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SEMEY STATE MEDICAL UNIVERSITY
LECTURE COMPLEX
1. Theme 1: Modern immunology, its problems and progress. Main principles of the
organization of the immune system functioning and organization.
2. Object: formation in students of the scientific notions about structure and functions of the
immune system on the organ, cellular and molecular level. Main principles of its functioning.
3. Thesis of lectures
An immune system is a collection of biological processes within an organism that protects
against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of
agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own
healthy cells and tissues in order to function properly. Detection is complicated as pathogens can
evolve rapidly, producing adaptations that avoid the immune system and allow the pathogens to
successfully infect their hosts.
Layered defense
The immune system protects organisms from infection with layered defenses of increasing
specificity. Most simply, physical barriers prevent pathogens such as bacteria and viruses from
entering the organism. If a pathogen breaches these barriers, the innate immune system provides an
immediate, but non-specific response. Innate immune systems are found in all plants and animals.
However, if pathogens successfully evade the innate response, vertebrates possess a third layer of
protection, the adaptive immune system, which is activated by the innate response. Here, the
immune system adapts its response during an infection to improve its recognition of the pathogen.
This improved response is then retained after the pathogen has been eliminated, in the form of an
immunological memory, and allows the adaptive immune system to mount faster and stronger
attacks each time this pathogen is encountered.
Both innate and adaptive immunity depend on the ability of the immune system to distinguish
between self and non-self molecules. In immunology, self molecules are those components of an
organism's body that can be distinguished from foreign substances by the immune system.
Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self
molecules are called antigens (short for antibody generators) and are defined as substances that bind
to specific immune receptors and elicit an immune response.
Microorganisms or toxins that successfully enter an organism will encounter the cells and
mechanisms of the innate immune system. The innate response is usually triggered when microbes
are identified by pattern recognition receptors, which recognize components that are conserved
among broad groups of microorganisms, or when damaged, injured or stressed cells send out alarm
signals, many of which (but not all) are recognized by the same receptors as those that recognize
pathogens. Innate immune defenses are non-specific, meaning these systems respond to pathogens
in a generic way. This system does not confer long-lasting immunity against a pathogen. The innate
immune system is the dominant system of host defense in most organisms.
Leukocytes (white blood cells) act like independent, single-celled organisms and are the second
arm of the innate immune system. The innate leukocytes include the phagocytes (macrophages,
neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells. These
cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by
engulfing and then killing microorganisms. Innate cells are also important mediators in the
activation of the adaptive immune system.
Phagocytosis is an important feature of cellular innate immunity performed by cells called
'phagocytes' that engulf, or eat, pathogens or particles. Phagocytes generally patrol the body
searching for pathogens, but can be called to specific locations by cytokines. Once a pathogen has
been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome,
which subsequently fuses with another vesicle called a lysosome to form a phagolysosome. The
pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases
free radicals into the phagolysosome. Phagocytosis evolved as a means of acquiring nutrients, but
this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism.
Phagocytosis probably represents the oldest form of host defense, as phagocytes have been
identified in both vertebrate and invertebrate animals.
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Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of
invading pathogens. Neutrophils are normally found in the bloodstream and are the most abundant
type of phagocyte, normally representing 50% to 60% of the total circulating leukocytes. During the
acute phase of inflammation, particularly as a result of bacterial infection, neutrophils migrate
toward the site of inflammation in a process called chemotaxis, and are usually the first cells to
arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and
produce a wide array of chemicals including enzymes, complement proteins, and regulatory factors
such as interleukin 1. Macrophages also act as scavengers, ridding the body of worn-out cells and
other debris, and as antigen-presenting cells that activate the adaptive immune system.
Dendritic cells (DC) are phagocytes in tissues that are in contact with the external environment;
therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines. They are named
for their resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic
cells are in no way connected to the nervous system. Dendritic cells serve as a link between the
bodily tissues and the innate and adaptive immune systems, as they present antigen to T cells, one
of the key cell types of the adaptive immune system.
Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory
response. They are most often associated with allergy and anaphylaxis. Basophils and eosinophils
are related to neutrophils. They secrete chemical mediators that are involved in defending against
parasites and play a role in allergic reactions, such as asthma. Natural killer (NK cells) cells are
leukocytes that attack and destroy tumor cells, or cells that have been infected by viruses.
The adaptive immune system evolved in early vertebrates and allows for a stronger immune
response as well as immunological memory, where each pathogen is "remembered" by a signature
antigen. The adaptive immune response is antigen-specific and requires the recognition of specific
“non-self” antigens during a process called antigen presentation. Antigen specificity allows for the
generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability
to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen
infect the body more than once, these specific memory cells are used to quickly eliminate it.
The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B
cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells
in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are
involved in cell-mediated immune response.
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Notion about the immunity
2. Structure of the immune system
3. Immune system cells
4. Central and peripheral organs of the immune system
5. Functions of the immune system.
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1. Theme 2: Humoral immunity system.
2. Object: formation of the scientific notions about structure and functions of the humoral
system, and role of the humoral mechanisms in the immune response.
3. Thesis of lectures
Antibodies (also known as immunoglobulins, abbreviated Ig) are gamma globulin proteins that
are found in blood or other bodily fluids of vertebrates, and are used by the immune system to
identify and neutralize foreign objects, such as bacteria and viruses. They are typically made of
basic structural units—each with two large heavy chains and two small light chains—to form, for
example, monomers with one unit, dimers with two units or pentamers with five units. Antibodies
are produced by a kind of white blood cell called a plasma cell. There are several different types of
antibody heavy chains, and several different kinds of antibodies, which are grouped into different
isotypes based on which heavy chain they possess. Five different antibody isotypes are known in
mammals, which perform different roles, and help direct the appropriate immune response for each
different type of foreign object they encounter.
Antibodies can come in different varieties known as isotypes or classes. In placental mammals
there are five antibody isotypes known as IgA, IgD, IgE,IgG and IgM. They are each named with an
"Ig" prefix that stands for immunoglobulin, another name for antibody, and differ in their biological
properties, functional locations and ability to deal with different antigens, as depicted in the table.
The antibody isotype of a B cell changes during cell development and activation. Immature B
cells, which have never been exposed to an antigen, are known as naïve B cells and express only the
IgM isotype in a cell surface bound form. B cells begin to express both IgM and IgD when they
reach maturity—the co-expression of both these immunoglobulin isotypes renders the B cell
'mature' and ready to respond to antigen. B cell activation follows engagement of the cell bound
antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody
producing cell called a plasma cell. In this activated form, the B cell starts to produce antibody in a
secreted form rather than a membrane-bound form. Some daughter cells of the activated B cells
undergo isotype switching, a mechanism that causes the production of antibodies to change from
IgM or IgD to the other antibody isotypes, IgE, IgA or IgG, that have defined roles in the immune
system.
Antibodies that bind to surface antigens on, for example, a bacterium attract the first
component of the complement cascade with their Fc region and initiate activation of the "classical"
complement system.] This results in the killing of bacteria in two ways. First, the binding of the
antibody and complement molecules marks the microbe for ingestion by phagocytes in a process
called opsonization; these phagocytes are attracted by certain complement molecules generated in
the complement cascade. Secondly, some complement system components form a membrane attack
complex to assist antibodies to kill the bacterium directly.[22]
To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them
together, causing them to agglutinate. Since an antibody has at least two paratopes it can bind more
than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating
the pathogen, antibodies stimulate effector functions against the pathogen in cells that recognize
their Fc region.]
Those cells which recognize coated pathogens have Fc receptors which, as the name suggests,
interacts with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular
antibody with the Fc receptor on a particular cell triggers an effector function of that cell;
phagocytes will phagocytose, mast cells and neutrophils will degranulate, natural killer cells will
release cytokines and cytotoxic molecules; that will ultimately result in destruction of the invading
microbe. The Fc receptors are isotype-specific, which gives greater flexibility to the immune
system, invoking only the appropriate immune mechanisms for distinct pathogens.
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
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3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. System of the humoral immunity
2. Primary and secondary immune response
3. Functions of the humoral immunity system
4. B-lymphocytes receptors
5. Characteristic and structure of the immunoglobuline
6. Functions of the immunoglobulines
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1. Theme 3: Antigen presentation cells. Processing and presentation of the antigens. Role of
the complement in immune response
2. Object: formation of the scientific notions about classification and main types of the antigen
presentation cells and its role in the specific immune response, mechanism of the processing and
formation of the antigens.
3. Thesis of lectures
Antigen presentation is a process in the body's immune system by which macrophages,
dendritic cells and other cell types capture antigens and then enable their recognition by T-cells.
The basis of adaptive immunity lies in the capacity of immune cells to distinguish between the
body's own cells, and infectious pathogens.
In the upper pathway; foreign protein or antigen is taken up by an antigen-presenting cell. The
antigen is processed and displayed on an MHC II molecule, which interacts with a T helper cell. In
the lower pathway; whole foreign proteins are bound by membrane antibodies and presented to B
lymphocytes, which process and present antigen on MHC II to a previously activated T helper cell,
spurring the production of antigen-specific antibodies.
The host’s cells express “self” antigens that identify them as such. These antigens are different
from those in bacteria ("non-self" antigens) or in virally-infected host cells (“missing-self”). The
ability of the adaptive immune system to survey for infection requires specialized pathways of
enabling recognition of pathogen-derived antigens by T cells.
Antigen recognition
Unlike B cells, T cells fail to recognize antigen in the absence of antigen-presentation, with the
important exception of the superantigens. The T cell receptor is restricted to recognizing antigenic
peptides only when bound to appropriate molecules of the major histocompatibility complex
(MHC), also known in humans as Human leukocyte antigen (HLA)).
Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper"
CD4+ cells.
Extracellular antigens: Class II
Dendritic cells (DCs) phagocytose exogenous pathogens, such as bacteria, parasites or toxins in
the tissues and then migrate, via chemotactic signals, to T cell enriched lymph nodes. During
migration, DCs undergo a process of maturation in which they lose phagocytic capacity and
develop an increased ability to communicate with T-cells in the lymph nodes. This maturation
process is dependent on signaling from other pathogen-associated molecular pattern (PAMP)
molecules through pattern recognition receptors, such as the members of the Toll-like receptor
family.
The DC uses lysosome-associated enzymes to digest pathogen-associated proteins into smaller
peptides. In the lymph node, the DC will display these antigenic peptides on its surface by coupling
them to MHC Class II molecules. This MHC:antigen complex is then recognized by T cells passing
through the lymph node. Exogenous antigens are usually displayed on MHC Class II molecules,
which interact with CD4+ helper T cells. CD4+ lymphocytes, or TH, are immune response
mediators, and play an important role in establishing and maximizing the capabilities of the
adaptive immune response.
Expression of Class II is more restricted than Class I. High levels of Class II are found on
dendritic cells, but can also be observed on activated macrophages, B cells, and several other host
cell types in inflammatory conditions.
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
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1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Non specific factors of the defense
2. Functions of the complement system and macrophages.
3. Structure of the complement system.
4. Main stages of the complement activation (classic way)
5. Main stage of the complement activation (alternative way)
6. Biological action of the complement activation products.
7. Antigen presentation cells.
8. Main functions of the macrophages.
9. Presentation of the antigen of the macrophage and dendrite cells.
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1. Theme 4: Cellular immunity system.
2. Object: formation of the scientific notions about structure and function of the cellular
immunity system, main subpopulations of the T-lymphocytes and their functions, natural and
induced immunological tolerance.
3. Thesis of lectures
T cells (and B cells) are part of the adaptive immune response that takes 4-7 days after
infection to become effective. T cells are lymphocytes or cells of the lymphatic system. T cells are
so called because they develop in the thymus, an organ located in the upper chest just above the
heart. T cells are of two types: helper T cells (which have a marker on their cell surface called CD4)
and killer T cells (which have the CD8 marker on their surface). Killer T cells (also called cytotoxic
T lymphocytes or CTLs) directly attack body cells that are infected with a virus or malignant or
abnormal tumor cells, cells that antibodies would never perceive.
Helper T cells are the "generals" of the immune system, calling into play and directing the
activity of killer T cells. The helper T cells are essential for an effective immune response since
they activate other immune cells including most B cells to produce antibody. Individual T cells are
targeted against the specific antigen signatures of viruses and bacteria, and when helper T cells
encounter their specific antigens, they become activated and quickly expand in number. In AIDS,
the virus HIV attacks activated T helper cells, it kills off the very cells that should coordinate the
body's antiviral defenses, and as a result people with HIV usually have few or no HIV-specific T
helper cells!
T cells act by releasing certain chemicals known as cytokines. Cytokines are proteins (secreted
by other immune cells too) that are responsible for activating cells, triggering them to grow and
divide or to die. A complex network of cytokines is secreted by the helper T cells that determine the
course of the immune response. Killer T cells, on the other hand, release cell-damaging enzymes
that create holes in the membranes of the target cells and trigger them to undergo programmed cell
death.
Cytokines, are now being used-alone or in combination to treat various disorders such as
cancer, rheumatoid arthritis and AIDS among others. The aim of these treatments is to mimic part
of the immune response that fools the cells to either get activated and divide such as in the case of
the immune deficiency disease AIDS or to slow down a destructive immune response such as in the
case of the autoimmune disease rheumatoid arthritis.
Association of a T cell with MHC class I or MHC class II, and antigen
Killer T cells directly attack other cells carrying foreign or abnormal antigens on their surfaces.
Killer T cell are a sub-group of T cells that kill cells infected with viruses (and other
pathogens), or are otherwise damaged or dysfunctional. As with B cells, each type of T cell
recognises a different antigen. Killer T cells are activated when their T cell receptor (TCR) binds to
this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this
MHC:antigen complex is aided by a co-receptor on the T cell, called CD8
Helper T cells
Function of T helper cells: Antigen presenting cells (APCs) present antigen on their Class II
MHC molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4
co-receptor (CD4+). The activation of a resting helper T cell causes it to release cytokines and other
stimulatory signals (green arrows) that stimulate the activity of macrophages, killer T cells and B
cells, the latter producing antibodies. The stimulation of B cells and macrophages succeeds a
proliferation of T helper cells.
Helper T cells regulate both the innate and adaptive immune responses and help determine
which types of immune responses the body will make to a particular pathogen. These cells have no
cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the
immune response by directing other cells to perform these tasks.
γδ T cells possess an alternative T cell receptor (TCR) as opposed to CD4+ and CD8+ (αβ) T
cells and share the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions
that produce responses from γδ T cells are not fully understood. Like other 'unconventional' T cell
subsets bearing invariant TCRs, such as CD1d-restricted Natural Killer T cells, γδ T cells straddle
the border between innate and adaptive immunity. On one hand, γδ T cells are a component of
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adaptive immunity as they rearrange TCR genes to produce receptor diversity and can also develop
a memory phenotype. On the other hand, the various subsets are also part of the innate immune
system, as restricted TCR or NK receptors may be used as pattern recognition receptors. For
example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules
produced by microbes, and highly restricted Vδ1+ T cells in epithelia will respond to stressed
epithelial cells.
Newborn infants have no prior exposure to microbes and are particularly vulnerable to
infection. Several layers of passive protection are provided by the mother. During pregnancy, a
particular type of antibody, called IgG, is transported from mother to baby directly across the
placenta, so human babies have high levels of antibodies even at birth, with the same range of
antigen specificities as their mother. Breast milk also contains antibodies that are transferred to the
gut of the infant and protect against bacterial infections until the newborn can synthesize its own
antibodies. This is passive immunity because the fetus does not actually make any memory cells or
antibodies--it only borrows them. This passive immunity is usually short-term, lasting from a few
days up to several months. In medicine, protective passive immunity can also be transferred
artificially from one individual to another via antibody-rich serum.
The time-course of an immune response begins with the initial pathogen encounter, (or initial
vaccination) and leads to the formation and maintenance of active immunological memory.
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Main functions of the T-system immunity.
2. Antigen-dependent and antigen-independent differential of the T-lymphocytes.
3. The structure of the antigen receptors of the T-lymphocytes.
4. Processes of the positive and negative selection in the thymus, its role in the formation of
the tolerance.
5. Subpopulation of the T-lymphocytes and their functions.
6. The role of the T-lymphocytes in the search of the antigens and induction antigens in the
immune response.
7. The stages of the interaction of the T-killers with cell.
8. Regulatory T-lymphocytes, cells-supressors in the immune response.
9. Immunological tolerance.
10. Natural and induced tolerance.
11. Central and peripheral mechanisms of the tolerance.
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1. Theme 5: Regulation of the immune response. Cytokines, main characteristics. Perspectives
and problems of the cytokine and anti-cytokine therapy.
2. Object: formation of the scientific notions about classification, main characteristic of the
cytokines and usage in the therapy.
3. Thesis of lectures:
Cytokines is the class of soluble polypeptide molecules secreted by activated cells of immune
system (in some cases - by cells of non-immune nature). Cytokines perform signal and regulatory
function of short-distant intra-cellular communications necessary for development and functioning
of the immune system, and also for its interactions with other systems of organism. These
bioregulatory molecules define type and duration of immune response, control cellular proliferation,
angyogenesis, hemopoiesis, inflammation, reparation and regeneration of tissues and many other
processes connected with active defense of organism from biological aggression. Cytokines act on
the base of receptor mechanism and do not have specificity to antigens. Class of cytokines consists
of interleukins, interferons, chemokines, tumor necrosis factors, colony-stimulating factors. System
of immune response regulation - "cytokine network" - formed by these cytokines includes cellproducents, cytokines, cell-targets with receptors specific for certain cytokines and, in some cases,
cytokine's antagonists or their receptors. Cytokines have the following properties:
The advantages of cytokine preparations in comparison with other immune modulators are
obvious:
 the effectiveness of cytokine drugs is confirmed by the results of international multiplecentered randomized scientific study (during more than 15 years),
 at the present time international methodological standards of prescription cytokine drugs for
the treatment of specific diseases and immune disorders have been developed,
 it is possible to precisely predict and control immune effect when recombinant cytokines are
used,
 expression of immune therapeutic effect depends upon used dose of cytokine drug,
 high immunotrophic activity of cytokines is achieved when small therapeutic doses are used,
 recombinant cytokines have more pronounced and selective effect on immune correction
comparing to non-specific immune modulators.
Interleukin-2 is historically first cytokine which has been identified and described on molecular
level as T-cells growth factor (TCGF) [Morgan et al., 1976]. In 1979 on conference in Ermatingen
(Swiss) have been proposed nomenclature of immune mediators acting at the present time, and the
term "interleukin" appeared for molecules transmitting signal information between leukocytes. This
caused TCGF renamed into interleukin-2 (IL-2). Consequent development of IL-2 conditionally can
be divided on three phases: first - detailed characteristic of biological activity [Morgan et al., 1976;
Gillis and Smith, 1977, 1978; Baker et al., 1978, 1979], then - study of biochemical structure of
molecule [Robb and Smith, 1981, 1983] and at the end - identification of structure of IL-2 gene
[Robb and Smith, 1981, 1983; Taniguchi et al., 1983].
Biological role of endogenous IL-2. For understanding action mechanisms of drugs based on
IL-2 it is extremely important to take into consideration immunological role of endogenous (native)
IL-2 and all surrounding factors that influence on its immunotherapeutical activity.
The major endogenous IL-2 producents are activated Th1 CD4+ lymphocytes (90% of
endogenous IL-2 production) and also cytotoxic CD8+ lymphocytes (10% of endogenous IL-2
production). IL-2 Receptors. High-affinity IL-2 receptor consists of 3 chains: light a-chain (CD25),
heavy b-chain (CD122) and g-chain (p64, CD132). a-chain bonds ligand, b - and g -chains provide
signal transmission. a-chain itself is able to bond IL-2 with low affinity not causing absorption
(internalization) of formed complex and switching on growth signal. Heavy b-chain for IL-2 placed
on the membranes of resting T-cells, NK-cells and monocytes is responsible for internalization of
cytokine-receptor complex and transmission of the signal into cell. g-chain spontaneously expresses
on lymphocytes surface, and its combination with b-chain forms receptor with intermediate affinity
on NK-cells.
Cell-targeting for IL-2. IL-2 has relatively narrow spectrum of targets in immune competent
cells. The major cells are activated T- and B-lymphocytes and NK-cells for which IL-2 is growth
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and differentiation factor (Fig.1). IL-2 is also influence on monocytes carrying IL-2 receptor on
their surface enhancing generation of oxygen active forms and peroxides.
T-lymphocytes. The major role of IL-2 for antigen activated CD4+ and CD8+ lymphocytes is
stimulation of their proliferation. Impacting on T-lymphocytes IL-2 influences on secretion of many
monocytes and expression of corresponding receptors (Fig.2). IL-2 promotes realization of CD4+
lymphocytes function increasing the production of IFN-gamma etc. IL-2 prevents activated Tlymphocytes from apoptosis, prohibiting development of immunologic tolerability and is able to
cancel it. IL-2 influences on Th1/Th2 balance by autocrine influence on Th1 cells and paracrine on Th2 subpopulation. IL-2 is growth and differentiation factor for CD8+ lymphocytes, stimulates
their cytotoxic activity. After primary immune response IL-2 promotes the formation of memory Tcell population [Ehlers and Smith, 1991].
B-lymphocytes. Activated B-lymphocytes express high-affinity IL-2R and response on IL-2.
Contrary to T-lymphocytes IL-2 is not necessary growth factor for B-lymphocytes but it influences
on some stages of transcription. IL-2 is able to increase IgM, IgG, IgA synthesis by plasma cells, in
some cases IL-2 lets avoid Ir-gene controlled formation of antibody. B-lymphocytes response on
IL-2 depends on type of stimulation. For example, LPS (lipopolysaccharides) are potent stimulator
but IL-4, IL-5 and transforming growth factor do not influence on choice on antigen isotype.
NK-cells. NK-cells play major role in defending organism from viruses and tumor cells. In
most cases, influence of IL-2 on NK-cells increases their cytotoxic activity, enlarges spectrum of
cytotoxic action but practically doesn't influence on their proliferation. But some NK-cells
expressing high-affinity IL-2R (LAK-cells) in mononuclear cell culture response on IL-2
stimulation by increasing of cytotoxicity and by enhancing proliferation. This mechanism is the
basement of so-called LAK-therapy and TIL-therapy of tumors with IL-2 recombinant products.
Monocytes. Action of IL-2 on monocytes stimulate their ability to kill tumor cells and bacteria.
IFN-g and LPS stimulate expression of high-affinity IL-2R on monocyte's membrane thus
increasing their receptivity to IL-2. As a result of IL-2 stimulation monocytes produce large
quantities of biologically active substances and mediators of inflammation: free forms of oxygen,
H2O2, prostaglandin E2, tromboxane B2, TNF-a (tumor necrosis factor). Biggest part of these
compounds is the cause of side effects in patients receiving drugs on base of rIL-2. Therefor, to
avoid these undesirable reactions non-steroid anti-inflammatory (NSAI) drugs are used.
Neutrophil granulocytes. IL-2 significantly increase anti-micotic (anti-fungi) activity of
neutrophils due to stimulation of their production of lactoferrin and TNF-a.
Thus, interleukin-2 is pleiotropic cytokine of cytokine-hemopoetin family, its major function is
growth factor, IL-2 influences on non-specific (NK-cells and monocytes) part of immunity and on
specific antigen dependent immune response that is realized through T- and B-lymphocytes.
Action of IL-2 other cell types. IL-2 increases development of eosinophils and trombocytes but
suppresses myeloid and erythroid parts of hemopoiesis, causes development of extra-medullar sites
of hemopoiesis.
IL-2 and its recombinant forms are able to activate processes of tissue reparation and
regeneration.
Biological activity of IL-2 connected to its participation in regulatory processes is extremely
important because it provides simultaneous work of integrative biological systems: immune,
endocrine, nervous.
Use of Roncoleukin in complex therapy of infections, oncological diseases, exogenic secondary
immune deficits of different ethiology permit to solve problems that are not possible to overcome
by methods of traditional basic therapy.
Principles of treatment by immune therapy using recombinant cytokines:
 determination of pathogenically determined statements and targets of immune therapy
(prophylactics, stimulation, replacement therapy);
 evaluation of absolute and relative containdications to cytokine therapy, possible side effects
and reactions;
 creation of program of cytokine therapy and its laboratory monitoring;
 correction of basic therapy depending upon plan of cytokine therapy;
 estimation of effect of conducted cytokine therapy.
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4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Notion and classification of the cytokines, their main characteristic.
2. Interleukins and their role in the immune response.
3. Factors of the interaction-lymphocyte-macrophage.
4. Role of the interferons in the immune response.
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1. Theme 6: Anti-tumoral immunity
2. Object: formation of the scientific Tumor recognition is a complex
3. Thesis of lectures
Tumor recognition is a complex, challenging problem for the immune system, which must
distinguish proper cellular growth and organization from neoplastic transformation.
This process involves
-recognition of tumor antigens by effector cells and
-response of organ against tumor,
-induction of immunity
Tumor antigens
Many neoplastic cells produce antigens
- Antigens are in the bloodstream or
- Remain on the cell surface
Tumorantigens
Tumor specific antigens (TSA) are unique to tumor cells.
Tumor-specific mutations that generate unique epitopes
New antigens, these are only in the tumor cells
p53
adeno cc
caspase 8
head and neck
CDK4
melanoma
Tumor-associated antigens are relatively restricted to tumor cells
Ag-s overexpressed by tumor cells compared to normal tissue
Melan-A
melanoma
HER-2/neu (growth factor R)
breast, Ovarium
telomerase
The effector mechanism: CTL
Alteration of oncogenes: mutations, will be antigens, new functions, -generate a novel protein
sequence
Tumor-testis antigens (tumor specific Ag-s)
Non-mutated ‘self’ antigens that are found only in testis
Natural killer cell (NK) tumoricid activity
NK: CD16R (IgG binding R)
CD56 adhesion molecule
Cytokine binding R (IL-2)
•NKT cell line (T cell marker- TCR, CD3+)
• Tumor cell present Ag-s to T cells as peptide fragments on the surface of MHC molecules. In
the absence of co-stimulatory signals, tolerance may result.
Prevention of tumor cells
Therapy against the tumor
ACTIVE increasing the self immunoreactivity
PASSIVE the patients receiveantibody or
cellular components
Passive immunotherapy
• Lymphokin-activated killer cells (LAK)
no evidence of benefit
• TIL = tumor infiltrating lymphocytes
+ in vitro IL-2 stimulation
Results: 10-20% (melanoma, renal tumor)
or
Activated LAK
Activated TIL
+ in vivo IL-2
Side effect: cytokine release syndrome, capillary leak syndrome, lung and brain oedema
2. Tumor specific cytotoxic T cell
allogenic bone marrow transplantation – my developed
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e.g. EBV associated lymphoma
Treatment:
Donor specific T cells (EBV sensitive cytotoxic T cells) to recipient (clonally
Page 13of 21
reactive T
cells)
may provide clinical benefit
3. Stem cell therapy
a/After chemotherapy bone marrow deficiency
peripheral stem cell pool
allograft or autograft
b/ Hematopoetic malignancies
graft bone marrow T cells or
peripheral T cells damage
normal tissue Ag +
the tumor cells
4. HSP therapy
HSP was obtained from tumor (hsp70, hsp90, grp94/pg96)
HSP adjuvant, and binding the tumor protein –
increase the T cell response
5. EBV associated tumors
EB-V--- B cell transformation
EBV associated tumors: immunoblastic lymphoma
nasopharyngeal cc
Hodgkin disease
Virus membrane Ag components into the recipient – develop anti-viral antibody (CTL -CD8+
T) lyses the tumor cells
Cytokines used as adjuvants for immunotherapy
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
Modern sight on the etiology of the malignant tumors, oncogens. Role of the cancerogens in
the activation of the oncogens and depression of the tumors supression’s gens
2. Antigen contents of the blast cells.
3.Blocking factors of the blood serum of the tumor carriers (IgG, circulated tumor antigen,
circulated immune complexes).
4. Cell mechanisms of the anti-tumor immunity, role of the T-cell, macrophage, natural
killer and K-cells..
5. Role of the cytokines in the anti-tumor immunity (IL-1, IL-2, IL-12, IFN-α, IFN-γ, TNFα, β).
6. Modern methods of the immune diagnostic and immune therapy of the tumors
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1. Theme 7: HLA system, locus structure and functions. Immunological tolerance. The bases
of the transplantation immunity.
2. Object: formation of the scientific notions about human MHC structure, their locuses
functions, and role of the HLA-antigens as a genetic markers of the predisposition to hereditary
diseases, immunological problems of the transplantation.
3. Thesis of lectures:
The major histocompatibility complex (MHC) is a large genomic region or gene family found
in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an
important role in the immune system, autoimmunity, and reproductive success. The proteins
encoded by the MHC are expressed on the surface of cells in all jawed vertebrates, and display both
self antigens (peptide fragments from the cell itself) and nonself antigens (e.g. fragments of
invading microorganisms) to a type of white blood cell called a T cell that has the capacity to kill or
co-ordinate the killing of pathogens and infected or malfunctioning cells.
In humans, the 3.6-Mb (3 600 000 base pairs) MHC region on chromosome 6 contains 140
genes between flanking genetic markers MOG and COL11A2.[1] About half have known
immunological functions (see human leukocyte antigen). The same markers in the marsupial
Monodelphis domestica (gray short-tailed opossum) span 3.95 Mb and contain 114 genes, 87 shared
with humans.
Codominant expression of HLA genes.
Main article: Human leukocyte antigen
The best known genes in the MHC region are the subset that encodes antigen presenting
proteins on the cell surface. In humans, these genes are referred to as human leukocyte antigen
(HLA) genes, although people often use the abbreviation MHC to refer to HLA gene products. To
clarify the usage, some of the biomedical literature uses HLA to refer specifically to the HLA
protein molecules and reserves MHC for the region of the genome that encodes for this molecule.
This convention is not consistently adhered to, however.
The most intensely studied HLA genes are the nine so-called classical MHC genes: HLA-A,
HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLADRB1. In humans, the MHC is divided into three regions: Class I, II, and III. The A, B, and C genes
belong to MHC class I, whereas the six D genes belong to class II.
MHC has also attracted the attention of many evolutionary biologists, because of the high
levels of allelic diversity found within its genes
Molecular biology of MHC proteins
TCR-MHC bindings.
The classical MHC molecules (also referred to as HLA molecules in humans) have a vital role
in the complex immunological dialogue that must occur between T cells and other cells of the body.
At maturity, MHC molecules are anchored in the cell membrane, where they display short
polypeptides to T cells, via the T cell receptors (TCR). The polypeptides may be "self," that is,
originating from a protein created by the organism itself, or they may be foreign ("nonself"),
originating from bacteria, viruses, pollen, and so on. The overarching design of the MHC-TCR
interaction is that T cells should ignore self-peptides while reacting appropriately to the foreign
peptides.
The immune system has another and equally important method for identifying an antigen: B
cells with their membrane-bound antibodies, also known as B cell receptors (BCR). However,
whereas the BCRs of B cells can bind to antigens without much outside help, the TCRs require
"presentation" of the antigen through the help of MHC. For most of the time, however, MHC are
kept busy presenting self-peptides, which T cells should appropriately ignore. A full-force immune
response usually requires the activation of B cells via BCRs and T cells via the MHC-TCR
interaction. This duplicity creates a system of "checks and balances" and underscores the immune
system's potential for running amok and causing harm to the body (see autoimmune disorders).
MHC molecules retrieve polypeptides from the interior of the cell they are part of and display
them on the cell's surface for recognition by T cells. However, MHC class I and MHC class II differ
significantly in the method of peptide presentation.
MHC evolution and allelic diversity
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MHC gene families are found in essentially all vertebrates, though the gene composition and
genomic arrangement vary widely. Chickens, for instance, have one of the smallest known MHC
regions (19 genes), though most mammals have an MHC structure and composition fairly similar to
that of humans. Gene duplication is almost certainly responsible for much of the genetic diversity.
In humans, the MHC is littered with many pseudogenes.
MHC and sexual selection
It has been suggested that MHC plays a role in the selection of potential mates, via olfaction.
MHC genes make molecules that enable the immune system to recognise invaders; generally, the
more diverse the MHC genes of the parents, the stronger the immune system of the offspring. It
would obviously be beneficial, therefore, to have evolved systems of recognizing individuals with
different MHC genes and preferentially selecting them to breed with.
Yamazaki et al. (1976) showed this to be the case for male mice, who show a preference for
females of different MHC. Similar results have been obtained with fish.
In 1995, Swiss biologist Claus Wedekind determined MHC-dissimilar mate selection
tendencies in humans. In the experiment, a group of female college students smelled t-shirts that
had been worn by male students for two nights, without deodorant, cologne or scented soaps.
Overwhelmingly, the women preferred the odors of men with dissimilar MHCs to their own.
However, their preference was reversed if they were taking oral contraceptives. ] The hypothesis is
that MHCs affect mate choice and that oral contraceptives can interfere with this. A study in 2005
on 58 test subjects confirmed the second part - taking oral contraceptives made women prefer men
with MHCs similar to their own.. However, without oral contraceptives, women had no particular
preference, contradicting the earlier finding. However, another study in 2002 showed results
consistent with Wedekind's--paternally inherited HLA-associated odors influence odor preference
and may serve as social cues.
Active memory and immunization
Long-term active memory is acquired following infection by activation of B and T cells. Active
immunity can also be generated artificially, through vaccination. The principle behind vaccination
(also called immunization) is to introduce an antigen from a pathogen in order to stimulate the
immune system and develop specific immunity against that particular pathogen without causing
disease associated with that organism. This deliberate induction of an immune response is
successful because it exploits the natural specificity of the immune system, as well as its
inducibility. With infectious disease remaining one of the leading causes of death in the human
population, vaccination represents the most effective manipulation of the immune system mankind
has developed
Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are
based on acellular components of micro-organisms, including harmless toxin components. Since
many antigens derived from acellular vaccines do not strongly induce the adaptive response, most
bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells
of the innate immune system and maximize immunogenicity.
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
G-041.07.05.13-2013
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6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Human MHC structure.
2. Role of the 1 and 2 classes of the antigens in the intercellular interaction.
3. Methods of the HLA system antigens estimation.
4. Immunological tolerance.
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1. Theme 8: Hypersensitivity mechanisms
2. Object: formation in students mechanisms of hypersensitivity
3. Thesis of lectures
Hypersensitivity reactions can be triggered by a number of antigens, and the reasons for them
are different in different people.
Certain forms of the antigen by repeated contact with the organism can cause a specific
reaction.
It includes nonspecific cellular and molecular factors of the acute inflammatory response.
This phenomenon is excessive or inadequate manifestations of acquired immune reactions
called hypersensitivity.
There are two forms of high reactivity:
immediate hypersensitivity that includes three types of hypersensitivity (type I, II and III)
and delayed hypersensitivity (IV-w) type (as Gell and Coombs classification).
In practice, the types of hypersensitivity optionally occur separately.
If immediate hypersensitivity due to humoral immune mechanisms, or delayed
hypersensitivity-type cell.
However, for some of hypersensitivity reactions such classification is not appropriate because
the mechanism of the complex.
For all types of hypersensitivity are critical dose of antigen and a method of penetration into the
body.
Type I Mechanism
Mast cells display a high affinity receptor for IgE
IgE is synthesised in response to certain antigens (allergens)
Allergens are deposited on mucous membranes and taken up and processed by antigen
presenting cells (e.g. Dendritic cells or B cells)
Under normal conditions listed mediators contribute to the development of protective acute
inflammatory reaction with symptoms of asthma or rhinitis. In certain conditions, such as atopy,
there is an intense release of anaphylatoxin that is a danger to life.
Mast cell mediators
Type II hypersensitivity reactions (also called cytotoxic antibody) antibody mediated usually
class IgG (less IgM) for cell surface antigens and extracellular matrix. Antibodies may occur and to
intracellular components, but they are often non-pathogenic.
In type II hypersensitivity target cell damage caused by the interaction of antibodies to antigens
with the complement and various effector cells (K-cells, platelets, neutrophils, eosinophils,
macrophages / monocytes).
Type II Hypersensitivity
Antibody mediated
hypersensitivity
Antibody directed
against membrane and
cell surface antigens
(autoantibodies)
Antigen-antibody reactions activate complement producing membrane damage
Examples include: transfusion reactions and haemolytic disease of the newborn
Adhered to the surface of cells or tissue antibodies bind and activate the complement
components.
Effector cells were reacted with antibodies through Fc-receptor fragments.
Activation of C3 – component of complement can directly lead to complement-dependent lysis
of target- cells or promote binding phagocytes to their targets.
Type II
Mechanism
Antibodies bind to
cell surface
Phagocytes bind to
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Page 18of 21
the antibody via their
Fc - receptor
Phagocytosis of
target - cell
Type III Hypersensitivity
Immune complex
mediated
Excessive formation
of immune complexes
e.g. persistent low-grade
infection, repeated inhalation of antigens
Examples of Type III hypersensitivity
include:
Farmers lung, immune complex
glomerulonephritis
Quite large complexes after interaction with complement, digested phagocytes and then
excreted.
At the same time, small complexes formed with an excess of antigen may be adsorbed to
various organs and tissues.
In this case, the disease develops immune complexes or Type III hypersensitivity reaction.
Large poorly soluble complexes may also be deposited in tissues of complement deficiency.
Diseases caused by the formation of immune complexes can be divided into three groups:
Associated with persistent infection
Associated with autoimmune diseases
Associated with inhalation of antigenic material.
In the first case, the combination of chronic infection with a weak humoral response results in
permanent formation of immune complexes and their deposition in tissues (in leprosy, malaria,
dengue hemorrhagic fever, viral hepatitis, and staphylococcal endocarditis).
In autoimmune diseases, immune complex disease is caused by the continuous production of
antibodies against autoantigens (with the etiology of the disease include rheumatoid arthritis,
systemic lupus erythematosus (SLE) and polymyositis).
Inhalation antigenic material immune complexes may be formed on the surface of the cavities.
For example, in the lungs during inhalation repeated antigenic components actinomycetes, as
well as antigens of vegetable or animal origin.
For diseases with the etiology include of pulmonary disease farmer, pulmonary disease fancier.
At a time when the body has a pre-existing IgG-antibodies and specific antigen penetrates the
skin, develops a local inflammatory process, called Arthus reaction.
At high levels of serum antibody precipitate formed in the penetration of the antigen in the
body.
Skin reactions are characterized by polymorphonuclear infiltration, edema and erythema,
reaching a maximum after 3-8 hours.
The resulting layers of fabric complex activates the complement system, whereby the
components accumulate C5a, C3a - inflammatory mediators.
They provide the beginning of the local inflammatory response, increasing the permeability of
blood vessels.
As a consequence of the inflammation accumulate neutrophils, platelets, increasing the amount
of liquid.
Arthus reaction is protective in nature, which prevents the penetration of antigen in the inner
region of the body.
Introduction of an intact organism large foreign protein frequently leads to the development of
a serum disease.
Type IV Mechanism
APC resident
in the skin process
antigen and migrate
to regional lymph nodes
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where they activate
T - cells
Sensitised T cells migrate back to the the skin where they produce cytokines which attract
macrophages which cause tissue damage
Delayed type hypersensitivity.
delayed-type hypersensitivity reaction, consists of the following steps:
Native antigen introduction into the body leads to the accumulation of specific CD4 T-cell
inflammatory (TH1).
2. With repeated subcutaneous infiltration of antigen is its capture tissue macrophages. On the
surface of macrophages derived antigen fragments complexed with MHC class II molecules.
3. Preexisting antigen-specific TH1 cells interact with the immunogenic complex on the surface
of macrophages. This is a key event for the subsequent development of all hypersensitivity
reactions IV-type.
After the last interaction TH1-cells begin secretion of a set of cytokines:
Macrophage inhibitory (MIF), macrophage chemoattractant (IHF), granulocyte-macrophage
colony-stimulating factor (GM-CSF) factors
Interferons, IFN-gamma and IFN-beta,
Tumor necrosis factor-beta (TNF-beta),
Interleukin-3 (IL-3).
conclusion
Allergy 1, 2, and 3 types of antibodies due
Allergies Type 4 is caused by cellular factors
An allergic reaction is aimed at removing allergens in different ways
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London,
2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Classification of the hypersensitivity on Cumbs and Gell.
2. Pathohenesis, clinical examples and diagnostic of the atopic allergy.
3. Role of the IgE in the pathogenesis of the atopia. Role of the hereditary factors in the
pathogenesis of the atopic allergy.
4. Anaphylaxis. Pathogenesis of the anaphylactic shock, its prophylaxis.
5. Differences and similar between the atopia and anaphylaxia.
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1. Тopic 9: Anti-infectious immunity
2. Object: formation of the scientific
3. Thesis of lectures
Specific and non-specific immune defenses
• Under the specific protection understood is specialized cells, that can fight with only one
antigen.
• Non-specific immunity factors, such as phagocytes, natural killer cells and complement
(specific enzymes) can fight off the infection, both independently and in cooperation with a specific
protection.
The main types of immune responses and what they protect.
• antibody
• complementary lysis
• phagocytosis
• Delayed-type hypersensitivity reaction (formation of macrophage granulomas)
• Cellular cytotoxicity (Killing)
• Immune response to introduction of the virus
• Destruction or inactivation of the virus without destroying virus-infected cells
• The destruction of the modified virus host cell
• Lack of response to the latent persistence of virus
• Cellular cytotoxicity - the main defense against viral infections
• In addition, lymphocytes and other cells synthesize alpha-, beta-and gamma-interferons
• Interferons are a signal for the infected cells to the virus are not reproduced, for helth cells
are not admitted to it
• IgG antibodies bind virus outputs from broken cells, and complement can damage
superkapsid
• Complement can neutralize some viruses coated with antibodies
• Without complement antibodies capable of inactivating viruses (retroviruses, etc.) have
receptors for C1
• Macrophages destroy viruses by phagocytosis
The mechanism of violations of immunoreactivity associated with:
• With the multiplication of the virus and cell destruction (Epsheyn-Barr virus transforms BL, the chickenpox virus, herpes, inhibit the proliferation of T-l, HIV destroys CD4)
• macrophage activation, cytokine release from, inhibition of the expression HLA-antigens
against adhesion, cooperation cells (HIV, hepatitis viruses, influenza)
• Apoptosis induced by virus Tx, stimulation Tx1 and Tx2 imbalance, leading to the
development of allergy or CID (influenza, measles, adenoviruses)
• The suppression of cytokine synthesis by viruses (CMV, v.gepatita)
• Suppression of neutrophil bactericidal (measles, flu)
• Viruses induce immunopathological reaction
Antiparasitic immune response
• Protozoan infestations in the blood (malaria, trypanosomiasis) tension of immunity
determine humoral factors, and when the parasites multiply in the tissue - cellular
• Many parasites showed high variability of surface antigens in the process of parasitism in a
host
• Causative agents of leishmaniasis, malaria, toxoplasmosis can multiply inside macrophages
• All parasites cause non-specific suppression of host immunity
• Protection against protozoa, parasites intracellularly provide Th1, release of IFN γ activating
macrophages
• When protozoal infections, there are allergic reactions due to enhanced synthesis of IgE
• The main effector antiparasitic protection, eosinophils, which are attached to IgE connect
with helminths, degranulate and secrete cytokines (IL 1,3,4,5,8), peroxidase, a cationic protein etal.,
that lyse skin worms
• Many parasites resistant and can persist for a long time in the body.
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• Most of antigenic variability, the low efficiency of specific antibodies and immune cells can
not create a vaccine against parasitic infections.
• Fungal antigens (80) are contained in the spores, the cell wall and cytoplasm
• The spores of non-pathogenic and opportunistic fungi contain in large quantities in spring
and autumn and can be a cause of respiratory allergy
• Pathogenic fungi can affect the skin, subcutaneous tissue deeply lying tissue. Candidiasis
develop against IDS
The mechanisms of antifungal immunity
• similar antibacterial
• Congenital due neutrophils, macrophages and alternative by complement activation
• Specific immunity is mainly Th1, that produce IFNγ, activating macrophages and T-killer
• Susceptibility to fungal infection is caused by the activity of Th2, suppressing cytokines IL4, 10 - Th1
• The protective effect of antibodies seen in opsonization of fungi for phagocytosis
• IgE antibodies are detected by fungal infections or develop on non-pathogenic fungi
allergens
• Detection of antibodies and antigens in the blood of patients used for the diagnosis of fungal
infections
• To allergens fungi was immediate and delayed skin test
4. Supporting data: Point Power presentation
5. Literature
main:
1.Khaitov R.M. Immunology.-Moscow, Geotar, 2013.
2.Kindt T.J, Goldsby R.A., Osborne B.A. // Kuby Immunology, 6th edition, W.H. Freeman and
Co, 2007, New York
3.DeFranco A.L., R.M. Locksley, M. Robertson // Immunity, New Science Press, London, 2007
4.Basic Immunology Updated Edition by Abul K. Abbas 2010
additional:
1.Cellular and Molecular Immunology, 5th Edition 2013
2.Immunology: Short Course by Richard Coico"
3.Challenges in Immunology, Science, 2007, V.317, Iss. 5838, p.p. 611-629
4.Иммунология: учебник / А. А. Ярилин . - М : ГЭОТАР-Медиа, 2012. - 752 с.
5.Словарь – справочник по иммунологии/ под ред.С.В. Кожановой Алматы, 2011
6.Иммунология: атлас / Р. М. Хаитов, А. А. Ярилин, Б. В. Пинегин. - М: ГЭОТАР-Медиа,
2011. - 624 с.
6. Advancement questions (followed up)
1. Specific and non-specific immune defenses
2. Immune response to introduction of the virus
3. The mechanisms of antifungal immunity
4. Antiparasitic immune response