Applications of Immune Responses
Kathy Huschle
Northland Community and Technical College
Historical Aspects of Immunology
long before vaccinations were invented, it was known that
people who recovered from certain diseases, were immune
to that disease thereon
–the Chinese exploited this idea by having children inhale
dried smallpox scabs
this deliberate exposure to infected material is called
variolation
–in 1717, Lady Mary Montagu observed the practice of
variolation while in Turkey and brought it home to England
in 18th century England the mortality rate for smallpox
variolation was 1%, a significant improvement over the
expected 50% mortality rate
in 1798 Edward Jenner began experimenting with the
deliberate inoculation of people with cowpox in an attempt to
prevent smallpox
–this was the beginning of vaccinations
–by 1977 the last case of naturally occurring smallpox was
documented in Africa
polio and measles are targeted for elimination through the
use of vaccination
Immunity
active immunity
–an immune response that is the result of exposure to an
antigen
–can be either natural or artificial
naturally acquired (active) immunity
–antibody production in response to an infectious disease
artificially acquired (active) immunity
–antibody production in response to a vaccination
Immunity
passive immunity
–an immune response that is the result of transfer of
antibodies produced by other individuals or animals
–can be natural or artificial
natural passive immunity
–involves the natural transfer of antibodies from a mother to
her infant
–this transfer takes place across the placenta
–breast milk is another example of natural passive immunity
artificial passive immunity
–involves the introduction of antibodies into the body
–these antibodies are collected from an animal or person
who is already immune to the disease
–is capable of preventing the disease before or after
exposure
antiserum: serum preparation of protective antibodies
–is capable of blocking the action of microbial toxins
antitoxin: a preparation of antibodies that protect against a
given toxin
–one example of artificial passive immunity is a post
exposure rabies vaccination
when immune serum globulin from an individual who is
immune to the disease is injected into the body (artificial
passive) it conveys immediate protection against the disease
unfortunately this protection is short lived
–the antibodies are degraded by the recipient (non-self cells)
–generally the lifespan of injected antibodies is about 3
weeks
with natural passive immunity, the newborn is protected a
few months: long enough in most cases for the newborn to
begin developing their own acquired immune system
Immunization
Many communicable diseases can be controlled by
behavioral and environmental methods, such as proper
sanitation or the use of condoms. For many other diseases
science has developed vaccinations.
Immunization
vaccination is the process of conferring immunity by
administering a vaccine
a vaccine is a preparation of killed, inactivated, or
attenuated microorganisms or toxoids to induce artificially
acquired active immunity
the function of a vaccination is to provide resistance to a
disease without actually getting the disease
–in order for this to happen, exposure to the correct disease
causing antigen must be achieved
any macromolecule can be used as an antigen, it is NOT
the entire pathogen
vaccines used against viruses are generally more effective
or long-lived than those developed for bacterial diseases
–it is thought that the protein coat of a virus better stimulates
the production of antibodies thaN the polysaccharide outer
surface of bacterial components
–an anamnestic (memory) response develops following
vaccination
not only does vaccination protect the individual from
disease, it also protects the general public
if enough people are immune to a disease, either through
actual contact or vaccination, epidemics do not occur
–herd immunity is when approximately 70% of a population
has immunity to a disease
–this large number of immune people allows for the chain of
the disease to be interrupted and is responsible for the
dramatic decrease in childhood diseases worldwide
–at times complacency against childhood diseases may
cause parents to fail to have their children vaccinated
state laws in the US requiring vaccination for children
before entering school helps maintain herd immunity
Immunization
vaccines
–are a preparation of antigens that is artificially administered
–do not cause disease
–only need to stimulate production of antibodies
–can be
weakened or attenuated
killed or inactivated
Attenuated Vaccines
use living, but attenuated (weakened) microbes
–more closely mimic an actual infection
–lifelong immunity, especially with viruses, is often achieved
without a booster immunization
–effectiveness rate of 95% is common
–microorganisms are attenuated by
heat, chemicals, dessication (removal of water)
disadvantage to attenuated vaccines
–is the possibility of reversion to an active form through
mutation or recombination
–they require refrigeration (difficult to use in the wilds of
South America)
attenuated vaccines should not be given to people with
inadequate immune systems: would be capable of causing
the actual disease
examples of attenuated vaccines include measles, mumps,
rubella (MMR), polio
Inactivated Vaccines
consist of killed bacteria or viruses that are unable to
replicate
–antigenic properties are retained
–because they can’t replicate the immune response is limited
so several booster vaccinations are needed to provide
immunity
these vaccines can usually be used without risk
to enhance antigenicity of inactivated vaccines, adjuvants
are often used
–adjuvants are chemicals added to improve the effectiveness
of the vaccination
disadvantage or problems that are encountered with
inactivated or killed vaccines include
–inadequate inactivation
rushing the preparation of a vaccine can cause failure to
inactivate correctly and can result in an outbreak of the
disease instead of protection
examples of inactivated vaccines include influenza and
pneumonia
Other Types of Vaccinations
toxoids
–inactivated toxins that are directed at toxins produced by a
pathogen
subunit vaccines
–are composed of antigenic fragments of a microorganism
conjugated vaccine
–combine the desired antigen with a protein to boost the
immune response
polysaccharide vaccine
–composed of polysaccharides found in the capsules of
certain organisms
Development of New Vaccines
edible vaccines
–creation of these vaccines involves the genetic transfer of
key antigens into plants
DNA based vaccines
–using segments of DNA from infected organisms and
introducing them into the muscle of the host
in addition to research involving the development of
vaccines for emerging diseases, science is studying the
possibility of vaccinations for cancer, diabetes, or to control
fertility
Immunizations
regardless of the type of vaccination that is used it is
important that they all be
–safe
–provide lasting protection
–cheap
–stable
–easy to administer
the development vaccinations has dramatically increased
the life expectancy of the world
Diagnostic Immunology
the presence of antibodies or antigens in a patient can be
determined with an assortment of tests based on the
interactions of antibodies and antigens
many of these tests use serology, which uses known
antibodies to detect the presence of antigens, or uses known
antigens to detect the presence of antibodies
some examples of these tests include
–precipitation reactions
the interaction of soluble antigens with IgG or IgM
antibodies leads to precipitation reactions
–agglutination reactions
the interaction of particulate antigens (cells that carry
antigens) with antibodies leads to agglutination reactions
–immunofluorescence tests
use of antibodies labeled with fluorescent dyes to identify
microorganisms
–radioimmunoassay
use of a radioactively labeled antigen
–ELISA (enzyme linked immunosorbent assay)
link antibodies to an enzyme
this type of testing is used to test donated blood for the
presence of HIV
Immunologic Disorders
not all immune responses produce desirable responses,
such as immunity to a disease
–the same mechanisms that protect us from disease, under
certain circumstances, can be detrimental
the mechanism of immunological response is exactly the
same, whether protective or damaging
hypersensitivities
–causes tissue damage
transplant rejection
autoimmune disease
–response against self-antigens
immuodeficiency
–not enough immune system response
Hypersensitivity Reactions
hypersensitivity is an antigenic response beyond that which
is considered normal
–the term allergy is essentially synonymous
–hypersensitivity reactions are usually to harmless
substances
–reactions
excessive response to an antigen can be
–immediate
–delayed
the four principal types of hypersensitivity reactions are
–Type I – immediate IgE mediated (anaphylaxis)
–Type II – cytotoxic
–Type III – immune complex mediated
–Type IV – delayed-type mediated
Type I Hypersensitivity: Immediate IgE Mediated
IgE antibodies are produced that bind to mast cells and
basophils
–basophils are circulatory cells, mast cells are found in tissue
release mediators (histamines, serotonin) of the allergic
reaction
initiate anaphylaxis response
localized anaphylaxis includes hives, hay fever and asthma
systemic anaphylaxis is rare, but can be life threatening
Type 1 hypersensitivity is an immediate reaction
treatment for this type of hypersensitivity includes
–skin testing to determine the sensitivity to an antigen
–desensitization to the antigen is achieved by repeated
injections of the antigen, which leads to the formation of
blocking antibodies
Type II Hypersensitivity: Cytotoxic
antibodies are directed toward foreign cells or host cells
–complement fixation may result in cell lysis
–macrophages may also damage the antibody-coated cells
involves
–incompatible blood transfusions
–hemolytic disease of the newborn
incompatible blood
–hemolytic reactions occur when the recipient's serum
contains antibodies directed against the corresponding
antigen found on donor red blood cells
this can be an ABO incompatibility or an incompatibility
related to a different blood group antigen
–the most common cause for a major hemolytic transfusion
reaction is a clerical error
–incompatible blood transfusions lead to the complement
mediated lysis of the donor red blood cells
hemolytic disease of the newborn
–about 85% of the world’s population possess the Rh antigen
these people are referred to as Rh+
an Rh- mother carrying an Rh+ fetus will produce anti-Rh
antibodies
–subsequent pregnancies involving Rh incompatibility may
result in hemolytic disease of the newborn
symptoms are jaundice and severe anemia, resulting in
death
Type III Hypersensitivity: Immune Complex-Mediated
antibodies against soluble antigens circulating in the serum
in the cases of excess antigen, small immune complexes
form that persist in the circulatory system or may be
deposited in the skin, joints and kidneys
–glomerulonephritis is an immune complex condition that
causes inflammation to the kidney glomeruli, which are the
sites of blood filtration
Type IV Hypersensitivity: Delayed
Cell-Mediated
these hypersensitivity reactions involve a cell-mediated
immune response and are caused mainly by T cells
the reactions to the exposed antigen is not apparent for a
day or more
–a major factor in the delay is the time needed for the T cells
and macrophages to migrate to and accumulate near the
antigen
responsible for
–contact dermatitis: poison ivy, poison oak
–rejection of tissue grafts
–tissue damage in some infectious diseases
thetuberculin skin test is an example of delayed-type
hypersensitivity
Transplantation Reactions
transplants recognized as non-self, are rejected and
attacked by
–by T cells that directly lyse the grafted cells
–macrophages that are attracted by T cells
Transplantation Reactions
in order to prevent rejection (destruction by the immune
system) people who have undergone transplants receive
large doses of drugs, such as cyclosporine
–cyclosporine suppresses the cell-mediated immune system
this suppression leaves the patient susceptible to viral
infection: bacterial infection is contained with the antibody-
mediated immune system
because the cell-mediated system is suppressed, which is
the immune system primarily responsible for protection
against abnormal cells, the risk of developing cancer is
increased
–cancer cells are abnormal cells
Autoimmunity
autoimmunity is the action of the immune system
responding to self-antigens and causing damage to one’s
own organs
affects about 5% of the developed world’s population
–75% of those affected are women
autoimmune diseases occur when the immune system has
lost the ability to discriminate self from nonself
Autoimmune Diseases
Graves’ disease
–caused by antibodies that are called long-acting thyroid
stimulators
–result is an increased amount of thyroid hormones are
produced
–symptoms include swelling o the thyroid and bulging,
staring eyes
Myasthenia gravis
–caused by antibodies interfering with the nerve impulses for
muscles
–muscles become progressively weaker
–respiratory arrest and death result
Systemic lupus
–production of antibodies directed at component of their own
cells
–damaging effects of the disease results from the deposit of
immune complexes
Rheumatoid arthritis
–immune complexes are deposited in the joints
–chronic inflammation caused by deposits leads to severe
damage to cartilage and bone of the joint
Multiple sclerosis
–T cells and macrophages attack the myelin sheath of
nerves
–symptoms range from fatigue and weakness to severe
paralysis
–progression of the disease is slow
can be slowed with treatment of drugs and interferons
Immunodeficiencies
failure of or having an inadequate immune system
2 type of immunodeficiencies
–primary
genetic or developmental
–secondary or acquired
result from environmental factors
Primary Immunodeficiency's
primary immunodeficiency
–some people are born with a defective immune system
–examples of primary immunodeficiency's include
severe combined immunodeficiency
–there are no functional B or T lymphocytes produced from
the bone marrow stem cells
–no protection against infectious disease
–bone marrow transplant can successfully produce stem
cells, which will in turn produce B and T cells, which result in
an immune system
David suffered from Severe Combined Immunodeficiency
Disease (SCID) from birth, and survived only by complete
isolation in a germ-free environment. He died at age of 12
following a bone marrow transplant. Other SCID patients
have been successfully treated by somatic gene therapy.
Primary Immunodeficiency's
DiGeorge Syndrome
–the thymus does not develop correctly or may not be
present at all
–no cell-mediated immunity
–because of the lack of T cells and thus TH cells, the
antibody-mediated immune system does not function 100%
TH play a role in activating the B cells of the antibody-
mediated system
Bruton Congenital Agammaglobulinemia
–B cells do not differentiate
–no antibodies are produced, thus no antibody-mediated
immunity
–cell-mediated immunity is OK
–affects males only
Secondary Immunodeficiency's
are a result of environmental factors such as
– malignancies of the lymphoid system
can decrease effective antibody-mediated immunity
–advanced age
as we age our immune system becomes less effective
–immunosuppressive drugs
these drugs are usually taken to purposely suppress the
immune system, as in the case of organ or tissue transplant
–viral infections
many viruses are capable of infecting and killing
lymphocytes, thus effectively lowering the immune response
other diseases such as syphilis and malaria attack T cell
populations and macrophage function, diminishing the cell-
mediated immune system
human immunodeficiency virus (HIV) infects and destroys
TH cells, diminishing both the antibody-mediated and cell-
mediated immune systems
The Future
The technology available for gene transfer appears to be the
best hope for correcting these many immunologic disorders.
Stem cell research holds much promise for correcting these
diseases. After all stem cells are the precursors to both B
cells and T cells. Cells critical to functioning immunity.