MINISTRY OF EDUCATION AND SCIENCE OF KYRGYZ REPUBLIC

Osh State University

INTERNATIONAL MEDICAL FACULTY
DEPARTMENT OF PATOLOGY, BASIC AND CLINIC PHARMACOLOGY DISCIPLINES.

"APPROVED"
at a meeting of the Department of ________
from "___" of ______________2019
Head. dept., Prof. ____________G. V. Belov.

METHODICAL INSTRUCTIONS FOR TEACHERS

SECTION: GENERAL PATHOPHYSIOLOGY.
TOPIC: ALLERGY.

Developed by: Teacher Esengeldieva O.

The methodical instruction was approved at the meeting of the department
____ ______________ 20__. Protocol No. ____

OSH
 TOPIC: ALLERGY.

Purpose of the lesson: Be able to conduct the pathophysiological analysis of allergic and immune
reactions.
.

The list of practical skills:

1. To be able to differentiate common and local signs of inflammation.
2. To be able to determine the stage of the inflammation.
3. To be able to conduct a pathophysiological analysis of clinical situations and
experimental results, the basis of which is the process of inflammation.

Educational goal:
 Strive to foster a sense of humanism, collectivity, respect for elders, mutual feelings of
subordination, responsiveness;
 Strive to foster a sense of responsibility for their work, sense of duty, integrity, sense of duty;
 Strive to develop a sense of pride in the chosen profession, ability to manage emotions.

Timing of the lesson:

No STAGES OF THE SESSION TIME

.
1 Introduction:
Announcement of the lesson theme, methodical and organizational5 5 min
instructions of the lesson
2 The relevance of the basic knowledge of students (exercises, game and
etc. necessary as a support for learning a new mother):
A. Benchmark control 10 min
B. Case-method 15 min

3 The initial motivation of educational activity ( to interest in the study of 5 min

the topic: the need for the professional activity.)

4 Study of new material (consistent presentation "from simple to complex"

with the opportunity to see visual demonstration)
A. Oral survey 40 min
B. Final level control test 10 min

5 Work in small groups:

a.Solving situational cases 10 min
b. Discussion of the results 15 min
c.Practical work 20 min
6 The final part of the session (summarizing the lesson, marks.) 5 min
 PRACTICAL PLAN
1. Contents of the lesson:
1. Allergy. Etiology. Pathogenesis.
2. Stages of allergy.
3. Types of allergy.
4. Modeling.
2.Class location: Department of Pathology. Bacis and clinical Pharmacology
3.Material and technical support:
I. Equipment:
1. Personal computer (laptop)
2. Multimedia projector
II. Chemical Reagents and Materials:
III. Animals:
IV. Tables:
V. Media file
1. Slides
2. Video

4. Tasks taking into account the competence approach to training:

 Form and develop skills of analysis on the material passed,
 To acquaint students with etiology, pathogenesis and clinical manifestations,
 Teach the principles of diagnosis and treatment,
 Teach basic principles of prevention,
 To teach to assess the severity of the condition, the outcome of the disease and the prognosis,
 Develop the personal qualities of a specialist,
 Form and develop the skill of effective communication between the doctor and the patient,
 Teach you how to work with information,
 Stimulate the continuous increase of knowledge throughout life ...

5. Expected results:
The student should know:
 The content and structure of the topic.
 Basic concepts of the theme
 The role of causes and conditions in the occurrence of inflammation.
 Mechanisms of development of typical pathological processes (inflammation), their
manifestations and significance for the organism.
 The importance of modeling and experimental therapy in the study of the etiology and
pathogenesis of pathological processes and diseases
The student should be able to:
 Apply this knowledge to the study of clinical pathophysiology and clinical disciplines
 Interpreting the results of clinical and laboratory studies
 Recognize the main typical pathological processes, which are components of various diseases
 Plan experiments on animals, process and analyze the results of experiments
 Model some pathological processes
 Independently work with scientific, educational and reference literature, catalogs in the
library, Internet sites
 METHODICAL AND ORGANIZATIONAL GUIDELINES FOR THE TEACHER TRAINING
1. The teacher explains the order of the lesson.
2. The first part includes a programmed control of students' knowledge and a theoretical
survey.
3. The second part of the session is the independent work of students and discussion of the
results.

CONTROL OF THEORETICAL TRAINING OF STUDENTS

1. Programmable control
2. Solving situational cases
3. Survey on the following questions:

Questions to repeat:

1. Structure and functions of the immune system. Cooperation of immunocompetent

cells. Characteristics of the main cells - T-lymphocytes, B-lymphocytes, plasma cells.
2. Humoral and cellular immunity - features of the cooperation of macrophages, T- and B-
lymphocytes. Effector cells and memory cells in humoral and cellular immunity. Plasma cells
and the stage of their differentiation.
3. Classes of immunoglobulins, their nature and the stick.
4. Regulation of immune reactions.
5. Classification of antigens.

Questions for the lesson:

1. Allergy. General characteristic of allergy.

2. Mutual relations of allergy and immunity.
3. Allergens. Classification. Nature of allergens.
4. Types of allergic reactions, their classification.
5. Stages of allergic reactions.
6. Characteristics of allergens, mediators and mechanisms of allergic reactions.
7. Autoimmune diseases. Etiology, pathogenesis, clinical forms.
8. The role of external and internal factors in the pathogenesis of autoimmune diseases .
9. Methods of diagnosis, prevention and treatment of allergy.

LITERATURE
1 Lee – Ellen C. Copstead and 1 more Pathophysiology 5th edition.
2 Gary D. Hammer and 1 more Pathophysiology of Disease 7th edition
3 Нarold J. Bruyere Jr. PhD 100 Case Studies in Pathophysiology
4 Сarol Porth RN MSN Phd – Essentials of pathophysiology 4th edition
5 Ysmeen Agosti and 1 more MedMaps for pathophysiology 1th edition

Educational-methodicalmanual:

1 Atlas of Pathophysiology / Kalmatov R. K..- OshSU - 2015. -210 С.

Abstract.
Allergy - a pathological form of the immunogenic reactivity. Formed, usually as a result of reexposure
of cells of the immune system to a foreign antigen. It is accompanied by a change (usually
- increase) the sensitivity to a given antigen. Characterized detection, and often the
destruction and
elimination of foreign antigen, as well as damage to the body's own structures, reduced its
adaptive
capacity and impaired his life.
Allergen is a substance that causes development of an allergic reaction. Allergens have all properties
of antigens (macromolecularity, mainly protein nature, foreign for a particular\ organism). However
allergic reactions can be caused by substances of not only antigen nature, but also substances, not
possessing these properties. To this group belong many officinal preparations, bacterial products,
polysaccharides, simple chemical substances (bromine, iodine, chrome, nickel). These substances are
called haptens. While entering the organism they become antigens (allergens) only after binding with
tissues proteins. Here with complex antigens, which sensitize the organism are formed.

The three stages are: -

1. Immunological stage. It covers all the changes in immune system during the penetration
of an allergen into the organism, formation of antibodies or sensitized lymphocytes and
their binding with the repeatedly entering allergen.
2. Pathochemical stage. Its sense is in formation of biological active substances. The
stimulus to their formation is the binding of allergen to antibodies or sensitized
lymphocytes at the end of immunological stage.
3. Pathophysiological stage. It is described by pathogenic action of formed mediators onto
cells, organs and tissues of the organism with a clinical display.

Types of allergy:
Type I hypersensitivity (or immediate hypersensitivity) is an allergic reaction provoked by re-
exposure to a specific type of antigen referred to as an allergen.[1] Type I is not to be confused
with type II, type III, or type IV hypersensitivities, nor is it to be confused with Type I Diabetes
or Type I of any other disease or reaction.

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. It typically
causes more than one of the following: an itchy rash, throat or tongue swelling, shortness of
breath, vomiting, light-headedness, and low blood pressure. These symptoms typically come on
over minutes to hours. Common causes include insect bites and stings, foods, and medications.
Other causes include latex exposure and exercise. Additionally, cases may occur without an
obvious reason. The mechanism involves the release of mediators from certain types of white
blood cells triggered by either immunologic or non-immunologic mechanisms. Diagnosis is
based on the presenting symptoms and signs after exposure to a potential allergen.

Type II hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an IgG
and IgM antibody mediated process in which an antibody is directed against antigen on cells
(such as circulating red blood cells) or extracellular material (such as basement membrane) and
subsequently leads to cell lysis, tissue damage or loss of function through mechanisms such as
1. Complement activation via the classical complement pathway
2. Antibody dependent cell-mediated cytotoxicity or
3. Anti-receptor activity.
 Type III hypersensitivity occurs when there is accumulation of immune complexes (antigen-
antibody complexes) that have not been adequately cleared by innate immune cells, giving rise
to an inflammatory response and attraction of leukocytes. Such reactions may progress to
immune complex diseases.

☻The foreign antigen is phagocyte by macrophages and get to T-helpers.

☻ at the same time macrophages secrete IL-1, which stimulates T-helpers. The latest excrete
the growth factor pro-T-lymphocytes – IL-2, which activates and supports proliferation of
antigen stimulated T-cells.
☻This process leads to formation of sensitized lymphocytes.
☻They belong to T-lymphocytes and in the cell membrane they have receptors of the antibody
type, which are able to connect with the antigen.
☻ In case of repeated penetration of the allergen into the organism it binds with the sensitized
lymphocytes.
Type IV allergic reactions
In Type IV hypersensitivity reactions (cell-mediated, delayed-type) not participating AT, and T-cells,
interacting with the respective antigen (sensitized T cells) that attract macrophages into the hearth of
allergic inflammation. The sensitized T cells after antigen binding have any direct cytotoxic effect on
target cells or their cytotoxic effect is mediated via lymphokines. Examples of reactions of the type IV
- allergic contact dermatitis, tuberculin skin test for tuberculosis and leprosy, and transplant rejection
reactions.
Causes - The components of micro-organisms (pathogens of tuberculosis, leprosy, brucellosis,
pneumococci, streptococci), single and multicellular parasites, fungi, helminths, viruses and
viruscontaining cells. - In-house, but modified (eg, collagen) and foreign proteins (including those
located in vaccines for parenteral administration). - Haptens example, drugs (penicillin, procaine),
small molecule organic compounds (dinitrohlorfenol).
Stage sensitization - There is a differentiation antigen-T cells, namely CD4 + helper T 2 (T-effector
delayed hypersensitivity reactions) and CD8 + cytotoxic T lymphocytes (killer T cells). These
sensitized T cells circulate in the internal environment of the body, performing a supervisory function.
Part of lymphocytes is in the body for many years, keeping the memory of the antigen. - Repeated
exposure of immune cells to the antigen (allergen) causes blast transformation, proliferation and
maturation of many different T-lymphocytes, but preferably T-killers. They exhibit together with
phagocytes and subjected to degradation foreign antigen, and - the bearer.

ALLERGIC REACTIONS TYPE I

(Reaginic, atopic, anaphylactic)
Allergies - ekzoallergeny
atopy: food, medicines, pollen, household, epidermal
anaphylaxis: drugs administered parenterally antibiotics (especially lactam series), procaine,
therapeutic and diagnostic serum in small doses

I . STAGE immune response

a) the sensitization phase (the first contact with the allergen organism):
- Macrophage phagocytosis of antigen, refining it;
- The reaction of cell cooperation;
- Synthesis of immunoglobulins: atopic form - of IgE , anaphylaxis - of IgG ;
- Fixing the antibody on the surface of target cells I order (basophils, mast cells ie current).
b) the authorization phase (with the repeated contact of the body with the allergen)
- The formation of the antigen + antibody on the surface of target cells in the order I cr about vie.
II. pathochemical STAGE
cell mediators:
 from about I target cells (basophils, mast cells):
- release preexisting mediators : histamine, heparin, Factor hemotaks and eosinophils ca (FHE-A),
neutrophil chemotactic factor (FHN-A), basophilic calli to rhein;
- synthesis of newly formed mediators : leukotrienes C E and D , prostaglandin D , F to the torus
4, 4 4 2

and to platelet activation (PAF), thromboxane A ; 2

 from the order of the target cells II:

- the release of pre-existing mediator : from neutrophils - cationic proteins, l and zosomalnyh
enzyme peroxidase; of eosinophils - histaminase, arilsulf and basins; platelet - serotonin, histamine;
- synthesis of newly formed mediators : leukotrienes (LT), prostaglandin (PG), tro m boksanov (T)
and lipid peroxidation metabolites;
humoral mediators
- kallikrein-kinin system (bradykinin, kallidin);
- proteins of the complement system (with anaphylactic forms of AR Type I);
- blood clotting factors (Hageman factor).

III. pathophysiological STAGE

- increased permeability of capillaries (histamine, serotonin, bradykinin, leukotriene D 4 , PG the
F 2a ) tissue edema;
- expansion of arterioles and capillaries (histamine, bradykinin) local hyper e mia;
- stimulation of pain receptors pain, itching;
- smooth muscle contraction (histamine, leukotriene D 4 , PG D 2 , PAF, TA 2 , PG the
F 2a ) bronchospasm; histamine spasm of the sphincter of the hepatic veins abnormal
deposited and of the blood hypovolemia decrease in blood pressure;
- increase mucus secretion (histamine);
- cell damage (lipid peroxidation metabolites, lysosomal enzymes).

CLINICAL MANIFESTATIONS
atopic form : atopic form of bronchial asthma, hay fever, urticaria, angioedema, food allergy;
anaphylactic forms : anaphylactic shock.
ALLERGIC REACTIONS TYPE II
(Cytotoxic, cytolytic)

Allergies - endoallergeny

primary (natural) - the brain, the lens, testicles, thyroid colloid (if damaged gistogematicheskih barriers);
secondary (acquired) - components of the cell and basal membranes, vidoizm e nennye under the
influence of drugs, chemicals, physical (cold, heat, for the sake of a tion) factors; not a fixed cage foreign
substance (hapten).
I . STAGE immune response

a) the sensitization phase (education autoallergenov):

- refining macrophage antigen;
- cell response cooperation;
- synthesis of autoantibodies ( Ig M, IgG ).

b) the authorization phase (with repeated contact with the allergen the organism):
- formation of antigen + antibody complex on the surface of target cells.

II. pathochemical STAGE

humoral mediators:
- components of the complement system (C 4b, 2a, 3b , C 3a , C 5a );

cell mediators:
- lysosomal enzymes;
- PAUL metabolites (superoxide anion, hydrogen peroxide, singlet oxygen, hydraulic on ksilny
radical).

III . pathophysiological STAGE

1. complement-dependent cytolysis 2. komplementnezavisimy cited for lys

activation of cytotoxic antibody components of the complement system through the complex a / r + a /
r action killer cells

CLINICAL MANIFESTATIONS

autoimmune hemolytic anemia, leukopenia (an autoimmune form of agranulocytosis), thrombocytopenia,

thyroiditis, nephritis, myocarditis, hepatitis.

ALLERGIC REACTIONS TYPE III

(Immunocomplex)

Allergies - ekzoallergeny

soluble protein parenterally administered in large amounts (treatment syvoro t ki, blood plasma, vaccines)
 3. STAGE immune response

a) the sensitization phase (during the initial contact with the allergen)
- refining of the antigen by macrophages;
- cell response cooperation;
- c Intesa precipitating antibodies, mostly of IgG , of IgM .
b) the authorization phase (with repeated contact with the allergen)
- education krupnomolekulyarnyh freely circulating komple to cos a / r + a / t.

4. pathochemical STAGE

humoral mediators:
- components of the complement system (C 3 , C 4 , C 5 );
- coagulation proteins in blood plasma system (Hageman factor, fibrinogen).

cell mediators:
- release preexisting mediators from mast cells : histamine, hep a width of, eosinophil chemotactic
factor (FHE-A), neutrophil chemotactic factor (FHN-A), basophilic kallikrein; of neutrophils - cationic
proteins lizosomal s enzymes, peroxidase; of eosinophils - histaminase, arylsulfatase; TPO m botsitov -
serotonin, histamine;
- synthesis of newly formed mediators : leukotrienes, prostaglandins, tromboks a new, cytokines (IL-1,
IL-6), lipid peroxidation metabolites.

III . pathophysiological STAGE

- cell damage (vascular endothelium, synovial membranes, mast cells, platelets, leukocytes)
complexes activated complement system, lysosomes of mum 's E enzymes, metabolites of lipid
peroxidation;
- the development of allergic inflammation with severe impaired microcirculation I tion, an
increase in blood clotting, fever.

CLINICAL MANIFESTATIONS
- vasculitis - periarteritis nodosa, hemorrhagic vasculitis, nodular erythema, glom e rulonefrit;
- rheumatoid arthritis;
- Arthus phenomenon;
- pancytopenia, granulocytopenia;
 DIC;
 serum sickness.

Type IV allergies
(Delayed, cell, tuberculin)
ALLERGIES
 ekzoallergeny: bacteria (pathogens of tuberculosis, brucellosis, salmonellosis), viruses (n p pesos,
measles), mushrooms, transplant;
 endoallergeny:
primary (natural) - the brain, the lens, testicles, thyroid colloid des e PS (at PWA Well Denia
gistogematicheskih barriers);
secondary (acquired) - components of the cell and basal membranes, Vido s Menen under the influence
of drugs, chemicals, physical (cold, heat, radiation) factors; not a fixed cage foreign substance
 (hapten); tumor glue t ki.

I. STAGE immune response

a) the sensitization phase (the first contact with the allergen organism)
- Refining macrophage antigen;
- Reaction cell cooperation;
- Formation of a clone to an allergen sensitized T lymphocytes;
b) the authorization phase (with repeated contact with the allergen the organism):
- The interaction of sensitized T cells to the allergen.

II. pathochemical STAGE

mediators - lymphokines

lymphokines acting on lymphocytes:

- transfer factor (transfer of HRT, increased cytotoxicity, increased blasttransform and tion);
- blasttransformiruyuschy factor mitogenic factor (determined blastoderm and mitogenic
and to ciency);
lymphokines acting on phagocytosis (micro and macrophages):
- factors chemotaxis (attraction center in micro- and macrophages);
- factors activating micro- and macrophages;
- factor depressing the migration of phagocytes (macrophages contributes to the accumulation of
the B field of allergic reaction);
lymphokines act on target cells:
- lymphotoxin (cytotoxic effect);
- interferon (antiviral activity, enhances cytotoxicity whether mfotsitov, act and viruet
phagocytes);
- factor inhibiting proliferation (inhibits growth of the cell cultures).

III. pathophysiological STAGE

4. infiltration hearth allergic inflammation lymphocytes, monocytes and Tami;

5. microcirculation disturbance in the outbreak, increased vascular permeability (kinins,
hydrological and cal enzymes, permeability factor) edema;
6. cell damage:
7. direct cytotoxicity of sensitized T lymphocytes ;
8. the cytotoxic effect of lymphotoxin ;
9. lysosomal enzymes .

CLINICAL MANIFESTATIONS
tuberculin reaction, infectious and allergic diseases, contact dermatitis, e to Zema, transplant rejection,
tumor immunity.

MCQ’S
 1. The Worldwide HIV/AIDS campaigns have made significant progress over the last years. The HIV
infection rates in Europe
a) Have been significantly decreasing
b) Have been unchanged
c) Have been increasing
d) Are unknown
Question 2

Inviduals suffering from inhalant allergies may also react to cross- reacting food allergens. A person
suffering from a natural latex allergy might not react to one of the following allergens
a) avocado
b) mango
c) peach

d) figs
Question 3

Infants and children with a suspected food allergy e.g. cow's milk allergy/intolerance could display the
following symptoms and signs:
a) Severe atopic dermatitis
b) Enter colitis
c) Diarrhoea

d) all of the above

Question 4

More and more detrimental effects of malnutrition during childhood and adult life have been
identified. The effects of over nutrition e.g. overweight and obesity are less well known. Overweight
and obesity are associated with which of the following
a) Cardiovascular disease
b) Breast cancer
c) Type 2 diabetes (maturity onset)

d) all of the options given are correct

Question 5

Food supplements, including trace minerals and vitamins are frequently advertised with promising
health benefits. Which of the following substance could be consumed in excess, i.e. well above the
recommended daily requirement?
 a) Vitamin C
b) Vitamin D
c) Zinc

d) Vitamin A
Question 6

Please complete the following statement: Bacteria with an assumed health benefit (probiotics):
a) Maintain their gut colonisation even after stopping intake
b) Exert normally strain specific effects only

c) Are a recent discovery

Question 7

Although theoretically any food protein could act as a food allergen, there are eight major food
allergens in Europe and North America which account for most of the allergic triggers observed in
childhood. Which of the allergens pairings contains an allergen, which is not part of the group of eight
major allergens?
a) Cow's milk, egg
b) Mustard seeds, lamb,
c) Soy, peanuts

d) Fish, shellfish
Question 8

Intestinal lactase deficiency leads to lactose maldigestion which subsequently can lead to lactose
intolerance, i.e. causing clinical symptoms. Infants and children normally express sufficient lactase
levels as not to experience clinical symptoms. Overall, adults can be classified as lactase-persisters or
lactase non-persisters. What is the approximate percentage of Lactase non-persisters worldwide?
a) 45%-50%
b) 70%-75 %
c) 10%-15%

d) 30%-35%

Question 9

It has been observed that a reduction in family size and improved sanitary condition have led to an
increase in allergic conditions. The 'hygiene hypothesis' suggests that
a) The frequent use of antiseptic swipes will reduce allergies
b) Living on a working farm will help reducing the development of atopic diseases
c) Particular care must be taken during breast feeding in high risk infants
 d) Living on a working farm will increase the development of atopic diseases
Question 10

Occasionally infants are born without a normally functioning immune system. What are the signs most
suggestive of a severe combined immunodeficiency?
a) Recurrent severe infections
b) Family history of unexplained death in infancy
c) Generalised spread of the Tuberculosis strain BCG after vaccination

d) All of the options given are correct