CHAPTER 18 PRACTICAL APPLICATIONS OF
IMMUNOLOGY
Long
before any understanding of the immune system and vaccines had come along, it
was recognized that people who had survived a case of an infectious disease
were often immune to that disease for the rest of their lives. The first record
we have of any type of deliberate exposure to a disease in an attempt to
produce immunity was called variolation. This involved injecting pus from a
smallpox patient into a healthy person. The result was usually a very mild case
of the disease which produced immunity. Unfortunately, some persons treated
this way died.
Edward
Jenner provided the next step, using the cowpox organism to provide immunity to
smallpox. This was a much safer procedure.
Currently,
we are able to produce safe vaccines for many infectious diseases. As a result,
smallpox has been eliminated worldwide, and polio and measles are targeted. Most childhood diseases, which
caused numerous deaths as recently as the first half of the 1900’s, are rare in this country today due to
vaccines.
Not all
diseases can be prevented by vaccines. There is no vaccine for AIDS. No
vaccines are available for chlamydias, fungi, protozoa, or helminths. Other
vaccines, such as those for cholera and typhoid fever, provide less than
complete protection and last a relatively short time.
A safe and effective vaccine stimulates the formation of
memory B and T cells without causing the actual disease.
1. Attenuated whole-agent vaccines—entire
microbes which are alive but have been weakened or changed in some way so that
they can no longer cause the disease but can still provoke an immune response.
These vaccines are generally very effective and often provide lifelong
protection. The organisms used often originate from mutations in long-term
cultures or may have been treated in some way to weaken them. Examples: Sabin
polio vaccine, vaccines against measles, mumps, and rubella (MMR). Rarely, the
organisms in this type of vaccine can revert to virulence (back-mutate) and
cause the disease.
2. Inactivated whole-agent vaccines---microbes
have been killed, usually by formalin or phenol. May not be as effective as the
vaccines that contain living organisms. Examples: human rabies vaccine,
influenza vaccine, Salk polio vaccine, cholera vaccine, pneumonia vaccine.
3. Toxoids—these are inactivated toxins,
which provoke the production of antibodies that will inactivate the toxin if it
is produced by pathogens in the body. These require a series of vaccines and
periodic boosters. Examples: tetanus toxoid, diphtheria toxoid.
4. Subunit vaccines—these contain only those
fragments of the pathogen that best stimulate the immune response, making them
100% safe as far as actually causing the disease. Most are produced by locating
the genes for certain proteins found on the outside of the microbe and
inserting them into cells by genetic engineering. Cells then make the protein,
which is recovered, purified, and serves as the vaccine. These are called
recombinant vaccines. Examples:
Hepatitis B vaccine and a new, more effective vaccine for whooping
cough. The whooping cough vaccine is not made by genetic engineering, it is
still a subunit vaccine, but is made by using parts of disrupted bacterial
cells.
5. Conjugated vaccines--used in young children.
Immune response to the polysaccharide of bacterial capsules does not work well
in very young children. Combining the polysaccharide with a protein allows an
immune response even in babies. Haemophilus
influenzae type B vaccine is an example.
6. DNA vaccines--newest idea in vaccines,
not yet in use in humans. Injection of "naked" DNA into muscle tissue
of animals results in production of whatever
proteins are coded in that DNA. These proteins stimulate an immune
response. In some cases the DNA degrades before achieving the full effect, but
these vaccines will most likely eventually become common in the future.
In addition to providing protection against
disease, immunologic functions are
widely used today to aid in diagnosis. For this purpose:
Known antibodies are used to detect
the presence of specific antigens
Known antigens are used to detect the
presence of specific antibodies
These
tests depend on the availability of monoclonal antibodies. These are made by
isolating a B cell that makes the desired antibodies and combining it with a
cancerous B cell, which will divide indefinitely. The combination is called a
hybridoma. These cells can produce unlimited amounts of very pure antibodies,
called monoclonal antibodies (Mabs). Monoclonal antibodies are also used in
treatment of several diseases.
1. Precipitation reactions—soluble
antigens react with antibodies to form complexes that settle out of a solution.
Immunodiffusion tests are precipitation tests carried out in an agar gel
medium. A line of visible precipitate develops in the gel.
2. Agglutination reactions—particulate
antigens react with antibodies to form visible clumps. Patient’s serum is
combined with a known antigen. If the patient has antibodies against the
antigen, the reaction will occur.
Hemagglutination
is the use of red blood cells in an agglutination reaction. This is used for
blood typing.
Viral
hemagglutination inhibition tests—used for influenza diagnosis.
Virus + RBC à
Agglutination
Virus + RBC +
serum with no antibodies à Agglutination
Virus + RBC +
serum with antibodies à
No agglutination
3. Neutralization reactions—harmful effects
of a bacterial toxin or a virus are eliminated by a specific antibody.
4. Complement fixation reactions---based
on the depletion of a measured amount of complement if an antigen-antibody
reaction occurs.
5. Fluorescent antibody techniques—a clinical
sample is fixed to a slide. Antibodies with a fluorescent dye attached are
mixed with the sample. If they find their antigen in the sample, they will
combine with it. If not, they will wash off the slide. The slide is viewed—if
it fluoresces, the test is positive.
6. Enzyme-Linked Immunosorbent Assay (ELISA)
tests
a. Direct—detects the presence of
antigens. Antibodies linked to an enzyme
are used.
b. Indirect—detects the presence of
antibodies. Antigens linked to an enzyme are used.