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Course: Immunology
Lecturer: Dr. Weam Saad
Lecture: Antigens
Antigens
Definitions:
Antigen (Ag): Any foreign substance that enters human body and is able to generate
specific immune response.
Immunogen - A protein that induces a complete specific immune response,
meaning induction of immune system to produce specific antibodies and memory
cells.
Hapten: a type Ag or foreign substance that cannot induce a complete immune
response alone, but with adding a carrier molecule (adjuvant) can become a
complete Ag and it is able to react with the specific Abs that result after immune
response induction, e.g. gelatin is not a good Ag, but after adding the tyrosine
(adjuvant) it became a good immunogenic Ag.
Epitope: it is a part of an Ag can be recognized by immune cells.
Antigenic determinant: A cluster (group) of epitopes.
Multivalent Ag: Ag has multiple epitopes.
Monovalent Ag: Ag has one epitope.
Surface Ag: it is the Ag on the surface of microorganism. e.g. somatic O Ag and
flagella H Ag of Salmonella sp.
Factors influencing immunogenicity of any Antigen:
A. Properties of good Immunogen:
1. Foreignness - The immune system normally distinguish between self and non-
self, so that only foreign molecules are immunogenic.
2. Size - In general, the larger size Ag molecule the more immunogenic it is.
3. Chemical Composition - In general, the more complex the substance is
chemically the more immunogenic it will be. The antigenic determinants are
created by the primary sequence of residues (or amino acids) in the polymer
and by the secondary, tertiary or quaternary structure of the molecule.
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4. Physical form - In general particulate antigens are more immunogenic than
soluble Ag, and denatured antigens more immunogenic than the native and other
forms.
5. Degradability - Antigens that are easily phagocytosed are generally more
immunogenic. Because the immune response needs the antigen to be
phagocytosed, processed and presented to helper T-cells by an antigen presenting
cell (APC). Also stable Ag is good in immunogenicity because its epitopes will
be stable and can be recognized be immune cells.
B. Biological factors affecting the immune System response to
Antigens (Ag):
1. Genetic Factors - Some substances are immunogenic in one species but not in
another. Also, some substances are immunogenic in a person but not in others.
2. Age - Age can also influence immunogenicity. Usually the children and the very
old people have a suppressed ability of immune response to an immunogen.
C. Method of Ags Administration:
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Dose - The dose of administration of an immunogen can influence its
immunogenicity. Optimal dose will start the immune response.
2. Route - Generally the subcutaneous route is better than the intravenous or intra
gastric routes. The route of antigen administration can affect the nature of the
response
3. Adjuvants - Substances that can enhance or increase the immune response to an
immunogen are called adjuvants. The use of adjuvants has many side effects such
as fever and inflammation.
Chemical Nature of Antigens:
A. Proteins –most good antigens are proteins. They are good immunogens,
may be pure proteins or they may be glycoproteins or lipoproteins. In
general, proteins are usually very good immunogens.
B. Polysaccharides - Pure polysaccharides and lipopolysaccharides are good
immunogens.
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C. Nucleic Acids - Nucleic acids are usually poorly immunogenic, they may
become immunogenic when they are single stranded or when complex with
proteins.
D. Lipids - In general lipids are non-immunogenic (haptens). Some
glycolipids and phospholipids can stimulate T-cells directly and produce
a cell-mediated immune response.
Types of antigens according to the specific immune response type that they
produce:
1. T-dependent Antigens
2. T-independent Antigens
Adjuvants (from Latin adjuvane, to help) are substances that, when mixed
with an antigen and injected with it, enhance the immunogenicity of that
antigen. Adjuvants are often used to boost the immune response when an
antigen has low immunogenicity or when only small amounts of an antigen
are available
.
They help in:
1. Staying of Antigen for long time.
2. Induction of stimulatory signals.
3. Increase local inflammation.
4. Stimulate the nonspecific proliferation of lymphocytes.
Freund's adjuvant is a solution of antigen emulsified in oil and used as
an immunopotentiator (booster). These adjuvants are in two types;
1.
Freund’s complete adjuvants composed of inactivated and
dried Mycobacterium tuberculosis and water in oil emulsion.
2.
Freund’s incomplete adjuvant is without mycobacterial components
(just the water in oil emulsion).
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Immunization
The importance of active immunization is to prevent infectious diseases
using prepared vaccine.
Types of Vaccines
A wide variety of immunizing agents were developed. The following
are some examples:
1. Killed vaccines are generally safe, but not effective like attenuated
vaccines.
a. Killed bacteria, such as the traditional pertussis vaccine prepared with
killed Bordetella pertussis (for whooping cough), the typhoid vaccine
prepared with acetone-inactivated Salmonella typhi, and the cholera vaccine,
prepared with killed Vibrio cholerae.
b. Killed viruses, such as Salk's polio vaccine, containing a mixture of the
three known types of poliovirus, after inactivation with formalin. This
vaccine has been as successful in the eradication of poliomyelitis as Sabin's
attenuated oral vaccine. Its main advantage is safety, but is not as effective
as the oral vaccine.
2. Component vaccines, which are safer than killed vaccines, but have
problem in efficacy:
a) Bacterial polysaccharides, such as those used for Streptococcus
pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type
b, and a vaccine for typhoid fever made of the Vi capsular
polysaccharide.
b) Inactive toxins (toxoids), such as tetanus and diphtheria toxoids which
are formalin-inactivated toxins that have lost their active site but
maintained their immunogenic determinants and induce antibodies
able to neutralize the toxins.
c) Recombinant bacterial antigens. A recombinant vaccine of
Rickettsia rickettsii (antigen produced in E. coli used for this bacteria
and the disease Rocky Mountain spotted fever).
d) Mixed component vaccines. e.g. For save vaccines for whooping
cough, a mixture of inactivated pertussis toxin used to replace the
killed pertussis vaccine.
e) Conjugate vaccines. Most polysaccharide vaccines have poor
immunogenicity in infants because of the fact that polysaccharides
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tend to induce T-independent responses with little memory. This
problem solved when the polysaccharide is conjugated to an
immunogenic protein like a hapten-carrier conjugate. The first
conjugate vaccines is the polyribositolribophosphate (PRP) of
Haemophilus influenzae type b (HiB) for children of less than 5 years
of age.
f) Viral component vaccines use the viral component .The best example
is the hepatitis B vaccine, prepared from the particles of hepatitis virus
outer coat protein (hepatitis B surface antigen or HBs Ag) isolated from
chronic carriers. Also, some of HIV vaccines are component vaccines
(contain envelope glycoproteins).
g) Synthetic peptide vaccines. The use of synthetic peptides for
vaccination is easy to manufacture and save in neutralizing specific
antibodies e.g. malaria vaccine.
h) DNA vaccines. Used recently by intramuscular injection of non-
replicating plasmid DNA encode for the hemagglutinin (HA) or
nucleoprotein (NP) of influenza virus induce humoral and cellular
protective immune response.
3. Attenuated vaccines. Attenuated vaccines are very efficient, but in rare
cases can cause the disease, they are designed to prevent and protect
people
especially
people
have
weak
immune
system
or
immunocompromised individual. Most antiviral vaccines are made of
attenuated viruses in the laboratory, including the classic smallpox
vaccine, the oral polio vaccine, and mumps-rubella-measles vaccine, the
attenuated bacteria, e.g. new bacterial vaccine against typhoid fever is
based on the use of an attenuated strain of Salmonella typhi that grows
poorly and is non-pathogenic but induces protective immunity in 90% of
the individuals.
4. Recombinant organisms. Recombinant technology is used to delete the
genes coding for virulence factors from bacteria, or to add genetic
information to attenuate viruses or attenuate bacteria. Experimental
vaccines for AIDS were developed by adding parts of the envelope coding
gene of HIV into the vaccinia virus genome.
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Examples for important vaccines:
1) BCG vaccine: (Bacillus Calmette-Guerin) vaccine:
Vaccine used against tuberculosis, usually given to healthy babies.
Live attenuated bacteria. Given by injection percutaneous.
2) MMR vaccine: (Mumpus, Measles and Rubella) vaccine:
Vaccine used against three diseases composed of combination or
mixture of live attenuated viruses of three diseases. Given by
injection (usually I.M.in hand).
3) DPT Vaccine: the Triple vaccine or Diphtheria, Pertussis and
Tetanus vaccine:
This vaccine is a type of component vaccine, composed of
diphtheria and tetanus toxoids and killed bacteria of pertussis
(whooping cough). Given by injection (usually I.M.in hand)