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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