MINISTRY OF PUBLIC HEALTH OF UKRAINE
BUKOVINIAN STATE MEDICAL UNIVERSITY
Approval on methodological meeting of the department of pathophisiology
Protocol №
Chief of department of the pathophysiology, professor Yu.Ye.Rohovyy
“___” ___________ 2008 year.
Methodological Instruction to Practical Lesson
Мodule 1 : GENERAL PATHOLOGY.
Contenting module 1.
General nosology.
Theme5 : Immunopathology disease. Allergy.
Chernivtsi – 2008

1.Actuality of the theme.
The immediate-type allergy is often met in practical activity of physicians of various specialties. That is because of the great environmental pollution by industrial products, chemical matters, and allergens of vegetable animal, bacterial, fungus origin and also due to wide use of various drugs. That type of allergy can develop suddenly. The severity of their proceeding is various – from slight reactions to anaphylactic shock dangerous for one’s life.
Preventing and treatment of the allergy reactions is based on knowledge about their development mechanisms.
2.Length of the employment –
2 hours.
3.Aim:
To khow that allergy is a complex of breaches, appearing in our organism by the humoral and cellular immunological reactions. Both inflammation and allergy is protective response on the exo- and endogenous factor.
To be able: to analyse of the Pathogenesis of allergy by A.D. Ado.
To perform practical work: to analyse the mechanisms of
Anaphylactic type
Cytotoxic type
Immune complex disease
Cell – mediated
(delayer) hypersensivity
Stimulating allergic reactions.
Via hormones,
BAS, mediators immunologycally mediated disorders by Coombs and Yell (1968)
№ Type Prototype disorder Immune mechanism
3.
4.
5.
2.
1. Anaphylaxia, some forms of bronchial asthma
Autoimmune anemia, hemolytic erythroblastosis fetalis, cytotoxic reactions the action of large doses of
Bogomglets’s ACS
(antireticular serum) cytotoxic
Arthus reaction serum sickness, systemic lupus erythematosus, certain forms of acute glomerulonephritis
Tuberculosis, dermatitis, rejection contact transplant
Collagen diseases, connective tissue diseases, rheumatoid arthritis and other.
Formation of IgE (cytotropic) antibody → release of vasoactive amines and other mediators from basophils and mast cells.
Formation of IgG, IgM → binds to antigen on target cell surface → phagocytosis of target cell or lysis by C8,9
Ag + Ab →activated Co → attracted complexes neutrophills → release of lysosomal enzymes
Sensitized thymus-derived
T-lymphocytes
→ release of lymphokines and T-cell-mediated cytotoxicity.
The cells, containing Ag, begin to function intensively under the influence of Ab. Than cells are secreted hormones or mediators.

The name of the previous disciplines
1.
2.
3.
4. Basic level. histology biochemistry physiology
The receiving of the skills
Structure and function of organs and vessels.
Immunity and its mechanisms.
Antigens and antibodies, their structure and function.
5. The advices for students.
1. Define allergy, autoimmunity and alloimmunity.
Hypersensitivity is an excessive immunologic reaction to an antigen that results in a pathologic response after reexposure to the same antigen. Allergy, autoimmunity, and alloimmunity are hypersensitivity response; the difference is the source of the antigen to which the hypersensitivity is directed.
Allergy is a hypersensitivity response against an innocuous environmental antigen that is harmful to the individual.
Autoimmunity occurs when tolerance to one’s self-antigens breaks down and antibody is formed against one’s own antigens. Self-antigen are recognized as foreign in autoimmunity, and host tissues are destroyed by autoantibodies.
Alloimmunity is the development antibodies against antigens from an individual of the same species. It is observed during immunologic reactions against transfusions, grafted tissue, or a fetus during pregnancy.
2. Characterize the classification of allergens.
Classification and characteristic of allergens.
By origin and nature: Endogenic, Exogenic
By ways of penetration into an organism: food, natural, acquired, respiratory, alimentary, medicinal, brain, uninfectious, infectious, «contact», dustle, lens, cold, simple, parenteral, pollens, sexual glands, burn, complex, transplacental, epidermal, thyroid gland, radiation, tissue-microorganism, tissue-toxine, everyday chemical compounds, serous, infectious-parasitogenic.

3.
Describe pathogenesis of allergic reaction
Activation of mast cells in type 1 hyper-sensitivity and release of their mediators:
ECF- eosinophil che-motactic factor; NCF- neutrophil chemotac-tic factor; PAF- pla-telet-activating factor.

Delayed Hypersensitivity (Type IV)
4. Compare the hypersensitivity disorters.
Type I. IgE mediated. Anaphylactic. Humoral/Immediate. Antigen reacts with
IgE bound to mast cells, histamine release, histamine effects. Allergy: Allergic rhinitis, asthma, urtcaria, food allergies, anaphylactic shock

Type II. Cytotoxic. Tissue specific. Humoral/Immediate. IgG or IgM reacts with antigen on cell’s membrane, complement is activated, lysis or phagocytosis by macrophage of cell, cell mediated cytolysis, antibody, binding to receptors.
Allergy: Immediate drug reaction. Autoimmunity: Hemolytic anemia, Graves disease. Alloimmunity: Transfused blood cells, hemolytic disease of the newborn
Type III. Immune complex. Humoral/Immediate. IgG or IgM unite with antigen to form a complex is deposited in vessel walls or tissues, neutrophil attraction, complement activation, lysosomal enzymes injure tissue. Allergy: Arthus reaction, that of allergic alveolitis. Autoimmunity: Serum sickness, celiac disease, glomerulonephritis, systemic lupus erythematous
Type IV. Cell-mediated. Cellular/Delayed. Reaction sensitized T-lymphocytes with antigen lead to lymphokine release, recruitment of macrophages and lysosomal release. Allergy: Contact dermatitis. Autoimmunity: Hachimoto thyroidites, rheumatoid arthritis. Alloimmunity: Graft rejection. Seldom a particular disorder is associated with a single mechanism.
5. Describe the likely causes of autoimmune disease; cite examples.
Self-antigens are usually tolerated by the host’s own immune system. This immunologic tolerance develops in humans during the embryonic period.
Autoteactive lymphocytes are either eliminated or suppressed. Autoimmunity is a breakdown of tolerance in which the body’s immune system begins to recognize self-antigens as foreign. The mechanisms of breakdown are varied and often unknown. Some of the mechanisms implicated in the development of autoimmunity include (1) exposure within the body of a previously sequestered antigen, (2) the development of a neoantigen, (3) the complications of an infectious disease, and (4) an alteration of suppressor T cells.
To be tolerated after birth, a self-antigen must be present in the fetus and exposed to the developing fetal immune system. Some self-antigen never encounter antigen-processing cells in the draining lymph nodes or other lymphoid organs. They are sequestered or hidden from the immune system. Later, the immune system will recognize these antigens as foreign, if the structure of a site having sequestered antigen is disturbed and the previously sequestered antigens are released from the damaged tissue and enter the lymphatics. A primary immune response occurs against these antigens that can inflict extensive immunologic damage to other, similar antigenic, untraumatized sites.
Many neoantigens are haptens that become immunogenic after binding to host proteins. The immune reaction against the neoantigen may lead to an immunologic reaction against unaltered host protein.
Foreign antigens from infectious microorganisms can initiate autoimmune disease. They do so either by forming immune complexes that precipitate in host tissues and cause inflammatory disease or by closely resembling a particular selfantigen. The antibodies produced against the similar antigenic sites of the infectious agent also recognize the self-antigen as foreign. Group A streptococci are capable of initiating both of these mechanisms usually as sequelae to streptococcal pharyngitis.

One of the roles of suppressor T cells is to suppress the immune responses against self-antigens. Therefore suppressor T cell dysfunction could result in autoimmune disease. If a single antigen-specific population of suppressor cells is affected, a tissue-specific autoimmune reaction could result. A generalized autoimmune reaction could occur if many suppressor cell populations were dysfunctional. Systemic lupus erythatosus (SLE) may be caused by a general breakdown in the suppressor cell network.
The cause of some immune diseases is quite apparent. For example, in thrombocytopenia (or few platelets), there is likely integration of a drug or its metabolite into the plasma membranes of the platelet. The immune system recognizes the altered plasma membranes as new and foreign. B cells are stimulated to produce antibody against the drug-cell complex, and immune processes destroy the host cells. Viruses can induce autoimmune reaction by altering the plasma membranes of host cells.
Other common autoimmune diseases include rheumatoid arthritis, multiple sclerosis, pernicious anemia, and ulcerative colitis. It is fairly well established that autoimmune diseases are familial.
Affected family members may not all develop the same disease, but several members may have different disorders characterized by hypersensitivity. An individual with a specific genetic HLA type may have inappropriate or exaggerated immune responses against a microorganism that result in a hypersensitivity reaction.
6. Characterize alloimmune graft rejection.
Alloimmunity occurs when an individual’s immune system reacts against of the tissues of other members of the same species. Transplantation of organs is commonly complicated by an alloimmune response against donor antigens. The primary mechanism of the rejection of transplanted organs is a type IV, cellmediated reaction. Because HLA antigens are the principle targets of the recipient this greatly enhances the possibility of a successful graft.
Transplant rejection is classified as hyperacute, acute, or chronic depending on the amount of time that elapses between transplantation and rejection. Hyperacute rejection usually occurs in recipients having preexisting IgG or IgM antibody to antigens in the graft. As circulation to the graft is reestablished, antibody binds to the grafted tissue and activates the inflammatory response. This response initiates the coagulation or blood clottirng cascade that results in cessation of blood flow in into the graft.
Acute rejection is a cell-mediated immune response that occurs approximately 2 weeks after the transplantation. The recipient develops an immune response against unmatched HLA antigens and shows an infiltration of lymphocytes an macrophages characteristic of type IV hypersensitivity reaction. Chronic rejection occurs after months or years of normal function. It is characterized by slow progressive organ failure. Chronic rejection may be caused by inflammatory damage to endothelial cells lining blood vessels. It is likely a result of a weak immunologic reaction against minor histocompatibility antigens on the grafted tissue.

5.1. Content of the theme.
Define allergy, autoimmunity and alloimmunity. Characterize the classification of allergens. Describe the pathogenesis of allergic reaction. Compare the hypersensitivity disorders.
Describe the likely causes of autoimmune disease; cite examples. Characterize alloimmune graft rejection.
5.2. Control questions of the theme:
1. Define allergy, autoimmunity and alloimmunity.
2. Characterize the classification of allergens.
3. Describe the pathogenesis of allergic reaction
4. Compare the hypersensitivity disorders.
5. Describe the likely causes of autoimmune disease; cite examples.
6. Characterize alloimmune graft rejection.
5.3. Practice Examination .
I.
Circle the correct answer or answers for each question.
1.
Immunologic response(s) recognized as disease is/are:
A. Immediate hypersensitivity
B. Delayed hypersensitivity
C. Both A and B are correct
D. Neither A nor B correct.
2. Which is not characteristic of hypersensitivity?
A. Specificity
B. Immunologic mechanisms
C. Inappropriate or injurious response
D. Prior contact unnecessary to elicit a response.
3. When the body produces antibodies against its own tissue, it is a/an:
A. Hypersensitivity
B. Immunologic reaction
C. Cell-mediated immunity
D. Autoimmune disease
E. Opsonization
4. Viruses can:
A. Decrease cellular protein synthesis
B. Alter host cell antigenic properties
C. Transform host cells into cancerous cells
D. A and C are correct
E. A, B and C are correct.
5. Damage in glomerulonephritis is due to the formation of antigen/antibody complexes mediated by:
A. IgE
B. Mast cells
C. The cell-mediated immune system
D. The humoral immune system
E. Lymphokines.
6. The classical complement cascade begins with

A. Antigen/antibody complexes binding to a component of the complement system
B. Opsonization
C. Chemotaxis
D. Cytolysis.
7. An alloimmune disorder is:
A. Graft rejection
B. Insulin-dependent diabetes
C. Myxedema
D. All of the above are correct
E. None of the above is correct.
II.
Match the with the immunologic mechanism condition .
8. Serum sickness
9. Allergic rhinitis
10. Systemic lupus erythematous
11. Contact dermatitis
12. Hemolytic anemia
13. Rheumatoid arthritis
A. IgE mediated
B. Cytotoxic/tissue specific
C. Immune complex
D. Cell-mediated
Literature:
1. Gozhenko A.I., Makulkin R.F., Gurcalova I.P. at al. General and clinical pathophysiology/ Workbook for medical students and practitioners.-Odessa, 2001.-
P.107-115.
2. Gozhenko A.I., Gurcalova I.P. General and clinical pathophysiology/ Study guide for medical students and practitioners.-Odessa, 2003.- P.105-116.
3. Robbins Pathologic basis of disease.-6 th ed./Ramzi S.Cotnar, Vinay Kumar,
Tucker Collins.-Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.-1999.