MINISTRY OF HEALTH OF UKRAINE
Vinnitsa National Medical University. MI Pirogov
"Approved"
Vice Rector for Academic Affairs
Professor Yu Guminsky
(Signature)
"_29_" _08__2013 G.
Methodical development
Self extracurricular
prepare for practical training for students of the 5th year of the Medical Faculty
Subject number 4
Academic discipline
Module number 1
Content module number 1
Subject lessons
To urs
F akultet
K The number of hours
"Clinical Immunology and Allergology"
"Clinical Immunology and Allergology"
Immune status, age
features. Immunodeficiency efitsity and other
immune diseases, principles of diagnostics,
immunotherapy, immunization and
immunorehabilitation.
Congenital and acquired immunodeficiencies
and secondary immune deficiency. Tions he
Transplatatsi immunity immunology of
reproduction, tumor immune aspects of
autoimmune disorders.
5th
"Medicine", "Pediatrics", "Medicalpreventive work"
4
1 March 20
I. Hot Topics: Despite significant advances fundamental honey Yiqing, including immunology,
development of new technologies of diagnosis and treatment on immunopathology rotyazhenii n
recent decades, distribution estrangement immunopathology (immunodeficiencies, allergic,
autoimmune lymphoproliferative (tumor) disease) increased.
Diagnosis of acquired immunodeficiency scale global medical and social
problems. According to the European Association of the prevalence of genetic
immunodeficiencies (primary) immunodeficiency composition it possible 1:250-500, severe
immune deficiencies - 1:10 000. Thus, Quantity Part of these patients in Europe should total 1
million 300 thousand patients, and in Ukraine - about 20 thousand, at a dispensary only about
1000, and 110 patients adulthood. Individuals with common variable immunodeficiency, which
manifests itself in adulthood, would have numbered about 2 million in Ukraine, and verified on a
total of 12 cases. According to Russian experts frequency of primary immunodeficiencies is
3:1000 births, yet the list of separate clinical entities and reaches hundreds of gene mutations per
1000 population. With the increasing incidence of tumors in Ukraine over the past 5 years by 25%,
onkoimunologiya occupied a special place among the areas of basic immunology. There is a great
need for studying the mechanisms of immune surveillance during tumor process and the creation
of immunotherapeutic agents. The prevalence of autoimmune disease compared with other
nosology low (8-17%), it is not the cause of high mortality as oncopathology or cardio - vascular
system, however, it is this disease is the main output of disability in people of working age.
Today particularly important knowledge about the ins prich immunological infertility,
immunological mechanisms miscarriage conflicts "mother-fetus" and "mother-father" immune
genesis immunotherapy in obstetrics - gynecology
II. Learning objectives lessons.
Students must:
1. To interview and physical examination of patients with congenital and acquired
immunodeficiency states.
2. Imunopatogeneticheskie determine factors in the development of immune diseases.
3. Justify the application of the basic immunodiagnostic methods used in clinical immunology,
define the indications and contraindications for their conduct in patients with various immune
diseases.
4. Interpret data phenotyping pair donor - recipient (index definition MHC) in preparation for
organ and cell transplantation.
5. Justify the use of immunosuppressive therapy in the post-transplant period.
6. Determine the clinical and laboratory signs of s development of hyperacute, acute and chronic
rejection crises.
7. A differential diagnosis between a crisis of rejection and infectious complications in patients
after organ transplantation.
8. Identify laboratory signs of systemic and local immunosuppressive mechanisms in normal
pregnancy.
9. Determine the mechanisms of development of immune forms of infertility.
10. Interpret data phenotyping male-female pairs (index definition MHC) in the diagnosis of
immune infertility form.
11. Analyze the results of the determination of indicators characterizing factors antineoplastic
protect a patient suspected of having a tumor.
12. Interpretation of th e data definitions tumor antigens asotsiiruetsya Hovhan for early diagnosis
of tumors, to assess the effectiveness of treatment and to determine the presence or absence of
metastases;
13. Justify the use immunotropic therapy in patients with tumors;
14. Be able to use clinical - immunological criteria in the diagnosis of autoimmune disorders;
15. Determine the basic immunological mechanisms in the development of autoimmune diseases;
16. Justify the use of immunosuppressive therapy in patients with autoimmune disorders;
17. To demonstrate the moral - a medical professional deontological principles and the principles
of professional subordination.
III. Personal development goals (educational purposes)
Form students on the theme material a sense of responsibility for the timeliness and accuracy of
professional activities in the diagnosis of immunodeficiency diseases and other
immunopathology. On the basis of ethical principles to teach young professional set psychological
contact with the patient and his relatives.
I V. M ezhdistsiplinarnaya integration
p/
p
2
A istsiplina
3
Histology and
Embryology
4
Normal
physiology
5
endocrinology
6
genetics
7
Pathological
Physiology
Normal anatomy
W nat
Organs of the immune, sexual and endocrine
systems
be able to examine the
immune organs, sexual
and endocrine systems
Tissues and cells of the immune system,
Microscopically
reproductive system (egg and sperm) ovarian
distinguish tissue and
tissue, zygote, trophoblast, amnion, chorion of
cells of the immune
placenta and other organs and systems.
system, the reproductive
system and other
systems.
The main function of the immune system, the function of
Specify the basic
sexual systems spouses
methods of estimation of
Blood group systems ABO and Rh
the reproductive system
of women and men, n
radio button for blood
grouping system for
ABO, Rh exercised when
testing
Thyroiditis, Addison's disease, insulin-dependent.Diabetes be able to diagnose
clinical and laboratory manifestations
HLA-system
genealogical history
Immunopathological reactivity changes in proteinograma,
leucogram with ID. Structural changes in the conditions of
neoplastic processes Definitions "tumor" and "neoplastic
process", the chemical, physical, viral carcinogenesis,
tumors and body interaction. Causes and mechanisms of
reproductive dysfunction in men and women associated with
their immune system. Immune aspects of autoimmune
disorders, and tanspl ntatsi he tion immunity.
8
Mr. ematologiya
7
Pulmonology
8
P ropedevtiki
therapy
be able to
Autoimmune hemolytic anemia,
thrombocytopenia, agranulocytosis: clinical and
laboratory signs
Extrinsic allergic alveolitis, sarcoidosis, fibrosing
alveolitis: clinical features, diagnosis, treatment
Know approaches to inspection organs and
systems
be able to prescribe the
methods of genetic
testing
interpret blood tests
proteinogramu,
immunogram with ID
and tumors
microscopically evaluate
morphological features
of cancer pathology. Rate
of disease syndromes and
reproductive systems of
men and women
associated with immune
system disorders
be able to diagnose
be able to diagnose
Conduct palpation,
percussion, organs
9
rheumatology
Criteria for RA, SLE, SSc, rheumatism
10
Neurology
Criteria for multiple sclerosis, myasthenia gravis
11
Obstetrics
Infertility problems with immune
mechanisms,Imunokonfliktnie syndromes
12
Oncology
Features examination of organs and systems of
patients with suspected oncopathology
13
F armakologiya
The main groups of immunosuppressants,
immunomodulators. Regulations prescribing
conduct the clinical
examination of patients
conduct clinical
examination
Identify immune-disease,
complications,
imunokonfliktni
syndromes in women
Evaluate the results of
clinical, laboratory and
instrumental methods of
examination of patients
with suspected
oncopathology
prescribe, prescribe
appropriate treatment
V. Content of the topic classes.
Teacher reminds students of the importance of carefully collected history, talks about the
impact of environmental factors trigger the formation of immunopathology.
Study questions:
5.1 Immunodeficiencies
1. Classification ID
2. Clinical - medical history and laboratory diagnostic criteria.
3. treatment of immunodeficiencies
5.2 Immunology tumors
1. tumor antigens
2. Mechanisms of tumor recognition of tumor antigens
3. The effector mechanisms of the immune response against tumor cells.
4. Immunological mechanisms that contribute to tumor growth.
5. Laboratory diagnosis of tumor immunological processes.
6. Immunotherapy of tumors.
5.3 Immunopathology reproduction
1. Antigens of sperm and egg.
2. Immune status of pregnant women, lactation immunology.
3. Forms of immune infertility in marriage and immunodiagnosis.
4. Immunological mechanisms of miscarriage.
5. Immunological conflict in the "mother-fetus": diagnosis, treatment, prevention.
5.4 Transplant immunity
1. Phenotyping pair donor - recipient (index definition MHC) in preparation for organ
and cell transplantation.
2. Application of immunosuppressive therapy in post-transplant period.
3. Clinical and laboratory features of s development of hyperacute, acute and chronic
rejection crises.
3. Differential diagnosis between a crisis of rejection and infectious complications in
patients after organ transplantation.
5.5 Immune aspects of autoimmune disorders
1. Symptoms of an autoimmune disease.
2. What is immunological tolerance, support mechanisms and the causes of its failure.
3. Congenital immunodeficiencies, contributing to the development of autoimmune
pathology.
4. Principles of treatment of autoimmune disorders, new immunosuppressive drugs.
Content of the topic:
5.1 Immunodeficiencies - are diseases associated with persistent violations of the
immune response characterized by an increased tendency to infectious diseases and cancer,
especially in children and young age. In most developed countries, including Ukraine, there is a
decrease in immune reactivity due to different causes: genetic, environmental, social, etc. . As a
result of immunodeficiency developing infections which tend to be chronic process of forming
the complications that lead to high levels of disability and death, including among children. In
addition, abnormalities in the immune system can manifest the formation of malignant tumors
(especially lymphomas) of allergy, autoimmune diseases especially in children and young adults.
Immunodeficiencies are divided into genetic (primary) or acquired (secondary). Primary
immunodeficiencies are formed as a result of genetic mutations acquired - as a result of
prolonged exposure to toxic factors (medications, environmental factors, chemical contamination
of water, food), lymphotropic infections (HIV, hepatitis B and C, herpes group of viruses). They
occur under the guise of many chronic diseases in association with viral and bacterial infections
polyvalent, often in a generalized form. Is necessary to draw attention to the fact that if the
beginning of the century the ratio between chronic and acute diseases was 10:90, then at the
present stage, the ratio is 90:10.
5.1.1 Classification of ICD - 10:
Primary (congenital)
• hereditary (genetically determined) D 80 -83;
• congenital formed prenatally D 80 -83;
secondary:
• acquired immunodeficiency syndrome (formed intra - and postnatally)
- HIV - associated,
- HIV - non-associated D 84.8; D 84.9;
Other disorders involving the immune mechanism D89.8; D89.9.
Immunodeficiency diseases also can be classified in the corresponding defect immunity:
macrophage - monocyte, the complement system, cellular, humoral units or a combination
thereof. Etiological factors of immunodeficiency diseases is genopatii, fetopathy and
embryopathy. In contrast to the primary, secondary dysfunction of the immune system are not
associated with genetic defects, but depend on the effects on the body of harmful environmental
factors (ionizing and non-ionizing radiation, chemical pollution, unbalanced diet, stress, etc.)
infections. Primary immunodeficiencies are characterized by stable clinical (sometimes have
characteristic clinical markers) and laboratory immunological features and are difficult to treat
(pathogenic, Causal). Acquired DHS, especially immunodeficiency disorders, which are usually
transient (unstable), may disappear after the termination of the harmful factor and / or conduct
adequate etiotrop, pat ogeneticheskogo immunotropic or treatment.
Identify signs of DHS GP can based clinical - anamnestic data (determination of causal factors,
clinical features, family, immunology, vaccination, physical history), physical examination, the
results of skin tests with T-dependent antigens (tuberculin, fungal allergens) and laboratory
immunological monitoring (determination of the absolute number of leukocytes, neutrophils,
lymphocytes and platelets serum major classes of immunoglobulins IgA, IgM, IgG; CH50
hemolytic complement activity that are screening laboratory tests). Summary analysis (3 or more
signs) these data can lead the doctor to believe that the patient has signs of immunodeficiency (n
ervichnogo, secondary). Research and practical experience suggests that among DHS acquired
immunodeficiency disorders more than immunodeficiencies (primary acquired).
5.1.2 Clinical - anamnestic criteria DHS
I. Etiologic and pathogenetic factors of development: stress, infection, harmful
environmental factors, physical and chemical, metabolic (nutritional, hypoxic, endocrine),
depletion of antioxidant system in chronic infection, radiation injuries, diseases of the internal
organs - the toxic effect of products of free radical oxidation the blockade of enzymes, their
inactivation intoxication of various origins; iatrogenic factors of various origins: long-term
administration of drugs possessing immunosuppressive effect of hormonal drugs
(glucocorticoids, contraceptives, etc.). , Cytostatic agents, antivirals, antibiotics, etc. , Surgery
(especially on immune organs), trauma, burns.
II. The essence of the complaints of patients with signs percent varied and depends on the
clinical lead - anamnestic syndrome (infectious, allergic, autoimmune lymphoproliferative),
chronic fatigue.
The main complaints are the temperature rise of more than 12 days of unclear origin, constant
fatigue, which is not dependent on the physical and intellectual load, frequent respiratory
infections, enlargement of peripheral lymph nodes, rash on the skin and mucous membranes,
myalgia, arthralgia, and others.
III. Medical history and life:
Infectious signs:
- Increased frequency of uncomplicated infectious diseases caused by pathogenic conventional
infectious agents: acute infectious disease of the respiratory tract, oral cavity, bronchitis (6 or
more cases per year);
- Frequent complications of acute inflammatory diseases of ENT - organs and respiratory tract:
sinusitis, otitis, pneumonia (2 or more during the year);
- Frequent complications of acute inflammatory processes, the urethra (4 or more times a year);
- Atypical for infectious diseases;
- Infectious Bole situ caused slabovirulentnymi (low pathogenicity), atypical and opportunistic
pathogens;
- Frequent relapses lyabialnoi and / or genital herpes infection;
- Activation flaccid (latent) infection with systemic clinical manifestations cal and suppressing
the tendency to lesions of the nervous system and organ of vision (Epstein - Barr virus,
cytomegalovirus, Toxoplasma);
- Mixed forms of infections, change of causative infectious agent during the illness;
- Systemic mycoses;
- Recurrent dysbacterioses;
- Development of purulent processes of the skin and / or internal organs: generalized pyoderma,
furunculosis, carbuncles, cellulitis, deep abscesses, recurrent abscess;
- Urogenital infections (chronic purulent vulvitis, adneksit, pyelonephritis with frequent
exacerbations;
- Gastroenteropatii with chronic diarrhea of unknown etiology, dizbiozom;
- Protozoal and helminth diseases (malaria, toxoplasmosis, trichinosis, leishmaniasis,
trypanosomiasis, schistosomiasis, and others.)
- Bacterial infections (tuberculosis, rec. Pneumo - meningitis -, staphylococci -, gonococcal and
others.)
- Viral infections (measles, rubella, influenza, mumps, and others.)
- Development of osteomyelitis, meningitis, sepsis, peritonitis (2 or more);
- Resistance to standard patterns of causal and pathogenetic therapy (for 2 or more months of
treatment);
- The need for antibiotics "standby" and / or the need for intravenous infusion, anti-infective
agents;
Clinical immunological characteristics: prolonged hyper -, hypothermia, have regional or
systemic lymphadenopathy, chronic lymphadenitis, hyper - hypo -, aplasia tonsils splenomegaly,
hypo -, asplenia; continued hepatomegaly, is not associated with toxic factors and hepatotropic
viruses (more than 1 - th months), kriopatii syndrome, chronic fatigue syndrome, autoimmune
complications and exacerbation of infectious diseases after vaccination, increased fatigue effect,
inadequate physical, intellectual and other load for six months or more.
Other clinical signs of malabsorption syndrome, the rapid change in body weight signs of
premature aging TERM; prolonged tissue regeneration; early formation of oncological diseases,
autoimmune endocrinopathies, hypo / hyperpigmentation, alopecia or total alopetsіya
ineffectiveness of standard methods and treatments.
Family history:
- Undetermined deaths of infants and young children associated with infection, cystic
fibrosis, etc. ;
- Chronic and recurrent infections with relatives (tuberculosis, etc.);
- Allergic, autoimmune endocrine diseases and malignant neoplasms in the family;
-. kinship parents.
Vaccination history:
1. The emergence of a disease against which vaccination was conducted (eg, measles).
2. The emergence of post-vaccination reactions and complications (especially the nervous
system).
3. Low titers of specific antibodies 3 weeks after the vaccination.
Clinical - anamnestic benchmarks that allow to specify the damaged immune system link:
• manifestations of insufficiency of macrophage - monocyte system: chronic recurrent
suppurative infections of the skin, mucous membranes, lymph nodes, bones, joints,
bronchi, and other organs and systems; generalized infection (sepsis);
• manifestations of insufficiency of cellular immunity: relapsing chronic viral, fungal,
parasitic infections malignancies (lymphoma, lymphosarcoma, lymphocytic leukemia,
Hodgkin's disease, etc.);
• manifestations of insufficiency of humoral immunity chronic recurrent bacterial
infections of the skin, conjunctiva, paranasal sinuses, middle ear, bronchus, lung, pleura,
gastrointestinal tract, urinary and biliary systems, atopic dermatitis, asthma, hay fever,
autoimmune pathology (rheumatoid arthritis, aggressive hepatitis and t . etc.).
Cutaneous T-tests dependent antigens
Normally, in response to I / subcutaneous administration of T-dependent hypertension
(tuberculin, candida, etc.) in 24-72 hours recorded at the injection site papule (blister) up
to 5mm. Negative skin tests on all entered antigens show a decrease in the functional
activity of cellular immunity factors. Local immunological response - 5-30 mm indicates
sensitization (giperchuvst Indeed delayed type) to anti causal gene and thus the
preservation of functional activity of cellular immunity. Today in Ukraine can use the
following T-dependent antigens: tuberculin allergens conditionally - pathogenic fungi:
Alternaria, Aspergillus mixed, Cladosporium, Chr isonilla, Monilia, Penicillinum,
Botrytis cinerea).
A aboratornye signs:
1. Long-term changes in indicators of blood cells and humoral immunological parameters
common (more than 1 month): leukopenia, lymphopenia, lymphocytosis, neutropenia,
monocytosis, hemolytic anemia, thrombocytopenia, hypogammaglobulinemia,
gipoimunoglobulinemiya G, hypo / giperimunoglobulinemiya M
gipoimunoglobulinemiya A.
2. Slow ESR on the background of bacterial infections.
3. Below protective levels of specific antibody titers 3 weeks after the vaccination.
4. Persistent changes in cellular immunity (in vivo, in vitro).
5.1.3 Treatment immunodeficiencies:
1) intravenous immunoglobulin. 2) Causative: antibacterial, antiviral, and antifungal. 3)
Bone marrow transplantation. 4) Gene Therapy. 5) Tsitokinoterapiya. 6) Possible
metabolic and thymic immunostimulants (based on sustainable changes in immunogram
x).
5.2 Immunopathology tumors
5.2.1 Tumor antigens - is pathologically altered (under the influence of physical,
chemical, viral, and other factors) ay toantigeny human body. Are divided into groups:
- Antigens that are present on tumor and on normal unmodified cells (e.g. antigen
encoded by CAMEL, slices is presented HLA-A2, has an epitope MLMAQEALAFL,
present on tumor cells, melanoma cells, and normal testis, placenta, heart, skeletal
myazevoi tissue Pancreas);
- Differentiated antigens that are present on tumor cells and normal cells from which the
tumor occurs;
- "General" antigens are present on several types of tumors (e.g. antigen encoded by the
gene MAGE-A1, slices is presented HLA-A1, has an epitope EADPTGHSY, present on
melanoma cells, breast tumors, lung tumors);
- Antigens specific for tumors, are present only in tumor cells (usually of human tumors
are not specific tumor antigens, but there are exceptions, such as the beta - catenin,
modified by reason of point mutations is presented slices HLA - A24, the epitope has
SYLDSGIHF, there only on certain types of cells, melanoma);
- Antigens called oncofetal present on embryonic tissues, normally disappear during
differentiation (alpha-fetoprotein, carcinoembryonic antigen).
- Tumor-specific transplantation antigens play a significant role in tumor rejection by
generating a cellular immune response, they are different in tumors arising under the
influence of carcinogens and identical in tumors arising influenced by oncoviruses.
Separate category of tumor antigens comprise antigens present in the tumors, which are
involved in the pathogenesis of virus
5.2.2 Mechanisms of immune recognition of tumor antigens:
- Detection of T - lymphocytes (in antigens in most cases presented by MHC molecules
of class 1 lymphocytes T CD8 + (suppressor). Known, reduced expression or absence of
MHC class I molecules on tumor cells correlates with malignancy. Upcoming tumor
antigens that are presented as MHC class II molecules lymphocytes T CD4 + (helper)
found tumor antigens that are presented by different molecules, HLA-DR)
- Using antibody detection is carried out such tumor antigens:
and / antigens of B-cell lymphoma receptor CD 19, CD 20, CD 21, CD 22, CD 37;
b / carcino - embryonic antigen (CEA receptor CD 66E, present in tumor cells of the
colon, pancreas, stomach);
in / alphafetoprotein (on tumor cells and normal cells of the liver, gall bladder);
g / tumor antigen CA - 125 (present on tumor cells of ovary, pancreas, lung);
d / prostate-specific antigen (PSA) (as present on fetal cells and on tumor cells of the
prostate).
5.2.3 effector mechanisms of the immune response against tumor cells.
Immunological mechanisms of suppression of tumor development (protiblastomni
factors):
- Activity NK - cells;
- Action T - lymphocytes - cytotoxic;
- Effect of cytokines synthesized T - lymphocytes (including T - helper);
- The cytotoxic effects of activated macrophages and neutrophils;
- Effect of cytokines synthesized by macrophages;
- Cellular Cytotoxicity-dependent antibodies;
- Cytotoxicity of antibody-dependent complement.
Natural antitumor mechanisms can be grouped into two areas of action:
- Activate the monocyte / macrophage (ie, activation of T - helper cells, the synthesis of
interleukin-12, which activates Th1 and NK; secretion of proinflammatory cytokines IL1, IL-6, TNF - alpha, increased inflammation and integration of security forces)
- Activation of T - helper (synthesis of IL-2, which stimulates the proliferation of T helper T - cytotoxic, monocytes / macrophages, NK - cells, synthesis of IFN - gamma,
TNF - alpha to affect the anticancer properties of monocytes - macrophages); synthesis of
IL-3, and colony-stimulating factors for stimulation of hematopoiesis).
5.2.4 Immunological mechanisms that contribute to tumor growth.
Immunosuppression : exogenous origin (some medications, viral infections); endogenous
origin (cells - suppressors and suppressor factors).
Imunoselektsiya:
- Reduced expression of molecules of MHC, molecules lack kostimulyuyuchih
CD 80 and CD 86 on the tumor cells;
- Poor immunogenicity of tumor antigens, the presence of different antigens on the tumor
cells and primary tumor metastases
- Education of soluble forms of tumor antigens
- Tumor cells that lose receptor for TNF, become resistant to apoptosis
- In tumor cells enhanced expression of receptors for growth factors
Immunomodulation (avoidance of immunological surveillance) masking of antigen on the
tumor cells, the formation of complexes with a tumor antigen-specific antibodies and
effector cells of the respective lock, stimulation of the growth of tumor cells by specific
antibodies present in small quantities;
opsonization and destruction of cells able to phagocytose tumor cells, the activity of antiidiotypic antibodies;
stimulation of tumor cell growth and product synthesis lymphocytes etc. .
Custom immunological phenomenon, contributing to the development of neoplasms,
called "immunological prispishennyam" . It is implemented such mechanisms:
5.2.5 Laboratory diagnosis of tumor immunological processes
Before carrying out specific laboratory methods for the determination of tumor antigens
is necessary to determine the general condition of the patient's immune system, and
take into account age critical periods of development of tumors :
1/.Dityachy age (during the formation of the immune system)
2/.Yunatsky age (restructuring of hormonal regulation of the immune system)
3/.Pohily age (period of declining activity of the immune system)
According to WHO, 60% -70% of the total number of tumors actually arise during these
periods of life.
Laboratory markers of malignant growth is:
- Tumor-specific antigens (PSA in the early period of development of prostate cancer,
CA 19-9 cancer of the gastrointestinal tract, pancreas,
CA -125 breast cancer and ovarian cancer, CA 15-3 in breast
cancer)
- Other antigens (eg P -53 in bladder tumors, SCC in lung cancer, esophagus and rectum)
- Carcinoembryonic antigen (a marker for colon cancer, liver
pancreas, stomach, thyroid, and breast cancer, bladder)
- Hormones (napr.beta - human chorionic gonadotropin in horionomah, uterine tumors,
testicular)
- Enzymes (eg LDH)
- Glycoproteins (eg alpha - fetoprotein in cancer gepatotselulyatnomu)
- Lipids
- Proteins (eg acute phase: lactoferrin increases in Hodgkin's disease, lymphosarcoma,
CRP - for all tumors)
5.2.6 Immunotherapy tumors.
The basic principle of the use of immunotherapy in cancer patients - support for
traditional methods of treatment (surgical removal of the tumor, chemotherapy and
radiotherapy). Only in a few cases, immunotherapy may be the first level of care .
Tumors in which treatment can be used immunotherapy: melanoma, kidney cancer, nonHodgkin's lymphoma, hairy cell leukemia, colon cancer, ovarian cancer, glioma, soft
tissue sarcoma.
Form tumor immunotherapy:
1 /. Active : specific - feed the patient tumor cells or antigens. Antineoplastic "grafting" a classic form is fed to the patient are killed or irradiated autologous or allogeneic tumor
cells or their extracts in the form of modified tumor cells or antigen or adjuvant supplied
with cytokines (IL-2, IL-3, GM-CSF). "Vaccination" is best suited for the treatment of
tumors with well-defined antigens (eg melanoma). The newest generation of
"immunization" - the introduction of genetically engineered genes in tumor cells (for the
cytokines IL-2, IL -4, IL -7, GM-CSF, TNF, IFN - gamma for the molecule in the 7,1) as
well as tumor-associated molecules viruses.
- Non-specific - activation of immunological mechanisms patient immunostimulatory
drugs, including cytokines; This is achieved by the patient administering an
immunostimulating agents (BCG levamisole) or cytokines (TNF, IL-2, IL -4, IL-12,
interferons, and in various combinations as monotherapy), a combination of cytokines,
cytostatics
2 /. Passive : administering to a patient-specific monoclonal antibodies, often specially
modified (modification of the structure of a monoclonal antibody reduces its molecular
weight and immunogenicity).
3 / Adaptive : intravenously or topically administering to the patient immune cells: a /
TIL - lymphocytes (lymphocytes infiltrating tumor), isolated and cultured with the
addition of IL-2 b / LAK (lymphokine - activated killer same or cytokines) in monocytes
/ patient .
5.3.1 Immunopathology reproduction.
Sperm antigens: surface: provide interaction with the egg
- Primary RN - 20 (on the acrosome) binds to the corresponding receptor on the egg
- Supporting RN - 30 (fertilin) is responsible for the penetration of sperm into the egg, these
processes are mediated C1qR, CR3, FcR, CD46
acrosomal: participate in further interaction of gametes (penetration of the clear zone).
- TLX (trophoblast - lymphocyte - krosreaguyuchy), it is called membrane cofactor protein MCP
or CD46 - binds to and inhibits the complement component C3b and C4b
antigens sperm nucleus (internal): histones, which in the process of spermatogenesis
transformed into protamines
HLA-antigens of: the surface of the spermatozoon in the particles generally contain the classic
HLA - A, B, C and in the cytoplasm - nonclassical E, F, G, providing immunological tolerance
(HLA - E).
Immunological properties of seminal fluid:
• inhibition of sperm antigen presentation by monocytes and macrophages
• Inhibition of the enzymatic activity of macrophages and neutrophils
• reduction of T - L, B-l, l-NK
• attenuation cytotoxic reactions and antibody-mediated complement.
Antigens egg - it's mostly antigens transparent zone (Zona pellucida) ZP -1, ZP -2, ZP -3. Their
main functions: ZP -1 characteristic outer surface glycoprotein egg; ZP -2 binds
tripsinopodibnoyu proteinase causes limited proteolysis and "stverdnennya" transparent zone
(braking polyspermy) ZP -3 recognizes and binds sperm induces the acrosomal reaction in
sperm.
Acrosomal reaction - this destruction (under the influence of proteases, lipases, phosphatases,
glycosidases) of the inner acrosomal membrane of sperm, which provides the interaction of
gametes, ie Penetration of the clear zone of the egg.
The process of oocyte maturation is due to immunoregulatory functions of the glandular cells of
the ovary. Glandular cells of the ovary:
- Interaction with the immune system factors (cytokines synthesized by macrophages in ovarian
tissue, contribute to the formation-stimulating factor SC, which accelerates the maturation of the
follicle);
- IL-1 and IL-2 was synthesized by macrophages in ovarian tissue, inhibit the synthesis of estriol
17 beta, luteinizing hormone and progesterone, indirectly regulate
menstrual cycle.
5.3. 2. Immune status of pregnant
Adaptive mechanisms contributing content fetal physiological pregnancy in circumstances:
- Prepared immunologically uterus due to relaxation response of T - cell immunity (suppressive
effect of hormones: hCG, placental lactogen, steroid hormones: alpha - fetoprotein alpha proteins
from group 2 - globulin: protein pregnancy PZP, pregnant macroglobulin proteins from group -2
beta - globulin: protein SP-1, 2,3, pregnancy-specific beta - globulin, beta 1 - glycoprotein);
- Isolation of fruit - the mother with a small circulation cell infiltration in both directions
- Availability trophoblast nonclassical histocompatibility antigens HLA-E, F, G
(With weak capacity for antigen presentation), especially HLA-G, which blocks the activity of
NK - cells;
- Synthesis of trophoblast factors that contribute to the stability of the trophoblast to cytotoxic
antibodies and antigen-antibody complexes - complement (as MCP, DAF, Protektin);
- Synthesis of macrophages endometrial suppressor factors (prostaglandins)
- Increase in the endometrium of the uterus and placenta cells with regulatory / suppressor
function
- Synthesis of endometrial cells and blastocysts immunoregulatory factors contributing to
implantation (LIF and mucin)
- Accumulation blastocysts implanted around large granular lymphocytes (Fc R receptor and
CD56), which release suppressor factors like TGF - beta (which inhibit the formation of T lymphocytes and activation of cytotoxic NK - cells, macrophages, secretion of toxic oxygen
derivatives, TNF - alpha)
- Restructuring of systemic immunity - the changing balance between helper (downward) and
regulatory / suppressor T - lymphocytes (increase), the predominance of T - helper 2 - order by
helper 1 - order
On the basis of current knowledge of cytokine regulation of fetal development formed
"imunotrofichna hypothesis." This hypothesis is that the process of recognizing the antigens of
the fetus and the placenta of maternal immune responses (and particularly T - lymphocytes)
leads to the local release of cytokines, such as IL-3 and G - CSF, M-CSF, which promote growth
of tissue of the fetus and placenta .
There are three variants of these tissues under the influence of various cyto kin: imunodistrofiya
immuno trophy immunosuppression . Imunodistrofiya (restraining the growth of fetal and
placental tissue) observed in tissue infiltration by macrophages and cytotoxic cells and
synthesis of their respective cytokines) imunotrofiya means promoting certain cytokines growth
of fetal tissues and placenta, immunosuppression means actually support
imunodistrofii cytokines, hormones and prostaglandins.
5.3.3 Immunology lactation
Lactation - is an energy efficient mechanism that ensures the rational feeding of children 1 - tion
year of life, because breast milk contains protective substances and active is the perfect food for
the newborn.
Colostrum - sticky yellowish fluid that fills the alveoli of the breast during the last trimester of
pregnancy, and even made a few days after birth. Its quantity varies from 10 to 100 ml per day,
gradually increases and reaches a mature milk composition after 30-40 hours
postpartum. Colostrum contains less lactose, fat and water soluble vitamins than mature milk,
however, has a higher protein and fat soluble vitamins (A, E, K) and a certain minerals (sodium,
zinc). Has high concentrations of immunoglobulins and other protective factors.
Antiviral factors contained in human milk.
F actor
Secretory Ig A
Active to:
Papillomavirus types 1, 2, 3
Coxsackie virus type A9, B3, B5
Rotavirus, cytomegalovirus, reovirus type 3 virus, Rubella,
herpes virus, mumps virus, influenza virus, respiratory syncytial
virus
Rubella virus, cytomegalovirus, respiratory syncytial virus
Herpes viruses, influenza viruses, virus encephalitis
Ig M, Ig G, Ig G1
Unsaturated fatty acids and
monoglycerides
M akromolekuly
Herpes virus, vesicular stomatitis virus KoksakiV4, reovirus №,
neimunoglobulinovoy
cytomegalovirus, respiratory syncytial virus
nature
Alpha-2-macroglobulin (like)
Influenza virus, mumps virus
Ribonuclease
Leukemia virus Murin
Mr. emagglyutinin inhibitors
Mumps and influenza viruses
Product synthesis "dairy" cells
There interferon induced Rubella virus, herpes,
measles, mumps, respiratory syncytial
5.3.4. Immunodependent form of infertility in marriage
Causes of infertility in marriage :
• chronic inflammatory genital organs (75%) (acquired immunodeficiency infectious origin)
• endocrine imbalance - immunological mechanisms leading to the development of acquired
immunodeficiency syndrome (10%)
• causes of infertility of unknown etiology (10%)
• immunological causes of infertility (5%), mainly due to the formation of antibodies to sperm and a
higher degree of histocompatibility couple on system HLA (relative infertility)
5.3.5 Immunological mechanisms of miscarriage:
A) The reactivity of maternal lymphocytes against napivallotransplantatu (embryo) with a high
degree of histocompatibility between parents:
- Insufficient number of blocking antibodies to the surface antigens of paternal origin of the embryo
(these antibodies protect the embryo before the attack Motherboard reactive lymphocytes). Most
often they are not enough there is the presence of common antigens of the HLA system in both
parents;
- Available in both mother and father identical set of complex TLX (trophoblastic
krosreaguyuchih leukocyte antigens), whereby no sufficient immunogenicity to induce protective
immune response by the mother;
B) due to the increasing number of Miscarriage NK - cells with molecules CD57 +, and reducing the
number of NK cells with the phenotype CD16 - / CD56 +, which secrete cytokines that stimulate
the development of the placenta;
B) Autoimmune reactions and inflammatory processes in the body of the mother:
- The presence of antiphospholipid antibodies (may cause thrombosis of the placenta
premature and its affiliates);
- The presence of a large number of immune complexes - the trigger of development
systemic inflammatory response syndrome (SIRS) with late preeclampsia;
- The presence of specific antibodies in the mother class of Ig G in certain autoimmune diseases (eg
diabetes 1 - type, systemic lupus erythematosus, thrombocytopenia, autoimmune thyroid disorders,
Miastenia gravis) can induce symptoms of the disease in the fetus.
5.3.6 Immunological conflicts "mother-fetus": diagnosis, treatment, prevention
- Inter-group conflict (in the case of incompatibility of mother and fetus ABO fetal red blood cells
immunized mother and initiate production antigrupovih antibodies);
Most intergroup conflict observed if maternal blood group 0 (1) and the fetus A (II). Other ABO
incompatibility have no practical importance because the antigen is not observed in
immunogenicity and, moreover, the blood group in (III) and AB (IV) are much rarer. Clinically
manifest conflict threatened abortion or miscarriage. Treatment : intravenous infusion mother
neogemodez, poliglyukina, reopoliglyukina to reduce the titer of alpha - izoantitel the antigen
A1. Prevention: Only the first pregnancy of this kind threatens the embryo, with subsequent
pregnancy cytotoxic antibodies rarely show their negative effects on the fetus
- Rhesus - conflict due to the incompatibility of the pregnant woman and the fetus Rh - antigen
(D) and develops when the fetus is Rh - positive and mother - Rh-negative, anti-D is a cytotoxic
anti body. Diagnosis : performed by anamnesis and detection of anti - D-antibodies after childbirth
and during the next pregnancy. Treatment: administration of an anti - Rh - Ig G. Prevention:
prevention of specific human antirhesus carried Ig G.
5.4 Transplant immunity conflict "graft versus host"
The following types of transplants: autologous transplantation - transplantation own
tissues; homeotransplantation - the transplantation of organs and tissues within the same
species; xenotransplantation - the transplantation of organs and tissues from different species;
izotransplantatsiya - transplants between identical twins or between genetically identical animals.
Due to the fact that the donor cells have on their surface antigens, which differ from the recipient
antigens, the immune system produces an immune response last for a transplant. The result is a
graft rejection.
Method, which is more or less reduces resentment, selection (selection) of the pair donor - recipient
antigenically gistosumistnosti that humans are united in HLA (Human leucocyte antigens). These
transplantation antigens are also known.
To assess the degree gistosumistnosti histocompatibility index was proposed. When the identical one
of the donor HLA antigen iretsipienta gistosumistnosti index is 25%, for two - 50%, 75% at three,
four at 100%. At the same time assess the degree gistosumistnosti antigenically so-called classical
loci HLA. Proper selection involves the selection of a pair of donor - recipient, in which the
smallest donor differs from the recipient to antigens of HLA. In order to identify HLA - typing
performed phenotype of peripheral blood lymphocytes of the donor and recipient.
Typing lymphocyte antigen class I (HLA - A, B, C) is used in micro limfotsitotoksichny test
modifications Paul Terasaki. To detect antigen class II (HLA-DR, DP, DG) limfotsitotoksichny
prolonged use test cell suspension enriched in B-lymphocytes, which are presented on the surface
of these antigens.
Breeding pairs of donor - recipient, except for the selection of HLA-antigens involves determination
of the degree of specific and nonspecific pre sensitization recipient HLA antigens of the
donor. Also, define the input immune status (absolute number of T - helper and Tsupresoriv/kileriv), as well as their relative proportions - an indicator of the IRI (immunoregulatory
index) of the recipient, which usually affects the course of post-transplant period.
Allograft structures endowed with foreign antigens initiates the recipient immune response. As a
result of graft rejection is developing, which is called in the clinic rejection crises. Distinguish
rejection: 1) hyperacute that develops immediately after connecting the bloodstream transplant
recipient 2) acute that develops during the first three weeks after transplantation 3) chronic ,
observed in a few months or years.
In modern circuit immunosuppressive therapy in allotransplantation for the prevention and treatment
of rejection crises often include: 1) azathioprine (Imuran) - 2 fusion protein antimetabolite)
Corticosteroids - prednisone, dexamethasone, hydrocortisone, etc. 3) Cyclosporin A (Sandimun).
5.5 Immune aspects of autoimmune disorders
5.5.1 Symptoms of autoimmune disease
 Manifestations of the disease depends on the mechanisms that underlie the immune response,
namely the cytokine profile of specific antibodies or cytotoxic lymphocytes .
 The disease is chronic in nature with lingering signs of self-maintenance.
 Patients suffering from autoimmune diseases bubbled s must be detected circulating autoantibodies
and / or delayed hypersensitivity reaction to develop.
 autoantigens must be established that causes the reaction.
5.5.2 Autoimmune tolerance - is the inability of an immune response induced by autoantigen. When
maturation in the thymus autoreactive cells are eliminated (negative selection). Normally, there is
a small amount of autoreactive cells that are intended to eliminate waste autoantigens own cells
and their structures. upon completion of their function, they die by apoptosis, so do not cause
autoimmune diseases, they are only "nurses" internal environment.
Mechanisms for maintaining self-tolerance:
 Culling at thymic autoreactive T - lymphocytes.
 anatomically sequestered organs (eyes, central nervous system, testes, thyroid gland) have
mechanisms of destruction of autoreactive cells.
 signals from anergy antigenprezentuyuchih cells and helper - regulatory (CD4 + CD25 +).
 anti-idiotypic antibodies that block aktoreaktivni antibody.
Disruption of immunological tolerance is the basis of autoimmune disorders.
Following reasons : violation of anatomical barriers; disfuntsiya thymus; antigenic
mimicry, modification of autoantigens viruses, chemical and physical factors, medications, loss of
suppressive
activity
helpers
regulatory
(CD4
+
CD25
+)
mutations,
congenital immunodeficiencies, polyclonal activation superantigenamy (herpes viruses, bacterial
LPS), the excess circulation autoantigens violation phagocytosis.
5.5.3 Congenital immunodeficiencies sho cause autoimmune pathology:
- Hypo - agammaglobulinemia (selective IgA, hyper - IgM, total variable
immunodeficiency) - cause SLE, JRA, Sjogren's syndrome, scleroderma, DM, vasculitis, diabetes,
myasthenia gravis, pernicious anemia, autoimmune hepatitis, poliendoktrinopatiyu, primary
adrenal insufficiency, autoimmune arthritis.
- Defects C2, C4 complement - cause SLE.
- Defects in phagocytosis - cause the formation of antinuclear, anti-neutrophil
antibodies, autoimmune arthritis.
5.5.4 Principles of treatment of autoimmune disorders
- Replacement of lost function (diabetes, hypothyroidism).
- Immunosuppression (cyclosporin, cyclophosphamide, mercaptopurine, preperaty gold,
penicillamine, Plaquenil, leflunomide, glucocorticosteroids, NSAIDs, heparin, pentoxifylline,
antibiotics, chloramphenicol, rapamycin, monoclonal antibodies antilymphocytic serum).
- Immunomodulation (thymus preparations, cytokines, antibodies to cytokines and their receptors
immunoglobulins).
- Efferent methods.
- Oral administration of antigens that stimulate the production tolerance via sIgA.
VI. Plan and organizational structure of classes
Do
Methods for
Methodological
Time
Main stages of classes, functions and
humectant
monitoring and
support materials
in
content
1
assimilation
training
2
3
min.
4
5
1. Preparatory phase:
business classes
learning objectives
Control the input level of knowledge, skills:
- Factors of innate immunity in tumor protection
- Tumor antigens and anti-tumor antibody
- Features of the immune response (local and
systemic) in women and men
- Identify key immunological mechanisms in the
development of autoimmune diseases;
- Interpret the data phenotyping pair donor recipient (index definition MHC) in preparation
for organ and cell transplantation.
2. main etap
Formation of professional knowledge and skills:
1. - Be able to criteria based on the early
diagnosis of immunodeficiency
- Determine the main factors
immunoresistance tumors
- Post basic principles of tumor immunological
- Establish the basic directions tumor
immunotherapy
- Know immunological conflicts pregnancy
immunology of pregnancy, lactation
- Identify immunodependent infertility
- Be able to use clinical - immunological criteria
in the diagnosis of autoimmune disorders;
- Identify the clinical and laboratory signs of
development of hyperacute, acute and chronic
rejection crises. .
2.Ovolodity skills examination of the patient
with immunopathology, interpret laboratory
tests and additional studies.
3. Spend curation of patient with
immunopathology studied in class
1. final etap
Monitoring and correction of professional
knowledge and skills:
- Summarize the basic knowledge of the
mechanisms of antitumor protection
- Establish causes immunological resistance of
tumors
- Identify promising areas of cancer
immunotherapy
- Predict immunological conflict;
- Characterize immunogram pregnant woman;
- Be able to according to immunological studies
predict risk of miscarriage.
- To justify the use of immunosuppressive
therapy in patients with autoimmune disease
and in post-transplant period.
1
2
2
wheel poll
Rapid survey
Test control
(input)
Individual
survey
(checklists)
Professional
training in
solving typical
situational
problems ("Step
2")
Tests
scheme
Tables, charts,
maps
immunological
surveillance
typical situational
problems
25
180
2
3
3
3
3
Testing
(baseline)
individual
survey
Professional
training in
solving
situational
problems
atypical
Tests, atypical
case studies
Summarizing lessons
Homework to the next topic
VII. Methodology of the educational process at the practical (seminary) lesson.
20
15
7.1. Preparatory stage.
After setting specific learning tasks teacher supervises the input level of knowledge of natural
immunity factors in tumor protection, tumor antigens, the characteristics of the immune response
(local and systemic) in women and men, the basic immunological mechanisms of autoimmune
diseases, the ability to interpret phenotyping pair donor - recipient (definition histocompatibility
index) in preparation for transplantation of organs and cells.
7.2. main stage
This phase involves the execution of each student independently under the supervision of a teacher
following these practical works.
Task 1
Students conduct survey and objective examination of the patient with immunological disorders,
using inspection, palpation, auscultation, percussion.
Task 2
Number
Job
1.
Of features characterizes primary immunodeficiency syndrome (Bruton)?
2.
What is the basis of "graft versus host"?
3.
A pregnant woman suffered flu. What is the name of the newborn developed influenza
immunity?
4.
Responder cells which mainly provide the resistance to tumors nonspecific?
5.
Feature is not typical for infectious diseases in patients with combined immunodeficiency?
6.
Characteristic signs of hemogram in acquired immunodeficiency?
7.
8.
9.
10.
What attributes characterize autoimmune syndrome dysfunctions of the immune system?
Cells that are not targets for natural killer ...?
Development of an autoimmune disease is not induced ...?
What are the signs of acquired immunodeficiency?
11.
In which period the treatment of cancer patients is most advisable to appoint
immunostimulants?
What prognosis of subsequent pregnancies with Rh immune - the conflict in the first
pregnancy?
A. Without dynamics.
B. Increase signs immune conflict.
B. weakened immune conflict.
G. disappearance of immune conflict.
12.
Task 3
1. What caused the long latency period of tumor development process?
A phenomenon of carcinoma in situ
B. mutational changes in cancer cells
B. selection of antigens on cancer cells
G. eliminate malignant cells by immunocompetent cells
D. differentiation antigens.
Answer - G. eliminate malignant cells
2. The most immunogenic tumors are those that occur under the influence of:
A. Pesticides
B. nitrates, nitrites
B. Viruses
G. ionizing radiation
D. Radionuclide
1. Answer - B. Viruses
3. The best evidence that points to the value of immune surveillance in the development
of a tumor of the process are:
A. The hereditary nature of the tumor
B. Maximum frequency of tumors in the age group of 10 to 50 years
V. Rapid transformation of healthy (normal) cells in cancer
in vitro (where there is no immune surveillance)
G. Significant increases in the frequency of malignant tumors among those with
congenital or acquired immunodeficiencies
D. Association of the tumor process in violation of the idiotype-antiidiotpichnoi
regulation of immune response.
Answer - G. significant increase in the frequency of malignant tumors among those with
congenital or acquired and mmunodefitsitami.
4. Which of these cells exhibit antitumor effect regardless of the expression of HLA receptors?
A. T - cytotoxic cells.
B. Macrophages.
B. NK cells.
D. B-lymphocytes.
D. T - helper cells.
Answer - B. NK cells
Zavdannya 4
№/№
Job
1.
The child found the combination of otitis, eczema, and thrombocytopenic purpura. What ki
2.
Bruton's disease is ...?
3.
What attributes characterize lymphoproliferative syndrome immune system dysfunction?
4.
5.
6.
7.
8.
9.
Clinical signs of primary immunodeficiency which a child 6 months. , From the first pregna
toxemia) that convulsive syndrome with hypocalcemia, malformations of the facial skeleton
hypoplasia?
The patient patient with autoimmune dysfunction syndrome immune system changed immu
answer.
In what cases can be suspected rezusnesumisnist in the "mother-fetus"?
A mother Rh (+), father (-).
B. Rhesus mother (-), the father (+).
B. Rhesus mother (+), grandmothers (-).
15.Prichiny recurrent miscarriage: Availability TORCH - infections, hormonal and genetic
disorders, immunological reasons: all of the above.
Which of the following can reduce the intensity of the immune conflict "mother-fetus" in ci
and the fetus Rh +:
A. The denial of the introduction of anti-D globulin mother with Rh -.
B. Introduction of anti-D globulin mother regardless of its sensitivity to anti - gene D.
B. The difference on ABO antigens between mother and fetus.
D. Massive blood hit the mother of a newborn, such as cesarean section.
Specify the main function of secretory IgA in local immune defense:
10.
A. Covers the mucosa of the reproductive system, where binds bacteria and toxins.
B. It stimulates the synthesis of acute-phase proteins.
B. Includes the complement system.
G. Activates phagocytosis.
D. bind circulating immune complexes and promotes their excretion.
What ids in transplant you know?
Problems of the second level
Problem number 1.
Patient 14 years for 3 - years suffers frequent respiratory infections (0 8-1 times a year) is a chronic
recurrent herpes simplex, chronic obstructive bronchitis with frequent relapses, athlete's foot. Over
7 years in areas of enhanced radiation monitoring. In a laboratory examination in the general
analysis of blood observed leukopenia, lymphopenia, slow sedimentation rate during exacerbation
of chronic infections akterialnyh b. To 5 - year-old child developed according to age, not sick.
What may indicate that data?
Answer: Acquired immune deficiency, infectious form
Problem number two.
Boy 2 years. At 4 months after vaccination against poliomyelitis in he developed right
hemiparesis. At 6 months, underwent bilateral purulent otitis, 1.5 years - twice acute bronchitis
with obstructive syndrome.
OBJECTIVE: child listless, pale shadows under the eyes, mucous throat pale, rear wall granular,
tonsils are not visualized. In lung auscultation hard breathing, no wheezing. Percussion root
expansion of the lungs.
Laboratory: 1.Gemograma: anemia, the number of leukocytes, lymphocytes - N;
2. Immunogram: - T - lymphocytes - B cells - the number is reduced - the level of
IgG <2 g / l; IgM, IgA not determined.
Your diagnosis?
Answer: The primary hereditary immunodeficiency, X - zscheplena agamoglobulinemiya syndrome
(Bruton).
Problem number 3.
Child B., 12 years old, suffers from childhood eczema with frequent colds (4-6 times a
year). Transferred all childhood infectious diseases. With 12 years of anxious repeated nosebleeds,
ear infections, about which regularly treated at the ENT doctor. On examination, attention is drawn
to the delay in physical development. Height 158 cm, weight - 50 kg. Skin dry, highlighted areas
of depigmentation on the back and chest, traces of scratching the skin folds of the elbows, shins
and popliteal fossa, the phenomenon of eczema: crack uch ASTK hemorrhage moknuttya,
lichenification, crusts. Peripherin regional lymph nodes as small (d -0, 3), but thick consistency.
Complete blood count: Er. - 3.0 × 1012 / L Hb - 120 g / l, MP - 0.9; leukocytes - 4.2 x 109 / l; segments
-68% eosinophils - 2% -5% monocytes, 15% lymphocytes ESR -20 mm / h; platelets - 110000.
Urinalysis: specific gravity -1018; protein-No sugar - does not exist; epithelial cells - individual in
sight leukocytes -5-8 in sight.
Immune status: CD3 (T-lymphocyte) - 45% (N -50 -75%); CD4 (T-helper) - 30% (N -30 -45%); CD8
(T c / k - suppressors) - 17 % (N -18 -35%); CD16 (NK-cell) - 9% (N-10-20%); CD20 (Blymphocytes) - 17% (N -15 -30%); SD22 -16% (N -15 -30%); CD25 receptor (IL) -18% (N-1020%); IgG -16 g / L (N -8, -12 0, 0 g / l) IgA - 2 , 3 g / L (N-1.4-2.0 g / l) IgM - 0.7 g / L (N -0, 8
-1, 5 g / L) IgE - 220 IU (N -0 -175 IU ).
Preliminary diagnosis of the patient?
A: Immune deficiency (congenital): Wiskott - Aldrich, vaccinated with X - chromosome (affects only
boys), autosomal - recessive inheritance.
Problem number 4.
Patient B., 13 years old, admitted to the hospital with complaints of fever up to 38 ° C, generalized
pyoderma with itching, sensation of heat in the skin, neck, arms, legs, I moknutt with an unpleasant
odor in the area of damaged skin. In the history - the flu, 3 months rubella. Above listed complaints
emerged after an illness.
On examination found pyoderma in the neck and forearms, peripheral regional lymphadenitis. Pulse
100 beats. / Min .. Rhythmic, muffled heart sounds, light over hard breathing, the abdomen is soft,
painless on palpation, the liver is increased by 1.5 cm, the spleen is enlarged by 2 cm in the study
of blood on the immune status revealed the absence of IgM, with normal values of other
immunoglobulins.
1. Preliminary diagnosis of the patient?
2. Forecast?
About Twet:
1. Acquired immune deficiency: selective IgM deficiency with clinical pyoderma.
2. The prognosis is favorable, subject to adequate immune.
Problem number 5.
Patient P., aged 17, complained of weakness, fatigue, dry cough and periodic Bookmarks nose. Sick
about 8 - months when after suffering a left lower lobe oh pozagospitalnoy pneumonia on a
background of a massive drug therapy has been revealed mild splenomegaly and there were
periodic bouts of fever with the above complaints.
From history we know: to grow and develop under normal conditions. At age 14, according to his
mother, suffered rubella, then ill sinusitis, bronchitis and otitis more frequently ill SARS and
conjunctivitis. Physician diagnosed chronic bronchitis, chronic rhinitis, chronic suppurative
bilateral sinusitis, X-ray examination at WGC - fibrosis case (S8 -9). Idiopathic
splenomegaly. Aplasia of the right kidney. Patients were examined at a hematologist, oncologist,
infectious disease.
Complete blood count: er. - 4.3 × 1012 / L; Hb - 136 g / l MP 0, 9; thrombocytes - 253.7 x 109 / L
WBC - 6.2h109 / l; segments - 59% 1% eosinophils; young -1%; coli - 4% -7% monocytes,
lymphocytes - 28%.
Immune status: CD3 (T-lymphocyte) - 58% (N -50 -75%); CD4 (T-helper) - 46% (N -30 -45%);, the
ratio of CD4 / CD8 - 1,7 (N -1,4-3), CD8 (T-suppressor) - 32% (N -18 -35%); CD20 - 20% (N 15 -30%);; IgG-0,3 g / L (N - 8.0-12.0 g / l) IgA - 0 (N-1, 4, 2, 0 g / l) IgM - 0 (N-1, 4, 2, 0 g /
l). Phagocytic index - 75% (N - 4,0-9,0%), HCT - spontaneous 11% (N -5 -12), HCT-stimulated 41% (N -20 -40%),. Phagocytic number -15% (N -50, -80 0, 0%). With repeated (2) studies no
significant difference in immunological parameters were found.
Blood cultures for sterility - growth is not obtained. Sowing scourages bronchi (bronchoscopy) obtained by moderate growth of fungi Candida. Sputum culture for Mycobacterium tuberculosis not found.
Bronchoscopy: endobronhit catarrhal inflammation in I. Ro - Distribution of the sinuses - cystic
sinusitis on both sides.
DNA detected by PCR of Epstein - Barr virus, cytomegalovirus. Herpes simplex virus DNA I-II and
VI types were found.
1. Preliminary diagnosis of the patient? 2. Forecast?
answer:
1. Secondary immunodeficiency: agammaglobulinemia infectious syndromes of different
localization (otitis media, sinusitis, bronchitis, etc.).
2. The prognosis is favorable, subject to adequate immune (prescriptions immunoglobulins
thymomimetic)
Tasks third level
Problem number 6
Patient G., 36 years old, the doctor-Impression, party elimination of the Chernobyl NPP, enrolled for
the treatment of dermatitis, onychomycosis of hands and feet, regional lymphadenitis, long
subfebrile (3 months to 37.5 C), general weakness. After prolonged exercise, and work on the
night shift the patient's condition deteriorated and turned to survey the district. These general
analysis of blood, urine, blood chemistry within normal limits.
Common leukocytes - 2.5 x 109 / L Lymphocytes - 21% CD3 (T-lymphocyte) - 40% (N -50 -75%);
CD4 (T helper) - 19% (N -30 -45%); CD8 (T-ts/k-supresory) - 20% (N -18 -35%), the ratio of
CD4 / CD8 - 0.9, CD16 (NK-cell) - 9% (N-10-20%); CD20 (B-lymphocytes) - 10% (N -15 -30%);
CD25 receptor (IL) -23% (N-10-20%); IgG-8,5 g / l (N -8, 0 - 12 0 g / l) IgA - 0.2 g / L (N-1, 4,
2, 0 g / l) IgM - 2.0 g / L (N -0, 8 -1, 5 g / l).
1. Preliminary diagnosis of the patient?
2. Recommendations.
About Twet:
1. Immunodeficiency acquired combined immune dysfunction (decreased cell, impaired immune
regulation, changing receptor cytokine profile and dizimunoglobulinemiya deficient IgA). IN I-II
degree.
2. Recommended clinical and laboratory dynamic immunological surveillance in clinical
immunology, immunotherapy and holding immunorehabilitation.
Problem number 7
Patient 19 years, smoking at age 11, moved from the TB clinic. From history we know: a child ill
with all infectious diseases, contact with TB patients were not. At the age of 15 years, was
convicted and was in prison for juvenile child. Over the past year while in prison by 2-3 times ill
COPD, sinusitis, otitis. Has recurrent herpes, candidiasis stop. On Po - gram OGC found focal
pneumonia of the upper lobe of the left lung. The patient received medical therapy, but for 2 years repeated pneumonia. After following pneumonia patient was transferred to the TB clinic for
specific therapy. Conducted specific TB treatment did not produce the desired effect, the clinical
manifestations of inflammation (low-grade fever, weakness, sweating), an increase of peripheral
cervical, axillary lymph nodes were stored. In the study there was no blood γ - fraction of
immunoglobulins. In sputum Office not found.
Complete blood count: er. - 3.9 × 10 12 / l; Hb - 111 g / l, MP - 0.9; leukocytes - 6.8 x 10 9 / l;
segments - 68% monocytes -8% -40 ESR mm / h; segments - 70% ; coli - 8% lymphocytes - 30%.
Urinalysis without pathology.
Immune status: CD3 (T-lymphocyte) -52% CD4 (T helper) -35% CD8 (T-suppressor) -26% CD20
(B-lymphocytes) - 20%; IgG 2.0 g / l IgA - 0.2 g / l IgM - 0.9 g / l; phagocytic index - 80%. ,
Phagocytic number - 4%.
1. Preliminary diagnosis of the patient?
2. Causal factors, the forecast?
answer:
Immunodeficiency with gipoimunoglobulinemieyu exclude common variable immunodeficiency.
2. Causal factors: number of immune stress in patients during adolescence
(Climate change, nervous stress, poor living conditions and malnutrition, smoking, antituberculous therapy massive. Forecast favorable provided the dynamic observation and
immunocorrective therapy.
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.Kliniko - anamnestic criteria immunodeficiencies
2. Laboratory evidence of immunodeficiency.
2. Trigger factors immunodeficiencies.
3. Types of tumor - associated antigens
4.Mehanizmy antitumor protection.
5.Imunologichni factors of tumor resistance.
6.Osnovni immunotropnyh approach to prescription treatments for cancer patients.
7.Aktivna, passive and adaptive immunotherapy of cancer patients.
8.Osobennosti immune response (local and systemic) in women / men.
9. Immunological tolerance to sperm woman husband.
10.Imunologiya normal pregnancy
11.Zahisni properties of human milk
12.Prichiny miscarriage
13.Imunologichni conflicts pregnancy, their diagnosis, treatment and prevention.
14.Vidy of immune infertility, their diagnosis.
15. Basic immunological mechanisms of autoimmune diseases
16. Clinical and laboratory evidence of the development of hyperacute, acute and chronic rejection
crises.
IX. conclusions:
1. Defined criteria for diagnosing early immunodeficiencies
2. General knowledge about the main types of tumor antigens.
3.Sformulovani basic mechanisms of antitumor immune protection.
4.Sformovani basic principles of tumor immunological
5.Viznacheni indications for immunotherapy of tumor diseases.
6. Mastered knowledge of the antigenic structure of male and female gametes.
7. The prevailing understanding of the immune response during pregnancy.
8. The main immunological causes of infertility.
9. General knowledge about the basic immunological mechanisms of autoimmune diseases
10. Mastered clinical and laboratory signs of s development of hyperacute, acute and chronic rejection
crises
Tasks for independent work on this topic:
1 / Make a list of the main groups of tumor antigens
2 /. Develop a table (schema) functioning of the major parts of the immune system of a person in
normal and cancer pathology
3 /. Make a plan immunological laboratory examination of the patient with suspected oncopathology
4 / Create a list of antigens of sperm and egg
5 /. Chart a survey couple with suspected increased degree of histocompatibility antigens HLA-on
system
6 /. Develop a table of differential diagnosis of various types of immunological conflict "motherfetus."
Practical Skills:
The student should be able to:
- Assess data from clinical and laboratory immunoassays in patients with immunodeficiency and other
immunopathology;
- Identify indications for immunotherapy of cancer patients;
- Assess the immunological parameters of local and systemic immune human
centuries and women;
- Predict the immunological conflict, the risk of miscarriage;;
- Characterize immunogram pregnant woman;
H. LIST UCH EBNO - methodical 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
PhD, Associate Professor OB Bondarchuk
Guidelines approved by the faculty meeting
"29" 08 "in the 2013 Protocol number 1
Head of Department
MD Professor BM Pukhlik