LECTURE 1.

INTRODUCTION TO IMMUNOLOGY

1. THE HISTORY OF IMMUNOLOGY

2. THE PLACE OF IMMUNOLOGY IN THE SYSTEM OF SCIENCES AND
ITS INTERDISCIPLINARY RELATIONS
3. CONCEPT OF IMMUNITY
4. CONCEPT OF ANTIGEN

1. THE HISTORY OF IMMUNOLOGY

Immunology is an applied medical science by its origin. Its prehistory dates

back 2000 years. Immunology as a particular research area arose from the practical
need to fight infectious diseases. As an independent scientific branch, immunology
was started only in the second half of the 20th century.

In 6th century in the Byzantine Empire, plague (nosology - the bubonic plague)
lasted 50 years and killed 100 million people. 1/4 of the European population died of
plague - 10 million people. The plague was called the Black Death. Centuries of
observation of infectious diseases have laid the foundation for modern immunology.
Despite the wide spread of plague, people did not develop this disease twice, at least in
a lethal way, and those who had already been ill and recovered were used to bury the
corpses.

Smallpox is a disease that has become the springboard for immunology

formation. There is evidence that the first smallpox inoculations were carried out in
China a thousand years before Christ. The inoculation of the contents of smallpox
pustules to healthy people in order to protect them from the acute form of the disease
then spread to India, Asia Minor, Europe, and the Caucasus.

Smallpox epidemics broke out everywhere, and attempts were made to find a cure for
it. Sorcerers were involved in the "treatment" and fought the infection by spells and
putting on red clothes designed to draw the infection out of the body. The first
effective method of fighting smallpox in the Old World was variolation which is the
extraction of biological material from the pustules of convalescents and their
inoculation into healthy people by stretching infected threads under the incised skin.

This method came to Europe in 1718 from Turkey, from where it was brought to
Europe by a British ambassador's wife. Although variolation did not give a 100%
guarantee, among those vaccinated, the percentage of sick people, as well as their
mortality rate, significantly decreased. The fear of smallpox was so great that after a
while, the family members of a British monarch George the First ordered to be
vaccinated.

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 Inoculation was replaced by the vaccination method (from Latin “vacca” -
cow), developed at the end of 18th century by the English physician E. Jenner. He
noticed that the milkmaids taking care of sick animals sometimes fell ill with cowpox
in an extremely weak form, but they never got natural smallpox. Such an observation
gave the researcher a real opportunity to fight the disease in people. In 1796, 30 years
after the start of his research, E. Jenner decided to test vaccination with cowpox. The
experiment was a success and since then the method of vaccination according to E.
Jenner has been widely applied all over the world.
The origin of infectious immunology is associated with the name of an
outstanding French scientist Louis Pasteur. The first step towards a targeted search
for vaccine preparations that create a stable immunity to infection was made after
Pasteur's observation of the pathogenicity of the pathogen of chicken cholera. From
that observation, Pasteur concluded that an aged culture, having lost its pathogenicity,
remains capable of creating resistance to infection. This fact determined the principle
of creating vaccine material for many decades, i.e. in one way or another (depending
on a pathogen) to achieve a decreased virulence of the pathogen while preserving its
immunogenic properties.
The Russian evolutionary biologist Ilya Ilyich Mechnikov stood at the origins
of cellular immunity. In 1883, he made the first report on the phagocytic theory of
immunity at the congress of physicians and naturalists in Odessa. Humans have
amoeboid mobile cells - macrophages, neutrophils. They "eat" food of a special kind -
pathogenic microbes; the function of these cells is to fight microbial aggression.
At the same time as Mechnikov, a German pharmacologist Paul Ehrlich was
developing his theory of immune protection against infection. He knew that in the
blood serum of animals infected with bacteria, protein substances appear that can kill
pathogenic microorganisms. He later called these substances "antibodies." The most
characteristic property of antibodies is their pronounced specificity. Once formed as a
protective agent against some particular microorganism, they neutralise and destroy
only it, remaining indifferent to others (the theory of humoral immunity).
By the end of the 40s - the beginning of the 50s of 20th century, the first
period in the development of immunology was over. A great number of vaccines had
been created against a wide range of infectious diseases. Plague, cholera and smallpox
epidemics stoppoed killing hundreds of thousands of people. Some sporadic outbreaks
of these diseases are still there, but these are only rather local cases that are of no
epidemiological, and even more so, pandemic importance.
XX - XI centuries - a rapid development of immunology. It was during these
years that the selection-clonal theory of immunity was created; the functioning
regularities of various components of the lymphoid system as a single and integral
system of the immunity were revealed.
Immunology, as an independent branch of science, started ranking with truly
biological disciplines: molecular biology, genetics, cytology, physiology, and
evolutionary doctrine.

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2. THE PLACE OF IMMUNOLOGY IN THE SYSTEM OF SCIENCES AND
ITS INTERDISCIPLINARY RELATIONS

IMMUNOLOGY IS a SCIENCE OF BIOLOGICAL INDIVIDUALITY AND

MECHANISMS OF ITS PRESERVATION

Immunology is an interdisciplinary medical science that studies the structure,

evolution and functioning of the immune system of various organisms (humans,
animals, and plants), the mechanisms and methods of defence reactions aimed at
maintaining their structural and functional integrity and biological individuality.
About once every seven years The Nobel Prize is awarded for research in
immunology.
Immunology became an independent science more than 100 years ago. Over a
short history, immunology has grown into an independent branch with independent
institutes, journals, national and international societies.
Currently, general and specific (applied) immunology are distinguished.
General, or fundamental immunology, studies the structure and function of
molecules, cells and organs of the immune system, the functioning of the latter as a
single homeostatic, self-governing system, as well as its connection with other systems
- nervous, endocrine, etc.
Immunoprophylaxis, infectious immunology, immunopathology,
immunobiotechnology, transplant immunology, reproductive immunology, clinical,
veterinary, ecological and transgenic immunology, and immunogen therapy are
important areas of private immunology.

MEDICAL IMMUNOLOGY

• General immunology • Specific immunology

- molecular - immunization (vaccinology)

- cellular - allergology
- physiology of immunity - immuno-oncology
- immunochemistry - transplant immunology
- immunogenetics - immunology of reproduction
- evolutionary immunology - immunopathology
- immunobiotechnology
- immunopharmacology
- ecological immunology
- clinical immunology

The study of the structure and patterns of antibody formation revealed the secret of
their infinite diversity and led to the creation of hybridoma technologies that allow
obtaining monoclonal antibodies of any specificity. One of the achievements of
immunology is the development of fundamentally new diagnostic methods: at the

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crossroads of biochemistry and immunology - an enzyme immunoassay (ELISA), at the
crossroads of radiology and immunology - a radioimmunoassay (RIA).

Discipline cartography (interdisciplinary relations)

The main interdisciplinary relations of immunology identified in the course of analysis
of dissertations

Problems of 21st century: tuberculosis, measles, rubella, endemic parotitis.

New infections: HIV, Lyme disease, ehrlichiosis, legionellosis,
enterohemorrhagic Escherichiosis, Viral fevers Lassa, Ebola, Marburg.
Campylobacteriosis, Hepatitis E, C, D, F, G. X-infections are diseases that are not yet
known but are to be diagnosed.

Objectives and prospects of immunology development

1. Creating immune process control systems, ensuring the body's resistance to
biological, environmental, medical and other negative influences;
2. Developing programs and models of forming the body's resistance to adverse
conditions, taking into account age, profession and other factors;
3. Solving the problem of total effective immunoprophylaxis of all socially
significant infections, including HIV infection, viral hepatitis and other socially
significant infectious diseases;
4. Developing immunological and immunogenetic methods for the prevention
and treatment of malignant neoplasms;
5. Deciphering the antigens of the histocompatibility complex, as well as
methods of tolerance induction, which will create an opportunity for a wider
introduction of organ and tissue transplantation;
6. Preventing and treating immunological conflicts between the mother and the
foetus at all stages of reproduction;
7. Developing effective methods for gene therapy of congenital
immunodeficiencies and preventing secondary immunodeficiencies of various
etiologies.

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 3. CONCEPT OF AN ANTIGEN

Antigens are substances that carry signs of genetically foreign information that
can induce an immune response aimed at removing them.
An epitope or antigenic determinant is a region of an antigen molecule
recognized by IS (immune system), which specifically binds to antigen-recognizing
receptors of IS cells and antibodies.

Figure: Antigenic determinants (epitopes)

Most often antigens are proteins of another organism. The minimum size of a
peptide molecule capable of being an antigen is 8-10 amino acid residues (from 10
kDa). Compounds of proteins with residues of fatty acids (lipoproteins), sugars
(glycoproteins) can also act as antigens.

Antigens can be complex, consisting of protein and non-protein components, for

example, viral particles or bacterial cells. Under certain conditions, polysaccharides,
phospholipids and some other molecules can have antigen properties.

Antigen properties:
• foreignness
• specificity
• antigenicity
• immunogenicity

Antigenic determinants of a bacterial cell

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 • Foreignness is a property of an antigen in relation to the organism into
which the antigen enters. The following antigens are distinguished by foreignness:
Xenogenic (heterologous) antigens are antigens of other biological species.
They have got the greatest foreignness.

Allogeneic (homologous) – characteristic of different individuals of the same

biological species. Within a species, individuals can be found both similar and very
different in genetic composition. Foreignness can be different.

Isoantigenic (syngeneic) – characteristic of individuals with the same genetic

code (identical twins). Isoantigens, as a rule, do not cause IR (immune response),
since they are perceived by the immune system as antigens of its own body.

Autoantigens (autologous) – antigens of the body itself. Normally they are not
perceived by the immune system. They cause IR in autoimmune diseases.

• Specificity – structural features of an antigen that determine its uniqueness.

The specificity lies in the structure of the antigen molecule (sequence of amino acid
residues, tertiary structure of the protein). These features are recognized by the
immune system and an immune response is generated.

Antigenic determinant (epitope) is a site of an antigen molecule that

determines its specificity, binds to antigen-recognizing receptors of T-lymphocytes
(TCR) and B-lymphocytes (BCR) and antibodies. Most antigen molecules have
several antigenic determinants.

• Antigenicity – the ability of an antigen to induce an immune response in a

given organism. Different antigens cause an immune response that is different in
strength and direction. Primarily antigenicity depends on the number and variety of
antigenic determinants.

• Immunogenicity – the ability of an antigen to form immunity or

immunological memory. For pathogenic microorganisms, immunogenicity
determines immunity to a given infection after an illness or vaccination.
Immunogenicity can be enhanced by attaching immunostimulating components to
the antigen. Substances that nonspecifically increase the immunogenicity of an
antigen are called adjuvants.

Antibody (Ab) - immunoglobulin (Ig), is a large, Y-shaped protein used by

the immune system to identify and neutralize foreign objects such as pathogenic
bacteria and viruses

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 4. CONCEPT OF IMMUNITY

Immunology (from Latin immunis – free, liberated, freed from anything +

Greek λόγος – knowledge) is a biomedical science that studies the body's reactions to
foreign structures (antigens): the mechanisms of these reactions, their manifestations,
the course and outcome in norm and pathology, as well as developing research and
treatment methods.
The main subject of research in immunology is the knowledge of the
mechanisms of a specific immune response formation of the organism to all
antigenically foreign compounds.
Immunity (Latin- immunitas) is a way of protecting the body from the action of
various substances and organisms that cause the destruction of its cells and tissues,
characterized by a change in the functional activity of immunocytes in order to
maintain homeostasis of the internal environment.

INNATE IMMUNITY is the body's ability to react and neutralize foreign and
potentially dangerous biomaterial. It recognizes classes of pathogens (microorganisms,
transplants, toxins, tumor cells, virus-infected cells)

Innate immunity factors:

1. Cellular factors – phagocytes (MC, MPh), granulocytes (NPh, BPh, EPh)
2. Humoral factors – signaling cytokines, inflammatory mediators, factors of
nonspecific resistance -IL, IFN, TNF, CC, CSF, GF, COMPLEMENT system.

Functions and characteristics of innate immunity:

1. Reacting to certain classes of antigens characteristic of pathogenic organisms
(polysaccharides of the bacterial cell wall, double-stranded RNA of some viruses,
etc.).
2. Directing cells of the immune system to the area of the pathogen penetration by
producing chemical factors, mediators and cytokines;
3. Activation of the components of the complement system;
4. Detection and removal of foreign bodies from organs and tissues using leukocytes;
5. It’s inherited
6. It functions regardless of an antigen presence (antigen-independent)

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 ADAPTIVE IMMUNITY (old names – acquired, specific)– the ability to
recognize and respond to individual antigens, is characterized by a clonal response,
lymphoid cells are involved in the reaction, there is an immunological memory,
autoaggression is possible.

Adaptive immunity factors:

1. Cellular factors (T-lymphocytes, B-lymphocytes)
2. Humoral factors – antibodies (Ig G, M, E, A) produced by B-lymphocytes;
complement system

Functions and characteristics of adaptive immunity:

1. It’s able to neutralize specific antigens and pathogens (microorganisms or toxin
molecules)
2. It’s the result of the work of a highly-specialized-cells system (T and B
lymphocytes) located throughout the body
3. It’s not inherited (depends on immune experience)
4. It forms immunological memory
5. It’s formed only in the presence of hypertension (antigen dependent)

Types of adaptive immunity:

Natural immunity

1. Active immunity – after an illness

2. Passive immunity – in a newborn up to 6 months – occurs when ready-made antibodies are
transferred from mother to fetus through the placenta or with breast milk. It provides
immunity of newborns to certain infectious diseases for several months.

Artificial immunity
1. Active immunity – arises after the introduction of a vaccine into the body (a preparation of
killed or weakened pathogens). Formed in 1-2 weeks and persists for years or tens of years.
2. Passive immunity – occurs when immune serum is injected into the body (serum contains
antibodies against the corresponding microbes or toxins, traditionally used for the bites of
poisonous snakes).

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Types of adaptive
The IMMUNE RESPONSE is a chain of sequential complex cooperative processes
in the immune system in response to the action of an antigen in the body.

There are:
1) Primary immune response (occurs at the first encounter with an antigen);
2) Secondary immune response (occurs at the re-encounter with the antigen).

Phases of the immune response:

1) Inductive (afferent link) – presentation and recognition of an antigen. There
is a complex cooperation of cells with subsequent proliferation and differentiation;
2) Productive (efferent link) – there are products of the immune response.
With a primary immune response, the inductive phase can last a week, with a
secondary – up to 3 days due to memory cells.

Development of the immune response:

In the immune response, antigens that enter the body interact with antigen-
presenting cells (macrophages), which express antigenic determinants on the cell
surface and deliver information about the antigen to peripheral organs of the immune
system, where T-helpers are stimulated.

Further, the immune response is possible in the form of one of two options:
1) Cellular immune response;
2) Humoral immune response;

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 Characteristics of the immune response:

1) Specificity – reactivity is directed only to a specific agent, which is called an

antigen;
2) Potentiation – the ability to produce an enhanced response in case of a
constant invasion by the same antigen;
3) Immunological memory is the ability of the immune system to respond more
quickly and efficiently to an antigen (pathogen) with which the body had prior contact.
This memory is provided by lymphocytes. As a result of the first meeting of a
programmed lymphocyte with a specific antigen, two categories of cells are formed:
effector cells that immediately perform a specific function – secrete antibodies or
implement cellular immune responses, and memory cells that circulate for a long time.
When this antigen is reintroduced, they quickly turn into effector lymphocytes,
which react with the antigen. With each division of the programmed lymphocyte, after
meeting with the antigen, the number of memory cells increases.

The phenomenon of «immunologic memory» is characterized by the fact that

repeated contact with the antigen causes an accelerated and enhanced development of
the immune response, which provides a more effective defense of the body in
comparison with the primary immune response. This feature of the secondary immune
response underlies the meaning of vaccination, which successfully protects against
most infections.

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 MATERIAL FOR LABORATORY AND PRACTICAL WORK
TYPES OF ANTIGENS

1. By their physicochemical properties, antigens can be divided into soluble

and corpuscular.
Corpuscular are complex structures that carry many antigenic determinants.
These antigens include particles of viruses, bacterial cells, and pollen.
Soluble antigens include bacterial toxins, zootoxins that can dissolve in
biological fluids.

2. By the ability to involve T-lymphocytes in the immune response, antigens

are divided into thymus-dependent and thymus-independent.
Thymus-dependent – antigens, to which the immune response develops with the
obligatory participation of T-helpers. Most natural antigens are thymus-dependent. The
immune response is carried out as a result of the interaction of T and B lymphocytes.
Thymus-independent antigens are able to trigger an immune response by
activating B-lymphocytes without the participation of T-helpers. An example is the
cell wall lipopolysaccharides of gram-negative bacteria, dextran, bacterial flagellin.
They cause cross-linking of antigen-recognizing receptors of B-lymphocytes and
activation of these cells.

An important type of antigens are superantigens.

3. Superantigens are capable of nonspecifically interacting with a variety of
antigen-recognition receptors of lymphocytes and causing polyclonal activation of
these cells. As a result of the increased proliferation of many clones and a sharp
increase in cytokine production, a severe systemic reaction with signs of shock and
multiple organ failure can develop. In addition, excessive activation of lymphocytes
leads to their apoptosis and the development of immunodeficiency. Some bacterial
products (staphylococcal enterotoxin, streptococcal exotoxin, etc.) have properties of
superantigens.

4. Toleragens are capable of causing the development of immune tolerance

(anergy, nonresponsiveness). Typically, these are low molecular weight antigens. They
are not captured by antigen-presenting cells, as a result of which the presentation
process does not occur and the immune response does not develop.

5. Haptens are low molecular weight chemicals that trigger an immune response
only when combined with a larger host. The body's own proteins and cells can act as a
carrier. As a result, the immune response against haptens can damage its own
structures. The most common haptens include: nucleic acids (DNA, RNA), drugs,
inorganic molecules (bromine, nickel), etc.

6. Allergens are antigens that cause the production of IgE, which mediates the
development of allergic reactions. Usually, allergens do not pose a threat to humans

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and are harmless proteins. However, in some people, they cause the development of
allergic reactions, in some cases even life-threatening.
The most common classification of allergens in our country is the following groups:

• non-infectious – household (dwelling aeroallergens), epidermal, food, insect,

medicinal.
• infectious – fungal and bacterial allergens.

Household allergens
House dust has a complex composition, which includes house dust mites and
their waste products, plant and inorganic particles, mold spores, bacteria, hair and
excreta of pets and rodents (mice, rats), cockroach allergens, as well as formaldehyde
and volatile organic connections (linoleum, synthetic flooring, accessories, furniture,
etc.).
Pyroglyph mites (Dermatophagoidespteronyssimus and
Dermatophagoidesfarina) are of primary importance. These are the smallest
arthropods, about 0.3 mm in size, which feed on the scales of the exfoliated epidermis
of humans and animals. The best conditions for the life and reproduction of mites are
high humidity > 60% at t 22-27 °, therefore bed (pillows, blankets, mattresses),
upholstered furniture, carpets are among the favorite habitats of mites. Cockroaches
are extremely allergenic. The role of food for aquarium fish is well known (the cause
is an allergy to daphnia – the main component of this food).
Epidermal allergens
Allergens of various animals and birds: cats, dogs, hamsters, horses, feathers of
birds. Allergens are not so much wool as proteins of the epidermis, saliva, products of
sweat and sebaceous glands, urine, seminal fluid, animal feces.
The most common culprits for epidermal allergies are cat allergens, and to a
lesser extent dogs’ ones. Epidermal allergens can be found not only in the indoor air
where these animals live, but also in house dust, carpets, and furniture. When the
animal is removed, the high concentration of the allergen in the room is maintained for
6 months. and more. Mice, rats, guinea pigs can cause allergies in those who come into
contact with them.

Pollen allergens
The most common cause of pollinosis is light pollen from wind-pollinated
plants. The concentration of pollen allergens is higher on dry hot days and decreases
after rain. Pollen grains are living male gametophytes of higher plants; they contain an
inner cellulose membrane (intina) and a two-layer outer membrane (exine). The
diameter of ragweed pollen grains is 20 microns, tree pollen – 20-60 microns, grass
pollen – 30-40 microns. Plants are capable of producing massive amounts of pollen.
One ragweed bush releases up to 1 million pollen grains per day. The peak production
of ragweed pollen occurs in the early morning hours.

Trees (birch, alder, hazel, oak)

Cereals (hedgehog, timothy, fescue, bluegrass, ryegrass)

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 Weeds (ragweed, wormwood, quinoa, thistle)

Food allergens
Animal and vegetable products (milk, eggs, chicken, peanuts, nuts, soy, seafood,
fish, wheat).

Mold spores
In the air of residential and industrial premises, basements, as well as in the air,
more than 100 types of molds are determined. A high concentration of mold fungi is
found in basements, bathrooms, libraries, poorly ventilated living quarters. Most of the
fungi reproduce year-round, although the concentration of some increases during the
autumn months.
The most common fungal allergens include fungi of the families Alternaria,
Cladosporium, Aspergilus, Penicillium.
They are conventionally divided into off-home and intra-home.

Off-home antigens
- Alternaria (The main allergen is Alt a 1. A total of 32 AGs, 19 have allergenic
properties).
- Cladosporium (The main allergens are Clah1 and Clah2. A total of 60 AH, 2
main, 10 intermediate, 25 - small).
Alternaria and cladosporium actively reproduce on decaying parts of plants and
in the soil at a relatively high (22-25%) moisture content. The content of spores in the
air is seasonal (from early spring to late autumn).

Intra-home antigens
- Aspergillus (A. Fumigatus) (The main allergen of Aspf 1. Total 44 AGs, 18
have allergenic properties).
- Penicillum (green mold).
They cause rotting of stored grains, fruits and vegetables. They are found in
basements, damp, poorly ventilated places.

Insect allergens
Insect allergens that can enter the body by inhalation or by stinging or biting.
When stung by insects, insect allergy most often develops to the venom of bees,
wasps, bumblebees, hornets. Less common are allergic reactions to the bites of blood-
sucking insects – mosquitoes, midges.

Stinging insects (poison) Honey bee Bumblebee Hornets Wasps, Ants

Non-stinging insects Mosquitoes (secretion of salivary glands), Cockroaches

(body and chitinous cover), Bloodworms, Moths, Fleas, mosquitoes (saliva)

Medicinal allergens

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Allergenic properties of drugs depend significantly on their structure and molecular
weight. High molecular weight compounds (serum, streptokinase, insulin) are able to
induce an immune response. Low molecular weight compounds (haptens) cause
allergic reactions after binding to serum proteins (albumin, globulins), tissue proteins
(procollagens, histones) or cells.
Complete drug allergens
Immune sera, Insulin, Enzymes (asparakinase, streptokinase), Vaccines, Latex

Haptens
NSAIDs, acetylsalicylic acid, β-lactam antibiotics, Sulfonamides, Anti-
tuberculosis drugs (isoniazid, rifampicin), Anesthetic drugs (muscle relaxants,
thiopental), Allopurinol, Psychotropic drugs
Iodine-containing X-ray contrast agents, Antihypertensives (ACE inhibitors,
methyldopa), Local anesthetics

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