CLINICAL IMMUNOLOGYCLINICAL IMMUNOLOGY

CLINICAL IMMUNOLOGY -DISEASES OF IMMUNE SYSTEM

CLINICAL IMMUNOLOGY -DISEASES OF IMMUNE SYSTEM

Clinical immunology is a separate field of human medicine. It represents research, diagnostics and therapy of diseases of

the immune system.

Many of primary diseases is often associated with disorders of the immune system.

DISEASES OF THE IMMUNE SYSTEMDISEASES OF THE IMMUNE SYSTEM

IMMUNODEFICIENCIESdisorders of one or more parts of the immune system it leads to a decreased activity of the immune system

primary, secondary

HYPERSENZITIVITYlocal or systemic immune reaction leading to tissue damage mediated by antibodies, cells or immune complexes

1st, 2nd, 3rd, 4th type

AUTOIMMUNE DISEASESspecific immune reaction against self-antigens leading to damage

systemic, organ-specific

LYMPHOPROLIFERATIVE DISEASEStumor diseases originating from cells of the immune system

leukemias, lymphomas, myelomas, gamma-pathies

IMMUNODEFICIENCIESIMMUNODEFICIENCIES

Disorders of one or more parts of the immune system

Common clinical signs include chronic or recurrent infections caused also by organisms in normal circumstances less

pathogenic

IMMUNODEFICIENCIES - TERMINOLOGYIMMUNODEFICIENCIES - TERMINOLOGY

PRIMARY IMMUNODEFICIENCIES congenital, genetically mediated disorders

SECONDARY IMMUNODEFICIENCIES acquired disorders originating under influence of many external or internal factors

Immunosuppression - decreasing of the immune system activity due to concrete reason - usually transient

Immunodeficiencies - disorder of the immune system persisting also after disappearing of primary reason

PRIMARY IMMUNODEFICIENCIESPRIMARY IMMUNODEFICIENCIES

Numbers of syndromes have been described. Some of them have been described on genus level, in other only clinical signs.

Based on type of affection, they can be divided to combinedT lymphocyteB lymphocyte and antibodiesphagocytosiscomplement

Prevalence of primary immunodeficiencies is low.

Severity of clinical signs depends on type of impairment

IMMUNODEFICIENCIES IN DIFFERENT PHASES OF CELL DEVELOPMENT

IMMUNODEFICIENCIES IN DIFFERENT PHASES OF CELL DEVELOPMENT

lymphoidprecursor

myeloidprecursor

progenitorcell

LAD SYNDROME

GRANULOCYTOPATIC SYNDROME

CHÉDIAK-HIGASHI SYNDROME

macrophage / monocyte

granulocyte

SCID

SCID

AGAMMAGLOBULINEMIA SELECTIVE Ig DEFICIENCIE

plasma cell

preT

preB B

T

TYPES OF PRIMARY IMMUNODEFICIENCIESTYPES OF PRIMARY IMMUNODEFICIENCIES

Combinedsevere impairment, whole cell types are missing, dysgenesis of organs, death during first weeks of life

T lymphocytesevere impairment, systemic infections, defects mainly in functional characterization of T lymphocytes

B lymphocytelow level of immunoglobulins - agammaglobulinemia is rare, selective deficit of particular isotypes is more frequent IgA deficiency - respiratory, enteral or cutaneous infections

Complementmainly impairment of C3 fraction, severe bacterial either systemic or organ infection

Phagocytosismany syndromes, impairment of different character, often chronic or recurrent purulent infections

PRIMARY IMMUNODEFICIENCIESPRIMARY IMMUNODEFICIENCIES

Combined Basset Hound defect of gene for IL-2R, thymic B and T deficit Arabic horse aplasia, decreased level of Ig

T deficit assoc. Weimaraner deficit of a growing hormone, with dwarfism aplasia of a thymic cortex

Congenital Bull Terrier impairment of zinc metabolism acrodermatitis hypolasia of im.organs, skin

Selective dogs of diff. decreased level of IgA, normal IgA deficit breeds level of IgG and IgM

Selective IgM horse decreased level of IgM, normal deficit level of IgG and IgA

Defect of C3 Spaniels septicemia, bacterial infections fraction of complement

PRIMARY IMMUNODEFICIENCIESPRIMARY IMMUNODEFICIENCIES

Cyclic Collie defect of progenitors granulopoesis cyclic neutropenia

Leucocyte adherence Irish Setter defect of CD11/CD18deficience cattle (BLAD) bacterial infections

Granulocytopatic Irish Setter impairment of a bactericidal syndrome Weimaraner activity

Chediak-Higashi Persian cat defect of a lysosome syndrome cattle - Hereford degranulation

Pelgret-Huet cats neutrophil hyposegmentation anomaly

CAUSES OF SECONDARY IMMUNODEFICIENCIESCAUSES OF SECONDARY IMMUNODEFICIENCIES

Infection and parasitic diseases

Noninfection diseasestumors, chronical renal failure

Diseases of endocrine systemCushing´s syndrome, hypothyreosis

Effect of trauma or stresstrauma of a big extension, burning, splenectomy, long-lasting (transport, temperature, psychic) stress

Nutritional disordersdeficiency of proteins, energy, trace elements (Zn, Se), vitamins

Long-lasting therapycorticosteroids, cytostatics, chloramphenicol

EXAMPLES OF INFECTIONES CAUSING SECONDARY IMMUNODEFICIENCIES

EXAMPLES OF INFECTIONES CAUSING SECONDARY IMMUNODEFICIENCIES

Viral immunodeficiency of cats (FIV)

Viral leukemia of cats (FeLV)

Infectious peritonitis of cats

Distemper

Parvovirosis of dogs, panleukopenia of cats

Bovine viral diarrhea - mucosal disease

Classical swine fever

Bovine leucosis

Infectious bursitis - Gumboro disease

Marek´s disease

DIAGNOSIS OF IMMUNE SYSTEM IMPAIRMENTDIAGNOSIS OF IMMUNE SYSTEM IMPAIRMENT

Anamnesisfamily anamnesis, breed predisposition, effect of age and gender, chronicitydrugs and their efficacy, nutrition, prophylactic measures

Clinical investigationsnon-specific signs, temperament, chronic inflammatory or tumorous processes

splenomegaly, lymphadenopathy

Basic laboratory examinationshematological examinations (leukocyte counts)

biochemical examinations (level of immunoglobulins)

Laboratory examinations of immunological profile

CLINICAL SIGNS OF IMMUNODEFICIENCYCLINICAL SIGNS OF IMMUNODEFICIENCY

Chronical or recurrent infections

Infections with unusual or less pathogenic agents

Incomplete removing of infectious agents among clinical episodes

Weak response to therapy with antibiotics or sulphonamides

THERAPY OF IMMUNODEFICIENCIES THERAPY OF IMMUNODEFICIENCIES

THERAPY OF PRIMARY IMMUNODEFICIENCIESusually does not exist - removing of animals from breedingbone marrow transplantationsubstitution with gammaglobulins

THERAPY OF SECONDARY IMMUNODEFICIENCIESremoving of underlying causes (if it will work)therapy of infectious diseasessupplementation with gammaglobulinsimmunostimulation

NON-SPECIFIC IMMUNOSTIMULATIONnatural - nutritious substances (Se, vitamins)microbial preparations (Baypamun, Bronchovaxom)chemical preparations (levamisol, Isoprinosin)biological regulators (Lydium, cytokines)

MECHANISMS OF DEVELOPMENT OF HYPERSENSITIVITY AND/OR

AUTOIMMUNITY

MECHANISMS OF DEVELOPMENT OF HYPERSENSITIVITY AND/OR

AUTOIMMUNITY

GENETIC PREDISPOSITION

IMPACTS OFINFECTIONES

IMPACTS OF ENVIRONMENT

DYSREGULATION OF IMMUNE SYSTEM

AUTOIMMUNITYALLERGY

HYPERSENSITIVITY, AUTOIMMUNITY -TERMINOLOGY

HYPERSENSITIVITY, AUTOIMMUNITY -TERMINOLOGY

HYPERSENSITIVITY = ALLERGYallergen = antigen provoking allergic reaction

HYPERSENZITIVITY1st type - early, mediated by IgE antibodies

2nd type - cytotoxic, mediated by IgG (IgM) antibodies

3th type – mediated by immune-complexes Ag-Ab

4th type – delayed, mediated by cells

AUTOIMMUNITYautoimmune reaction – immune (antibody or cellular) reaction against self-antigens

autoimmune disease - immune reaction leading to tissue damage and clinical signs

COMPARATION OF HYPERSENSITIVE REACTIONSCOMPARATION OF HYPERSENSITIVE REACTIONS

1st 2nd 3th 4th

components IgE IgG, IgM complex T lymph.mast cells complem. Ag-Ab macrophage

Ne, Mφ,NK

reactive time minutes hours hours daysdays

autoimmunity - + + ±

transfer by serum serum serum cells

effect of + - - -antihistamine therapy

HYPERSENSITIVITY OF 1st TYPEHYPERSENSITIVITY OF 1st TYPE

early hypersensitivity

induced by allergen and modulated by Th2 type reaction

mediated by IgE antibodies, crucial cell is mast cell

IgE binding to Fc-receptor on mast cells, their cross-linking leads to degranulation and to releasing of inflammatory mediators

early mediators - histamine, serotonin, PAF

late mediators - metabolites of arachidonic acid -prostaglandins, leukotriens

atopy = genetically mediated hypersensitivity of 1st type to inhaled or swallowed allergen

anaphylaxis = acute systemic hypersensitive reaction of 1st

type

keratinocytesLangerhan´s cell

ALLERGEN

IgE

IL-8Th2

B

IL-4

IL-5

HYPERSENSITIVITY OF 1st TYPE

days to

years

NEW EXPOSITIONSENZIBILISATION LOCAL REACTION

SYSTEMIC SHOCK

minutes(days)

SENZIBILISATION TO ALLERGIC REACTION

fosfolipases

ARACHIDONIC ACID

fosfolipids of cell membranes

5-lipooxygenase

5 HPETE

cyklooxygenase

PGG2

LTC …LTD ...LTE

LEUKOTRIENS4 4 4 PGD PGE PGF

PROSTAGLANDINS2

PROSTACYKLINES

TROMBOXANES2 2a

METABOLISM OF ARACHIDONIC ACID ANAPHYLACTIC SHOCKANAPHYLACTIC SHOCK

acute systemic reaction caused by sudden release of inflammatory mediators (histamine, serotonin)

mechanisms of action:excessive contraction of smooth muscles (bronchoconstriction)vasodilatation, increased permeability of veinsincreased mucus secretion

it results in hypovolemic shock, edema of subcutis and organs, general hypotension, but pulmonary hypertension

ANAPHYLACTIC SHOCK IN DIFFERENT ANIMALSANAPHYLACTIC SHOCK IN DIFFERENT ANIMALS

species shock organ mediators signs, pathology

ruminants lung serotonin dyspnoe, lung edemaleukotriens hemorrhages

porcine lung, gut histamine? pruritus, cyanosissystemic hypotension

horse lung, gut serotonin dyspnoe, diarrheakinines hemorrhages in gut

dog vena portae histamine dyspnoe, vomitingliver leukotriens enlargement of liver

visceral hemorrhages

cat lung, gut histamine dyspnoe, diarrhea leukotriens vomiting, edema of

lung and gut

HYPERSENSITIVITY OF 2nd TYPEHYPERSENSITIVITY OF 2nd TYPE

cytotoxic reaction induced by complement or cytotoxic cells (ADCC)

reaction is mediated by IgG, (IgM) antibodies

these antibodies are often against self-antigensautoimmune hemolytic anaemia

similar reaction can be found after a blood transfusion

anti-receptor reaction which does not lead to a cell lysis but can modulate their function

binding to acetylcholine receptor – inhibition of activity

binding to receptor for TSH – stimulation of activity

C

C

TARGET CELL

RECOGNISING OF CELLCOMPLEMENT ACTIVATION

LYSIS

surfaceantigen

receptor forcomplement ions + water

terminalcytotoxic complex

HYPERSENSITIVITY OF 2nd TYPE

SENSIBILIZATIONFOR DESTRUCTION

SENSIBILIZATIONFOR ACTIVATION

surface cellularantigen Fc receptor

HYPERSENSITIVITY OF 3th TYPEHYPERSENSITIVITY OF 3th TYPE

mediated by immune-complexes of antigen and antibody

antibodies can be directed against self as well as non-self antigens

excessive amount of immuno-complexes can lead to pathological reaction

they can be deposited in blood vessels, kidneys etc.

vasculitis, glomerulonephritis, endocarditis, artritis

special type of reaction is serum disease

local type is called Arthus´ reaction

damage of blood vessel (even necrosis)

IMMUNE COMPLEX

complement

basophile

neutrophils

release of enzymes

embedded immune-complex

platelets

microtromes creation

HYPERSENSITIVITY OF 3th TYPE - VASCULITIS

HYPERSENSITIVITY OF 4th TYPEHYPERSENSITIVITY OF 4th TYPE

delayed hypersensitivity

it develops after induction by antigen, modulated by Th1type of response – reaction of cellular type

it is characteristic for reaction to intracellular bacteria, but also to some non-infectious antigens

immune reaction to mycobacterial infectionafter intradermal administration - tuberculin reaction

Th1 are called lymphocytes of delayed type of hypersensitivity TDTH activating macrophages

another type of reaction modulated by Th1 is mediated by effector Tc lymphocytes

contact dermatitis

keratinocytesLangerhan´s cell

SKIN REACTION

ALLERGEN

IL-2

M

IFNγ

Th1φ

Th1

HYPERSENSITIVITY OF 4th TYPE

COMPARATION OF HYPERSENSITIVE REACTIONSCOMPARATION OF HYPERSENSITIVE REACTIONS

1st 2nd 3th 4th

components IgE IgG, IgM complex T lymph.mast cells complem. Ag-Ab macrophage

Ne, Mφ,NK

reactive time minutes hours hours daysdays

autoimmunity - + + ±

transfer by serum serum serum cells

effect of + - - -antihistamine therapy

CAUSES OF AUTOIMMUNE DISEASES DEVELOPMENT

CAUSES OF AUTOIMMUNE DISEASES DEVELOPMENT

Polyfactorial charactergenetical predispositioninfectious agentseffect of environmentother immune-mediated diseases

Dysregulation of immune systemdysregulation of Th1 x Th2dysregulation of selection during differentiation

Changes of autoantigens or their presentation uncovering of so far inaccessible (cryptic) antigensantigenic mimicry with infectious antigens polyclonal activation by superantigens

ALLERGIC AND AUTOIMMUNE DISEASES

ALLERGIC AND AUTOIMMUNE DISEASES

ALLERGY ALLERGY

Allergy is frequent in animals and its importance increases

dogs – mainly skin diseases

cats – respiratory and skin diseases

horses – mainly respiratory diseases

cattle, pigs – also present, various forms

ALLERGY ALLERGY

Allergy - type I.

Atopic dermatitis – inherited skin reaction to the environmental allergen

often in dogs, rare in cats breeds – many: Terrier, Shar-pei, Dalmatin, Retriever, etc.marked pruritus, seasonalappears within 3 years of age

Flea bite allergythe most common allergy in dogs haptens of flea saliva bind to skin collagen - I. a IV.typemarked pruritic seasonal disease

ALLERGY ALLERGY

Allergic rhinitis or bronchitis- in dogs, horses – not common

Astma bronchiale- in cats

Chronic obstructive pulmonal disease (COPD)(hypersensitive pneumonitis) – in horsesreaction to the mold spores (arthropods, pollen)

new classification:RAO - recurrent airway obstruction

IAD - inflammatory airway disease

RAO – old horses, IAD yang racing horses

ALLERGY ALLERGY

Allergy of various types

Food allergy (I., III. IV. typ) – in all species– with different signs) -

Gluten enteropathy – in Irish Setters

Allergy to to the drugs or vaccines (I., III., IV. typ)- antibiotics, sulphonamides, hormons, vaccines

Sarcoidosis – granulomatous disease in horses(III. and IV. type, probably papillomaviruses), polyarthritis, erythema nodosum, uveitis

ALLERGY ALLERGY

Allergy type III.

Glomerulonephritis – often, reaction to the allergens, infection (and autoantigens) - streptococcus, staphylococcus, Feline peritonitis, infectious anaemia of horses

Vasculitis – reaction to the various antigens

Alergy type IV.

Kontact dermatitis – in various species- local reaction to drugs or chemicals

CAUSES OF AUTOIMMUNE DISEASES DEVELOPMENT

CAUSES OF AUTOIMMUNE DISEASES DEVELOPMENT

Polyfactorial charactergenetical predispositioninfectious agentseffect of environmentother immune-mediated diseases

Dysregulation of immune systemdysregulation of Th1 x Th2dysregulation of selection during differentiation

Changes of autoantigens or their presentation uncovering of so far inaccessible (cryptic) antigensantigenic mimicry with infectious antigens polyclonal activation by superantigens

SYSTEMIC AUTOIMMUNE DISEASES SYSTEMIC AUTOIMMUNE DISEASES

rheumatic diseaseschronic, with fever

nonspecific clinical signs (arthritis, myositis)

autoantibodies

Systemic lupus erythematosus

Rheumatoid arthritis

Idiopathic arthritis (I. - IV. type)

Polymyositis - dermatomyositis

Sjögrens syndrome

IMMUNE-MEDIATED ARTHRITISIMMUNE-MEDIATED ARTHRITIS

type disease

erosive rheumatoide arthritis

nonerosive idiopathic polyarthritis (four types)

nonerosive polyarthritis / polymyositis

nonerosive SLE

± erosive Sjögrens syndrome

SYSTEMIC LUPUS ERYTHEMATOSUS SYSTEMIC LUPUS ERYTHEMATOSUS

Patogenesisin dogs – German Shepherd, Poodle, Colie, Beagle, Irish Setter genetic predisposition with infection? and UV radiation cause dysbalance of the immune system, oligoclonal activation of B cells and production of autoantibodies against nuclear antigens

Signsfever answering to corticosteroids non-answering to antibioticsarthritis, glomerulonephritis, mucocutaneous leasions, myositis, anaemia, trombocytopenia, neutropenia

Diagnosis3 clinical signspositive antinuclear antibodies 1:100

IMMUNE-MEDIATED DISEASES OF MUSCLESAND NERVES

IMMUNE-MEDIATED DISEASES OF MUSCLESAND NERVES

Myositispolymyositis

dermatomyositis

myositis of maseters

Myastenia gravis

Immune-mediated neuritisakute polyradiculoneuritis

degenerative myelopaty of German Shepherds

AUTOIMMUNE DISEASES OF ORGANS AUTOIMMUNE DISEASES OF ORGANS

Blood cells

Skin

Idiopathic enteritis

Other internal organs

Endokrine organs

Eye

IMMUNE-MEDIATED ANAEMIAIMMUNE-MEDIATED ANAEMIA

type disease Coombs testIgG C3

primary autoimmune hem. anaemia + ±

secondary part of SLE ± -

caused by drugs ± -

postinfectious ± -

neonatal isoerytrolysis + ±

prim/second cold aglutinins disease - +

IMMUNE-MEDIATED DISEASES OF BLOOD CELLSIMMUNE-MEDIATED DISEASES OF BLOOD CELLS

AUTOIMMUNE HAEMOLYTIC ANAEMIA - AIHApredisposition - Cocker, Terrier (middle aged, female)autoantibodies against erytrocytes, intravascular activation of complement signs - acute, pain of abdomen, pale mucous membranes, icterushaematology – regenerative hemolysis, anaemia, reticulocytosis, sphaerocytosis, anisocytosis, autoaglutination, leukocytosisimmunology- direct or idnirect Coombs test

IMMUNE-MEDIATED ANAEMIA - IMHAsecondary

AUTOIMMUNE TROMBOCYTOPAENIAidiopathic trombocytopaenia

EVANS SYNDROMEAIHA and ITP

AUTOIMMUNE NEUTROPENIA

AUTOIMMUNE HAEMOLYTIC ANAEMIAAUTOIMMUNE HAEMOLYTIC ANAEMIAAUTOIMMUNE SKIN DISEASES AUTOIMMUNE SKIN DISEASES

PEMFIGUS COMPLEXinflamatory skin disease cases bz antibodies agains various parts of skin –

broken desmosomes base membrane, acantolysis

PEMFIGUS FOLIACEUS

PEMFIGUS VULGARIS

PEMFIGUS VEGETANS

BULLOUS PEMFIGOID

SKIN LESIONS as a part of SLE

INTERCELLULAR SUBCORNEAL BASE MEMBRANE

Pemfigus vulgaris Pemfigus foliaceus Bulous pemfigoid

AUTOIMMUNE DISEASES OF INTERNAL ORGANSAUTOIMMUNE DISEASES OF INTERNAL ORGANS

CHRONIC IDIOPATHIC ENTERITISlymfocytic-plasmacytic enteritis- the most common cause of chronic emesis or diarrhea in

dogs

immunoproliferative enteritis of Basenji dogs

eosinophilic enteritis

granulomatous enterocolitis

histiocytic ulcerative colitis

GLOMERULONEPHRITISautoimmune glomerulonephritis- autoantibodies against differnt structures of glomerulus

immunocomplex glomerulonephfritis

AUTOIMMUNE DISEASES OF INTERNAL ORGANSAUTOIMMUNE DISEASES OF INTERNAL ORGANS

ENDOCRINE DISEASES autoimmune hypothyreosis (Hashimoto d.) – in dogs, autoantibodies against thyreoglobulin or thyreoidal peroxidase

autoimmune hyperthyreosis (Graves d.) – in cats, autoantibodies against TSH receptor

diabetes melitus type I

THERAPYTHERAPY

ALLERGYantihistaminsadrenalin (acute respiratory diseases)to drop off alergensdesenzibilisation korticosteroids

AUTOIMMUNE DISEASES korticosteroids – immunosupresiveand antiinflamatory

prednison, dexametason

other immunosupresive drugsazathioprine

cyklofosfamide, cyklosporine A, chlorambucil

in human medicinedisease modified drugs (sulfasalazine, methotrexate)

nonsteroid antiinflamatorz drugs

intravenous immunoglobulins

IMMUNOLOGICAL ASPECTS OF TRANSPLANTATION

IMMUNOLOGICAL ASPECTS OF TRANSPLANTATION

TRANSPLANTATION IMMUNITY TRANSPLANTATION IMMUNITY

Transplantation is a transfer of cells, tissues or organs from one part of body to another or from one individual to another.

Transplantation reaction is based on genetic differences between donor and recipient

RELATIONSHIP BETWEEN DONOR AND RECIPIENTRELATIONSHIP BETWEEN DONOR AND RECIPIENT

autotransplantation – transfer within one organism

syngenic transplantation – transfer between two genetically identical individuals (inbred line)

alotransplantation – transfer between individuals of the same species with different level of genetic relationship

xenotransplantation – transfer between individuals of different species (for example from pig)

TRANSPLANTATION ANTIGENS AND REACTIONTRANSPLANTATION ANTIGENS AND REACTION

major histocompatible system – is a group of strong transplantation antigens – determine about intensity and speed of reaction

minor histocompatible antigens – are dispersed around whole genome – differences between them lead to slow graft rejection

transplantation reaction - is reaction of immune system against MHC (also to minor) antigens on donor cells

Graft versus host reaction (GVHR) – appears after transfer of immunocompetent cells

TRANSPLANTATION REACTIONTRANSPLANTATION REACTION

Recognition - (afferent phase)

direct – recognition of whole MHC alloantigens on strange cells

indirect – recognition of antigenic graft (MHC as well as minor histocompatible) using antigenic presentation to Th cells of donor

Central phase

Th lymphocyte – co-stimulation (CD28 - B7) polarization to Th1 will lead to acute phase, polarization to Th2 will lead to an antibody production and chronic phase

TRANSPLANTATION REACTIONTRANSPLANTATION REACTION

Effector mechanisms - (efferent phase)

Tc lymphocyte - cytotoxicity against cells expresing strange MHC I, with help of Th1 cytokinescytotoxic mechanisms: perforins, granzymes

NK cells – lack of self MHC I

Antibody production – cytotoxicity dependent on antibodies, complement activation

Result of transplantation reaction could be graft rejection

hyperacute – in the case when antibodies are present at the term of transplantation

acute – mediated by Th1 and cytotoxic cells

chronic – mediated by Th2 and antibodies

MEASURES IN TRANSPLANTATIONMEASURES IN TRANSPLANTATION

Selection of donors

Matching in blood group system

Matching (at least partial) in MHC antigens

Test for lack of antibodies (cross-match)

Suppression of transplantant reaction

Using immunosupresive treatment

Myeloablation in case of bone marrow transplantation

IMMUNITY AGAINST TUMORSIMMUNITY AGAINST TUMORS

ANTI-TUMOUR IMMUNITYANTI-TUMOUR IMMUNITY

Tumor disease appeared as a result of mutations in gens, which control cellular proliferation and differentiation.

Tumor antigens provokes immune reaction mainly of cytotoxic type. In some cases, they may escape for

attention of immune system.

TUMOR ANTIGENSTUMOR ANTIGENS

specific tumor antigensthey are not present on normal cells

molecules MHC I with abnormal fragments of cellular proteins

molecules MHC I with fragments of oncogenic viruses

abnormal forms of glycoproteins (glycosylation, sialylation)

idiotyps of myeloms and lymphomas

antigens associated with tumorsvthey may be present also on normal cells

oncofetal antigens

melanomic antigens

antigens of leukemic cells - CALLA

DEFENCE AGAINST TUMORSDEFENCE AGAINST TUMORS

majority of tumor antigens are antigenic but they are badly immunogenic

cytotoxicity mediated by Tc lymphocytes

presentation via MHC I

cytotoxicity mediated by NK cellslack of MHC I molecules on surface of tumor cells

macrofages infiltrate tumor tissuethey may increase vascularization and a tumor grow

they may induce cytolysis by TNFα or other soluble mediators

role of antibodies is unclear

ANTIBODIES IN DIAGNOSTICS AND THERAPY

ANTIBODIES IN DIAGNOSTICS AND THERAPY

POLYCLONAL ANTIBODIESPOLYCLONAL ANTIBODIES

Polyclonal antibodies are obtained from sera containing mix of immunoglobulins with various specifity

Polyclonal antibodies are obtained by collection of sera from different donors: reconvalescent sera or hyperimmune sera

For in vivo application we could use autologous or heterologous sera

Their using in diagnostics decreased

MONOCLONAL ANTIBODIESMONOCLONAL ANTIBODIES

Monoclonal antibodies are created in vitro from one clone of hybridoma cells.

They are targeted to one epitope.

Monoclonal antibodies play important role in diagnostics as well as in therapeutical protocols.