08 Pa Tho Physiology of Imunity

8/6/2019 08 Pa Tho Physiology of Imunity

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Pathophysiology of immunity


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The immune system (IS)

Main physiologic role:

- primary role of IS is to discriminate self from

nonself and to eliminate the foreign substance

- finely tuned network that protects the host

against forein antigens, particularly infection

agents

Pathophysiologic changes of immune system:

- the mentioned network can be broken down,

causing IS to react inappropriatelly


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Hypersensitivity

1) Exaggerated activity against environmental

antigens (allergy)

2) Misdirected activity against host s own cells(autoimmunity)

3) Activity directed against benefitial foreign tissues,

e.g. transfusion, transplants (isoimunity)

Hyposensitivity

1) Activity insufficient for protection of the body

(immune deficiency)

Main forms of inappropriate reactions ofimmune system


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Types of hypersensitivity are differentiated by the sorce of the antigens

against which the hypersensitivity is directed

A)Allergy it has two facets:a) immune response which is benefitial

b) hypersensitivity which is harmfulDefinition: Deleterious effects of hypersensitive

reactions to environmental (aerogenous)antigens expressed by disease

B) Autoimmunity disturbance in the immunologic tolerance of

self-antigens

immune system reacts against self antigens

by creating autoantibodies- autoimmune diseases


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Autoimmune disease

With main manifestation in:

Endocrine systemEndocrine system hyperthyroidism (Graves disease) autoimmune thyroiditis

primary myxedema (hypothyroidism) diabetes mellitus-type 1 Addison disease male and female infertility idiopathic hypoparathyroidism

partial pituitary deficiency

Skin pemphigus vulgaris vitiligo dermatitis herpetiformis


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Neuromuscular tissuesNeuromuscular tissues dermatomyositis

multiple sclerosis myasthenia gravis postvaccinal or postinfection encephalitis polyneuritis rheumatic fever (heart effects) cardiomyopathy

Gastrointestinal systemGastrointestinal system celiac disease (gluten-sensitive enteropathy)

ulcerative colitis Crohns disease atrophic gastritis primary biiary cirhosis antibodies against intrinsic factor


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Connective tissueConnective tissue ankylosing spondylitisankylosing spondylitis rheumatic arthritisrheumatic arthritis systemic lupus erythematosussystemic lupus erythematosus polyarteritis nodosa (necrotising vasculitis)polyarteritis nodosa (necrotising vasculitis) scleroderma (progressive systemic sclerosis)scleroderma (progressive systemic sclerosis)

EyeEye SjSjgrengrens syndromes syndrome uveitisuveitis

KidneyKidney immuneimmune complex glomerulonephritiscomplex glomerulonephritis GoodpastureGoodpastures syndrome (basement membrane ofs syndrome (basement membrane of

glomerulus)glomerulus)


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Hematopoietic systemHematopoietic system idiopathic neutropenia, lymphopeniaidiopathic neutropenia, lymphopenia

autoimmune haemolytic anemiaautoimmune haemolytic anemia autoimmune thrombocytopenic purpuraautoimmune thrombocytopenic purpura pernicious anemiapernicious anemia

Respiratory systemRespiratory system GoodpastureGoodpastures disease (interalveolar septas)s disease (interalveolar septas)

Autoantibodies are also produced by healthyindividuals, particularly by the elderly. This is one of

the mechanisms responsible for the ageing process(due to a deterioration of tolerance to self-antigens)

Yonger healthy individuals may produceautoantibodies without the development of overt

autoimmune disease (reaction is weak)


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Isoimmune disease

immune system of one individual produces animmune reaction against tissues of another

individual, e.g. against transfused Er, grafted tissue,

fetus during its intauterine life

Pathogenesis of hypersensitivity

it is not completly understood

Main pathogenetic factors genetic disorders infections another environmental factors- polutants in air, soil,

water, psychogenic

stressors....


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Most diseases related to hypersensitivityevolve because of interaction of at least3 variables:

a) an original insult which alters immunologichomeostasis

b) the individuals genetic makeup which determins

susceptibility to the effects of the insult

c) immunologic process that amplyfies the insult


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Type I hypersensitivity

1) Anaphylaxis rapid and severe reaction developedwithin minutes

a) systemic (generalised):itching, erithema, womiting, abdominal cramps,

diarhea, breathing difficulties, laryngeal edema,

angioedema, vascular collapse, shock, death

b) cutaneous (localised):

signes of local inflammation


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2) IgE mediated reactionsCharacteristics:Characteristics:

- production of antigen specific IgE after exposureto antigen

- the most common alleregic reactions are mediated

by IgE

- antigens which cause allergic reactions are called

allergens

3) AtopyCharacteristics:Characteristics:

- it expresses the proneness to allergy- the atopic persons produce more than normal IgE

and have more Fc receptors on their mast cells- subtle defect in T-Ly function (e.g. deficiency in

IgE-specific supressor cells) may account forhightened IgE production


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Type II hypersensitivity

Characteristics:Characteristics:

- destruction of target cells through the action of

antibodies against an antigen on the surface of cellmembrane

ExplanationExplanation::

- in addition to HLA system most tissue have tissue

specific antigens (TSA) = expressed only on the

plasma membrane of certain type of cells- because of limited distribution of TSA, type II disease

are limited to those tissue and organs that expressethe particular antigen


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Mechanisms involved in cells destructionin type II hypersensitivity

1) Antibody (Atb) is bind to TSA

Atb fixes complementp initiation of

complement cascade (CCD)p lysis of the cell

- e.g. autoimmune hemolytic anemia, transfusion

reaction to donor blood cells

2) Atb is bind to TSA macrophages are able to recognize and bind the

opsonised cellsp phagocytosisp lysis of cells


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3) Atb is bind to TSA

Fc receptors on cytotoxic cells are able

to recognize the antigen on the target cellsp

p binding of cytotoxic cells on target cellsp

p cytotoxic cells release of toxic substancesp

p lysis of target cells

4) Atb is bind to TSA

Atb occupy and alters receptors on target cellsp

p blockade of normal ligands for these receptorsp

p changes in cellular functions

- e.g. Graves disease


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Type III hypersensitivity

Characteristics:Characteristics:

-- antigenantigen--antibodies complexes (antibodies complexes (ANtANt--ATbATb--CC) are created) are created

in circulating bloodin circulating bloodpp deposition ofdeposition ofANtANt--AtbAtb--CC in thein the

vessel wall or in other extracellular tissuesvessel wall or in other extracellular tissues

-- this reaction is not organthis reaction is not organ specificspecific

-- harmful effect ofharmful effect ofANtANt--AtbAtb--CC is caused by activation ofis caused by activation ofcomplement and by attempt of NEcomplement and by attempt of NE--Le to ingestLe to ingest

these complexesthese complexes pp releasing of lysosomal enzymesreleasing of lysosomal enzymespp

pp tissue damagetissue damage


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Diseases caused by immune deficiencyDiseases caused by immune deficiency

Primary T-cell defects

- severe combined immune deficiency (SCID)- Di George syndrome (thymic aplasia or hypoplasia)

Primary B-cells defects

- agammaglobulinemia

- selective IgA, IgM, IgE deficiencies

Phagocytic defects

a) quantitative defects -e.g. congenital splenic aplasia,Sickle cell anemia,congenital neutropenia

b) chemotactic defects lazy leucocyte sy.c) microbicidal defect chronic granulomatous disease

myeloperoxidase deficiency

Complement defects


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08 Pa Tho Physiology of Imunity

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