Adaptive immunity

Attribute Innate Immunity Adaptive Immunity

Response Time Fast: minutes or hours Slow: days

Specificity Only specific for molecules and Highly specific! Can discriminate
molecular patterns associated with between pathogen vs. non-pathogen
general pathogens or foreign particles structures, and miniscule differences
in molecular structures

Major Cell Types Macrophages, Neutrophils, Natural T cells, B cells, and other antigen
Killer Cells, Dendritic Cells, Basophils, presenting cells
Eosinophils

Key Components Antimicrobial peptides and proteins, Antibodies

such as toxic granules

Self vs. Nonself Innate immunity is based on self vs. Not as good as the innate immune
Discrimination nonself discrimination, so it has to be system, but still pretty good at
perfect determining which is which. Problems
in self vs. nonself discrimination result
in autoimmune diseases
 innate versus adaptive immune responses

Innate Adaptive Memory

1 2 3 4 5 6 7 8 9 10 11 12 13 14
Phagocytes
inflammatory cytokines
interferon-antiviral long-lived
complement memory
B & T cells
CD4 & CD8 T cells
cytokines& cytotoxicity
activation of B cells
B cells
antibody production
 B cells versus T cells

Adaptive
delayed response
specific & has ‘memory’

Cell-Mediated Humoral Immunity

Y
Y Y

Y Y
Y
T cells Y
Y

Y
fight against endogenous
pathogens 🡪 things that live B cells
IN our cells effective against
exogenous pathogens
viruses, bacteria, & some
parasites
 Innate vs. Adaptive immunity

takes 3-4 days after exposure to invading pathogen

immune system DOES NOT recognize the whole microbe

but tiny pieces of it

ANTIGEN

PATHOGEN
 Adaptive Immunity : Antigens

Adaptive immune cells respond to SPECIFIC antigens

Antigens: molecules that trigger a specific immune response

(viruses, bacteria, fungi, protozoa, and parasites all have/are antigens)

FOREIGN ANTIGENS
Usually proteins or polysaccharides of pathogens

EPITOPES
specific 3D on an antigen
 Adaptive Immunity : Antigens

antigens gives our adaptive immune

response its specificity

1 bacteria = lots of different antigens

1 antigen = multiple epitopes

What makes a good (easy for our

body to recognize) antigen?
🡪rigid structure, larger molecules,
complex shapes
 Types of antigen: exogenous

Exogenous: enter the body from the outside (inhaled, ingested, injected,
infected)

usually taken up by antigen-presenting cells (APCs)

dendritic cells, macrophages, neutrophils

presented on MHC II

Ex
og
en
ou
PATHOGEN s
 Types of antigens: endogenous

Endogenous: incorporated into host cytoplasmic membranes

generated within normal cells because of intracellular infection

presented on MHC class I molecules

INFECTED
HOST En
do
CELL ge
nou
s
Types of antigens: endogenous vs exogenous
How does our body know the difference between us
& a pathogen?
How does our body know the difference between us
& a pathogen?
SELF NON-SELF

Antigen

Epitope
 CD4 vs CD8 T cells

Adaptive
delayed response
specific & has ‘memory’

Cell-Mediated Humoral Immunity

Y
Y Y

Y Y
Y
T cells Y Y

Y
B cells

B cells express antibodies on their cell surface, which can also be called
membrane-bound antibodies.
 Antibody : function

Antibodies bind epitopes on antigens

AGGREGATION (agglutination)
clumps microbes together, more easily ingested
 Antibody : function

OPSONIZATION
coats a pathogen with antibodies stimulate phagocytosis
 Antibody : function

NEUTRALIZATION
stops pathogen/toxin by blocking their attachment site
 Antibody : function

CELL-MEDIATED CYTOTOXICITY
target cell/pathogen is killed without phagocytosis
Antibody : function

COMPLEMENT
activate complement cascade
 Memory immune response

Innate Adaptive Memory

1 2 3 4 5 6 7 8 9 10 11 12 13 14
Phagocytes
inflammatory cytokines
interferon-antiviral long-lived
complement memory
B & T cells
CD4 & CD8 T cells
cytokines& cytotoxicity
activation of B cells
B cells
antibody production
 Memory B-cells

Do not secrete antibodies like plasma cells

Long-lived 🡪 decades
(but not forever)

Primary adaptive response may take days to

weeks

Secondary “memory” response is much

faster

this is how vaccines work, every vaccine

we have induces memory B cells
Immune Responses
Primary vs to an
secondary immune Antigen
response
Clonal expansion
Clonal expansion
 Memory immune response

Innate Adaptive

1 2 3 4 5 6 7 8 9 10 11 12 13 14

memory response is faster because there are more B and T

cells whose receptors ‘match’ the pathogen

so clonal expansion happens faster

 Types of adaptive memory responses

Naturally Acquired Active

response to environmental antigens
(you get it, you fight it = memory)

Naturally Acquired Passive

placental transfer of Abs & breast feeding
(you get it but you didn’t fight it ≠
memory

Artificially Acquired Active

immunization
(you inject it, you ‘fight’ it = memory

Artificially Acquired Passive

injection of antibodies (often live stock)
needed when pathogen is fast acting
(rabies, anti-toxins)
You inject it, you didn’t fight it ≠ memory
 Think-Pair-Share
1. An individual acquires H1N1 virus (Swine flu) and is sick for approximately 1 week
before recovering.

What type of immunity has occurred?

Will this individual have a memory response?

2. An individual is bitten by a black widow. The toxin is fast acting so the individual is
immediately injected with anti-toxin antibodies by an emergency worker.

What type of immunity has occurred?

Will this individual have a memory response?

3. A child is receives a flu vaccine shot that contains many antigens

carried by a flu virus, but no active virus.

Can the child get sick from this shot?

What type of immunity has occurred?

4. A nursing infant acquires antibodies from its mother.

What type of immunity has occurred?

Will this individual have a memory response?
 Immunization

People understood that individuals who survived/recovered

from certain disease were didn’t get that disease again
🡪 IMMUNE

Scientists wanted to exploit this phenomenon

🡪 IMMUNIZATIONS

Artificial passive (administration of antibodies directly)

Artificial active (administering antigens)

 Vaccines

VACCINE:
suspension of organism or
parts of organisms that is used
to induce a memory immune
response

ADJUVANTS:
additives to vaccines that
increase the effectiveness,
usually by triggering a more
severe inflammatory reaction
 History of immunizations

12th-17th century in China:

small pox vaccination = dried scabs from children
with mild cases ground to a power and
administered to uninfected children

1717 Turkey
first description by Lady Mary Montagu
saw it in Turkey but likely came from China
led to a week of mild illness 🡪 fairly successful
problem was about 1 to 2% of patients died

1798 England
Jenner discovered cowpox conferred resistance
Milk maids told Jenner they could not get small
pox because they had cow pox (hand blistering)

1900s
vaccination was fairly routine (vacca = cow)
Within another 100 years small pox was eradicated
 Types of vaccines: attenuated whole live

Attenuation is the process of reducing virulence

(don’t want to inject virulent/dangerous pathogen)

Grow viruses/bacteria on the cells they infect for many generations

Eventually they lose the ability to cause disease

 Types of vaccines: attenuated whole live

GOOD

Inject these living ‘weaker’ attenuated microbes into people

Induces a larger immune response because multiple antigens are

introduced and the organism actively replicates in body

example: TB, yellow fever, and original oral polio vaccines

BAD

Can produce a reaction in immuno-compromised individuals

Reversion (go back to being virulent!)

 Types of vaccines: inactivated whole dead

next best method is to permanently remove pathogenic genes completely

Virus can NOT revert, can NOT cause disease

Then use a chemical is to inactivate and kill the microbes

Safer because they cannot replicate or revert

 Types of vaccines: toxoid

Use chemically inactivated toxins instead of the actual

infectious agent

examples : tetanus or diphtheria (DTap vaccine)

Problem:
often requires repeated immunization because you have
fewer antigens (smaller molecule being injected)
 Types of vaccines: subunit vaccine

Never contained any “living” pathogen

Contain parts (antigenic fragments) of a microorganism

examples: hep B & flu vaccines

Produced by modifying other organisms DNA (recombinant vaccines)

PRO: can not reproduce in the host, have fewer side affects

CON: limited antigens produces smaller memory response

 Types of vaccines: conjugated

created by attaching a poor antigen to a carrier protein

(preferably from the same microorganism)

makes the poor antigen ‘better’, now B & T cells ‘see’ it

examples: Meningococcal & Pneumococcal vaccines

Types of vaccines: mRNA
 Types of vaccines

Teded How vaccines work

https://www.youtube.com/watch?v=rb7TVW77ZCs
 Modern vaccine development

Goal is safety, effectiveness, and cost

Problems always related to $$$$$$$$$$

Eliminating the disease with a single shot does not provide a steady income
stream

Better to have someone sick that needs daily meds

National Childhood Vaccine Injury Act (1986) prevents vaccine makers from
repercussions in case of negative reactions (usually allergies)
 Benefit and safety of vaccines

Assess risk of side effects (inflammation, etc.) vs risk of disease

AT THE POPULATION LEVEL

risks 🡪 anaphylactic shock & allergic reaction

benefits 🡪 herd immunity

if the majority of a population is vaccinated than those who are not gain
additional protection because the disease is unlikely to spread
(immuno-compromised individuals, infants, pregnant women, etc)
Some of the current available vaccines

HepB: Hepatitis B (subunit)

RV: rotavirus (subunit)

DTaP: Diptheria, Tetanus, Pertussis (toxoid and subunit)

HiB: Haemophilus influenze type B (conjugated subunit)

PCV: Streptococcus pneumonaie (subunit)

IPV: polio (inactivated)

Influenza: yearly, (inactivated and recombinant)

MMR: Measles, Mumps, Rubella (attenuated)

 MMR vaccine: measles

MEASLES

• highly contagious

• respiratory disease

• caused by a virus Morbillivirus

• spreads through coughing and sneezing

• starts with cold-like symptoms, followed by rash

• 3/10 people develop complications

• complications include pneumonia (infection of the lungs)

and encephalitis (swelling of the brain)

• 1/500 children who get measles will die from it

Measles outbreaks
Measles outbreaks
 MMR vaccine: mumps

MUMPS

• Caused by the mumps virus

• Cold-like symptoms followed by swelling of salivary glands

• Most common complication is temporary or permanent deafness, more rare

complications are male sterility

• In 2014, mumps outbreaks have been reported four US universities:

Ohio State University

Fordham University in New York

University of Wisconsin-Madison

University of Illinois at Urbana-Champaign

Mumps outbreaks
 MMR vaccine: rubella
Rubella

• Rubella is not the same as measles (rubeola)

• ‘German measles’ or ‘3-day measles’

• infection is usually mild with fever and rash

• If a pregnant woman contracts rubella, 90% chance infant will have

Growth retardation
Cataracts
Deafness
Congenital heart defects
Mental retardation

• The highest risk to the fetus is during the first trimester, but exposure later in
pregnancy also is dangerous.
 DTaP vaccine

DTaP= Diphtheria, Tetanus, and Pertussis (bacterial diseases), developed in 1981

Diphtheria
causes a thick covering in the back of the throat
leads to breathing problems, paralysis, heart failure, and even death.
Tetanus (lockjaw)
painful tightening of the muscles, can "lock” jaw so can’t swallow/eat.
leads to death in about 1/10 cases
Whooping cough (pertussis)
highly contagious respiratory tract infection
initially resembles a cold, very dangerous in infants

www.youtube.com/watch?v=S3oZrMGDMMw
DTaP vaccine: whooping cough
Why the rise in preventable diseases?
supposed link between vaccines and autism comes from a
single paper

In 1998, British doctor Andrew Wakefield released a scientific paper, in the

journal Lancet, claiming to have linked the measles, mumps, and rubella
(MMR) vaccine to the onset of autism.

To date, no other scientists have replicated his findings

In 2004 journalists found that Wakefield had serious financial conflicts of

interest that he had not disclosed and that he had falsified his data
 1996
paid (~$750,000) to attack MMR by a lawyer who hoped to raise a class
action lawsuit against drug companies who made the vaccine

1997
filed patent for alternative ‘safer’ measles vaccine

1998
publishes paper, announces this is “a moral issue for me,” calls for boycott
of MMR in favor of single vaccine shots. "I can't support the continued use
of these three vaccines, given in combination," he said, "until this issue has
been resolved."

2004
Discovered that Dr. Wakefield stands to make over 44 million/year from the
MMR panic he triggered

All the children used in study had been pre-selected through MMR
campaign groups, and most of their parents were clients and contacts of
the lawyer that had paid for the studies.

2006
First British measles death reported in 14 years
 2010
after 197 days of evidence - a panel of three doctors and two lay members
found Dr. Wakefield guilty (against a criminal standard of proof) of some
three dozen charges and his medical license was revoked.

Lancet fully retracted the paper from the scientific literature.

2013
 2016
Andrew Wakefield releases new anti-vaccine documentary
 Myth #1: vaccines cause autism

Based on 1997 study published by Andrew Wakefield

Andrew Wakefield lost his medical license

paper was retracted

despite decades of research findings never reproduced

we can now identify symptoms of autism in children well before they

receive the MMR vaccine

more recent research provides evidence that autism develops in utero,

long before vaccinations

time spend debunking vaccines could have been spent researching

autism
 Myth #1: vaccines cause autism

Denmark did a retrospective study of every single child that had received
the MMR vaccine, all 537,303, born in Denmark between January 1991
and December 1998 and found no correlation with autism even when the
took into account the children's sex, weight and gestational age at birth,
and age at diagnosis of autism or of a related disorder; the
socioeconomic status of the parents; and the mother's education.

a study in JAMA in April 2015 was one of the largest; involved analysis of
96,000 children and found no harmful association between MMR vaccine
receipt and [autism spectrum disorder]

original paper by Andrew Wakefield looked at 12 children

 Myth #1: vaccines cause autism

experts now have evidence to suggest that autism occurs due to a

combination of genetic and environmental factors such as: age of father
and exposure to certain pesticides

CDC said the most recent jump from 2011 to 2014 in autism cases may
have a very mundane reason behind it: a change in the questionnaire the
agency uses to track cases
 Myth #1: vaccines cause autism

correlation is NOT causation!

there is NO mechanism that has withstood scientific testing to

explain how vaccines are causing autism
Myth #2: a babies immune system can’t handle vaccines

Based on the number of antibodies present in the blood, a baby would

theoretically have the ability to respond to around 10,000 vaccines at once

Even if all 14 scheduled vaccines were given at once, it would only use up
slightly more than 0.1% of a baby’s immune capacity

In reality, babies are exposed to countless bacteria and viruses every day,
and immunizations are negligible in comparison
Myth #3: we don’t need to vaccinate babies for sexually
transmitted ‘adult’ diseases
there is a high failure rate for completing the vaccine series (2 shots, 6-12
months apart) in adolescents and adults for the HPV vaccine

so many providers recommend it at younger ages where well child visits

will assure completion of the series

there are no adverse effects associated with it, beyond the normal risks of
an allergic response, and protection is still solid through adulthood.

About 1/4 adults and teens are infected with HPV, most have no symptoms
and infections do resolve on their own but in some people it does develop
into cancer

teens and preteens are often uncomfortable getting the vaccine because
the associate it with being sexually active and promiscuous

anti-vaxxers say HPV vaccine increases the risk of multiple sclerosis and
other demyelinating diseases, Danish study reviewed records of 3,983,824
Danish females who either did or did not get the vaccine and found no links
 Myth #4: vaccines contain unsafe toxins

People have concerns over the use of formaldehyde, mercury or

aluminum in vaccines

It’s true that these chemicals are toxic to the human body in certain
levels, but only trace amounts of these chemicals are used in FDA
approved vaccines
Myth #4: vaccines contain unsafe toxins
 Myth #4: vaccines contain unsafe toxins

much of the debate about autism and vaccines was centered around the use of
thimerosal adjuvant which contained trace amounts of mercury, which is no
longer used
Myth #5: natural immunity is better than vaccine immunity

In some cases, natural immunity — meaning actually catching a

disease and getting sick– results in a stronger immunity to the
disease than a vaccination.

However, the dangers of this approach far outweigh the relative

benefits.

If you wanted to gain immunity to measles, for example, by

contracting the disease, you would face a 1 in 500 chance of death
from your symptoms

In contrast, the number of people who have had severe allergic

reactions from an MMR vaccine, is less than 1 in 1,000,000
 Myth #6: Better hygiene and sanitation are actually
responsible for decreased infections, not vaccines

Vaccines don’t deserve all the credit for reducing or eliminating

rates of infectious disease

Better sanitation, nutrition, and the development of antibiotics

helped a lot too

antibiotics don’t stop viruses

even when we control for these and rates of infectious disease are
scrutinized, the role of vaccines cannot be denied
Myth #7: Vaccines can infect you with what they are trying
to prevent or cause severe allergic reactions

Only a live attenuated vaccine could potentially infect you

subunit, conjugated, dead, or toxoid vaccines can not

there is only one recorded instance in which a vaccine was shown to

cause disease. This was the Oral Polio Vaccine (OPV) which is no
longer used in the U.S.
Myth #7: Vaccines can infect you with what they are trying
to prevent or cause severe allergic reactions

The Vaccine Adverse Event Reporting System (VAERS) was

established in 1990 by congress and by law doctors must report all
adverse effects, these are available to the public.

VAERs then classifies the adverse effects and investigates those

that are 'unexpected' so something other than soreness or cold like
symptoms.

If enough adverse effects are reported a vaccine is pulled, especially

during the probationary period.
 Myth #8: We don’t need to vaccinate in the US

so long as a large majority of people are immunized in any population, even

the unimmunized minority will be protected

But if too many people don’t vaccinate themselves or their children, they
contribute to everyone’s collective danger
 Myth #9: Vaccines are a way for big pharma to make
money

Vaccines are produced by for-profit business, but they are not very profitable,
single treatment for a lifetime + high liability costs

vaccine market estimated at $24 billion, but only 2-3% of trillion-dollar

worldwide pharmaceutical industry

anti-vaccination movement is also a large market from which people make a

lot of money

therefore it is always important to ask who is funding the research and who is
doing the research when it comes to your health