Szabad, Biology booklet 24.
24. BIOLOGY OF THE IMMUNE SYSTEM.
Nonspecific defense systems against pathogens. The
immune system, specific defense system against
pathogens. Cellular and humoral immune responses.
Immunization and vaccination. Immunological
memory. Clonal selection. Distinction between self
and nonself. The immunoglobin proteins. Genetic
basis of immunoglobin diversity. Diseases of the
immune system.
INTRODUCTION
To sustain their life, heterotrophic organisms
require organic materials that had been synthesized
primarily by the autotrophic organisms. Pathogens are
disease-causing agents like viruses, bacteria, fungi,
several species of protists and worms. While
attacking, pathogens basically search for life
conditions. Naturally, the attacked organisms try to
protect themselves. What are the protection
mechanisms against pathogens? How do nonspecific
and specific protection mechanisms function? How
are antibody molecules produced against pathogens?
The following chapter provides an overview of the
protective mechanisms against pathogens. It should
be noted, however, that physiological and
pathological aspects of the immune system are
covered in different subjects. The present chapter
deals with mostly molecular biology of the related
processes.
NON-SPECIFIC DEFENSE MECHANISMS
To achieve their goals, pathogens must reach and
invade the organisms. Once inside, they "hope" to
survive, reproduce while making preparation to attack
the next organism. Obviously the attacked organisms
try to keep the pathogens away and develope
protective mechanisms. The so-called non-specific
defense mechanisms represent a collection of
methods that provide protection against a wide range
of pathogens. The most important nonspecific defense
mechanisms are as follows.
- The skin provides a highly compact covering
over the outer surface of the organisms that is
difficult to cross.
- The normal flora is a collection of species of
mostly bacteria and fungi that live on the outer
and internal surfaces of our body that may be
exposed to pathogens. The normal flora
competes with the pathogens by producing toxic
products that establish unfavorable conditions for
life of the pathogens.
- Mucus forms in some parts of the visual,
respiratory, digestive, excretory and urogenital
system. Secretions like tears, saliva, nasal drips
contain an enzyme called lysozyme that attacks
cell wall of the bacteria. Bacteria without cell
wall are vulnerable to e.g. the immune system.
Most of the secretions also contain IgA
molecules, one type of immunoglobins that fight
against specific types of pathogens.
- The phagocytes - macrophages and neutrophil
granulocytes (see table 24.1.) - are special types
of white blood cells that engulf pathogens and
digest subsequently with enzymes stored in their
lysosomes.
- The natural killer cells are ancient types of white
blood cells that attack and lyse virus-infected and
some types of tumor cells.
- Inflammation involves the leakage of blood
plasma, phagocytes and antibodies from
capillaries and local heating; improper conditions
for life of the pathogens.
- Fewer are body-wide responses that inhibit
proliferation of many of the pathogen organisms.
- Struggle for iron implies fight for iron ions
between pathogens and cells of the organism.
Since iron ions are required for life of the
pathogens and in healthy organisms the iron is
associated with proteins, the limited amount of
free iron limits life of the pathogens.
- Interferons are glycoproteins composed from
about 16 amino acids. Virus-infected cells
release interferons that bind to surface receptors
of other cells and induce the synthesis of anti-
virus enzymes.
- The complement system includes some twenty
different types of protein molecules. Proteins of
the complement system lyse microorganisms,
enhance phagocytosis and assist in inflammatory
responses.
Although the present chapter deals mostly with the
immune system and organisms with immune system,
it worth mentioning two non-specific defense systems
that plants use against pathogens and also the one that
unicellular organisms use to secure life conditions.
We make use of both of them in fight against
pathogens.
- Phytoelaxins are small plant protein molecules
that plants synthesize to fight against pathogens.
- Antibiotics are different types of chemical
molecules produced by bacteria and fungi to
prevent growth of the other types of
microorganisms.
SPECIFIC DEFENSE MECHANISM: THE
IMMUNE SYSTEM
The specific defense mechanism specifically
eliminates pathogens like viruses, bacteria, fungi
worms and macromolecules. The specific defense
mechanism has three important features. It (i)
recognizes (ii) specifically eliminates and (iii)
remembers the pathogen. Remembering the pathogen
implies fast and efficient elimination of the pathogen
following repeated exposure of the organisms to the
pathogen. Organisms that had been exposed to a
pathogen are immune (exempt) to the pathogen, and
hence the specific defense mechanism is called the
immune system.
 Szabad, Biology booklet 24. 2

The immune system characteristic function in the bone marrow, the T

The most important components of the immune
system are the white blood cells and the different
components of the lymph system (Table 24.1 and Fig.
24.1). In humans there are about 7x106 white and
5x109 red blood cells in 1 ml blood. Red and white
blood cells derive from common stem cells in the red
bone marrow. The B lymphocytes attain their
lymphocytes in the thymus. The specific defense
mechanism is the result of well-coordinated activities
of the different types of white blood cells (Table
24.1). Cytokines are growth factor types of small
protein molecules, products of the different types of
white blood cells. Cytokines regulate white blood cell
function and kill certain types of tumor cells.

Table 24.1. Human blood cell types and some of their characteristics

Cell type Function Cells/ml

Red blood cells O2 and CO2 transport 5x109
White blood cells
Granulocytes
Neutrophils Phagocytosee antibody-coated pathogens. 5x106
Eosinophils Kill antibody-coated parasites. Modulate allergic and inflammatory reactions. 2x105
Basophils Release histamine and –in some immune reaction –serotonin. 4x104
Monocytes Differentiate to macrophages. The macrophages phagocytose, engulf and 4x105
digest microorganisms, foreign proteins. Modulate function of the other types
of white blood cells.
Lymphocytes
B cells Differentiate to (i) plasma cells, that secrete antibodies, and to (ii) memory 2x106
cells.
T cells Kill virus-infected, several types of the mutant and the foreign cells. Regulate 1x106
function of other types of white blood cells.
Natural killer cells Attack and lyse virus-infected, foreign and several types of tumor cells. 1x105
Platelets Products of megakaryocytes in the bone marrow. Initiate blood clotting. 3x108
Notes: there are some 5 liters of blood in an average human body, comprising about 7% of body weight. Red and
white blood cells amount to about 45 and 1% of blood volume. Blood plasma is the liquid component of blood.

Immunization and vaccination

Fig. 24.2. The change in time of antibody

concentration against the same pathogen during the
primary and the secondary immune responses. Note
the logarithmic scale of the antibody concentration.

Following exposure to a pathogen, specific types of

Fig. 24.1. Components of the human immune system.
antibody molecules appear in the blood after a few
days during the course of the so-called primary
immune response (Fig. 24.2). The antibodies
specifically recognize and destroy the pathogen. In
the secondary immune response, upon second
exposure to the pathogen, the antibody concentration
(i) increases faster than in the primary response and

(ii) reaches higher concentrations as during the
primary response (Fig. 24.2). The secondary response
clearly shows that organisms "remember" the first
exposure to the pathogen and are able to efficiently
fight against it: as the consequence of the primary
response the organism became immunized against the
pathogen. Following recognition of the phenomenon
of immunization weakened forms or only harmless
components of the pathogens are intentionally
introduced into organisms in the process called
vaccination. (In case of e.g. snakebite, antibodies
against the snake venom - produced in e.g. horses or
with the monoclonal antibody technique - are
introduced to humans to fight against the pathogen in
the process called passive immunization.) What types
of events lead to the production of antibodies? How
does the immune system work? What are bases of the
immune memory?
Fig. 24.3. Structure of the different types of
antibodies.
Clonal selection and antibody production
Niels K. Jerne and MacFarlane Burnet answered the
above questions in the 1950s. An important step
along antibody production is the formation of some
108 B-lymphocytes in our body every day. There are
specific receptor proteins on surface of the B cells
that can establish contact with the antigens, special
structures of the pathogens. It should be noticed that
the receptor molecules do not originate upon antigen
action. They are produced randomly well before
exposure of the organism to the pathogen. As it will
be discussed in a subsequent paragraph, the receptor
molecules on surface of the B cells are produced in a
process unique for the animal kingdom.
Szabad, Biology booklet 24. 3
Fig. 24.4. During clonal selection, only that B cell
differentiates into plasma and memory cells which
carries the appropriate antibody on its surface to react
with the antigen. While the descending plasma cells
secrete antibody molecules, memory cells are set
aside for future use.
The B cell surface molecules belong to the IgM
class of the immunoglobins (see Table 24.2, Fig.
24.3). There is only one type of antigen receptor on
the surface of any B cell, however in multiple copies.
Of the several million B cells, only that can establish
contact with the antigen which has the appropriate
receptor (the IgM molecules) to bind the antigen.
The process in which an appropriate B cell is
selected to recognize an antigen is called clonal
selection (Fig. 24.4). While the "selected" B cell
proliferate and differentiate, the non-selected B cells
die (through apoptosis) within a few days.
Differentiation of the selected B cell leads to the
formation of two cell types: (i) the plasma cells and
(ii) the memory cells (Fig. 24.4). The plasma cells
secrete the antigen specific largely IgG antibody into
the blood plasma where they fight against the
pathogen. The plasma cells die after a few days. The
memory cells are put aside for future use. Upon
repeated exposure to the antigen there are many
memory cells to encounter the antigen, to differentiate
to plasma cells. As described above, the plasma cells
synthesize and secrete IgG antibody molecules to
eliminate the pathogen. The memory cells live up to
the end of our life. All the plasma cells that produce
the same type of antibody and the sister memory cells
are descendants of the same B cell, i.e. they form a
clone.
The antibody molecules recognize and bind to the
antigens, pathogens. The antibody-coated antigens
(pathogens) are destroyed through phagocytosis
(Table 24.1). Antibodies produced in course of the
primary immune response belong to the IgG class.
The IgG molecules possess the same antigen
specificity characterized the IgM antibody. However,
the IgG molecules are components of the blood
plasma and not the cell membrane. The production of
different types of antibodies with the same antigen
specificity is called class switching. (Table 24.2).
 Szabad, Biology booklet 24. 4

Table 24.2. Types and function of the different types of antibodies.

Immuno- Function Heavy
globin
class chain
IgM Antigen receptor in the B and memory cell membrane. 
IgD Cell surface receptor of the mature B cells. Important in B cell activation. 
IgG Most abundant antibody type from the secondary immune response. It can cross the placenta 
and provide passive immunity to the fetus. It amounts to about 80% of the blood plasma
antibodies.
IgE Present on surface of mast cells and basophils. When bound to antigens, triggers release of 
histamine from mast cell or basophils. Histamine, a local hormone, contributes to
inflammation and some allergic responses. Tool in fight against parasites (worms).
IgA Protects mucosal surfaces. Fights against pathogens in saliva, tears, milk and other body 
secretions.
Antigen presentation. Role of macrophages and
the TH helper cells
The above chapter summarized essence of the
antigen-receptor interaction and its consequences. In
reality the process is more complex. The B cells
establish contact with the antigen (or a segment of it
called antigen determinant) only when the antigen is
simultaneously present on the surface of both the B
cell and a so-called TH (helper T) cell (Fig. 24.5).
The process is called antigen presentation and begins
with phagocytosis of the pathogen by a macrophage.
The antigen is partially digested by the lysosomal
enzymes first. The antigen associates next with a
protein. In mice, the protein is a member of the so-
called MHC (major histocompatibility complex)
protein family. The antigen, associated with the MHC
protein, appears on surface of the macrophage, i.e. the
antigen is presented for further white blood cell types.
A note: the MHC gene complex encodes mostly cell
surface proteins and thus determines cell identity.
About 50 genes compose the MHC complex. Each of
the MHC genes is highly polymorph. For some of the
MHC genes there are as many as 70 known alleles.
Name of the MHC corresponding human gene
complex is HLA, human leukocyte antigens. The
success of organ transplantation depends on the HLA
genes and their alleles: the more donor and recipient
HLA alleles match, the higher the transplantation
success rate will be. The TH cells recognize the
antigen presented on surface of the macrophage cell.
The cytokine molecules secreted by the antigen
containing macrophage activate the TH cells. (The
cytokines are growth factor types of molecules.
Facilitate proliferation and differentiation of white
blood cells.) The TH cells secrete another type of
cytokines which facilitate TH cell proliferation. In
between, the antigen associated with the receptor on
the B cell surface, gets inside the B cell through
endocytosis, just like in case of the macrophages, and
becomes partially degraded. The partially degraded
antigen combines with MHC proteins and reaches B
cell surface where it associates with TH cells (Fig.
24.5). Cytokines are produced upon B and T H cell
interactions. The cytokines stimulate B cell
proliferation and differentiation to plasma and
memory cells. The plasma cells secrete antibodies to
fight against pathogens (Fig. 24.5). The memory cells
will “remember” the antigen, the pathogen.
Fig. 24.5. Mechanism of antigen presentation

Immunological tolerance
Are we born with a functional immune system? Or
do we acquire it in the course of our life? Answers to
the above questions came after recognizing the
phenomenon called immunological tolerance. It has
turned out that although blood of the non-identical
cattle twins contains blood cells of both organisms,
yet cattles do not fight against the "foreign" blood
cells. Instead they tolerate the foreign cells and accept
as their own cells. The existence of immunological
tolerance implies the formation of immunity as we
age.
Fig. 24.6. Experiments to illustrate the existence of
immunological tolerance.
The mechanism of immunological tolerance was
elaborated largely in the following types of
experiments (Fig. 24.6). White blood cells taken from
an A stain of mice were injected into newborn B
strain mice. (Strain is a collection of principally
identical twins generated through several generations
of inbreeding.) Upon growing up, the injected B mice
tolerated skin grafts from A mice. The uninjected
control B mice rejected A skin grafts. Naturally B
mice accepted B skin grafts and rejected C skin
grafts, irrespectively whether they were or were not
injected with A cells shortly after birth (Fig. 24.6). In
humans development of the functional immune
system takes about a year. Newborn babies and young
children are protected from pathogens by the IgA
class immunoglobins present in the mother's milk
(Table 24.2 and see below).
The phenomenon of immunological tolerance not
only showed that (i) our functional immune system
forms gradually after birth but also revealed that (ii)
the immune system can distinguish between self and
nonself antigens.
Szabad, Biology booklet 24. 5
Distinguishing self from nonself: clonal deletion
and the TS cells
There are tens of thousands of self proteins in our
body. How does the immune system make difference
between self and nonself antigens? The question is
important knowing that sometimes there are only
minor differences between self and nonself proteins.
There seem to be two mechanisms that allow to
distinguish between self and nonself. (i) During
clonal deletion the unmatured B cells are deleted (i.e.
die through apoptosis) already in the bone marrow
upon encountering self-antigens. (ii) There are so-
called suppressor TS cells that prevent B and TH cell
functions. Although some 90% are eliminated of the
108 B lymphocytes produced every day, still there are
so many antigen receptors produced that basically not
a single antigen can escape attention of the immune
system. Sometimes, however, the immune system
recognizes self-antigens as nonself, launches immune
response and so-called autoimmune diseases develop.
Structure of the immunoglobulins
Fig 24.7. Structure of the different types of
immunoglobins.
What kinds of molecules are the antibodies or
immunoglobins? How did experts find out about their
structure? G. A. Edelman and R. M. Porter described
first the structure of the immunoglobin (Ig) molecules
in the 1960es. The Ig molecules are proteins. One
typical Ig molecule is composed from two of the same
heavy chain and from two of the same light chain
protein molecules (Fig. 24.7). Mass of the heavy and
the light chains are 55 and 23 kDa. Disulfide bonds
stabilize the structure of the heavy and the light
chains and also bound the chains together. The heavy
as well as the light chains contain both variable and
constant regions (Fig. 24.7). While the variable
regions ensure antigen specificity, the constant region
determines type (class) of the Ig molecules (Table
24.2). There are IgM, IgD, IgG, and IgA types of
immunoglobin molecules with the same antigen-

specific variable region but with different constant
regions. The different types of Ig molecules form
through the process called class switching.
Monoclonal antibodies
Fig. 24.8. Method for the generation of monoclonal
antibodies.
C. Milstein and G. Köhler developed – in the mid
1970es – a method for the production of large
quantities of the same type of antibody. Principles of
the so-called monoclonal antibody technique are as
follows. A plasma cell produces only one type of
antibody for only a few days. Some myeloma cell
lines divide unlimitedly but do not produce antibody.
Upon fusion of the two cell types so-called
hybridomas form that possesses features of both cell
types: they each produce and secrete one type of
Szabad, Biology booklet 24. 6
antibody molecules and divide unlimitedly (Fig.
24.8).
Let's inject into a mouse a tiny sample of e.g. cobra
toxin protein as antigen. Some of the B cells (i) will
recognize the cobra toxin, (ii) selected in the clonal
selection process and (iii) differentiate to plasma
cells. Let's isolate spleen from the mouse, storage
organ of many lymphocytes. Isolate the lymphocytes
next and fuse them with myeloma cells for the
generation of hybridomas (Fig. 24.8). Dilute the
hybridoma suspension next such that a hybridoma cell
will end in every of the little culture wells. A sample
of every culture medium is screened next for the
production of anti-cobra toxin antibody. The desired
hybridomas can subsequently be propagated in large
quantities for the production of anti-cobra toxin
antibody that can be used e.g. in passive
immunization, i.e. injected into cobra-bitten man,
catlles, horses and so on to eliminate the toxin.
Monoclonal antibodies have many important
applications, like serology, Western blot, ELISA
(enzyme-linked immuno-adsorbent assay),
immunocytology, the FISH (fluorescence in situ
hybridization) technique, to name a few.
The genetic basis of antibody diversity
Since the antibodies are proteins, there must be
genes encoding the synthesis of the light and the
heavy chains of the Ig molecules. What are features
of the immunoglobin coding genes? How many such
genes exist? How do they function?
It is estimated that some 1011 different types of B
cell receptors form in us during our life, a
combination of 2.4x107 types of heavy chains and
4x103 light chains. The astrological number (1011) is
perhaps surprising since there are only as "few" as
3x109 base pairs in the human genome. How can a
genome of 3x109 bp size encode the synthesis of
some 1011 different types of protein molecules? Of
course there must be room left beside the so-called
immunoglobin genes for the other some 22,000 genes
in the human genome.
As mentioned earlier, there is a single type of
receptor (in millions of copies) on the surface of a
single B cell. Most likely a single gene encodes the
synthesis of the receptor. Since a B cells is diploid,
either the maternally or the paternally derived
immunoglobin encoding gene becomes inactivated in
the course of a process called allele exclusion. In fact,
the gene complex in one of the homologous
chromosomes becomes heterochromatinized and
inactivated in a process very similar to Barr body
formation in XX vertebrate embryos. (As described in
Chapter 12.)
The astronomical number of the different types of
Ig molecules result largely from two types of events:
(i) from DNA rearrangement and from (ii)
hipermutability of the Ig-encoding genes.
In a germ cell, there are three gene complexes to
encode the synthesis of the Ig chains: two for the light
and one for the heavy chains. The gene complex for
synthesis of the so-called κ light chain immunoglobin

proteins resides in the 2nd chromosome. The so-called
λ light chain gene complex is linked to the 22nd
chromosome. The heavy chain coding gene complex
is part of the 14th chromosome. (Naturally, there are 2
x 3 gene complexes in a diploid zygote. One of each
of the three complexes will be inactivated during
allele exclusion and one of each will remain available
for future use.)
V genes
Recognition signal
Germ
Fig. 24.9. Organization of that segment of the human
DNA from which - after DNA rearrangement - the
Joining through
functional κ light chain-coding gene forms. The Vκ
genes are tandemly arranged frequently with opposite
orientation. The insert on the bottom left shows the
arrangement of a single Vκ gene.
The functional gene which encodes synthesis of the
κ light chains is assembled through rearrangement of
an 800 kbp segment of the 2nd chromosome DNA
(Fig. 24.9). There are about 100 so-called Vκ light
chain genes arranged in tandem fashion over a stretch
of 740 kbp DNA (Fig. 24.9). One of the Vκ genes will
become part of the κ chain coding functional gene
during DNA rearrangement and encode much of the
variable segment of the κ light chain. A Vκ gene is
some 400 bp long and the adjacent Vκ genes are
about 7 kbp apart. Some 20 kbp downstream (i.e.
towards the 3’ end) of the Vκ genes five so called Jκ
genes follow (Fig. 24.9). (J stands for joining.) A Jκ
gene is only 30 bp long and the five Jκ genes spread
over some 1.4 kbp in the DNA. Downstream to the J κ
genes the only Cκ gene follows. It will encode - after
DNA rearrangement - the constant region of the κ
light chain. How does the functional κ light chain
coding gene form from the above DNA segments?
During maturation of the B cells, the DNA segment
illustrated on Fig. 24.9 goes through rearrangement.
During DNA rearrangement, one of the Vκ genes
joins one of the Jκ genes (Fig. 24.10). The joining
procedure is random: any Vκ gene may join any of the
Jκ genes. Joining is mediated by a so-called site-
specific recombinase enzyme. The enzyme binds to
two sites in the DNA. One is towards the 3’ end of
the “selected” Vκ gene the other is towards the 5’ end
of one of the Jκ genes (Fig. 24.9). There are two
possible outcomes of the site-specific recombinase
action.
(i) When the joining Vκ and Jκ genes are in the same
orientation, the DNA segment between the two genes
Szabad, Biology booklet 24. 7
is eliminated (Fig. 24.10). (ii) An inversion forms
when the joining Vκ and Jκ genes are oppositely
oriented. In either case, however, a functional κ
chain-coding gene forms in which the Vκ, the Jκ and
the Cκ DNA segments join to form a functional gene
(Fig. 24.10). (The remaining DNA segments become
inactivated.) The newly formed gene encodes the
synthesis of one of the many types of κ chains. The
now joined Vκ, Jκ and Cκ segments are transcribed
together and pre-mRNA molecules form. During
splicing of the mRNA molecules the introns are
eliminated for the formation of matured mRNA
molecules. The mRNA molecules are exported from
the nucleus of the maturing B cell into the cytoplasm
where the mRNA molecules are translated and κ light
chain protein form. Naturally, the κ chains have both
variable and constant regions (Figs. 24.7 and 24.10).
The Vκ and the Jκ-derived segments of the functional
κ gene encode the variable region of the κ chain.
cell
Joining through
inversion
excision
Excision
Inversion
Transcription
pre-mRNA
RNA splicing
mRNA
Translation
K chain
variable constant
Fig. 24.10. Scheme to illustrate the formation of a
functional gene encoding the synthesis of one type of
κ light immunoglobin chain protein through DNA
rearrangement in maturing B cells: by removal of
DNA segments (top, left) or by inversion (top, right).

As a result of the above described process –
naturally in different maturing B cells – 100 x 5 =
500 different κ light chains form. (The number of
possible λ chains is 100 x 6 = 600.) In reality, many
more than 500 different κ chains form. How is that
possible? What mechanisms increase the diversity of
the κ light chains? There are three reasons for the
unexpectedly high degree of diversity of the κ (also
the λ and the heavy) chains.
(1) The imprecise joining of the Vκ and the Jκ DNA
segments. Different numbers of nucleotides are lost
from the ends of the Vκ and the Jκ DNA segments
before the joining process.
(2) Before joining of the Vκ and the Jκ DNA segments
a so-called terminal transferase enzyme adds a few
nucleotides to the ends of the joining Vκ and the Jκ
DNA segments. The nucleotide addition process is
random. The above two processes involve a special
section of the gene. The special section encodes that
region of the κ chain, which interacts with the
antigen. Increased variability of the antigen-
interacting region ensures greater variability and
efficiency in the fight against pathogens.
Fig. 24.11. Organization of the different types of
genes from which the functional Ig heavy chain
coding gene forms during DNA rearrangement
(above). The mechanism of Ig heavy chain gene
formation and expression (below).
Szabad, Biology booklet 24. 8
As the above mentioned processes happen
randomly it is to be expected that 2/3 of the joining
processes result in so-called out-of-phase joints and
only 1/3rd of the joints is in-phase joint. The out-of-
phase joints create usually STOP codes shortly after
the ATG start code and thus do not allow the
formation of functional κ chains. (Only the in-phase
joints lead to the formation of functional κ chains.)
Although the production of out-of-phase joints may
appear as a waste, the random joining system still
allows great variability of the κ (also the λ and the
heavy) chains and thus well worth the efforts.
(3) The mutation rate is several orders of magnitude
higher in the immunoglobin genes as compared to any
other gene in the genome. Wile the spontaneous
mutation rate is 10-9/base pair/replication, it is as high
as 10-3(!)/base pair/replication in the immunoglobin
genes. The so-called hipermutability further increases
the variability of the immunoglobin molecules.
The mechanism that leads to the formation of the
heavy chain immunoglobin genes is rather similar to
the one described above. The so-called heavy chain
gene family is part of the 14th chromosome. It
contains some 300 V (variable), 20 D (diversity), 4 J
(joining) and 8 C (constant) genes (Fig. 24.11). The
functional heavy chain coding gene forms while one
each of the V, D and J genes combine with the block
of the eight C genes with the mechanisms described
above (Fig. 24.11). (The rest of the V, D and J genes
are either eliminated or inactivated.)
The mechanism of class switching
First IgM type of receptor molecules form during the
early periods in life of a B cell. They are
transmembrane proteins with essential function in
antigen (pathogen) recognition (Fig. 24.3. and Table
24.2). The constant region of the IgM heavy chain is
encoded by the μ segment of the C part of the gene
(Fig. 24.11). The question is simple: how are the IgM
transmembrane molecules replaced by IgG molecules
(with the γ segment type in the heavy chain) that are
dissolved in the blood plasma such that the antigen
specificity is preserved in the IgG molecules?
In the course of B cell maturation and the primary
immune response, different segments of the C gene
are eliminated (in well-controlled fashion) and
consequently the variable part of the heavy chain
gene is combined with a subsequent segment (δ, γ, ε
or α) of the C gene (Fig. 24.12). As a consequence of
the second DNA rearrangement novel types of
antibody classes form (IgD, IgG, IgE or IgA) (Fig.
24.12). The process is called class switching.
(Naturally class switching is irreversible.) The benefit
of class switching is apparent: the newly produced
type of antibody has different function as the IgM
molecules, however, maintains unchanged antigen
specificity. In practice, the membrane bound IgM
molecules recognize the antigen, the IgG molecules
fight in the blood plasma against the same antigen
(pathogen). Following another class switching, IgA
molecules form that are secreted into e.g. the milk to
fight against the pathogen and provide protection to

the child. The heavy chain of the IgA molecules
allows their uptake into cells with special receptors,
their transport across the cells and secretion into the
outside of the cell into the lumen of e.g. a milk gland,
tears and so on (Fig. 24.13).
Fig. 24.12. The mechanism of class switching.
Intercellular space Epithelial cell
IgA receptor Duct
IgA
Endocytosis
IgA secreted into
the duct
Fig. 24.10. Cells with the appropriate receptor take
up the IgA molecules, transport them across the cell
and empty on the other end of the cell.
T cells and the cellular immune response
Products of the B-lymphocytes, the IgG
immunoglobin molecules are dissolved in the blood
plasma. They represent the so-called humoral part of
the immune system. T lymphocytes, that will be
mentioned only briefly, represent the cellular part of
the immune system. T cell receptors, like the IgM
molecules, are cell membrane proteins of the T cells
that recognize different proteins involved in the
immune system. There are three different types of the
T cells. (i) The cytotoxic TC cells eliminate the virus-
infected and the tumor cells. The helper T H cells
Szabad, Biology booklet 24. 9
mediate immune response (Fig. 24.5). The T S
suppressor T cells block activities of the B and the T
cells, and are essential components of differentiation
between self and foreign antigens. T cell receptors
form similarly as the Ig molecules (Fig. 24.11)
Fig. 24.14. The T cell receptors are antigen-specific
transmembrane proteins.
Diseases of the immune system
Diseases of the immune system are classified
according to their origin.
1. Immunodeficiency means the absence of some or
every types of the lymphocytes. It may come
about due to heritable and acquired reasons. HIV
(human immunodeficiency virus) causes the
acquired immunodeficiency syndrome (AIDS).
Upon HIV infection the TH cells fuse, lose
function and consequently function of the
immune system is eliminated.
2. Different types of leukemia form following
tumorous (cancerous) proliferation of different
types of white blood cells. The uncontrolled cell
proliferation can be achieved not only through
action of an oncogene, but also by elimination of
function of the system that leads – under normal
circumstances – to death of the white blood cells.
3. In autoimmune diseases the immune system
attacks self-antigens of the organism. Rheumatic
arthritis, lupus erythematosus, ulcerative colitis,
myasthenia gravis and some types of multiple
sclerosis are examples of the autoimmune
diseases.
 Szabad, Biology booklet 24. 10

SUMMARY
During evolution organisms developed different
types of mechanisms to protect themselves against
pathogens to keep integrity of their body. Different
elements of the nonspecific defense mechanisms
provide continuos protection against the different
types of pathogens. The immune system is on
constant alert with its B and T lymphocytes against
pathogens that enter the body. The lymphocytes
produce antigens randomly, some of which may be
useful against an unforeseen pathogen. In this chapter
principles of the immune system were briefly
reviewed. A separate subject called immunology
covers different aspects of the specific defense
system. In summary, understanding the bases of
immunity not only provided means to cure several
diseases but also - through vaccination - to avoid
infectious diseases. Medicine makes use of the
antibodies every day in techniques like Western blot,
ELISA, immune histology, passive immunization and
organ transplantation. Immunology is a relatively new
field of life sciences with many future perspectives.

REFERENCES
1. Purves, W.K. et al., Life the Science of Biology,
400-428, 1998.
2. Lodish, H. et al., Molecular Cell Biology, 70-71,
189-191, 315-319, 2000.