Pathophysiology of immunity
Prof. J. Hanacek, MD, PhD
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
Main forms of inappropriate reactions of
immune system
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)
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 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
Autoimmune disease
With main manifestation in:
Endocrine system – hyperthyroidism (Grave’s 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
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
– Crohn’s disease
– atrophic gastritis
– primary biiary cirhosis
– antibodies against intrinsic factor
Connective tissue
– ankylosing spondylitis
– rheumatic arthritis
– systemic lupus erythematosus
– polyarteritis nodosa (necrotising vasculitis)
– scleroderma (progressive systemic sclerosis)
Eye
– Sjögren’s syndrome
– uveitis
Kidney
– immune –complex glomerulonephritis
– Goodpasture’s syndrome (basement membrane of
glomerulus)
Hematopoietic system
– idiopathic neutropenia, lymphopenia
– autoimmune haemolytic anemia
– autoimmune thrombocytopenic purpura
– pernicious anemia
Respiratory system
– Goodpasture’s disease (interalveolar septas)
• 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)
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 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....
Most diseases related to hypersensitivity
evolve because of interaction of at least
3 variables:
a) an original insult which alters immunologic
homeostasis
b) the individual’s genetic makeup which determins
susceptibility to the effects of the insult
c) immunologic process that amplyfies the insult
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
Type I hypersensitivity
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
2) 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
Type II hypersensitivity
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
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
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. Grave’s disease
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
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
• Rayanaud’s phenomenon:
- temperature-dependent 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
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
- tuberculin reaction
- tumor rejection
- reaction to contact
with e.g. metals or ivy
Diseases caused by type IV
hypersensitivity
• Rheumatoid arthritis - antigen is type II collagen in
joint tissue
• Hashimoto’s disease - antigen is protein present in
thyroid cells
• Diabetes mellitus-type 1- antigen is a protein of the
-cells of Langerhans islets
Pathogenesis of hyposensitivity
This disorder results from deficiciences in immunity
and leads to development of different clinical
manifestations. These 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
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