 Carefully studied before being put into full scale use
• Development
 New products tested before approval
 Government agencies such as the FDA are involved
 Prototype is developed – research model that is carefully tested
• Prototype
 Becomes a pattern for the production of similar products
 After being fully tested, full scale production begins.

• The Biotechnology Century and Its Workforce
• Chapter 1 Contents
• 1.1 What Is Biotechnology and What

Does It Mean to You?
• 1.2 Types of Biotechnology
• 1.3 Biological Challenges of the 21st

Century
• 1.4 The Biotechnology Workforce
• 1.1 What Is Biotechnology and What Does It Mean to You?
• Biotechnology – using living organisms, or the products of living organisms, for human benefit
to make a product or solve a problem
• Historical Examples
– Fermentation
– Selective breeding
– Use of antibiotics
• Example of Biotechnology – Selective Breeding
• What feature of Casper makes it a "model organism" to study migration of cancer cells
compared to wildtype fish?
• Based on this tree,

can you become
successful in the
biotech industry
only studying
biology?
• Modern Examples
– Gene cloning
– Genetic engineering
– Recombinant DNA technology
– Human Genome Project
• Example of "modern" biotechnology:
– recombinant DNA technology started modern biotech as an industry
• Examples of applications
– development of disease-resistant plants
– food crops that produce greater yields
– "golden rice" engineered to be more nutritious
– genetically engineered bacteria that can degrade environmental pollutants
• Work in groups to come up with more examples of applications
• Look at the two chromosomes and determine which chromosome has more than one gene
involved in promoting breast cancer. Explain your answer.
– Now use the link to further study the diseases involved in these chromosomes
• http://ghr.nlm.nih.gov/chromosome
• Most drugs are developed to combat diseases affecting humans – Why?
• Which disease has the most drug candidates? Why does that disease have more drug
candidates than hepatitis C?
• Use genetically modified cultured cells to make protein of interest

• Products of Modern Biotechnology
– Example of proteins created by gene cloning called recombinant proteins
• Microbial Biotechnology
• Agricultural Biotechnology
• Animal Biotechnology
• Forensic Biotechnology
• Bioremediation
• Aquatic Biotechnology
• Medical Biotechnology
• Regulatory Biotechnology
• Microbial Biotechnology – manipulation of microorganisms such as yeast and bacteria
– Create better enzymes
– More efficient decontamination processes for industrial waste product removal
– Used to clone and produce large amounts of important proteins used in human
medicine
– United Nations Food and Agricultural Org. predicts by 2050, we will need to feed a
world population of 9.1 billion! This requires raising food production by approximately
70%!
– Work in groups to brainstorm a few solutions to better feed the world by 2050.
– Plants more environmentally friendly that yield more per acre (genetically engineered)
– Resistance to diseases and insects

– Foods with higher protein or vitamin content
– Drugs developed and grown as plant products
– These better plants ultimately reduce production costs to help feed the growing world
population
– Work in groups to discuss how you can use this technology in a third world country to
create a better corn crop (main crop in that country) that contains all of the 22
essential amino acids.
• Will improved crops that are created to satisfy world hunger reduce available land for biofuel
crops? Discuss in groups.
– Animals as a source of medically valuable proteins
• Antibodies
• Transgenic animals
– Animals as important models in basic research
• Gene "knockout" experiments
• Design and testing of drugs and genetic therapies
– Animal cloning
• Source of transplant organs
– transgenic animal: way to achieve large scale production of therapeutic proteins from
animals for use in humans
– Female transgenic animals express therapeutic proteins in milk (contains genes from
another source)
– Example: human genes coding for clotting proteins can be introduced into female goats
for production of these proteins in their milk
– Gene knockout:
• Disrupt a gene in the animal and then look at what functions are affected in the
animal as a result of the loss of the gene
• This allows researchers to determine the role and function of the gene
• Since humans are similar to rats and mice, gene knockout studies in rats and
mice can lead to better understanding of gene function in humans.
• Work in groups and give an example of a gene you would like to knockout in mice.
– DNA fingerprinting
• Inclusion or exclusion of a person from suspicion
• Paternity cases
• Identification of human remains
• Endangered species
• Tracking and confirmation of the spread of disease
• Based on DNA results

from this gel, did the
defendant commit this
crime? Explain based
on the gel results.
• Bioremediation
– The use of biotechnology to process and degrade a variety of natural and manmade
substances
• Particularly those that contribute to environmental pollution
– Example – stimulated growth of bacteria that degrade components in crude oil
• 1989 Exxon Valdez oil spill in Alaska
• 2010 Deep Water Horizon spill promoted research into natural oil-degrading
organisms and enzymes
• Bioremediation – adding nutrients to stimulate growth of bacteria to clean up oil spill
– Aquaculture – raising finfish or shellfish in controlled conditions for use as food sources
• 50% of all fish consumed by humans worldwide
– Genetic engineering
• Disease-resistant strains of oysters
• Vaccines against viruses that infect salmon and

other finfish
• Transgenic salmon that overproduce growth hormone
http://www.webmd.com/food-recipes/news/20100922/genetically-engineered-salmon-faq
– Bioprospecting: rich and valuable sources of new genes, proteins and metabolic
processes with important applications for human benefits
• Marine plankton and snails found to be rich sources of antitumor and anticancer
molecules
• Why create transgenic salmon overproducing growth hormone?
• How does this modified salmon help humans?

• Medical Biotechnology
– Involved with the whole spectrum of human medicine
• Preventive medicine
• Diagnosis of health and illness
• Treatment of human diseases
– New information from Human Genome Project
• Gene therapy
– Stem cell technologies
• Stem cells – grown in lab and then treated with different chemicals to allow them to develop
into specific kinds of tissues needed for transplant
• Current use: stem cells are used for diabetes; spinal cord injuries
• Work in groups to come up with a list of other diseases you have read about in the newspaper
or heard on the news that scientists are testing with stem cells.
• Medical biotechnology
– Genes are headline news items
• Regulatory Biotechnology
– Quality Assurance (QA)
• All activities involved in regulating the final quality of

a product
– Quality Control (QC)
• Part of QA process that involves lab testing and

monitoring of processes and applications to ensure consistent product
standards
• Together QA and QC ensure that biotechnology products meet strict standards
for purity and performance
• Why as a consumer should you care about a product undergoing intense regulations?
• 1.3 Biological Challenges of the 21st Century
• How will medical biotechnology change our lives in the years ahead?
– Human Genome Project
• Research on the function of human genes and controlling factors that regulate
genes
– Human proteome
• Collection of proteins responsible for activity in a

human cell
– Single Nucleotide Polymorphisms (SNPs)
• Single nucleotide changes (mutations) in DNA sequences that vary from

individual to individual
• These variations are the cause of some genetic diseases (sickle cell anemia)
• SNPs will help identify genes involved in medical conditions including arthritis,
stroke, cancer, heart disease, diabetes, and behavioral and emotional illnesses
• Example of SNPs and breast cancer
• Identification of SNPs in BRCA1 and BRCA2 genes involved in promoting breast cancer led to
development of better targeted treatments for people who have those specific gene mutations
• Can you think of how this knowledge might be useful for someone who is not already
diagnosed with cancer? (Hint: think of your basic knowledge of genetics.)
• Example of how we can benefit from the human genome project
• Based on the figure, why doesn't person 2 develop a genetic disease due to the SNP (G → T)?
• How can you test one person's DNA for many different SNPs?
• Microarray (gene chip)
– Isolate DNA from patient
– Apply this sample to a microarray which contains many DNA sequences
– Compare patterns of DNA binding between patient's DNA and DNA on microarray to
reveal patient's SNP patterns
– Pharmacogenomics is customized medicine
• Tailor-designing drug therapy and treatment strategies based on the genetic

profile of a patient
– Do microarray analysis and then design drugs against genes that are
mutated for an individual patient
– Metabolomics
• A snapshot of the small molecules produced during cellular metabolism
– Glucose, cholesterol, ATP, and signaling molecules
– Can distinguish between disease process and physiological adaptation
– Nanotechnology
• Applications that
incorporate extremely
small devices
• Small particles that

can deliver drugs
to cells

• Gene therapy technology
– Replacing or augmenting defective genes with normal copies of the gene
• Still have barriers to overcome before this technology becomes safe and
effective
• Obstacles include:
– How can normal genes be delivered to virtually all cells in the body?
– What are the long-term effects of introducing extra genes in humans?
– What must be done to ensure the proper protein is made after the
genes are delivered to the body?
• Small interfering RNA (siRNA) is emerging technology to silence genes that are involved in
disease progression
• Stem cell technology
– Stem cells are immature cells that grow and divide to produce different cell types
– Most stem cells are from embryos called embryonic stem cells (ESCs) but they are
controversial since the process involves death of an embryo
– Some stem cells are from adult cells (ASCs)
• Either type of stem cell can be coaxed to grow into cells of interest to replace
damaged tissue or failing organs (liver, pancreas, retina)
• Work in groups to explain why scientists are doing more research using embryonic vs. adult
stem cells.
• 1.3 Biotechnology in the 21st Century
• ESCs can give rise to many types of differentiated cells
– Regenerative medicine
• Genetically modifying stem cells of patients to
treat genetic disease conditions
• In future scientists will be able to…
1. Isolate adult stem cells from a patient with a
genetic disorder
2. Genetically manipulate these cells by gene

therapy approaches
3. Reinsert the cells into the same patient to help

treat their genetic disease
• Biotechnology is a global industry
– Generates more than $63 billion in worldwide revenues
– $40 billion in sales of biological drugs in the United States
• Differences between a biotech and pharmaceutical company
– Pharmaceutical companies is involved in drug development (chemically synthesizing or

purifying compounds to make the drug)
– Pharmaceutical company does not use living organisms to grow or produce a product
– Biotech company is involved in drug development using live organisms
– Biotech companies also create products that are not drugs

Insecticides
 PESTICIDE CHARACTERISTICS
Age
 Best used when mixed, don’t store after mixing
Thatch
 Excessive thatch (>1/2”) binds insecticide
UV degradation
 Breaks chemical bonds
 Biologicals most susceptible
pH impact
 Neutral pH is best
Microbial degradation
 Bacteria and fungi feed on organic portion of pesticide
 Can break down within hours
 GENERAL CLASSIFICATION
Stomach poisons
 Enter insect through the gut when eaten
Systemic poisons
 Translocated within plants
 Insects exposed when feeding

 Most effective on piercing-sucking insects
 Receive greater dose
Contact poisons
 Enter body when insect walks over treated surface
Insect Growth Regulator (IGR)
 Interferes with normal growth
 Prevents molting (juvenile hormones)
 Very safe, delayed effect
Biorational (Biological)
 Beneficial fungi, nematodes or bacteria
 MODE OF ACTION
Nerve poisons: most conventional insecticides
a) Narcotics
 Physical action in nervous system
 MODE OF ACTION
Nerve poisons
b) Synaptic
 Interrupt synaptic transmission of nervous system
 Synapse (gap) is the junction between a neuron and another cell (muscle, gland, etc)
 MODE OF ACTION
Nerve poisons
b) Synaptic
 In central nervous system, acetylcholine transmits an impulse across synapse to next cell
 Chemicals tie up acetylcholine and cause malfunction
 MODE OF ACTION
Muscle poisons
 Disrupting muscle membrane
 MODE OF ACTION
Physical toxicants
 Horticultural Oil
 Clog the spiracles that breathe
 MODE OF ACTION
Physical toxicants
 Insecticidal soap
 Strips cuticle and dehydrates insect
 MODE OF ACTION
Physical toxicants
Diatomaceous earth
 Crushed fossils
 Cut insects walking over it
 Dehydrate
 SOURCE CLASSIFICATION
 Inorganic: lack carbon
 Organic: possess carbon
 Natural are produced from natural substances: botanicals and oils
 Synthetics are manmade
 MAJOR CLASSES OF ACTIVE INGREDIENTS

Pesticide rotation
 Rotate chemical classes
 Change mode of action (MOA)
 http://www.irac-online.org/
ORGANOPHOSPHATES (OP)
 Unstable in light
 Was most widely used insecticides
ORGANOPHOSPHATES (OP)
Malathion,
Diazinon and Chlorpyrifos (Dursban)
 Cancelled
CARBAMATES
 Low persistence in environment
 Noted toxicity to pollinators
CARBAMATES
Carbaryl
 Greatest use is fruit production
 Controls insects and fruit-thinning agent
CARBAMATES
Carbofuran (cancelled)
 Ineffective when used continuously
 Microorganisms quickly degrade
CHLORINATED HYDROCARBONS
 Most persistent insecticide class
DDT Cancelled in US in 1973
Extremely stable
 Resistant to MO, heat, and UV light
Fat solubility
 Other classes broken down in animals by enzymes
DDT: 2 characteristics for cancellation
1. Stability allows more to be taken up by animals
2. Accumulates in body fat
 Found traces in milk fat and in human body fat
DDT
Biomagnification
 As predators consume organisms, DDT accumulates in fat of predator
 Thin egg shells, reproductive failure…

BOTANICALS
 Derived directly from plants
 Organic gardening
 Considered safer, some exceptions
 Most are expensive and impractical on commercial scale
BOTANICALS
Pyrethrum
 Extracted from Chrysanthemum
 Wide spectrum and rapid knockdown
 Breaks down rapidly in sunlight
BOTANICALS
Rotenone
 Second most used botanical
 Extremely toxic to fish
BOTANICALS
Rotenone
 New research released in the United States on Monday shows a link between the use of two
pesticides, rotenone and paraquat, and Parkinson's disease. People who used either pesticide
developed Parkinson's disease approximately 2.5 times more often than non-users.
BOTANICALS
Neem
 Oil from neem tree
 Primarily repellent
 Also medicinal and toothpaste
 http://www.azasol.com/
PYRETHROIDS (SYNTHETIC)
 Replacing many older insecticides: effective and safe
 Synthetic pyrethrum
PYRETHROIDS (SYNTHETIC)
Permethrin
 High toxicity at low rates
 Quick knockdown
 More stable
 Permethrin, Cyfluthrin, Deltamethrin
PHENYL PYRAZOLES
 Low mammalian toxicity
 Very effective
 Fipronil, season long control of ants
CHLORONICOTINYLS
 Translocates within plant
 Merit is absorbed through roots

 Suspected in CCD (bees)
 Banned in Canada
 Colony Collapse Disorder (CCD)
• Adult bees fly off to die
• Causes include parasites, viruses, bacteria, poor nutrition and pesticides
• No proof of cell tower
BIORATIONAL (Biological)
 Not substitute for conventional insecticides
 More scouting and repeat applications
Bt (Bacillus thurigiensis)
 Protein produced by Bt that damages gut
 Death in couple days
Varieties have specific host
 Var. kurstaki kills caterpillars (Dipel)
 Genetically modified corn contains protein
 Monarch butterflies?
 Var. israliensis kills mosquitoes
Spinosad
 Derived from bacterium
 Effective flea control

Pesticides
• Pesticides Defined: Any substance or mixture of substances, intended for preventing,

destroying, or mitigating any pest, or intended for use as a plant growth regulator, defoliant or
desiccant. (FIFRA)
• Technically includes biocontrols and plants bred for pest resistance. Common usage excludes
these.
• Pesticide Classification
Pesticides are commonly classified several ways:
• Chemical class -- Increasingly diverse
• Target Organism
• Mode of Action
• Application timing or usage
• Pesticides Classified by Target
• Target classification may also specify growth stages
• Ovicides – Eggs
• Larvicides – Larvae
• Adulticides -- Adults
• Mode of Action Examples
• Broad Spectrum -- Kills broad range of pests, usually refers to insecticides, fungicides, and
bactericides
• Contact Poison -- Kills by contacting pest
• Disinfectant (Eradicant) -- Effective against pathogen that has already infected the crop
• Germination Inhibitor -- Inhibits germination of weed seeds, fungus spores, bacterial spores.
• Nonselective -- Kills broad range of pests and/or crop plants, usually used in reference to
herbicides
• Nerve Poison -- Interferes with nervous system function
• Protectants -- Protects crop if applied before pathogens infect the crop

• Repellents -- Repels pest from crop or interferes with pest’s ability to locate crop
• Systemic -- Absorbed and translocated throughout the plant to provide protection
• Stomach Poison -- Kills after ingestion by an animal
• Classification by Timing
Annual Crops
• Seed Treatment -- Pesticide coats or is absorbed into the seed.
• Pre-Plant -- Pesticide applied any time before planting
• At-Planting -- Pesticide applied during the planting operation
• In-Furrow -- In the planting row, direct contact with crop seed
• Side-Dress -- Next to the row, no direct contact with crop seed
• Broadcast -- Distributed over the soil surface.
• Pre-Emergent -- Before the crop has emerged from the ground
• Post-Emergent -- After the crop has emerged from the ground
• Lay-By -- Final operation before harvest sequence
Perennial Crops
• Dormant -- Applied during winter dormancy
• Bud Break -- Applied as dormancy is broken
Harvest-Related Timing
• Pre-Harvest -- Just before crop is harvested
• Post-Harvest -- After crop is harvested
• Benefits of Pesticides in IPM
• Inexpensive
• Greater control confidence
• Effective and rapid
• Therapeutic
• Management efficiency
• Can enable other management practices
• Costs of Pesticides in IPM
• Greater human health threat
• Greater environmental cost
• Detrimental effects on non-target species
– Those useful in the CPS
– Those useful outside the CPS
– Those with no established uses
• Interferes with other aspects of IPM
– Secondary pests
– Re-entry Intervals & scouting
– Limits other control options
• Less sustainable
• Role of Pesticides in IPM
• Pest complex – Some require pesticides
– Multiple, simultaneous species in same group
– At least one species that causes excessive damage at low density
– Important species new/poorly understood
– Key pest(s) lacking control alternatives
– Key pest(s) especially vulnerable to pesticide placement/timing
• Pesticide Strategy Vs. Tactic
As a group, pesticides may be therapeutic or preventative, broad or narrow spectrum, fast or

slow acting, long or short lived, etc.
As individuals, each pesticide occupies one point on this multidimensional continuum.
The key is to consider each individual pesticide as a separate tactic in an overall IPM plan.
• The Selectivity Concept
• Key concept in pesticide usage in IPM
• Pesticides often classified as “selective” or “non-selective”
• Meaning of these terms in common usage is context-dependent (weeds vs. insects)
• More formally, there are two types of selectivity – Physiological and Ecological
• Physiological Selectivity
• Relative toxicity of pesticides under controlled application conditions
• Species-specific susceptibility to a pesticide.
– Measured as a ratio of LD50’s of non-target/target species (cf. table handout)
– Assumes all individuals & species equally dosed.
• Three general methods:
– Residues (cf. handout)
– Topical application to individuals
– Before/after assessment of field populations
– Ecological Selectivity
• Differential mortality based on pesticide use
– Formulation (e.g. granules result in more mortality on soil pests than on foliar NE’s)
– Placement (e.g. spot sprays, seed treatments, wicks, in-furrow).
– Timing (e.g. pre vs. post-emergent applications, diurnal timing for bees)
– Dosage – Reduced dosage usually used in conjunction with one of those above
• Uses of Selectivity in IPM
• Mammalian toxicity of decreasing significance except in urban/structural IPM
• Insecticides – Physiological selectivity favored (target & non-target intermingled)
• Herbicides – Historically favored ecological selectivity
• Bactericides/Fungicides – Non-selective pesticides usually favored.

• Types of Pesticides
Your book identifies two kinds (pp. 250 – 257)
• Traditional Toxic Chemicals
– Inorganic
– Organic (Synthetic)
• Biopesticides
– Living Systems (Microbial pesticides)
– Fermentation Products
– Botanical Pesticides
– Transgenic (Plant Incorporated Pesticides) – cover under host plant resistance

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• DEVELOPMENTAL IMMUNOLOGY

• The body’s capability to react to antigens depends on:

• Maternal factors also play a role in the body’s immune response

• Classical immunology ties in with the fields of epidemiology and medicine.

• Studying the immune system

• Early in evolution, simple multicellular organisms developed a defense system activated by

• This system is evolved to its present day immunology.

• This innate, prefabricated, one-size-fits-all immune system is immediately available. It stops

• The humoral response is a response of antibodies produced by the body to antigens.

• Immunology is the study of these two biological entities.

• Once exposed to antigens the body mounts a cellular response.

• Both activities are highly interdependent.

The Division of Allergy and Clinical Immunology was found in 1978.

 Begins with early civilization

 Developments in ag and food production

 Few records exist

 Ancient carvings and sketches sources of information

 Makes wide spread use of methods from ancient, especially fermentation

 Methods adapted to industrial production

 Meet demands of increasing population

 Manipulation of genetic material within organisms

 Roots involved the investigation of genes

 Not known when biotech began exactly

 Focused on having food and other human needs

 As food was available, ability to store and preserve emerged

 15,000 years ago, large animals were hard to capture

 People only had meat when they found a dead animal

 Came up with ways of capturing fish and small animals

 Food supplies often seasonal

 Winter food supplies may get quite low

 Domestication is seen by scientists as the beginning of biotech

 Adaptation of organisms so they can be cultured

 Involved the knowledge that the seed had to properly mature

 Raising animals in captivity began about the same time in history

 Learned that animals need food and water

 Learned about simple breeding

 How to raise young

 The beginning of farming.

 Products were gathered and stored

 Some foods rotted

 Others changed form and continued to be good to eat

 Foods stored in a cool cave did not spoil as quickly

 Foods heated by fire also did not spoil as quickly

 Immersing in sour liquids prevented food decay

 Using processes that prevent or slow spoilage

 Heating, cooling, keeps microorganisms (mo’s) from growing

 Stored in bags of leather or jars of clay

 Fermentation occurs if certain mo’s are present

 Creates an acid condition that slows or prevents spoilage

 One of the first food products made through biotechnology

 Began some 4,000 years ago

 Nomadic tribes in Asia

 Strains of bacteria were added to milk

 Caused acid to form

 Resulting in sour milk

 Enzyme called “rennet” was added

 Rennet comes from the lining of the stomachs of calves

 Rennet is genetically engineered today

 Not all cheese is made from produced rennet

 Long used in food preparation and preservation

 Yeast produces a gas in the dough causing the dough to rise

 Require the use of yeast in at least one stage of production

 Some are useful