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BT 13: history, types and functions of immunity and vaccines

History of immunology
Written records from over 2,500 years ago reveal an awareness that persons who recover
from certain diseases cannot contract them again. For example, one of the earliest
accounts of immunity comes from China, where they not only noticed that people who
recovered from smallpox were resistant to reinfection, but also that the various epidemics
varied in their severity - one year being usually fatal and other years being much milder.
Chinese physicians therefore deliberately infected healthy people with material (crusts or
fluid) taken from cases of mild smallpox, thus rendering them resistant during the serious
epidemics. Although this practice was introduced to Europe in the early 1700's it was at
best a risky procedure, since people occasionally died from these "mild" infections! It
was not until 1796 that Edward Jenner, an English country physician, put into practice a
well known countryside observation that the beauty of milk maids was often due to the
fact that they rarely contracted smallpox since they almost invariably caught cowpox
which made them immune to smallpox. This procedure was the first example of
vaccination (from Vacca which is the latin for cow), a term later coined by Louis Pasteur
in honor of Jenners contribution to include any procedure which induces immunity.
Nowadays vaccination is synonymous with immunization.
The next major step towards an understanding of immunology was not possible until the
late 1800's when Pasteur in France, and Koch in Germany demonstrated how microbes
cause disease. The initial studies on vaccination using a defined microbe were made in
Pasteur's laboratory where they were working on Chicken Cholera (Pasteurella
aviseptica). Pasteur, on returning from holiday, tried to use an old culture of the bacilli,
only to discover that it was apparently ineffective in producing the disease. Being a
careful person (or maybe mean!!) he tried to reuse the animals with a fresh isolate of the
microbe, and discovered that the old "attenuated" culture had induced immunity in the
chickens to challenge with the virulent organisms. This finding may have prompted
Pasteur to make his famous epigram that "chance favors only the prepared mind". Pasteur
later extended these findings to Anthrax and finally to Rabies, which after experiments in
animals was given to a small boy who survived and became the gate keeper of the Pasteur
In 1883 a Russian, Eli Metchnikoff first demonstrated the role of phagocytic cells in the
immune process. Again like the discovery of Pasteur, it occurred while he was on holiday
(actually he was unemployed, since he had resigned from his job!) Metchnikoff was a
Zoologist, and since he was on holiday near the sea he decided to examine some starfish
larvae that he found. He pushed a splinter of wood into one of the animals and was
surprised to see that many phagocytic cells surrounded the "foreign object". His
subsequent investigations elucidated much of the basic role of phagocytic cells in dealing
with infections. Much of Metchnikoff`s work was carried out at the Pasteur Institute
where Roux and Yersin had isolated a toxin from diphtheria bacilli which was responsible
for many of the symptoms of this disease.

The next major step forward was in the discovery (initially by Von Behring in Robert
Kochs laboratory in Berlin) that immunity could be passively transferred using serum
taken from a previously immunized animal. This serum component became known as
antibodies. The next step was the discovery that antibodies could not only protect an
individual from infection, but could directly lyse (in vitro) bacteria cultures such as
cholera . Soon afterwards two other phenomena of antibacterial serum were
demonstrated, precipitation and agglutination. These discoveries soon lead to the
development of serotherapy where serum from horses immunized with organism such as
diphtheria and tetanus would cure people if administered soon after the infection
developed. In 1899 Bordet discovered that immune serum contained two components, a
heat stable one that had the activity of agglutination and precipitation (the antibody
activity), and a heat labile one that was responsible for bacterial lysis (later known as
complement). At the beginning of the 1900's Landsteiner demonstrated that antibodies
could not only be produced against complex organism and proteins but also against
simple organic chemical such as diamino benzene sulphonate.
The development of these two different approaches to immunity, the cells of Metchnikoff,
and the antibodies of the German investigators lead to considerable controversy as to
which was the most important in immunity. This question was largely settled in the early
1900's when it became clear that both cellular and humoral factors were involved in
immune protection, and that immune serum could also act together with phagocytic cells
to increase phagocytosis (opsonization).
Between 1903 and 1910 the role of histamine in the phenomena of anaphylaxis was
elucidated, initially by Riche and Portier, and later by Dale and his colleagues. Up until
the late 1940's the actual substance responsible for antibody activity was not known until
the development of electrophoretic protein separation techniques by Tiselius in 1939. He
demonstrated that the gamma globulin fraction of serum increased in concentration
following immunization and that antibody activity was confined to this fraction.
The next 50 years saw the development and expansion of immunology into the major
discipline it is today

Timeline of immunology:

1549 - The earliest account of inoculation of smallpox (variolation) occurs in Wan Quan's
(14991582) Douzhen Xinfa
1718 Lady Mary Wortley Montagu, the wife of the British ambassador to
Constantinople, observed the positive effects of variolation on the native population and
had the technique performed on her own children.
1796 First demonstration of vaccination smallpox vaccination (Edward Jenner)
1837 Description of the role of microbes in putrefaction and fermentation (Theodore
1838 Confirmation of the role of yeast in fermentation of sugar to alcohol (Charles

1840 Proposal of the germ theory of disease (Jakob Henle)

1850 Demonstration of the contagious nature of puerperal fever (childbed fever) (Ignaz
1857-1870 Confirmation of the role of microbes in fermentation (Louis Pasteur)
1862 phagocytosis (Ernst Haeckel)
1867 Aseptic practice in surgery using carbolic acid (Joseph Lister)
1876 Demonstration that microbes can cause disease-anthrax (Robert Koch)
1877 Mast cells (Paul Ehrlich)
1878 Confirmation and popularization of the germ theory of disease (Louis Pasteur)
1880 1881 -Theory that bacterial virulence could be attenuated by culture in vitro and
used as vaccines. Proposed that live attenuated microbes produced immunity by depleting
host of vital trace nutrients. Used to make chicken cholera and anthrax "vaccines" (Louis
1883 1905 Cellular theory of immunity via phagocytosis by macrophages and
microphages (polymorhonuclear leukocytes) (Elie Metchnikoff)
1885 Introduction of concept of a "therapeutic vaccination". Report of a live
"attenuated" vaccine for rabies (Louis Pasteur).
1888 Identification of bacterial toxins (diphtheria bacillus) (Pierre Roux and Alexandre
1888 Bactericidal action of blood (George Nuttall)
1890 Demonstration of antibody activity against diphtheria and tetanus toxins.
Beginning of humoral theory of immunity. (Emil von Behring) and (Kitasato
1891 Demonstration of cutaneous (delayed type) hypersensitivity (Robert Koch)
1893 Use of live bacteria and bacterial lysates to treat tumors-"Coley's Toxins"
(William B. Coley)
1894 Bacteriolysis (Richard Pfeiffer)
1896 An antibacterial, heat-labile serum component (complement) is described (Jules
1900 Antibody formation theory (Paul Ehrlich)
1901 blood groups (Karl Landsteiner)
1902 Immediate hypersensitivity anaphylaxis (Paul Portier) and (Charles Richet)
1903 Intermediate hypersensitivity, the "Arthus reaction" (Maurice Arthus)
1903 Opsonization
1905 "Serum sickness" allergy (Clemens von Pirquet and (Bela Schick)
1909 Paul Ehrlich proposes "immune surveillance" hypothesis of tumor recognition and
1911 2nd demonstration of filterable agent that caused tumors (Peyton Rous)
1917 hapten (Karl Landsteiner)
1921 Cutaneous allergic reactions (Otto Prausnitz and Heinz Kstner)
1924 Reticuloendothelial system
1938 Antigen-Antibody binding hypothesis (John Marrack)
1940 Identification of the Rh antigens (Karl Landsteiner and Alexander Weiner)
1942 Anaphylaxis (Karl Landsteiner and Merill Chase)

1942 Adjuvants (Jules Freund and Katherine McDermott)

1944 hypothesis of allograft rejection
1945 Coombs Test aka antiglobulin test (AGT)
1946 identification of mouse MHC (H2) by George Snell and Peter A. Gorer
1948 antibody production in plasma B cells
1949 growth of polio virus in tissue culture, neutralization with immune sera, and
demonstration of attenuation of neurovirulence with repetitive passage (John Enders) and
(Thomas Weller) and (Frederick Robbins)
1951 vaccine against yellow fever
1953 Graft-versus-host disease
1953 Validation of immunological tolerance hypothesis
1957 Clonal selection theory (Frank Macfarlane Burnet)
1957 Discovery of interferon by Alick Isaacs and Jean Lindenmann[2]
19581962 Discovery of human leukocyte antigens (Jean Dausset and others)
19591962 Discovery of antibody structure (independently elucidated by Gerald
Edelman and Rodney Porter)
1959 Discovery of lymphocyte circulation (James Gowans)
1960 Discovery of lymphocyte "blastogenic transformation" and proliferation in
response to mitogenic lectins-phytohemagglutinin (PHA) (Peter Nowell)
1961-1962 Discovery of thymus involvement in cellular immunity (Jacques Miller)
1961- Demonstration that glucocorticoids inhibit PHA-induced lymphocyte proliferation
(Peter Nowell)
1963 Development of the plaque assay for the enumeration of antibody-forming cells in
vitro by Niels Jerne and Albert Nordin
1963 Gell and Coombs classification of hypersensitivity
1964-1968 T and B cell cooperation in immune response
1965 Discovery of lymphocyte mitogenic activity, "blastogenic factor" (Shinpei
Kamakura) and (Louis Lowenstein) (J. Gordon) and (L.D. MacLean)
1965 Discovery of "immune interferon" (gamma interferon) (E.F. Wheelock)
1965 Secretory immunoglobulins
1967 Identification of IgE as the reaginic antibody (Kimishige Ishizaka)
1968 Passenger leukocytes identified as significant immunogens in allograft rejection
(William L. Elkins and Ronald D. Guttmann)
1969 The lymphocyte cytolysis Cr51 release assay (Theodore Brunner) and (JeanCharles Cerottini)
1971 Peter Perlmann and Eva Engvall at Stockholm University invented ELISA
1972 Structure of the antibody molecule
1973 Dendritic Cells described by Ralph M. Steinman
1974 - Immune Network Hypothesis (Niels Jerne)
1974 T-cell restriction to MHC (Rolf Zinkernagel and (Peter C. Doherty)
1975 Generation of monoclonal antibodies (Georges Khler) and (Csar Milstein)[3]
1975 - Discovery of Natural Killer cells (Rolf Kiessling, Eva Klein, Hans Wigzell)
1976 Identification of somatic recombination of immunoglobulin genes (Susumu

1980-1983 Discovery and characterization of interleukins, 1 and 2 IL-1 IL-2 (Robert

Gallo, Kendall A. Smith, Tadatsugu Taniguchi)
1983 Discovery of the T cell antigen receptor TCR (Ellis Reinherz) (Philippa Marrack)
and (John Kappler)[4] (James Allison)
1983 Discovery of HIV (Luc Montagnier)
1985-1987 Identification of genes for the T cell receptor
1986 Hepatitis B vaccine produced by genetic engineering
1986 Th1 vs Th2 model of T helper cell function (Timothy Mosmann)
1988 Discovery of biochemical initiators of T-cell activation: CD4- and CD8-p56lck
complexes (Christopher E. Rudd)
1990 Gene therapy for SCID
1991 Role of peptide for MHC Class II structure (Scheherazade Sadegh-Nasseri &
Ronald N. Germain)
1992- Discovery of transitional B cells (David Allman & Michael Cancro) [5][6]
1994 'Danger' model of immunological tolerance (Polly Matzinger)
1995 Regulatory T cells (Shimon Sakaguchi)
1995 Dendritic cell vaccine trial reported by Mukherji et al.
1996-1998 Identification of Toll-like receptors
2000-Discovery of M1 and M2 macrophage subsets (Charles Mills)[7]
2001 Discovery of FOXP3 the gene directing regulatory T cell development
2005 Development of human papillomavirus vaccine (Ian Frazer)
2010 An immune checkpoint inhibitor, ipilimumab (anti-CTLA-4) is approved by the
FDA for treatment of stage IV melanoma
2011 Carl June reports a successful use of CAR T-cells for the treatment of CD19+
2014 The second immune checkpoint inhibitor, pembrolizumab (anti-PD-1) is approved
by the FDA for the treatment of melanoma
Types of immunity
All of us are exposed to a number of infections in our day to day life, but some agents
affect our body whereas others do not. To find out why, read this article about the defense
mechanism of human body.
Immunity is the ability of human body to fight against the disease causing organisms. The
human immune system has two types of immunity:
1 Innate immunity
2 Acquired immunity
Innate ImmunityThe innate immune system is the type of immunity that is
present naturally in the child at the time of birth. These natural protectors are
already present in human body.The first and the foremost important barrier which
prevents entry of the harmful micro-organisms in human body is skin. Skin acts as
a barrier to the entry of harmful micro-organism in many vital organs of the body.
Natural secretions of our body also help to prevent microbial growth in our body.

Vital systems such as respiratory, gastrointestinal, and urogenital are prevented by

the mucus coating of the epithelium lining these systems. fluids which are
protective in our body are acid in the stomach, saliva in the mouth and tears from
the eyes.White blood cells present in human blood also protect the body from
many infections. Macrophages in tissues help in the destruction of harmful
microbes entering into the body.Every one of us suffers from one or other type of
viral infection in our life. These viral infected cells produce special proteins called
interferon to protect healthy cells from further viral infection.
Acquired ImmunityAcquired immunity, also called the adaptive immune system,
involves two processes. The primary response is produced when our body encounters a
pathogen for the first time. This is a mild response produced by our body. The secondary
response is produced when our body encounters the same pathogen for the second time.
This secondary response is highly intensified.These responses are produced in our body
by two types of lymphocytes in our blood. These two special lymphocytes are Blymphocytes and T-lymphocytes. Whenever a foreign substance enters our body, Blymphocytes produce proteins to fight them. These proteins are called immunoglobulin or
antibodies. T-cells do not produce such proteins, but they help B-lymphocytes to produce
them. There are many different kind of antibodies produced in our body. Some of the
important antibodies present in human body are IgA, IgM, IgE and IgG.

Functions of immune system

The Immune System Fights Infections caused by various pathogens:
Our bodies are covered with bacteria and our environment contains bacteria on most
surfaces. Our skin and internal mucous membranes act as physical barriers to help
prevent infection. When the skin or mucous membranes are broken due to disease,
inflammation or injury, bacteria can enter the body. Infecting bacteria are usually coated
with complement and antibodies once they enter the tissues, and this allows neutrophils
to easily recognize the bacteria as something foreign. Neutrophils then engulf the bacteria
and destroy them (Figure 4).

When the antibodies, complement, and neutrophils are all functioning normally, this
process effectively kills the bacteria. However, when the number of bacteria is
overwhelming or there are defects in antibody production, complement, and/or
neutrophils, recurrent bacterial infections can occur.
Most of us are exposed to viruses frequently. The way our bodies defend against viruses
is different than how we fight bacteria. Viruses can only survive and multiply inside our
cells. This allows them to hide from our immune system. When a virus infects a cell,
the cell releases cytokines to alert other cells to the infection. This alert generally
prevents other cells from becoming infected. Unfortunately, many viruses can outsmart
this protective strategy, and they continue to spread the infection.
Circulating T-cells and NK cells become alerted to a viral invasion and migrate to the site
where they kill the particular cells that are harboring the virus. This is a very destructive
mechanism to kill the virus because many of our own cells can be sacrificed in the
process. Nevertheless, it is an efficient process to eradicate the virus.
At the same time the T-lymphocytes are killing the virus, they are also instructing the Blymphocytes to make antibodies. When we are exposed to the same virus a second time,
the antibodies help prevent the infection. Memory T-cells are also produced and rapidly
respond to a second infection, which also leads to a milder course of the infection.
A. Neutrophil (Phagocytic Cell) Engages Bacteria (Microbe): The microbe is coated
with specific antibody and complement. The phagocytic cell then begins its attack on the
microbe by attaching to the antibody and complement molecules.
B. Phagocytosis of the Microbe: After attaching to the microbe, the phagocytic cell
begins to ingest the microbe by extending itself around the microbe and engulfing it.
C. Destruction of the Microbe: Once the microbe is ingested, bags of enzymes or
chemicals are discharged into the vacuole where they kill the microbe.
The Immune System and Primary Immunodeficiency Diseases
Immune deficiencies are categorized as primary immune deficiencies or secondary
immune deficiencies. Primary immune deficiencies are primary because the immune
system is the primary cause and most are genetic defects that may be inherited.
Secondary immune deficiencies are so called because they have been caused by other
Secondary immune deficiencies are common and can occur as part of another disease or
as a consequence of certain medications. The most common secondary immune
deficiencies are caused by aging, malnutrition, certain medications and some infections,
such as HIV.
The most common medications associated with secondary immune deficiencies are

chemotherapy agents and immune suppressive medications, cancer, transplanted organ

rejection or autoimmune diseases. Other secondary immune deficiencies include protein
losses in the intestines or the kidneys. When proteins are lost, antibodies are also lost,
leading to low immune globulins or low antibody levels. These conditions are important
to recognize because, if the underlying cause can be corrected, the function of the
immune system can be improved and/or restored.
Regardless of the root cause, recognition of the secondary immune deficiency and
provision of immunologic support can be helpful. The types of support offered are
comparable to what is used for primary immune deficiencies.
The primary immunodeficiency diseases are a group of disorders caused by basic defects
in immune function that are intrinsic to, or inherent in, the cells and proteins of the
immune system. There are more than 200 primary immunodeficiency diseases. Some are
relatively common, while others are quite rare. Some affect a single cell or protein of the
immune system and others may affect two or more components of the immune system.
Although primary immunodeficiency diseases may differ from one another in many
ways, they share one important feature. They all result from a defect in one or more of the
elements or functions of the normal immune system such as T-cells, B-cells, NK cells,
neutrophils, monocytes, antibodies, cytokines or the complement system. Most of them
are inherited diseases and may run in families, such as X-Linked Agammaglobulinemia
(XLA) or Severe Combined Immune Deficiency (SCID). Other primary
immunodeficiencies, such as Common Variable Immune Deficiency (CVID) and
Selective IgA Deficiency are not always inherited in a clear-cut or predictable fashion. In
these disorders, the cause is unknown, but it is believed that the interaction of genetic and
environmental factors may play a role in their causation.
Because the most important function of the immune system is to protect against infection,
people with primary immunodeficiency diseases have an increased susceptibility to
infection. This may include too many infections, infections that are difficult to cure,
unusually severe infections, or infections with unusual organisms. The infections may be
located anywhere in the body. Common sites are the sinuses (sinusitis), the bronchi
(bronchitis), the lung (pneumonia) or the intestinal tract (infectious diarrhea).
Another function of the immune system is to discriminate between the healthy tissue
(self) and foreign material (non-self). Examples of foreign material can be
microorganisms, pollen or even a transplanted kidney from another individual. In some
immunodeficiency diseases, the immune system is unable to discriminate between self
and non-self. In these cases, in addition to an increased susceptibility to infection, people
with primary immunodeficiencies may also have autoimmune diseases in which the
immune system attacks their own cells or tissues as if these cells were foreign, or nonself.
There are also a few types of primary immunodeficiencies in which the ability to respond
to an infection is largely intact, but the ability to regulate that response is abnormal.

Examples of this are autoimmune lymphoproliferative syndrome (ALPS) and IPEX (an
X-linked syndrome of immunodeficiency, polyendocrinopathy and enteropathy).
Primary immunodeficiency diseases can occur in individuals of any age. The original
descriptions of these diseases were in children. However, as medical experience has
grown, many adolescents and adults have been diagnosed with primary
immunodeficiency diseases. This is partly due to the fact that some of the disorders, such
as CVID and Selective IgA Deficiency, may have their initial clinical presentation in
adult life. Effective therapy exists for several of the primary immunodeficiencies, and
many people with these disorders can live relatively normal lives.
Primary immunodeficiency diseases were initially felt to be very rare. However, recent
research has indicated that as a group they are more common than originally thought. It is
estimated that as many as 1 in every 1,2002,000 people may have some form of primary
A vaccine is a biological preparation that provides active acquired immunity to a
particular disease. A vaccine typically contains an agent that resembles a disease-causing
micro-organism and is often made from weakened or killed forms of the microbe, its
toxins or one of its surface proteins. The agent stimulates the body's immune system to
recognize the agent as a threat, destroy it, and keep a record of it, so that the immune
system can more easily recognize and destroy any of these micro-organisms that it later
Vaccines are dead or inactivated organisms or purified products derived from them.
There are several types of vaccines in use. These represent different strategies used to try
to reduce risk of illness, while retaining the ability to induce a beneficial immune
Some vaccines contain inactivated, but previously virulent, micro-organisms that have
been destroyed with chemicals, heat, radiation, or antibiotics. Examples are influenza,
cholera, bubonic plague, polio, hepatitis A, and rabies.
Some vaccines contain live, attenuated microorganisms. Many of these are active viruses
that have been cultivated under conditions that disable their virulent properties, or that
use closely related but less dangerous organisms to produce a broad immune response.
Although most attenuated vaccines are viral, some are bacterial in nature. Examples
include the viral diseases yellow fever, measles, rubella, and mumps, and the bacterial
disease typhoid. The live Mycobacterium tuberculosis vaccine developed by Calmette
and Gurin is not made of a contagious strain, but contains a virulently modified strain
called "BCG" used to elicit an immune response to the vaccine. The live attenuated
vaccine-containing strain Yersinia pestis EV is used for plague immunization. Attenuated
vaccines have some advantages and disadvantages. They typically provoke more durable
immunological responses and are the preferred type for healthy adults. But they may not

be safe for use in immunocompromised individuals, and may rarely mutate to a virulent
form and cause disease.
Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than
the micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria.
Toxoid vaccines are known for their efficacy. Not all toxoids are for micro-organisms; for
example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites.
Protein subunit rather than introducing an inactivated or attenuated micro-organism to
an immune system (which would constitute a "whole-agent" vaccine), a fragment of it
can create an immune response. Examples include the subunit vaccine against Hepatitis B
virus that is composed of only the surface proteins of the virus (previously extracted from
the blood serum of chronically infected patients, but now produced by recombination of
the viral genes into yeast), the virus-like particle (VLP) vaccine against human
papillomavirus (HPV) that is composed of the viral major capsid protein, and the
hemagglutinin and neuraminidase subunits of the influenza virus. Subunit vaccine is
being used for plague immunization.
Conjugate certain bacteria have polysaccharide outer coats that are poorly
immunogenic. By linking these outer coats to proteins (e.g., toxins), the immune system
can be led to recognize the polysaccharide as if it were a protein antigen. This approach is
used in the Haemophilus influenzae type B vaccine.
Electroporation System for experimental "DNA vaccine" delivery
A number of innovative vaccines are also in development and in use:

Dendritic cell vaccines combine dendritic cells with antigens in order to present the
antigens to the body's white blood cells, thus stimulating an immune reaction. These
vaccines have shown some positive preliminary results for treating brain tumors and are
also tested in malignant melanoma.
Recombinant Vector by combining the physiology of one micro-organism and the DNA
of the other, immunity can be created against diseases that have complex infection
DNA vaccination an alternative, experimental approach to vaccination called DNA
vaccination, created from an infectious agent's DNA, is under development. The
proposed mechanism is the insertion (and expression, enhanced by the use of
electroporation, triggering immune system recognition) of viral or bacterial DNA into
human or animal cells. Some cells of the immune system that recognize the proteins
expressed will mount an attack against these proteins and cells expressing them. Because
these cells live for a very long time, if the pathogen that normally expresses these
proteins is encountered at a later time, they will be attacked instantly by the immune
system. One potential advantage of DNA vaccines is that they are very easy to produce
and store. As of 2015, DNA vaccination is still experimental and is not approved for
human use.

T-cell receptor peptide vaccines are under development for several diseases using models
of Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to
modulate cytokine production and improve cell mediated immunity.
Targeting of identified bacterial proteins that are involved in complement inhibition
would neutralize the key bacterial virulence mechanism.
While most vaccines are created using inactivated or attenuated compounds from microorganisms, synthetic vaccines are composed mainly or wholly of synthetic peptides,
carbohydrates, or antigens.
Vaccines may be monovalent (also called univalent) or multivalent (also called
polyvalent). A monovalent vaccine is designed to immunize against a single antigen or
single microorganism. A multivalent or polyvalent vaccine is designed to immunize
against two or more strai ns of the same microorganism, or against two or more
microorganisms. The valency of a multivalent vaccine may be denoted with a Greek or
Latin prefix (e.g., tetravalent or quadrivalent). In certain cases a monovalent vaccine may
be preferable for rapidly developing a strong immune response.
Also known as Heterologous or "Jennerian" vaccines these are vaccines that are
pathogens of other animals that either do not cause disease or cause mild disease in the
organism being treated. The classic example is Jenner's use of cowpox to protect against
smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis
to protect against human tuberculosis.