MINISTRY OF HEALTH OF UKRAINE
Vinnitsa National Medical University
"Approved"
Vice Rector for Academic Affairs
Professor Y. Guminsky
______________________
(Signature)
"_29_" __ 08__2013.
Guidelines
for preparing for practical training for students of the 5th year of the Medical Faculty
Topic number 1
discipline
"Clinical Immunology and Allergology"
Module number "Clinical Immunology and Allergology"
1
Theme of
module
Immunne status, age features. Immunodeficiencies and other immune
diseases principles of diagnostics, immunotherapy, immunization and
immunorehabilitation.
Theme of class: Structure and function of the immune system. Age immunology. Major
histocompatibility antigens: structure and function.
Course
5th
Faculty
Medical number 1
amount of hours 4
2013
I. Hot Topics: Despite significant advances fundamental medicine, including immunology,
development of new technologies of diagnosis and treatment over the past decades
immunopathology prevalence immunopathology (immunodeficiencies, allergic, autoimmune
lymphoproliferative) acquired a global scale medical and social problems. In most developed
countries, including Ukraine, there is a decrease in immune reactivity due to different causes:
genetic, environmental, social, etc. .
The peculiarity of modern conditions and problems of medical practice needs to understand
and apply in clinical practice physician needed modern, in-depth knowledge on the basics of
basic immunology.Particularly important contemporary understanding of the processes that
underlie the formation of the immune response.
II. Learning Objectives lesson.
1. Be familiar with basic modern data on the structure and function of all parts of the immune
system, the age characteristics of its development, critical periods of development of the
immune response in children and the elderly.
2. Know the meaning of such concepts as immunity (congenital, acquired), the immune system,
the immune response: the stages and types of its regulation, immune status, major
histocompatibility complex antigens (GCS): structure and function.
3. Learn basic concepts such as subsystem of the immune system, cellular and humoral factors
of innate and acquired immunity of their function.
4. Know the structure of immunopathology.
5. Independently develop and prepare a presentation to 5 minutes on the immune mechanisms
of pathology in patients on the future profile of the specialty (neurology, pulmonology,
obstetrics, rheumatology, pulmonology, gastroenterology, cardiology, etc.). When the
opportunity to demonstrate to the supervised patients.
III. Personal development goals (educational purposes)
To acquaint the student with the age characteristics, stages of immune response types and its
regulation by theme material to develop a sense of responsibility for the timeliness and
accuracy of professional activities in the diagnosis of immunopathology. On the basis of ethical
principles to teach young professional set psychological contact with the patient and his
relatives immunopathology.
IV. Integrative communication topics:
4.1.Vnutrishnopredmetna integration: the topic of this practical training related topics
described in the course of general immunology: the organs and cells of the immune system, the
structure and function of the immunoglobulin types of immune response, antigens, innate and
acquired immunity.
4.2.Mezhdistsiplinarna integration:
Deestsipliny
Bi ology
W nat
Be able to
EV olyutsiyu immune system Est. enit features of the immune system of different
development of living
animals
organisms
An atom
Guystologiya
About RGANI immune system Isat op structure of the immune system
Tc Ani and cells of the immune Mi scopic distinguish immunocompetent cells and
system
tissues of the immune system
Phiziologiya
Wasps main functions of the Est. enit basic functions of the immune system
immune system
Bi ohimiya
Article swarming and function Ying interpret basic levels of immune proteins
of immune proteins
Ge kinetics
Aubin inheritance of wasps
About appreciate types of inheritance of traits
Patofiziologiya Wee dy immunological
Tr aktovat change the general immunological blood
reactivity
(leykograma, proteinograma) in terms of
immunopathology
Exopedevtika Wasps Aubin survey of the
Pa lpatsiya, percussion of the immune system,
therapy
immune system in adults and evaluation of the results of the Company and
children
instrumental methods of examination
V. Content of the topic classes
After becoming acquainted with the students, the teacher shows students the clinical database
on which the course of clinical immunology and allergy, and talks about the order of teaching
students in the department and then begin the study of the first theme.
6.1 Study Questions Topics:
6.1.1. Structure of the immune system, its basic properties, and functions
6.1.2. The main factors of innate immunity
6.1.3. Synergy factors of innate immunity
6.1.4. Antigens, allergens, haptens: types, clinical significance. Superantigens
6.1.5. Acquired (adaptive) immunity
6.1.6. The populations and subpopulations of lymphocytes, their function in the immune
response
6.1.7. Immunoglobulins, their types and functions
6.1.8. Regulation of human immune response
6.1.9. Stages of the immune response.
5.1.1.Struktura immune system, its features and basic functions
Teacher reminds students about such basic concepts: Immune system - a collection of lymphoid
organs, tissues and cells, providing biochemical, structural and functional identity of the
organism by the elimination of a foreign carrier of genetic information. The structure of the
immune system: the central organs (thymus, bone marrow), peripheral - (spleen, lymph nodes,
Peyer's patches, tonsils, adenoids, appendix, accumulations of lymphoid tissue (NALT, BALT,
GALT, MALT, etc.). Properties of the immune system ( specificity, five monuments, mobility,
fertility, the ability to transmit a signal within the system autonomy. Stresses that the main
function of the immune system is - immune surveillance, ie body's defense against endo - and
ekzoantigeny bearing signs of alien genetic information
Next, the teacher says that overall the immune system can be divided into two large sections
(parts, sub-systems), a joint operation which creates a very powerful multifactorial protection:
- Innate immunity (non-specific factors of natural resistance)
- Acquired adaptive immunity (to provide a specific immunological surveillance)
5.1.2. The main factors of innate immunity
The factors of innate immunity include: mechanical: skin and mucous membranes; treatment
reflexes, secretions, chemical: pH secrets, lactic and fatty acids, enzymes, etc. ; Physical
temperature biological body: microflora.
Cellular part of the innate immune cells represented by the following: mononuclear
phagocytes (monocytes, tissue macrophages) granulocytes (neutrophils, eosinophils) basophils
and mast cells, lymphocytes (natural killer (NK), in fact the killer (K) cells lymphokine (LAC)).
Phagocyte function: participate in the actual protection of the organism against foreign
substances by phagocytosis and antibody-dependent cell-mediated cytotoxicity; interact with
lymphoid cells, "including" and regulating mechanisms of adaptive immunity (antigen
presentation, cytokine production). The functions of monocytes / macrophages can be divided
into: locomotor (migration and chemotaxis) secretory (synthesis of cytokines and other
immunologically active substance), phagocytosis ability, ability for antigen processing and
presentation, the ability to spontaneous cytotoxicity and antibody.Antibody-dependent cellmediated cytotoxicity - Cytotoxic a reaction cell in which - the target antibody coated
destroyed because to Fc - receptor antibody coating the target cell, attached cytotoxic cells that
have Fc-receptor immunoglobulin moiety - macrophages, neutrophils, natural killer cells.
Neutrophil function: chemotaxis, phagocytosis, secretion in the pathogenesis of acute
inflammation, the implementation of immune tissue damage.
Eosinophil function: the destruction of major helminth parasites type; antiallergic activity,
chemotaxis, phagocytosis.
Functions basophilic granulocytes (basophils) and tissue basophils: are capable of chemotaxis
and phagocytosis; have on their surface the receptor for the Fc - fragment of IgE, which, after
binding to the IgE - allergen leads to degranulation of the cells and the release of active
ingredients in pellet environment; promote stimulation and inhibition of blood coagulation
contribute launch kallikrein - kinin system, activated platelets through the production of a
specific factor.
Lymphocyte function: natural or natural killer (NK), just killer cells (K) and lymphokine killer
cells (LAK)
1 \ natural or natural killer (NK)
- Performs the functions of immune surveillance, lysed cells - the target (almost all nucleated
cells, especially tumor and virus-infected) without prior sensitization, a process
called spontaneous cell - mediated cytotoxicity
- Carry out a regulatory function, highlighting various immunologically active substances
(cytokines, prostaglandins, protease inhibitors)
- Implemented antibody cell - mediated cytotoxicity
2 \ killer (K)
- Implemented antibody cell - mediated cytotoxicity
- Participate in the development of autoimmune diseases
- Take part in graft rejection
3 \ lymphokine killer cells (LAK)
- Implemented Keeling after IL-2 activation
- Antitumor supervision
Antigen-specific receptors on cells of nonspecific immunity called PRR (pattern recognition
receptors). These receptors respond to the corresponding structures on microbial cells PAMP
(pathogen associated molecular patterns) and are divided into groups:
- Receptors released (synthesized) which are often opsonized
- Surface receptors (phagocytes and antigenprezentuyuchih cells)
- Surface activating receptors on epithelial cells, endothelial cells, adipocytes, cardiomyocytes,
fibroblasts, ie cells, which are also capable of destroying microorganisms
Also on epithelial cells, endothelial cells and adipocytes contain Toll - like receptors called
TLR (Toll - like - receptors). These receptors are used for recognition and binding
peptidoglycans, lipoproteins, nucleic acids of the bacterial cells, which are then subject to
phagocytosis. Especially a lot of these receptors is on dendritic cells.
Function of dendritic cells: endocytosis and pinocytosis, phagocytosis, deposition in the lymph
nodes, the synthesis of cytokines, antigen presentation.
Humoral innate immunity:
The complement system - the system is thermolabile glycoprotein and serum protein factors,
which perform the following functions:
- Cytolysis and bactericidal;
- Education anaphylatoxin;
- Chemotactic effect on neutrophils, eosinophils, monocytes;
- Ensuring adherence, opsonization and phagocytosis;
- Provides non-specific resistance against viruses;
- Participate in the elimination of immune complexes;
- Affect the activity of clotting factors.
Activation of the complement system can occur in two ways - classic, or immune,
and alternative or properdine.
Differences of the classical pathway of complement activation of the alternative:
- To activate the complement system by the classical pathway is necessary to the formation of
specific immunoglobulins (IgG or IgM) and them. complexes takes time
- Activate the classical pathway of complement starts with the first, so-called early,
complement component C1 which is composed of three subcomponents (C1q, C1r, C1s), and
more C4, C2, and C3.
Alternative pathway of complement activation is triggered immediately after hitting the antigen
and is a kind of "first aid" for immediate protection until formed specific immunoglobulins and
immune complexes.
The biological consequences of activation of the complement system: education anaphylatoxin
(C3, C4a and C5a) formation of opsonic (C3b, etc.); education C3 - nephrotic factor; education
chemotactic factors for neutrophils (Ba and Bb) education membranoatakuyuchogo complex
(S5b6789).
Lysosomal enzymes are divided into two groups (kisnevozalezhni and kisnevonezalezhni)
- Oksigenzavisimye (myeloperoxidase, lactoperoxidase) cause the formation of reactive oxygen
species hydrogen peroxide promotes "respiratory burst" and killing of a pathogen
- Oksigenzavisimye (proteases, cationic proteins, lysozyme, lactoferrin) are proteolytic effect on
the pathogen.
Inflammatory proteins (acute phase proteins of inflammation) - four groups of proteins that
form a separate fraction during the electrophoretic separation of serum, called alpha 1, alpha 2,
beta, and gamma.Increasingly determined separately: C-reactive protein, alpha 2 macroglobulin, Beta 2 - micro globulin, antitrypsin, transferrin, etc. .
Natural antibodies - a group of Ig molecules of the monomer M, which is located on the surface
of mature B-lymphocytes are polyvalent specificity.
Hemolysin - antibodies against red cell antigens are divided into: geteroliziny (lysine against
foreign erythrocyte antigens izoliziny (lysine against erythrocyte antigens of its kind) autoliziny
(lysine against erythrocyte antigens of the organism).
Haemagglutinin - a characteristic component of many viruses that specifically binds in vitro to
the membrane of red blood cells, causing their agglutination and sedimentation.
Cytokines - it's common name of a group of biologically active substances (non-specific immune
response factors), which are produced by various cells and the ability to stimulate or inhibit the
differentiation, proliferation of immune cells by regulating cell-cell interaction. Features
cytokines:
- One cytokine can be produced by more than one cell type;
- One cell can produce more than one cytokine;
- A cytokine can act on more than one cell type;
- Several cytokines can induce the same function in the specific cell type.
Types of cytokines:
1 /. Interleukins - about 40 of them are known. Key:
• IL -1 - limfotsitatakuyuchy synthesized mainly monocytes / macrophages, is a
proinflammatory
• IL -2 - growth factor of T - lymphocytes, produced by T - helper 1 is proinflammatory
• IL -3 - colony
• IL -4-stimulating B-lymphocytes, anti-switches on the synthesis of IgG1 and IgG4 IgE
• IL -5 - eosinophilic factor switches on the synthesis of Ig G and IgE sIgA is an anti• IL -6 - factor differentiation of B-lymphocytes
• IL -7 - limfopoetin
• IL -8 - neutrophilic factor
• IL -9 - Growth Factor T - helper
• IL -10 - suppressor factor, anti• IL -11 - platelet factor
• IL -12 - maintains a balance between T - 1 and T helper - helper 2
• IL -13 - induced IgE synthesis
• IL -14 - factor B-cell memory.
2 /. Growth factors G-CSF - granulocyte colony-stimulating factor; M-CSF - monocyte colony
stimulating factor; TGF - beta - transforming growth factor (a negative regulator of
immunological reactions, regeneration of wounds) Erythropoietin; antitumor properties; TNF beta - lymphotoxin promotes apoptosis.
3 /. Chemokines: CXC - alpha - chemokines; CC - beta - C chemokines - gamma - chemokines;
SKH3S - delta - chemokines.
4 /. Interferons: Type 1: alpha - leukocyte, produced by macrophages, type 2: Beta - fibroblasny,
produced by fibroblasts, the third type: gamma - produced by activated T - helper 1 - order and
natural killer cells after antigen challenge.
5 /. Tumor necrosis factors (TNF) - alpha and beta. TNF - alpha - kaheksin, a powerful proinflammatory cytokine, has cytostatic, immunomodulatory, antiviral properties.
Cell adhesion molecules (adhesion molecules) - biologically active substances that promote
attachment (adhesion) one cell to another in the performance of its functions are divided into
three groups:
- Immunoglobulin superfamily (ICAM -1, LFA -3, VCAM -1, N-CAM)
- Integrins (LFA -1, VLA -1, VNR, MAC -1)
- Selectins (LECAM -1, GMP -140, ELAM -1, PECAM)
Differences between the innate and acquired immune response.
Congenital Acquired answer answer
1. On the list of fastest (immediate), not by a
few days
2. Receptors that recognize microorganisms
constant throughout a person's life
3. Selective (not attacks its own structure)
4. Not reserves the immunological memory
5. Develops independently of
specific immune response.
Ra zvivaetsya slowly, sometimes for several
days
The receptors that recognize the antigen are
created anew during each primary immune
response
Specific, but can be processes and autoreactive
Remains long-term immunological memory
For development is always needed nonspecific
immune response.
5.1.3. Antigens, allergens and haptens: types, clinical significance. Superantigens.
Antigens - substances that can be recognized by antibodies or antigen-specific T - cell receptor
can have both exogenous and endogenous origin. They have two basic properties:
- Immunogenicity (ability to induce a specific immune response, whereby antibodies are
produced by lymphocytes or specific);
- Antigens (ability to react specifically with antibodies or cells that produce the introduction of
the antigen).
Superantigen - an antigen that reacts with T - cell receptor recognizing the CD 4 + T cells,
bypassing the conventional mechanism for presentation via the major histocompatibility
complex molecules, which leads to more stimulation of T - lymphocytes than with antigen
stimulation, and which is represented protsesingiruetsya conventional manner.
There superantigens and B-lymphocytes. In contrast to conventional antigens, which can be
recognized only by cells specific thereto, supreantigeny may interact with any of the
lymphocytes that has beta - receptor chains contain certain types of variable domains. By the
degree of foreign antigens are divided into: autologous, syngeneic, allogeneic, xenogeneic;
sequestered. In chemical composition: protein; nucleoproteins; glycoproteins, polysaccharides.
Thimic-independent antigens and are divided into thymus-dependent.
Thimic-independent are those antigens to which antibody synthesis is carried out by Blymphocytes without T - lymphocytes.
Thymus-dependent - it antigens, the immune response to that carried out with the obligatory
participation of T - lymphocytes - helper cells and macrophages.
Adjuvants - are substances that induce immune response by increasing the expression of
immunogenic molecules without altering their chemical properties.
5.1.4 Acquired (adaptive) immunity
Acquired immunity - a way to protect you, the process of antigen recognition, its
differentiation from other people's products and antibodies (immunoglobulins) that are specific
for the antigen that caused their formation.
Acquired (adaptive) immunity is divided into:
- Humoral immunity (by means of antibody production of B-lymphocytes)
- Cell-mediated immunity (represented population of T - lymphocytes, among which secrete
helper 1 - and 2 - type, cytotoxic, regulatory / suppressor memory).
Features acquired immunity:
- T - and B-lymphocytes have specific receptors antigenrozpiznayuchi by which the process of
antigen recognition, differentiation of "its" from "foreign"
- If necessary, include a mechanism of production of antibodies - immunoglobulin or T - cells cytotoxic specific to antigens, which caused their formation
- As subsided immune response is specific immunologic memory, the existence of which allows
the immune system to respond more quickly when re-injected into the body already "familiar"
antigen
5.1.5. The populations and subpopulations of lymphocytes, their function in the immune
response.
All cells of the immune system originate from a single precursor - hematopoietic pluripotent
stem cells. Cell differentiation takes place under the influence of various growth factors. Cells
formed differ by the presence of various surface antigens - molecules that form lymphocyte
phenotype. CD - cluster of differentiation antigens called (claster of differentiation),
ie molecules that can be identified using specific monoclonal antibody specificity groups.
T - lymphocytes
Part immunologically immature stem cells migrate from the bone marrow to the thymus, where
under the influence of thymic microenvironment (epithelial cells and hormones timuca
thymosin, Thymopoietins, thymic humoral factor thymulin) mature into immunocompetent T lymphocytes. After the leg antigennezavisimogo differentsiirovaniya thymic mature T lymphocytes are settled through the bloodstream to specific areas of the peripheral lymphatic
system - thimic-independent zones of secondary lymphoid organs. On the surface of T lymphocytes have a tool by which the recognition of foreign material occurs - T - cell antigenspecific receptor. This - a heterodimer composed of two polypeptide chains. Most portion of
each of two receptor chains is outside the cell and in the form of twisted two domains - a
variable (V) and constant (C). The majority of T - lymphocytes carry receptors composed of an
alpha -, and beta chains. Sometimes these T - lymphocytes called "alpha - beta-T lymphocytes." T - cell antigen-specific receptor is coupled into a single complex with 5
transmembrane proteins: gamma, delta, epsilon, zeta, eta, which today are referred to as single
molecule differentiated CD 3. Another group of T - lymphocytes have receptors consisting of
gamma - and delta chains.
Thus, T - cell antigen-specific receptor (TCR) - a set that consists of:
- Alpha, beta chains
- Gamma delta chain
- Molecules CD 3 which contains 5 transmembrane proteins
Today (knowing the structure of TCR), T - lymphocytes can be divided into:
• T - alpha - beta (helper, cytotoxic and suppressor / regulatory)
• T - gamma - delta (intraepithelial)
Upon recognizing an antigen to implement a complete immune response of T - lymphocyte
proliferation is subject to (fission), whereby a single T - lymphocyte clone formed (group) cells
which share the same specificity as their ancestor.
Function of T - lymphocytes:
• ensuring the development of cellular immunity
• participate in the regulation of cellular and humoral immunity through the helper and
suppressor subpopulations synthesized and their cytokines
• provide antiviral, antitumor, transplantation immunity
T - lymphocytes present such CD - antigens: CD2, CD3, CD4, CD5, CD7, etc. .
T - lymphocytes are divided into subpopulations: T - helper cells, T - cytotoxic, Tregulyatorni/supresorni, T - lymphocytes memory.
T - lymphocytes - helper cells (CD 3 + / 4 +)
Functions T - helper:
- Stimulate the transformation of B cells into plasma cells
- Stimulate the formation of T - cytotoxic lymphocytes
- Stimulate macrophages
- Contribute to the formation of delayed-type hypersensitivity
Depending on the cytokine production by T - helper cells are divided into T - helper 1 - order
and T - helper 2 - Gogo order.
The balance between T - 1 and T helper - helper 2 supports IL -12 and IFN - gamma.
T - lymphocytes regulatory / suppressor (CD 3 + / 4 + / 25 +)
T-regulyatornih/supresornih function of lymphocytes:
1. Inhibition of the autoreactive T - lymphocytes
2. Tolerance to antigens that enter through the gastro - intestinal tract (so-called "food
tolerance")
3. Tolerance to the "modified" antigens
4. Tolerance to allogeneic grafts (e.g., pregnancy)
5. "Infectious" tolerance (tolerance transferred from one person to another)
These functions are performed:
- T - lymphocytes - helper 2 - Gogo order that synthesize IL-4 (inhibit antibody and cell mediated
immunity)
- T - lymphocytes - helper third order, which synthesize TGF - beta
- Т-лімфоцити-регуляторні/супресорні 1 - order that synthesize TGF - beta, and IL-10
- T - lymphocytes, CD4 + CD25 + CD62L + - their activity is not dependent on cytokines
synthesized
- T - lymphocytes CD8 + CD28 - Participating in the development of transplantation tolerance
T - cytotoxic lymphocytes (CD 3 + / 8 +)
Functions T - cytotoxic lymphocytes:
1. Kill cells presenting to foreign (allogeneic) MHC molecules (class 1)
2. Destroy antigens in conjunction with its own (avtoantigennimy) MHC molecules (class 1)
3. Destroy autologous cells infected with viruses and other microorganisms
4. Tumoricidal
Mechanisms of destruction (apoptosis induction) T - cytotoxic lymphocytes:
* Depending on the selection of perforin, granzyme B and granulizinu
* Dependent on the interaction of molecules in the TNF cytotoxic cell membranes and TNF receptors in the cell membranes - target (APO-1L/CD95L).
The phenotype of T - lymphocytes - cytotoxic divided into:
- T - lymphocytes alpha - beta (CD8 +)
- T - lymphocytes gamma - delta
- NKT lymphocytes
On the ability to synthesize cytokines T - cytotoxic lymphocytes are divided into:
- T - 1 cytotoxic - order (synthesized IL -4, 5, do not synthesize IFN - gamma)
- T - cytotoxic 2 - order (not synthesize cytokines).
T - memory lymphocytes (CD 4 + / 40 +)
Products T - lymphocyte memory (Tm) is induced by the primary immune response.
Features:
1. Recognize a specific antigen
2. Participate in anamnestic (secondary) immune response
Phenotypically related to CD4 + / 40 +, and as T - helpers are subject restriction MHC molecules
of class 2.
Life expectancy - 40 years, but effective memory contains 10-15 years
it can be extended further by immunizing antigen.
B-lymphocytes
The functions of B lymphocytes:
- Differentiation into plasma cells and antibody production
- Presentation of antigens
- Antibacterial Protection
- Antitoxic protection
After the birth of human B lymphocytes formed from the stem cells in the bone marrow under
the influence of bone marrow microenvironment. Maturation of B lymphocytes occurs in two
phases:
- Antigennezavisimaya (occurs in the bone marrow and ends with the formation of mature Blymphocytes);
- Of an antigen (antigen binding after the B lymphocytes are activated, start to proliferate and
form a clone of specific plasma cells);
A characteristic feature - the presence on the surface of B cell antigen receptor. He is
monomeric Ig M, has a heavy and light chains are interconnected by disulfide bonds. Light and
heavy chains form part of the antigen binding fragments (Fab), which occurs through
recognition and binding of antigen. Unlike antigenrozpiznayuchogo T cell receptor, B cell
receptor does not require the conversion of the antigen into peptides, and can recognize the
whole antigen. Part of the heavy chain Fc fragment forms a B-cell receptor which has a side
which protein molecules: Ig - alpha and Ig - beta. They perform the same function as the CD 3
structure in T - cell receptor antigenrozpiznayuchogo. By clusters of differentiation of Blymphocytes differentiate CD 19, CD 20, CD 21, CD 22, CD 23, CD 24, etc. . They can be divided
into groups depending on their synthesized antibodies - B1 and B2.
B1 - is synthesized mainly antibodies of class M with broad specificity for different antigens and
natural antibodies (no antigen challenge).
B2 - dominate in adults receive signals of antigen-specific differentiation and proliferation,
synthesis of various classes of immunoglobulins of high specificity prevail in the secondary
immune response.
5.1.6. Immunoglobulins, their types and functions
Withcontent
in serum
Ig M - 10%
()-2 ,4, 2 g / l
Ig G - 75%
(7-18 g / l) 4
isotype
(IgG1, IgG2,
IgG3, IgG4 )
Ig A - 15%
F Functions
Pe ntamer. Malospetsifichesky participates in the primary immune response. Does not
penetrate the vascular wall and the placenta. Activates complement by the classical
pathway. This class includes: bacteriolysin, cytolysins, Rh factor, rheumatoid factor,
izogemaglyutinininov antibodies against gram-negative bacteria, Shigella
Mo Room, participates in the secondary immune response, activates complement by
the classical pathway, is part of the immune complexes. This class includes: anti-virus,
neurotoxins, tetanus, Gram-positive bacteria, Plasmodium falciparum
Time emya Ne halfmaturation life of
To 1 g ode 4-5 d it
to life
Up to 4
21-23
years of life d nya
Sy vorotochny - monomer secretory - polymer (dimer). Whey activates complement by To 13 godes 5-6 d it
the alternative pathway and forms secretory Ig A. Serum antibodies against the peculiar life
(0,7-5 g / l)
and 2 isotype
A1 Ig, Ig A2
Ig E
(0.02-0.04 g /
L)
Ig D
(0,0000010,0003 g / l)
form of viruses and bacteria, izogemaglyutinininov. Secretory Ig NOT activates
complement, not cross the placenta
But rmalnye antibodies hearth alteration, activate macrophages, mast cells and
Up to 15
eosinophils, and enhance phagocytosis activity of neutrophils provide an anthelmintic years
and antiparasitic protection. Do not activate the complement system does not cross the
placenta.
Fu unctions is not fully known, has antiviral activity level increases during pregnancy and tumors. Found in the tissues of the tonsils and adenoids. Do not activate the
complement system, a marker of mature B lymphocytes.
Immunoglobulins in the body perform and function of antibodies synthesized by plasma cells,
which are the final stage of B-cell differentiation result of antigenic stimulus and the helper
signal.
Immunoglobulins are proteins and polyfunctional implement basic functions:
- Specifically recognize different antigens and haptens;
- Interact with other immunocompetent cells, which are relevant to them receptors
- Activates the complement system
The monomeric unit of an immunoglobulin consists of two identical heavy (H) and two identical
light (L) chains which are held together by covalent and non-covalent bonds. Light chains are of
two types: lambda () and kappa (), and heavy -5 types: alpha (), mu (), gamma (), delta (),
epsilon (). Heavy chains determine the class of immunoglobulins (A, M, G, D, E).
An immunoglobulin molecule consists of two types of fragments: Fab - antigen and Fc crystallizing.
Antibody specificity is determined by the primary sequence of amino acids in the variable
region of the Fab - fragment, which provides a link to an antigen and is considered the active
site of an immunoglobulin molecule.
Ability of immunoglobulins contact with antigens provided such their properties avidity and
affinity.
Avidity - is the total force, which are interconnected complex antigenic molecules from the
whole population of antibodies, which are produced at all epitopes (antigenic determinants),
available on the antigenic molecule
Afinitet - is the degree of conformity, which determines the strength of coupling between the
epitope and the antibody binding site, or sites of an antibody molecule, which has worked to
this epitope (antigenic determinant)
In addition to these functions of immunoglobulins related to their biochemical structure and
the ability to bind antigen, antibodies isolated groups on functional characteristics of
participation in a variety of immunological processes: agglutinins, precipitins, opsonins,
hemolysin.
T-dependent and T - independent production of antibodies
T-dependent antibody production - ripening clone of B-lymphocytes need:
- Binding of antigen recognizing B cell receptor;
2-3
d nya
3 d nya
- Absorption protsesinguvannya antigen and feeding it to the cell surface as a peptide molecule
in combination with MHC class II;
- Recognition of peptide T - cell receptor antigenrozpiznayuchim CD4 + Th;
- Products T - lymphocytosis - helpers interleukins 2,4,5 that affect B-lymphocyte;
- Kostimulyatsiynih binding molecule CD40L (T-lymphocytes) and CD40 (B-lymphocytes);
- Synthesis of B-lymphocytes, Ig M, switching synthesis on Ig M and Ig G Ig A. Further
T - independent antibody production (independent of T-lymphocytes - helper). This is - a quick
way to increase the amount of natural antigen-AO class IgM. Features:
- Induces due to the simultaneous binding of a large number of B-cell
antigenrozpiznayuchih receptors identical antigenic determinants of agent
- No need for activation of B - lymphocytes that antigen uptake and processing;
- Do not create immunological memory.
There are two variants of the immune response due to antibody production:
• primary immune response
- Biosynthesis of antibodies does not begin immediately after exposure to the antigen, and
after a latent period (3-5 days)
- Speed of antibody synthesis is relatively small
- Synthesized antibody titers do not reach maximum values
- First class antibodies are synthesized Ig M, and later - Ig G
- Later come (and not always) antibody Ig classes A and IgE
• secondary immune response
- The latency period is very short, within a few hours
- Curve, which characterizes the rate of accumulation of antibodies is significantly steeper
up than the primary immune response, and has a logarithmic
- Antibody titers reach their maximum values
- Are synthesized immediately class antibodies Ig G
One of the most important biological functions of immunoglobulins is antigen binding and
formation of immune complex (IC) . IR education - one of the components of the normal
immune response, permanently flowing in the human body and aims to support its internal
stability and biological activity seredovischa.Formuvannya IR depend primarily on the nature of
the antibody, antigen, and the relations between them. Primarily Matter:
- Properties of antibodies (class, affinity, valence, the ability to bind complement, the rate of
synthesis);
- Properties of antigen (size, valence, charge, solubility, density and spatial arrangement of
epitopes - antigenic determinants);
- The presence of immune complexes of complement components (C3, C4, C1q).
Immune complexes are transported in the bloodstream erythrocytes in normal phagocytized by
macrophages and monocytes, deposited in the liver, kidney, lung, and spleen.
Giperimunokompleksemii formed when:
• increased rate of formation of immune complexes
• the reduced ability of the immune system to eliminate
• deficiency of complement components
• defect of phagocytosis
Moderate amounts of immune complexes stimulates an immune response, an excessive
amount - suppresses immune response contributes to the formation of immune inflammation,
increases vascular permeability, activates blood clotting, can trigger the development of DIC.
5.1.5 Regulation of human immune response.
Carried out with the help of many factors. Known: genetic, cytokine,
hormonal, idiotype - anti-idiotypic regulation of immune response types.
Genetic regulation of the immune response
The essence of genetic regulation:
- Transplantation antigens dictate intercellular cooperation and ensure the implementation of
the immune response
- HLA - defines the region as a whole immune reactivity and susceptibility to several diseases
Genetic regulation of the immune response is one of the most important. This type of
regulation is carried molecules major histocompatibility complex (MHC) in the literature often
used the English abbreviation MHC (Major histocompability Complex) . This is - a complex of
genes on the short arm of 6 - chromosome that encodes the protein molecules, some of which
takes part in the presentation of antigens in the immune recognition. Proteins that are encoded
by genes of MHC play a crucial role in the immune response. First, they are markers of "his"
(self) to the immune system via their immune system distinguishes between "their" (self) from
its NOR (non - self). There are three class histocompatibility molecules. First class MHC
molecules are present on all nucleated cells in the body and encoded human predominantly
"classical" loci A, B, C, known as "non-classical" loci E, F, G. The first class of histocompatibility
antigens is involved in antigen presentation of T - lymphocytes cytotoxic (CD8 + cells).Class II
MHC molecules expressed on the cells antigenprezentuyuchih - macrophages, B-lymphocytes
and dendritic cells and is encoded in the human loci DR, DP, DQ. The second class of
histocompatibility antigens is involved in antigen presentation to T - lymphocytes - helper (CD4
+ cells). First and second class major histocompatibility complex combined common name - HLA
- Complex (Human Leukocyte Antigens). The third class of major histocompatibility complex
molecules involved in the determination of the synthesis components C2 and C4 complement
factor B, TNF - alpha microglobulin, cytochrome P450 enzyme, heat shock protein HSP70.
Cytokine regulation of the immune response.
Cytokines in the immune response may exhibit:
- Autocrine action zvyazuyuchis receptors on the membranes of the same cells
tsitokinprodukuyuchih
- Paracrine action by connecting with receptors on target cells, which are located directly
outside the cell tsitokinprodukuyuchih
- Endocrine action, entering into circulation and zvyazuyuchis remote cells
Hormonal regulation of the immune response.
Ak activation of the
immune response
Yr Neten immune
response
With matotropny hormone, vasopressin, oxytocin, melatonin, thymosin, thyroxine, insulin,
aldosterone, prolactin
AK TG альфамеланоцитостимулюючий hormone, corticosteroids, catecholamines,
progestins, androgens
Idiotype - anti-idiotypic regulation of the immune response.
Idiotype - this portion of the amino acid sequences within the variable region of the antibodies
or T - cell receptor recognition which is specific to them and capable of causing production of
anti-idiotypic antibodies.
Idiotype - antiidiopatichna grid - a regulatory interaction that is based on the fact that
antiidiopatichni and antibody idiotypes located on immunoglobulin and T - cell recognition
receptors interact to regulate the "severity" of the immune response.
5.1.6 Stages of the immune response.
Distinguish the following stages of the immune response:
• antigenic stimulation
• processing and antigen presentation
• differentsiirovanie antigen-specific T - lymphocytes
• Education subpopulations of T - lymphocytes, cytokine production
• transfer of antigen B-lymphocytes
• antigen-specific proliferation and differentiation of B-lymphocytes
• generation of plasma cells and synthesis of immunoglobulins
• primary and secondary immune response
• the formation of immune complexes
formation of immunological memory to the antigen
5.1.7 Age-related features of the immune response
The children in the first year of life the immune response induced by predominantly Th2 type,
that is, there is a physiological predisposition to allergies immediate, with 2 - year of life and
further immune response mediated by Th1; dominated by nonspecific humoral factors of
innate immunity (lysozyme, properdin t . etc.) reduced quantitative and functional
characteristics of the acquired cellular and humoral immunity, immune response AG is mainly
primary character; formation of acquired cellular immunity to ends 4 - years, humoral - up to
10-14 years. Isolated critical periods of development of the immune system in children.
In adults, there is a sharp decline in birth nonspecific resistance factors; acquired cellular
immunity (due to thymic involution), increased amounts of immunoglobulins, there are signs of
auto-aggression.
V. Plan and organizational structure of classes
Wasps main stages classes,
ur ovni
functions and content
assimilation
1
1. n odgotovitelny stage
business classes
learning objectives
Control the input level of
knowledge, skills:
Organs of the immune systemAntigens
Innate immunity-Acquired immunity
2. on stage he primary
2
Formation of professional
2
knowledge and skills:
3
-Describe the structure and
3
function of the immune system
3
links
-Form properties of the immune
system
-Analyze the functions of all
groups factors of innate immunity
-Evaluate the function of cellular
and humoral factors of adaptive
immunity
-Describe the structure and
properties of immune complexes
-Draw scheme hormone, cytokine
regulation of immune response
Reproduce the essence of geneticand-idiotype immune response
regulation antiidiotipichnoi
3
3. s FINAL stage
Monitoring and correction of
professional knowledge and skills
Me ods monitoring and
training
fr ontalny poll
Rapid survey
test control
(Input)
Ma forced ones
Time
methodological support min.
25
those sty
scheme
Ying vidual survey
(checklists)
Professional training in
solving typical problems
("Step 2")
210
that blitz
scheme
Maps immunological
surveillance
Typical case studies
Histological and
cytological preparations
immunograms
Those stirovanie
(baseline)
individual survey
cx emy
Tests
Unusual case studies
35
Species, immune response,
Decision atypical case
production of antibodies caused
studies
by
Stages of formation of immune
response
By dvedenie outcome studies.
Homework for the next topic.
VII. Methodology of the educational process at the practical (seminary) lesson.
7.1. Preparatory stage.
Structure and function of the immune system, especially age, immune response: types, types of
regulation, types of immunity and its cellular and humoral factors, the major histocompatibility
complex antigens. Structure of immunopathology.
Familiarize students with specific objectives and lesson plans.
Hold acquaintance of students with clinical base on which the rate of clinical immunology and
allergy. Conduct initial control level of preparation of students using test items 1 - and 2 - level.
7.2. main stage
This phase involves the execution of each student independently under the supervision of a
teacher below
these practical works.
Problem 1
Students conduct survey and objective examination of the patient with immunological
disorders, using inspection, palpation, auscultation, percussion.
Task 2
Tasks number-Standards of answers
1. Call the central organs of the immune system?
(Bone marrow, thymus)
2. Acquired (adaptive) immunity realized thanks ...? (Synthesis of specific antibodies and the
formation of specific lymphocyte clone)
3. Where is the maturation of T - lymphocytes? (In the thymus)
4. Of these substances is the strongest antigen? (Proteins)
5. Where is the maturation of B - lymphocytes? (In the bone marrow)
6. Of these substances is the product of a specific immune response only? (Ig M)
7. Large granular lymphocytes is ...? (Natural Killer (NK) cells)
8. Which cells are the main depot of histamine, heparin, serotonin? (Basophils)
9. To opsonines are ...?
(Fibrinogen, complement component C3, acute phase proteins, fibronectin)
10. Biological functions of natural killer cells:
(Control of cell proliferation and differentiation, cytotoxic reactions, cytokine production,
production of enzymes)
11. Acute phase responses - it ...?
(Very rapid growth in the synthesis of many proteins, especially the acute phase)
12. The complement system defect is detected in patients with ...? :
(Tendency to constantly recurrent bacterial infections)
13. Complement activation products can ...? (Stimulate neutrophil chemotaxis)
14. What cells synthesize antibodies? (Plasma cells)
15. Which cells are a secondary source of biologically active substances in the development of
reaginic type reaction? (Eosinophils)
Problem 3
Solve the test tasks:
1. What diseases are included within the scope of immunopathology?
Answer - allergic, autoimmune, lymphoproliferative, infectious.
2. Identify the main reasons for the growth of immune diseases and conditions?
Answer - environmental pollution, polypharmacy, endocrinopathy distress.
3. Give the definition of the subject "Clinical Immunology"
Answer - a clinical medical specialty which studies the factors of immunity and immune
homeostasis in normal conditions, etiology, pathogenesis and clinical manifestations of immune
diseases and conditions and their treatment, prevention and immunorehabilitation.
4. What are the functions of the immune system, you know?
answer:
- Immune surveillance
- Tsitokrinna
- Secretory
- Cytotoxic
7.3. The final stage.
Evaluates the current activities of each student during class, an analysis of student
performance, declared evaluation of each student and exhibited in the register of visits and
student performance. Warden group simultaneously enters evaluation timesheet achievement
and attendance of students, teachers assures his signature.
Advisable to brief students on the subject of the next lesson and instructional techniques to
prepare for it.
VIII. apps
8.1. Theoretical issues of the preparatory phase:
1. Interpret the concept of "immunity", types of immunity.
2. List the factors of innate and acquired immunity.
3. Stages of the immune response.
4. Types of immune response regulation.
5. Features of the immune status in children and the elderly.
6. Antigens main complex gistosumistnosti.
7. Immunoglobulins, their types and functions.
8. Cell types of innate and acquired immunity, and their functions.
9. Structure of immunopathology.
8.2 Formulate a clinical diagnosis
Tasks third level
Problem number 1.
Patient P., aged 42, complains of increasing the temperature to 38 ° C, dry cough with difficult
sputum, chest pain when coughing, runny nose, weakness. Sick about 3 - days ago after
hypothermia. OBJECTIVE: nasal breathing difficult. In light percussion dullness in the lower
parts of both lungs. Auscultation of the lungs breathing hard, in the lower divisions crepitus. Rhythmic activity of the heart, heart rate -88 beats / min, AT-125/85
mmHg Radiographically: WGC - bilateral lower lobe pneumonia. Changes in humoral immunity
in a patient?
Answer: Reduced IgG, a significant rise IgM, IgA normal level
Problem number two.
Patient H, 47 years old, diagnosed with nephrotic syndrome. Which will be observed in a
patient changes of humoral immunity?
Answer: Reduced IgG, IgA; normal and increased concentration of IgM
Problem number 3.
Female 35 years delivered to the surgical ward in a serious condition with complaints of severe
diffuse pain throughout the abdomen, nausea, vomiting. Deterioration occurred 2 days before
admission, when the skin of limbs appeared punctulate hemorrhagic rash, having cramping
abdominal pain, bleeding from the rectum.
2 weeks before that suffered an acute viral infection. OBJECTIVE: BP 90/60 mm Hg. Art. , Heart
rate 95 per minute, abdomen palpation tense peritoneal signs. The study of blood observed
leukocytosis and eosinophilia, reduction of red blood cells and hemoglobin. What are the main
pathogenetic mechanisms of this disease?
A: Immune vascular lesions
Problem number 4.
Patient 53 years old, an accountant by profession, on the background of a satisfactory general
condition appeared painful rash in the mouth, and then - on the skin and body. Dermatologist
diagnosed mihurchatku vulgar. Examination revealed chronic gastritis. Mechanisms for the
development of dermatosis can be considered the most likely in this case?
Answer: Autoimmune
Problem number 5.
To allergist patient appealed M, 40 years old, complained of watery eyes when going out on the
street, shortness of breath, redness and itching of the skin. Diagnosed with hay fever. What are
the common features of atopic diseases:
A: Availability (products) IgE - reagin
Problem number 6.
Patient toxic goiter. Mercazolilum gets a dose of 50 mg per day. After 3 weeks of treatment
increased body temperature to 38.1 C, there was a pain in the throat, painful sores in the
mouth. Complete blood count: er. - 3,1 × 1012 / L Hb - 94 g / l, KP - 1.0; Lake. 1,0 × 109 / L ESR 28 mm / hour. What is the most likely cause of the deterioration of the patient?
Answer: The development of agranulocytosis.
XI. conclusions:
9.1. Mastered knowledge of the structure and function of the immune system.
9.2. The prevailing understanding of innate and acquired (adaptive) immunity.
9.3. Students' understanding of the prevailing initial basic kinds of regulation of the immune
system.
9.4. Acquired understanding of the stages of the immune response.
Tasks for independent work on this topic:
1 /. Compile a list of specific features of the development of age-central and peripheral organs
of the immune system
2 /. Develop a table (schema) of the main differences in the functioning of organs and cells of
the immune system, depending on age
3 /. Form the main features of the functioning of the immune system in old age
H. LIST educational literature
Summary :
1. Chopyak VV , GA Potemkin , Gavriliouk AM Lectures on Clinical Immunology for
practitioners. - Lviv. - 2010.
1. GN Drannik: Clinical Immunology and Allergology. - K. - 2009.
2. BM Pukhlik: Allergy to the family doctor. - Vinnitsa. - 2012.
3. BM Pukhlik Allergology. - Vinnitsa. - 2004.
4. Pytsky VI et al .. Allergic diseases. - Moscow, 2010
5. BM Pukhlik: Elementary allergology. - Belgrade - 2002.
6. BM Pukhlik Allergology. - Belgrade - 2004.
7. M. Yakobisyak / Immunology. - Translated from the Polish edited
prof. VV Chopyak. - 2009.
8. Kazmirchuk VE Kovalchuk LV Clinical Immunology and Allergology. - M.: NEW BOOK. -2006.
9. Sokolov EI Clinical Immunology / M: Medicine. - 1998.
General:
1. G. Lawlor - Jr., T. Viter - Clinical Immunology and Allergology. - M. - 2000.
2. KA Lebedev, ID Ponyakina: immunogram in clinical practice. - M. - 2003.
3. DK Novikov, PD Novikov - Clinical immunology. - Vitebsk. - VSMU 2006.
4. BA Nikulin Evaluation and correction of immune status. - Moscow. -2007
5. BM Pukhlik: Practical Guide for immunodiagnosis and immunotherapy. - Vinnitsa. - 1992.
6. VI Pytsky, NV Hadrian. Allergic diseases. - Moscow, 2001.
7. LI Chernyshev, DV Samarin - Primary combined immunodeficiency in children K. - 2004.
8. Sidorenko EN Clinical Allergy. - Moscow - 2005.
9. Roy Patterson, Leslie K.Grezmer Paul. Allergic disease (diagnosis and treatment). - MA - 2000
10. Bazhora YI "Clinical Immunology" - Odessa, Odessa State Medical University. -2000.
11. Beloserov ES Immune system disease Elista: APP "Djangar", 2005.
12. Fundamentals of Clinical Immunology (textbook for medical schools) lane. from
English. E.. Csepel, M. Heine, C. Misbah, N. Snovden, M: GEOTAR Media, 2008.
13. Dig A. immunology / M: peace. -2000.
14. Rabson A. Fundamentals of Medical Immunology: lane. and English. M: World - 2006.
15. RM Khaitov "Immunology" textbook for medical schools - Izd. GEOTAR Media. - 2009. - + CD
ROM
Scientific benefits:
1. Yarilin A.A.Osnovy Immunology: Textbook. -M. : Medical. , 1999.
2. Clinical Immunology. Under. Ed. G. Lawlor - Jr., T. Fisher and David Adelman. Lane. from
English. - M., Practice, 2000.
3. Imunodifitsitnye state / red. - V.S.Smirnov and IS Freidlin - SP B "Tome", 2000.
4. Dig A. Brostrof J. Mayle, D. Immunologiya.Per. from English. - M.Mir 2002.
5. West S.dzh.Sekrety Per rheumatology. with Engl. - M.SPb. : Publisher Bion ", 1999.
6. Periodic magazines "Immunology and Allergy," "Immunology", "Clinical Immunology",
"Rheumatology", "Neurology" "Gastroenterology", "Pulmonary", "Medicine of Ukraine",
"Doctor", "The Art of treatment" in 2000 - of 2003.
methodical :
Mileryan VE Methodical bases of preparation and training sessions
in medical schools (handbook). - K. "Khreschatyk", 2004. -80 S.
Allowances for training:
1. Set presentation sessions for multimedia use.
2. Test control Croc 2 (computer-based) and a collection of case studies for the assimilation of
knowledge.
3. Metodrazrabotki for practical training.
4. Set of tables, slides
Guidelines prepared OB Bondarchuk
Guidelines revised and approved by the faculty meeting
"29" 08 "in the 2013 Protocol number 1
Head of the Department BM Pukhlik
MD professor