Transcript ANTIGENS AND ANTIBODIES. STRUCTURE OF IMMUNE SYSTEM

Medical biology, microbiology,
virology, immunology department
Antigen. Bacterial
antigens. Major
Histocompatibility
Complex
By as. E.V. Pokryshko
The name antigens (Gk. anti against,
genos genus) is given to organic
substances of a colloid structure
(proteins and different protein
complexes in combination with lipids
or polysaccharides) which upon
injection into the body are capable of
causing the production of antibodies
and reacting specifically with them.
Antigenic substances must have certain
properties: a colloid structure,
and solubility in the body fluids.
Antigenic properties are pertinent to
 toxins of a plant origin (ricin, robin, abrin, cortin,
etc.),
 toxins of an animal origin (toxins of snakes,
spiders, scorpions, phalangia, karakurts, bees),
 enzymes,
 native foreign proteins,
 various cellular elements of tissues and organs,
 bacteria and their toxins, rickettsiae and
viruses.
Antigens, consequently, are
characterized by the following
main properties:
1. the ability to cause the
production of antibodies
(antigenicity),
2. the ability to enter into an
interaction with the
corresponding antibodies
(antigenic specificity).
The features of molecules that
determine antigenicity and
immunogenicity are as follows:
1.Foreignness.
2.Molecular Size.
3.Chemical-Structural Complexity
4.Antigenic Determinants
(Epitopes)
Foreignness: In general,
molecules recognized as "self”
are not immunogenic; ie, we are
tolerant to those self-molecules.
To be immunogenic, molecules
must be recognized as "nonself,"
ie, foreign.
Molecular Size: The most potent
immunogens are proteins with high
molecular weights, ie, above 100,000.
Generally, molecules with molecujar
weight below 10,000 are weakly
immunogenic, and very small ones, eg,
an amino acid, are nonimmunogenic.
Certain small molecules, eg, haptens,
become immunogenic only when linked
to a carrier protein.
Chemical nature:
Protein and polysaccharides are most
antigenic. Lipids and nucleic acids are
less antigenic. Their antigenicity is
enhanced by combination with proteins.
A certain amount of chemical complexity
is required, for example, amino acid
homopolymers are less immunogenic than
heteropoymers containing two or three
different amino acids.
Antigenic Determinants
(Epitopes):
Epitopes are –
small chemical groups on the
antigen molecule that can elicit and
react with antibody.
An antigen can have one or more
determinants. Most antigens have
many determinants; ie, they are
multivalent.
Antigen epitopes
epitopes
Antigen
Hapten (incomplete antibody)
is a molecule that cannot induce
an immune response by itself
but can react with specific
antibody.
Nevertheless, haptens can induce
a response if combined with larger
molecules (normally proteins) which
serve as carrier.
Haptens are usually small. Many
drugs, eg, penicillins, are haptens,
and the catechol in the plant oil that
causes poison oak and poison ivy is a
hapten.
hapten
Immunogenic antigen
epitope
protein
No antibidies
produced
Antibody against
epitope on antigen
Immunogenic antigen as carier for hapten
epitope
hapten
Antibody against
epitope on hapten
Antibody against
epitope on antigen
It is well known that the properties of
chemical,
structural
and
functional
specificity are inherent in all natural
proteins. Proteins of different species of
animals, plants, bacteria, rickettsiae and
viruses
can
be
differentiated
by
immunological reactions. The antigenic
function of bacteria, rickettsiae and
viruses is characterized not only by
species, but also by type specificity.
A typical antigen:antibody reaction: gramnegative bacterial pathogen may have several
antigens, or immunogens (flagella, pili and cell
wall)
Antigenic structure of a bacterium
Antigenic structure of a virus
H
N
RNA
Protein М2
Protein М1
Lipid membrane
Antigenic properties of bacteria,
toxins, rickettsiae and viruses,
used in the practice of reproducing
artificial
immunity
against
infectious diseases, are of most
practical importance.
When the antigenic structures of
the host are similar to those of the
causative agent, the macroorganism
is incapable of producing immunity,
as the result of which the disease
follows a graver course. It is
possible that in individual cases the
carrier state and inefficacy of
vaccination are due to the common
character of the microbial antigens
and the antigens of the person's
cells.
It has been established that human
erythrocytes have antigens in
common with staphylococci,
streptococci, the organisms of
plague, E. coli. Salmonella paratyphi,
Shigella organisms, smallpox and
influenza viruses, and other
causative agents of infectious
diseases. Such a condition is called
antigenic mimicry.
Isoantigens are those substances
which have antigenic properties and are
contained in some individuals of a given
species.
Isoantigens of leukocytes, blood
platelets, lymphocytes, granulocytes,
blood sera, liver, and kidneys and interorgan (cell nuclei, mitochondria,
ribosomes, etc.) and pathological
(cancerous, bum, radiation) isoantigens
have been revealed.
Isoantigens have been found in the
erythrocytes of animals and man. At first
it was established that in human
erythrocytes there are two antigens (A and
B), and in the sera — beta- and alphaantibodies. Only heterogenic antigens and
antibodies (agglutinins) can be found in
human blood.
On the basis of antigenic structure the
erythrocytes of all people can be
subdivided into 4 groups (A, B, AB and 0).
These data are taken into account
during blood transfusion.
Autoantigens are substances
capable of immunizing the body from
which they are obtained.
Self antigens
 are ordinarily non-antigenic,
 not normally found free in circulation
or tissue fluids,
 are not recognized as self antigens.
Thus, they become modified and are
capable of bearing an antigenic function.
Autoantigens
These substances include
 the eye lens,
 spermatozoids,
 homogenates of the seminal gland,
 skin,
 emulsions of kidneys, liver, lungs
and other tissues.
Autoantigens
Under ordinary conditions they do
not come in contact with the
immunizing systems of the body,
therefore antibodies are not produced
against such cells and tissues. However,
if these tissues are injured, then
autoantigens may be absorbed, and may
cause the production of antibodies
which have a toxic effect on the
corresponding cells.
The origination of autoantigens is
possible under the influence of
 cooling, radiation,
 drugs (amidopyrine, sulphonamides,
preparations of gold, etc.),
 virus infections "(virus pneumonias and
mononucleosis),
 acterial proteins and toxins of
streptococci, staphylococci, tubercle
bacilli, paraproteins,
 aseptic autolysis of brain tissue,
 and other factors.
Histocompatibility antigens
There are the antigens present on the
cells of each individual of species . These
proteins are alloantigens; ie, they differ
among members of the same species.
These antigens are encoded by genes
known as histocompatibility genes which
collectively constitute major
histocompatibility complex (MHC), These
are located on the short arm of
chromosome 6.
Major Histocompatibility Complex
MHC products present on the
surface of leucocytes are known as
human leukocyte antigens (HLA).
The success of tissue and organ
transplants depends on the donor's
and recipient's human leukocyte
antigens (HLA). If the HLA proteins
on the donor's cells differ from
those on the recipient's cells, an
immune response occurs in the
recipient.
Major Histocompatibility Complex
Three of these genes (HLA-A, HLA-B,
and HLA-C) code for the class I MHC
proteins. Several HLA-D loci determine the
class II MHC proteins, ie, DP, DQ, and DR.
There are many alleles of the class I and
class II genes. For example, there are at
least 47 HLA-A genes, 88 HLA-B genes, 29
HLA-C genes, and more than 300 HLA-D
genes, but any individual inherits only a
single allele at each locus from each parent
and thus can make no more than two class I
and II proteins at each gene locus.
Expression of these genes is codominant,
ie, the proteins encoded by both the
paternal and maternal genes are produced.
Each person can make as many as 12 HLA
proteins: 3 at class I loci and 3 at class II
loci, from both chromosomes. Between the
class I and class II gene loci is a third locus,
sometimes called class III. This locus
contains several immunologically important
genes, encoding two cytokines (tumor
necrosis factor and lymphotoxin) and-two
complement components (C2 and C4).
Class I MHC Proteins. These are
glycoproteins found on the surface of
virtually all nude ated cells. There are
approximately 20 different proteins
encoded by the allelic genes at the A
locus, 40 at the B locus, and 8 at the C
locus.
Class II MHC Proteins. These are
glycoproteins found on the surface of
certain cells, including macrophages, B
cells, dendritic cells of the spleen, and
Langerhans cells of the skin.
BIOLOGIC IMPORTANCE OF MHC
The ability of T cells to recognize
antigen is dependent on association of
the antigen with either class I or class
II proteins. For example, cytotoxic T
cells respond to antigen in association
with class I MHC proteins. Thus, a
cytotoxic Tcell that kills a virusinfected cell will not kill a cell infected
with the same virus if the cell does not
also express the appropriate class I
proteins.
BIOLOGIC IMPORTANCE OF MHC
MHC genes and proteins are also
important in two other medical
contexts. One is that many autoimmune
diseases occur in people who carry
certain MHC genes, and the other is
that the success of organ transplants
is, in large part, determined by the
compatibility of the MHC genes of the
donor and recipient.
Disease
HLA
Addison’s disease
DR5
Behtyer’s
disease
of a
presence
at healthy
persons
Antigene on which
the immune answer
develops
70
20
Adrenal cortex
B27
89
9
Unknown
Hashimoto’s
thyreoiditis
DR3, DR5
51
24
Thyroglobulin
Juvenile
diabetes
DR3, DR4
72
24
Insulin receptor
Rheumatoid
arthritis
DR7,
59
21
Colagen, Fc
fragment of IgG
Frequency of
an antigene
at ill
persons
DR21
Narcolepsy
DR2
100
34
Unknown
Goodpasture’s
syndrom
DR2
88
29
Basement
membrane of a
kidney and lung