Crimea State Medical University Named After

MINISTRY OF HEALTH OF UKRAINE

STATE INSTITUTION

“CRIMEA STATE MEDICAL UNIVERSITY NAMED AFTER

S. I. GEORGIEVSKY“

Department of internal medicine #2

Manual

V.O. Biloglazov, Yu.A. Bisyuk, L.K. Znamenska

PRACTICE OF CLINICAL IMMUNOLOGY AND ALLERGOLOGY

For students of higher medical schools of III-IV accreditation levels.

7.110101 «Medicine»,7.110104 «Pediatrics»

Simferopol

2013

UDK 612.017.1

BBK 54.1

This manual is recommended by Central methodology commission of SI “Crimea state medical university named after S. I. Georgievsky “ of Ministry of Health of Ukraine as a textbook for clinical immunology and allergology course for 5th year students of high medical schools of III-IV accreditation levels in 7.110101 «Medicine» and 7.110104 «Pediatrics» specialties (protocol #6 from 18.09.2013)

Reviewers:

Ushakov O.V. – Dr. Med. Sc., prof., head of department of internal medicine #1 of SI “Crimea state medical university named after S. I. Georgievsky “

Khrenov O.A– Dr. Med. Sc., prof., head of department of internal medicine #3 of SI “Crimea state medical university named after S. I. Georgievsky “

Authors:Dr. Med. Sc., Prof. V.O. Biloglazov, PhD, Associate Prof. Yu.A. Bisyuk, PhD, Associate Prof. L.K. Znamenska

Manual “Practice of clinical immunology and allergology” is made according to study program “Basic of clinical immunology and allergology” of 2013th year for students studying ECTS system. In the manual material for practical classes and self-preparation is given.

Contemporary methods used in immunology, allergology and other fields of medicine are given in this manual. Complex approach for immune tests and spirometry evaluation is made clear as well as basic principles and stages of methods, that can be preformed during practical classes.

CONTENT

THEMe PLAN OF PRACTICAL CLASSES...... 4

THEMe PLAN of self-prepared work...... 6

THEME PLAN OF LECTURES...... 8

QUESTIONS LIST FOR FINAL MODULE CONTROL...... 8

LIST OF PRACTICAL SKILLS FOR FINAL MODULE CONTROL...... 10

FORMS OF CONTROL AND DISCIPLINE ESTIMATION...... 11

topic 1. The structure and principles of the immune system.

Developmental Immunology.Immunological research

methods.The concept of imunogram........ 12

topic 2. Immune inflammation and infectious diseases.

HIV infection: immunopathogenesis, immune-diagnostics,

immunotherapy.Main principles of designation immunotropic

therapy. Immunorehabilitation, immunoprophylaxis...... 31

Topic 3. Congenital immunodeficiency diseases. Acquired

immunodeficiency disease....... 35

topic 4. Fundamentals of transplantation immunity.

Immunology of tumors ........ 45

topic 5. Atopic diseases........ 49

topic 6. Bronchial asthma........ 62

topic 7. Other allergic (non atopic) disease: types,

immunopathogenesis, immune-diagnostics, immunotherapy.

Differential diagnosis pseudo allergy and allergy...... 76

topic 8. Immune aspects of autoimmune diseases...... 80

RECOMMENDED BOOKS FOR CLINICAL IMMUNOLOGY AND

ALLERGOLOGY....... 85

THEME PLAN OF PRACTICAL CLASSES

In “BASICS OF CLINICAL IMMUNOLOGY AND ALLERGOLOGY”

For students of medical faculties of 5th year with specialty

7.110101 «Medicine»,7.110104 «Pediatrics»

# / Topic / Hours
Content module 1:
IMMUNE STATUS, PRINCIPLES OF APPROACH, COURSES OF IMMUNE CORRECTION
1 / The structure and principles of the immune system. Developmental Immunology.Immunological research methods. The concept of immunogram. / 5
2 / Immune inflammation and infectious diseases. HIV infection: immunopathogenesis, immune-diagnostics, immunotherapy.Main principles of designation immunotropic therapy. Immunorehabilitation, immunoprophylaxis. / 5
Content module 2:
IMMUNODEFICIENCY DISEASES AND IMMUNODEPENDENT PATHOLOGY
3 / Congenital immunodeficiency diseases. Acquired immunodeficiency disease / 5
4 / Fundamentals of transplantation immunity.Immunology of tumors . / 5
Content module 3
ALLERGIC DISEASES
5 / Atopic diseases. / 5
6 / Bronchial asthma. / 5
7 / Other allergic (non atopic) disease: types, immunopathogenesis, immune-diagnostics, immunotherapy. Differential diagnosis pseudo allergy and allergy / 5
8 / Immune aspects of autoimmune diseases
Final module control / 5
Total / 40

Theme plan of practical classes

TOPIC 1. The structure and principles of the immune system. Developmental Immunology. Immunological research methods. The concept of immunogram .Definition and types of immunity. Primary and secondary organs of the immune system. Factors innate immunity: cellular ( monocyte- macrophage system, and granulocyte killer cells), humoral (complement system , cytokines , etc.). .Antigens and their characteristics. The specific immune system, its features, stages of formation and cooperation of immune cells involved in the formation of the immune response.Populations (T- and B- lymphocytes ) and subsets (T- helper 1 and 2, regulatory T , T- CTL ) lymphocytes stages of maturation and differentiation of function.Immunoglobulin structure function. Thymus-dependent and Thymus-independent mechanism of antibody synthesis .Structure and properties of circulating immune complexes.Major histocompatibility complex : structure , properties and function. Regulation of immunity.Features immunological history. Clinical methods for evaluating the immune system. Instrumental methods for evaluating the immune system. Laboratory methods for evaluating the immune system. Humoral innate protective factors . Assessment of cellular immunity. Comprehensive assessment of local immunity.An integrated approach to assess the immune status of the person. The main complaints of patients with immune disorders. Features immunological diagnosis. Determination of the main symptoms and syndromes of immune disorders. Physical symptoms of immune pathology. Methods of physical examination of patients with disorders of the immune system (ultrasound, radiology , immunohistochemistry, etc.). Immunogram, the interpretation of results. Possibilities and limitations of immunological methods. Features performances of immunological diagnosis.Age features of bone marrow, thymus and peripheral lymphoid organs. Age features of immune cells functioning. Age features of inflammatory reactions.The role of maternal immunity in shaping a child. The immune system of the fetus, the newborn child in different age periods.Thymus and aging. Immune regulatory processes in old age. Immune theory of aging. Immunopathology in elderly age.Approaches to the immunotropic treatment based on age .

TOPIC 2. Immune inflammation and infectious diseases. HIV infection: immunopathogenesis, immune-diagnostics , immunotherapy. Main principles of designation immunotropic therapy. Immunorehabilitation, immunoprophylaxis.Mechanisms of host defense in bacterial and viral infections. The role of the immune system in antifungal immunity and protection against helminthes. The value of the immune system in the development and opportunistic protozoan infections. Immunological methods in the diagnosis of infectious diseases.The immune response during acute inflammation . Dynamics of leykogram, proteinogram and immunogram of acute, chronic and relapsing inflammation.Types and characteristics of specific immunoprophylaxis of infectious diseases. Immunodependent reactions and complications of vaccination. Etiology, immunopathogenesis, diagnosis and immune therapy. Immunological methods in the diagnosis of AIDS. Dynamics ofimmunogram of HIV -infected and AIDS patients. Immunization of HIV.Classification of immunotropic drugs, their mechanism of action . The principles of clinical application of immunotropic drugs , indications and contraindications for the purpose,dose determination and immunological monitoring of therapeutic effectiveness : immunosuppresive preparations; immune correcting preparations; blockers of mediators of immune responses ; antiphlogogenic means; replacement therapy ; cytokine therapy, anti receptor drugs and others.Basic principles of immunization against bacterial and viral infections.The main types immunorehabilitation, its strategy, tactics and the basic principles.

TOPIC 3 Congenital immunodeficiency diseases. Acquired immunodeficiency disease.Congenital immunodeficiency disease: definition, classification, mechanisms of development. Clinical signs , immune-diagnostics , medical tactic , treatment approaches: combined , T - i B - dependent immunodeficiencies caused by disturbance immunity and phagocytic deficiency of complement proteins. Acquired immunodeficiency disease: definition, causes, mechanisms of development, classification, immune diagnostic . Role of immunodeficiency acquired diseases in the pathogenesis of various diseases. Early detection of the body secondary immunological failure. Basic approaches to treatment.Rapid fatigue syndrome , chronic fatigue syndrome.

TOPIC 4 Essentials transplantation immunity.Immunology of tumors.Concepts, terminology (auto -, - alo , xeno - transplant)pretransplantation monitoring. Mechanisms of allograft rejection: fulminant, acute and chronic. Postransplantation infectious complications , diagnostic criteria. Imunosuppresive therapy: mechanisms of action. New immunological methods of diagnosis and therapy in transplantation.Antyblastic and problasic mechanisms of the immune system of the body "host " and " tumor ". Factors of immunological resistance of the tumor. The concept of tumor-associated antigens. Immunosuppressive effects of tumors. Immune changes in cancer patients. Immunodiagnosis, including differential one according to the CD- phenotype of tumor cells. Current approaches to the immunotherapy of patients with cancer.

TOPIC 5.Atopic disease.The role of genetic factors and the environment in the immunopathogenesis of allergy. Modern ideas about the allergy and atopy. Atopy as a systemic disease.Types and main stage immunological reaction. Aspects of Allergic diagnosis. Screening methods in assessing allergies. Elimination and provocation tests in allergy. Types of skin tests .Principles of treatment of allergic diseases. Specific immunotherapy, indications and contraindications.Features immunopathogenesis, hives and others. Drug allergies: Causes, immunopathogenesis, clinical, and prevention.

TOPIC 6. Asthma: etiology, immunopathogenesis, modern classification, symptoms, diagnosis , treatment. Atopic form of asthma: symptoms, diagnosis, treatment.

TOPIC 7 Other allergic (non atopic) disease.Not atopic disease : types, immunopathogenesis, immunodiagnosis , clinical manifestations and differential diagnosis, clinical features and differential diagnosis.Cell- mediated allergic disease ( serum sickness, Arthus phenomenon , allergic alveolitis , etc.): immunopathogenesis , clinical, immune-diagnostics, immunotherapy .Differential diagnosis of diseases caused by allergic processes and pseudo-allergy reactions. Principles anti allergic therapy and immunotropic therapies in allergy.

TOPIC 8. Immune aspects of autoimmune diseases.The final module control. Definition of autoimmune reactions, autoimmune disease. Mechanisms of failure of immunological tolerance , the role of genetic factors. Immunodiagnosis, immunopathogenesis. The role of immunological methods in the early diagnosis and verification of autoimmune diseases. Autoimmune component in immune pathogenesis of various human diseases. Current approaches to application immunotropic new generation drugs in the treatment of patients with autoimmune diseases.

Theme plan of self-prepared work On “basics of clinical immunology and allergology”

For students of medical faculties of 5th year with specialty

7.110101 «Medicine»,7.110104 «Pediatrics»

# / Topic / Hours
Content module 1:
IMMUNE STATUS, PRINCIPLES OF APPROACH, COURSES OF IMMUNE CORRECTION
1. / Preparation for practice , including:
- Mastering the skills to analyze data immunological methods :
1. Orienting tests (I level ) ( quantitative cellular and humoral factors of innate and specific immunity , evaluation indexes phagocytosis et al.).
2. Analytical tests (II level) (estimate proliferative activity of T- and B -lymphocytes, natural killer activity assessment, determine the levels of various components of complement , etc.).
- Mastering the skills of interpretation of these physical examination of patients with disorders of the immune system (ultrasound, radiology , immunohistochemistry, etc.). / 5
2. / Inspection the patient with writing case history / 2
3 / Individual students' work:
1. Report an essay on the practice in extracurricular topics:

Immuno-neuro-endocrine regulation of body functions.
Apoptosis as the regulation of the immune response.
Immunology of mucous.

2. Writing abstracts of articles / 3
Total content module 1 / 10
Content module 2:
IMMUNODEFICIENCY DISEASES AND IMMUNODEPENDENT PATHOLOGY
1 / Preparation for practice , including:
- Master the screening clinic - medical history criteria to identify dysfunctions of the immune system:
1. Clinical symptoms ;
2. Family history ;
3. Antenatal history ;
4. Anamnesis of life and disease;
5. Immunological laboratory data.
mastering clinical - laboratory criteria for identification of congenital and acquired immunodeficiency states ;
mastering determine the severity of congenital and acquired immunodeficiency states ;
mastering the definition of clinical syndromes dysfunction of the immune system : infectious , allergic , autoimmune , immunoproliferative ;
mastering the principles of treatment of immunodeficiency diseases.
master the skills of interpretation of these phenotyping for selection of pair donor – recipient
master phenotyping data interpretation skills to address the availability of infertility in marriage;
- Master the skills of evaluation results and determination of tumor associated antigens onkofetalnyh in the diagnosis of tumors. / 2
2. / Inspection the patient with writing case history / 1
3 / Individual students' work:
1. Report an essay on the practice in extracurricular topics:
- Immunopathogenesis and immunotherapy of sepsis;
- Epstein - Barr virus infection: immunopathogenesis, immunotherapy
2. Writing abstracts of articles / 1
Total content module2 / 4
Content module 3
ALLERGIC DISEASES
1. / Preparation for practice, including:
- Mastering the skills to analyze data of allergy research methods;
- Mastering skills for prick test;
- Mastering the skills of care in patients with acute allergic reaction
- Mastering the evaluation of indicators of lung function in patients with bronchial asthma
- Mastering the skills of evaluation allergy therapy. / 3
2. / Inspection the patient with writing case history / 3
3. / Individual students' work:
1. Report an essay on the practice in extracurricular topics:
- Specific immunotherapy: Principles destination. Indications and contraindications, complications develop.
- Drug allergy.
2. Writing abstracts of articles / 5
Total content module3 / 11
Total module / 25

THEME PLAN OF LECTURES “BASICS OF CLINICAL IMMUNOLOGY AND ALLERGOLOY”

For students of medical faculties of 5th year with specialty

7.110101 «Medicine»,7.110104 «Pediatrics»

# / Topic / Hours
1 / Main tasks and problems of clinical immunology and allergy. The principles of the immune system, clinical and laboratory evaluation of disorders. / 2
2. / Diseases of the immune system. The principles of immune diagnosis, immunotherapy, and immunoprophylaxis and immunorehabilitation. / 2
3. / Fundamentals of transplantation immunity. / 2
4. / Antitumor immunity. Clinical and immunological aspects of autoimmune diseases. / 2
5. / Current views on atopic diseases as systemic disease. Allergic disease. Classification, clinical examples. / 2
Total / 10

QUESTIONS LIST FOR FINAL MODULE CONTROL

“Basics of clinical immunology”

The object and purpose of clinical immunology and allergy. History of immunology. The main directions of development.
The current understanding of the structure , function of the immune system.
Cellular innate protective factors and their interaction in the implementation of the immune response.
Monocyte - macrophage system: functions, features, role in the development and implementation of the immune response. Modern aspects of phagocytosis.
Killing effect as part of immunobiological supervision. The main types of killer cells , their function and properties. The role of granulocyte formation of blood cells in the immune response.
Humoral factors of innate immunity.
The complement system . Biological effects of activation of the complement system .
Antigens : structure, function. Hapten.
The stages of maturation and differentiation of T- and B- lymphocytes.
T- lymphocytes. Structure of the T cell receptor . Subpopulation of T lymphocytes. The main differentiation markers and clusters .
T - lymphocytes - helper 1 and type 2 . The value of the functional balance between T -helper (Th1 \ Th2).
Regulatory T cells , the main function.
Apoptosis as a special type of cell death. Its role in physiological and pathological processes.
B- lymphocytes. Key markers and functions. Structure of the receptor that recognizes the antigen. The concept of T- dependent and T -independent type of immune response.
Immunoglobulins: structure , functions and classes. The role of immune complexes in the development of pathology.
Cytokines - mediators of the immune system. Interleukins , classification, function and involvement in immune processes.
Growth factors , tumor necrosis factor, interferon , and adhesion molecules. Characteristics . Participation in the development of the immune response.
Mucosal immune system . Lymphoid tissue associated with the digestive tract.
The current understanding of the structure and function of major histocompatibility complex . The structure of the antigen HLA. Susceptibility to diseases based on HLA- phenotype.
Basic principles of classification of immunodeficiencies. Congenital immunodeficiencies combined immunodeficiency, and B- and T -cell links: mechanisms of development , clinical course, immune-diagnostics and treatment.
Congenital immunodeficiencies of phagocytic component of the immune system and complement: mechanisms of development , clinical course , immune-diagnostics and treatment.
The concept of acquired immunodeficiency . Causes , clinical features, immunodiagnosis and immunotherapy.
Prolonged fever syndrome : etiology , clinical, instrumental , laboratory and immunological criteria for diagnosis, differential diagnosis , the basic principles of immunotherapy and immunoprophylaxis .
Lymphadenopathy syndrome : etiology , pathogenesis , classification , research methods , immunological diagnostic criteria , differential diagnosis, the basic principles of immunotherapy and immunoprophylaxis .
Immunopathogenesis , stage of development , the classification of HIV - infection / AIDS.
Clinical and laboratory criteria for diagnosis, principles of treatment of AIDS .
Basic principles of prevention of AIDS in Ukraine . Health professionals as individuals "at risk" high risk of morbidity from AIDS .
Transplantation immunology. Immunological indications and contraindications for transplantation of organs and tissues. Selection of donor-recipient pairs . Pre-existing antilymphocytotoxic antibodies and their predictive value .
Features pre- and post transplantation immunological monitoring. Types of rejection crisis , their clinical and immunological characteristics and prognosis.
Antitumor factors, factors of immune resistance of tumor, problastic factors that suppress the immune system, as well as problastic factors that enhance tumor growth. The concept of tumor-associated antigens.
Immune changes in cancer patients. Immune-diagnostics in oncology. Current approaches to immunotherapy of patients with oncological diseases.
The reasons for the formation of Allergic disease. Stages of formation of an allergic reaction.
Allergy and atopy. Classification of allergens. Causes and mechanisms of allergic conditions .
Methods for diagnosing of allergies : laboratory methods , skin tests and provocative tests .
Principles of antiallergic therapy and immunotropic therapies in allergy. Specific immunotherapy , mechanisms of action , indications and contraindications , the forecast performance.
Hay fever, allergic rhinitis, allergic conjunctivitis : etiology, immunopathogenesis , clinical, allregic diagnosis, basic principles of immunotherapy.
Drug allergy. Immunopathogenesis, clinical, allergic diagnosis, treatment, allergoprophylaxis.
The concept of allergy and pseudo-allergy , differential diagnosis. Histamin liberating mechanisms of reactions. Treatment.
Development pseudo-allergy reactions in violation of activation of the complement system and metabolism of arachidonic acid. Treatment.
Definition of autoimmunity , autoimmune disease syndrome. Mechanisms of failure tolerance genetic preconditions for the development of autoimmune diseases.
Classification , general principles immunolaboratory diagnosis of autoimmune diseases. Current approaches to application immunotropic drugs.
Laboratory criteria for immunodiagnosis of autoimmune diseases.
Immune preparations Classification , mechanism of action , indirectly impact.
The principles of clinical application immune preparations , indications and contraindications.
Quantitative and functional immunological tests. Immunogram , key indicators .
Methods of quantitative and functional characteristics of T cells : rosette tests , tests using monoclonal antibodies RBTL of mitogen .
Methods of quantitative and functional characteristics of B- lymphocytes: rosette tests , tests using monoclonal antibodies RBTL with mitogen , level of CIC .
Methods for determining the phagocytic activity of lymphocytes.
Methods for determining the concentration of serum immunoglobulins main classes.

LIST OF PRACTICAL SKILLS FOR FINAL MODULE CONTROL