Download Disorders of the Immune System and Vaccination

Vaccination and Disorders of
the Immune System
The second half of Disorders of the
Immune System will be combined with
Diagnosing Infection due to the large
amount of material.
Types of Vaccines
• Attenuated whole-agent: weakened form of microbe or
virus due to mutations acquired during long-term culture
in the lab.
– Pasteur saw this happen while working with Fowl Cholera in the
lab. The longer he kept a particular culture in the lab and regrew it, the less virulent it became. Essentially, organisms will
not hang onto genes, or extra genetic material that they don’t
need. So if they don’t need virulence genes to live, they won’t
use them because it is costly from a metabolic standpoint.
– Lifelong immunity is more likely to occur from this form of
vaccine because it replicates just like a typical infecting organism
would until the immune system takes over.
– There is a chance that an organism could mutate back into an
infectious form.
– Ex. of vaccines that are attenuated whole-agents are Polio,
measles, mumps, rubella.
• Inactivated whole-agent: microbes that have
been killed or viruses that have been inactivated
chemically or physically (heat).
– Less risk of infection because the organism is not
able to replicate.
– Ex. Pertussis, Influenza vaccines.
• Toxiods: inactivated toxins.
– Require a series of injections for full immunity,
followed by boosters every few years to remain
sufficiently immune.
– Ex. Tetanus
• Subunit vaccines: use anitgenic
fragments of a microorganism that best
stimulate an immune response.
– Recombinant: The gene that makes a protein
on the outside of an pathogen is inserted into
an avirulent organism. This avirulent
organism then makes the protein and the
body makes antibodies to that protein without
ever coming into contact with the actual
pathogen.
– Acellular: Virulent cells are lysed and the
virulent proteins are retained for the vaccine.
– Ex. Hepatitis B
• Conjugated: developed to deal with poor
immune response in children under the age of
15-24 months.
– Infants under the age of 15-24 months don’t have a
well developed immune system. As a result the
immune system doesn’t respong well to antigens that
use T cells to make antibodies.
– To trick the immune system into recognizing the
antigen a chain of polysaccharides is combined with
the antigenic protein. The presence of the
polysaccharides activates the immune response.
– Ex. Haemophilus influenzae
• Nucleic-Acid: plasmids of naked DNA
injected into muscle produce protein which
in turn causes an immune response.
– This form of vaccine is still being researched.
– Problems: As soon as the DNA is degraded,
the vaccine is done. More research needs to
be done to figure out how to prolong the life of
the DNA to give the immune system sufficient
time to respond.
– No human vaccines yet available.
• One way to improve their effectiveness is
through the use of adjuvants.
• Adjuvant: chemicals added to increase
the immune response to a vaccine.
• Before the discovery of AIDS it was
thought that all the vaccines that were
ever going to be developed had already
been done. With the advances in
technology and our increased
understanding of Molecular biology, more
vaccines are currently being developed
and tested. Vaccines for at least 75
diseases are currently being developed.
• The newest vaccine that is currently
undergoing clinical trials is for a strain of
Genital Warts that can cause Cervical
Cancer.
• Now the challenge is in educating the general
public about the importance of keeping their
vaccinations current as well as having their
children vaccinate on time.
• Many parents have never seen most of the
childhood illness that we are vaccinating
against. They often feel that since that disease
is rarely seen, there is no need to have their
children vaccinated.
• Other people are worried that their child might
get the disease from the vaccine, however
statistics show that the chances of getting the
disease are greater when the child is not
vaccinated at all.
• There is also increasing evidence that
Autism is not a result of the MMR vaccine.
• Rather there seems to be a genetic
component to the disease as well as a
microbial component.
– A researcher here in Austin has found
evidence of intestinal cell changes consistent
with microbial infection in children with
Autism. Further research is being conducted
to better understand the disease.
Disorders of Immune System
• Hypersensitivity Reactions
– Aka. Allergy
– Occurs in individuals who have had previous
exposure to an antigen, sensitization. This means
that they have been sensitized to the antigen and
have made antibodies to that antigen.
– Once sensitized, on subsequent exposures, the
immune system reacts to that antigen in a damaging
manner.
– See Fig. 16.3 for a great summary of this process.
4 Types of hypersensitivity
• 1. Atopy and Anaphylactic Reactions:
– Allergens are foreign particles in the body, such as
pollen that the body suddenly reacts to with an
immune response. It usually does so by making IgE
antibodies.
– The allergens, antigens, combine with IgE antibodies,
causing a large histamine release. These chemicals
are responsible for the visible symptoms such as
sneezing, coughing, itchy eyes, difficulty in breathing,
etc.
– Fewer allergies are seen in developing countries
where parasite infection is frequent. IgEs appear to
play a role in defending against parasite infection. In
countries where parasite exposure and infection is
rare, allergies are more frequent. So in other words,
we have allergies because the IgEs need a job.
– Atopic reactions are localized reactions seen
in seasonal allergies. Anaphylactic reactions
are systemic, such as those seen with food
allergies.
– Localized:
• Usually associated with antigens that are ingested
or inhaled.
• Symptoms are teary eyes, congestion, coughing,
and sneezing.
• Treatment (Rx):
– 1. An antihistamine which competes for histamine
receptor sites. Antihistamines block histamine from
binding to their target cells. Thus preventing the
symptoms caused by histamine.
– 2. Avoidance of the allergen. Not easily done with
seasonal allergies.
– 3. Train the immune system to make IgG antibodies to
the allergen instead of IgE antibodies. The IgG
antibodies do not cause histamine response.
– Systemic:
• Injected antigens, such as insect stings, are most
likely to cause this type of allergic response.
• Some foods, such as peanut allergies, can also
cause this response. (Most food allergies are not
allergies, they are an intolerance. This is referring
to items that cause gastrointestinal responses,
such as gas or bloating or cramping.)
• The release of chemicals caused by systemic
allergens cause a drop in blood pressure (shock)
and difficulty in breathing.
• This can be fatal within minutes.
• Rx: self-administered epinephrine injection.
• 2. Cytotoxic Rxns:
– Blood transfusions with the wrong blood type
are an example of this type of hypersensitivity.
– ABO, Rh factors are proteins that are found
on the outside of Red Blood Cells.
– Let’s use the Rh factor as an example. Some
cells have the Rh protein on their outside
membranes and some do not.
– If a person normally does not have the Rh
factor on the outside of the cell then the body
recognizes only RBCs without Rh as “self”.
Anything different is foreign and an antibody
response will follow.
– The Rh factor only becomes a concern after a person
is sensitized to the Rh protein.
– So when an Rh negative mom is pregnant with an Rh
positive fetus for the first time no harm comes to the
baby because mom doesn’t have any antibodies to
the Rh factor in the fetus’s blood.
– The second time Rh negative mom gets pregnant
with a Rh positive fetus the antibodies are present
and destroy the fetus’s RBCs.
– The purpose of the RhoGAM shot is to prevent the
mother’s immune system from making antibodies the
first time by removing the fetal RBCs from the
mother’s blood.
• 3. Immune Complex Rxn:
– Occurs when certain ratio of antigen to antibody
exists
• Usually slightly more antigen than antibody.
• The antibody works to clump the antigen together so that it
can be easily phagocytosed and removed from the body.
– Some small immune complexes form that escape
phagocytosis.
– The immune complexes circulate in the blood until
they are deposited in blood vessel walls.
– All of a sudden the blood vessel wall has an
unfamiliar protein group attached to it and the body
mounts an immune response to get rid of it.
– Complement and other inflammatory cells are
activated that cause damage to surrounding tissues
as they try to remove the deposited immune complex.
• 4. Cell-Mediated Rxns: The classic example of
cell-metiated reactions is poison iv/oak.
– This reaction is caused mainly by T cells.
– It is a delayed reaction that is not apparent for a day
or more.
– The oil/antigen binds to the proteins on the host cells
causing the cell to look different to the body. (No
longer self.)
– Upon the first exposure the antigen is presented to
the T cells.
– A memory cell made.
– Upon reexposure, T cells are activated.
– T cells release chemicals to activate the inflammatory
response.
– Active macrophages are brought to the site and tissue
damage occurs in the area where the oil/antigen is
bound to the host cell.