Prezentace aplikace PowerPoint

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Pathophysiology of immunity
Prof. J. Hanacek, MD, PhD
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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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Main forms of inappropriate reactions of immune
system
Hypersensitivity 1) Exaggerated activity against
environmental antigens (allergy) 2)
Misdirected activity against hosts own cells
(autoimmunity) 3) Activity directed against
benefitial foreign tissues, e.g.
transfusion, transplants (isoimunity) Hyposensiti
vity 1) Activity insufficient for protection of
the body (immune deficiency)
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• Types of hypersensitivity
• are differentiated by the sorce of the
  antigens
• against which the hypersensitivity is
  directed
• Allergy it has two facets
• a) immune response which is
  benefitial
• b) hypersensitivity which
  is harmful
• Definition 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 agaqinst self antigens
by creating autoantibodies - autoimmune
diseases
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Autoimmune disease With main manifestation
in Endocrine system hyperthyroidism
(Graves disease)
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 tissues dermatomyositis
multiple sclerosis myasthenia gravis
postvaccinal or postinfection encephalitis
polyneuritis rheumatic fever (heart
effects) cardiomyopathy Gastrointestinal
system celiac disease (gluten-sensitive
enteropathy) ulcerative colitis
Crohns disease atrophic gastritis
primary biliary cirhosis antibodies against
intrinsic factor
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Connective tissue ankylosing spondylitis
rheumatic arthritis systemic lupus
erythematosus polyarteritis nodosa
(necrotising vasculitis) scleroderma
(progressive systemic sclerosis) Eye
Sjögrens syndrome uveitis Kidney immune
complex glomerulonephritis Goodpastures
syndrome (basement membrane of glomerulus)
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Hematopoietic system idiopathic neutropenia,
lymphopenia autoimmune haemolytic anemia
autoimmune thrombocytopenic purpura
pernicious anemia Respiratory system
Goodpastures disease (interalveolar septas are
influenced)
Autoantibodies are also produced by healthy
individuals, 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 produce autoantibodies without
the development of overt autoimmune disease
(reaction is weak)
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Isoimmune disease immune system of one
individual produces an immune reaction
against tissues of another individual, e.g.
against transfused Er, grafted tissue, fetus
during its intrauterine 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 hypersensitivity
evolve because of interaction of at least 3
variables a) an original insult which alters
immunologic homeostasis 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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Mechanisms involved in development different
types of hypersensitivity
Type I IgE mediated allergic
reactions Type II Tissue specific
reactions Type III Immune-complexes mediated
reactions Type IV Cell-mediated reactions
Time corse of hypersensitivity reactions
Immediate hypersensitivity reactions within
minutes Delayed hypersensitivity reactions
within sevral hours and days
from the time of exposure to antigen
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Type I hypersensitivity - IgE mediated 1)
Anaphylaxis rapid and severe reaction developed
within
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) Allegy - IgE mediated reactions
Characteristics - production of antigen
specific IgE after exposure to antigen - the
most common alleregic reactions are mediated by
IgE - antigens which cause allergic reactions
are called allergens
3) Atopy 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
for hightened IgE production
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• Type II hypersensitivity - Tissue specific
  reactions
• Characteristics
• - destruction of target cells through the action
  of antibodies
• against an antigen on the surface of cell
  membrane
• Explanation
• 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
  expresse
• the particular antigen

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Mechanisms involved in cells destruction in type
II hypersensitivity
1) Antibody (Atb) is bind to TSA Atb
fixes complement ? initiation of
complement cascade (CCD) ? 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
cells ? phagocytosis ? 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 cells ? binding of
cytotoxic cells on target cells ?
cytotoxic cells release of toxic
substances ? lysis of target cells 4) Atb is
bind to TSA Atb occupy and alters
receptors on target cells ? blockade of
normal ligands for these receptors ? changes in
cellular functions - e.g. Graves
disease
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• Type III hypersensitivity
• Characteristics
• antigen-antibodies complexes (ANt-ATb-C) are
  created
• in circulating blood ? deposition of ANt-Atb-C
  in the vessel wall
• or in other extracellular tissues
• this reaction is not organ specific
• harmful effect of ANt-Atb-C is caused by
  activation of
• complement and by attempt of NE-Le to ingest
  these
• complexes ? releasing of lysosomal enzymes
  ?tissue damage

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Diseases caused by type III hypersensitivity
Serum sickness (called according the foreign
serum used and symptoms
and signs development) - general
deposition of immune-complexes in blood vessels,
joints, kydney - symptoms and signs
fever, enlarged lymphonodes, rash, pain
Rayanauds phenomenon - temperature-depende
nt deposition of immune complexes in
peripheral vessel (cryoglobulins) Arthus
phenomenon - example of localised
immune-complexes-mediated inflammatory
response. It developes due to repeated local
exposure to exogenous antigen which
reacts with preformed antibodies in the
vessel wall
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• Type IV hypersensitivity
• Characteristics
• it is mediated by specifically sensitised T-Ly
• it does not involve antibodies
• types of sensitised Ly ivolved in reaction
• - cytotoxic T-Ly
• - lymphokine-producing T-cells
• Pathologic processes induced
• by type IV hypersensitivity
• - graft rejection - tumor
  rejection
• - tuberculin reaction - reaction to
  contact with
• 
  e.g. metals or ivy

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Diseases caused by type IV hypersensitivity
Rheumatoid arthritis - antigen is type II
collagen in joint tissue
Hashimotos disease - antigen is protein present
in thyroid cells Diabetes
mellitus-type 1- antigen is a protein of the

?-cells of Langerhans islets
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Pathogenesis of hyposensitivity
This disorder results from deficiciences in
immunity and leads to development of different
clinical manifestations. The manifestations are
the result of impaired function of one or more
components of the immune system e.g.
B-cells,T-cells, phagocytic cells,
complement Classification 1) Congenital
(primary) immune deficiency - due to
genetic disorders 2) Acquired (secondary)
immune deficiency - due to another
illness-e.g. cancer, viral infection -
due to physiologic changes- e.g. ageing
- intens stress
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Diseases 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