IMMUNOPATHOLOGY

Darya
Galata
 Immunopathology–

Pathologic changes of structure and

functions of the immune (lymphoid)
tissue
IMMUNE RESPONSE MAY BE SPECIEFIC
AND NONSPECIEFIC
NONSPIECIFIC IMMUNE RESPONSE
CONSISTS OF 3 MECHANISMS:

1. MECHANICAL DEFENCE;
2. HUMORAL MECHANISMS;
3. CELLULAR MECHANISMS;
 MECHANICAL DEFENCE

THIS IS A FIRST BARRIER AND IT IS

REPRESENTED BY EPITHELIUM DUE
TO MOVEMENT OF CILLIA
(COUGH, VOMITING, SNIFFING,
PERISTALSIS, CRY, ETC.).
 HUMORAL NONSPECIFIC
MECHANISM

Is provided by the ability of body

fluids to kill the parasite.
Blood, saliva, tear fluid, the secret of
the intestine are rich in lysozyme,
interferon, anti-bacterial
substrates).
NONSPECIFIC CELLULAR IMMUNE
RESPONSE

is due to cells, such as neutrophils,

basophils, macrophages, Kupffer
cells and other cells which can
PHAGOCYTE.
SPECIFIC IMMUNE RESPONSE CONSISTS
OF :

• SPECIFICITY;
• IMMUNE MEMORY;
• RECOGNITION.
Specificity - a protection only against a
particular pathogen.
Memory - a property of the body to
maintain immunity for all subsequent
life as a protection against re-
infection.
Recognition of "foreign or own" – the
ability to differentiate own tissues
from foreign and produce antibodies
against foreign cells.
 SPECIFIC IMMUNE RESPONSE

HUMORAL CELLULAR
(B-LYMPHOCYTES) (T-LYMPHOCYTES)
Central organs of immune system
• Bone marrow and thymus produce
immune-competent cells.
• The bone marrow contains the
progenitor cells for the other
lymphoid organs.
Progenitor cells
produced in the
bone marrow
circulate to the
thymus and
peripheral organs of
immune system,
where they develop
into mature
lymphoid cells.
 Populations of
bone marrow
cells that may
have
recirculated
back to the
bone marrow
can respond to
antigens and are
called B-
lymphocytes.
THYMUS
• The thymus
produces and
differentiates small
lymphocytes
(T-lymphocytes)
AGE INVOLUTION OF THE THYMUS
Peripheral organs of immune system

• Spleen
• lymphatic nodes
• MALT
- gastrointestinal associated
lymphoid tissue (GALT)
- bronchus associated lymphoid
tissue (BALT)
 The main immunocompetent cells are T-
lymphocytes, B-lymphocytes,
macrophages.
• T-cell function is to recognize "host" and
"foreign" cells.
• Transmission of the information
is the function of
macrophages.
The function of B-
cells is to produce
antibodies. At this
stage B-
lymphocytes are
transformed into
plasmoblasts and
plasmocytes.
 HUMORAL IMMUNITY
Classes
IgG IgA IgM IgD IgE
(Reagines)

Takes part in Produces on Takes part in Is part of Takes part if I

secondary the surface of primary antigenic type
response. mucous response, its receptor of B- hypersensitivit
Properties

Occurs in the membranes. presence cells. y reaction and

blood plasma Formation of means that exile of
and mucosa- there is parasites.
extravascular protective recent or
fluid. barrier. continuing
infection
Monoclonal antibodies to different immune cells are
usually used for identification of immunocompetent
cells (Cluster of differentiation - CD)
• CD3 – T-lymphocyte
• CD4- T-helper
• CD8-T-suppressor
• CD22-B-lymphocyte
• CD16-macrophages
• CD18-neutrophils
 Types of immunopathology
1. Hepersensitivity reactions;
2. Autoimmune diseases;
3. Immunediffeciency syndromes;
4. Amyloidosis.
 HYPERSENSITIVITY REACTIONS
(immune damage of tissues)
4 types of hypersensitivity reactions:
I type – immune response is accompanied by
releasing of vasoactive and spasmogenic
substances;
II type – cell damage is caused by antibodies which
make cells sensitive to phagocytosis or lysis;
III type – antigen-antibody binding  immune
complex formation which activate
complement which lures neutrophils
tissue damage;
IV type – sensitized lymphocytes assisted cellular
immune response.
 І TYPE (Anaphylaxis, Reagine)
Complex (Ig E + Fc-receptor of basophils and mast
cells) + АG
↓
basophils and mast cells degranulation
↓
Release of anaphylactic mediators (vasoactive
amines)
↓
Clinical symptoms
 Two phases:
Primary response phase:
Contact with allergen
↓
Vasodilatation (after 5-30 minutes)
↓
Increase of vascular permeability, spasm of smooth muscles,
increased secretion of glands.

Late phase:
Second contact with allergen (after 2-8 hours)
↓
Infiltration of tissues eosinophilis, neutrophils, basophils,
monocytes, damage of mucosal epithelium.
І type reaction may be of two
types:
v

- systemic (anaphylaxis)
v

- focal (atopic)
Anaphylaxis – after injection of hormones, enzymes,
antiserum, polysaccharides and other substances (e.g.
penicillin). Severity of case depends on the level of
previous sensitization.
That is a rare but extremely life-threatening systemic
reaction. Getting of vasoactive amines in the
bloodstream causes contraction (spasm) of smooth
muscles and increase of vascular permeability with liquid
getting out from the vessel into the tissues. Emerging
with peripheral vascular insufficiency may lead to death
within a few minutes (anaphylactic shock).
In less severe cases, the increase of vascular
permeability causes allergic edema, which is the most
dangerous in the larynx, as cause fatal asphyxia.
Atopy - a family history of pathological response to some
allergens.
Skin immediate redness, swelling (Sometimes with blisters)
itching; severe dermatitis or eczema. Antigen may contact
with skin directly at the injection (including and insect bites)
or oraly enters the body (in the food or drug allergies).
Nasal mucosa - if inhaled allergen (E.g., pollen, wool of
animals) in the nasal mucosa there is mucus hypersecretion
(Allergic rhinitis).
Lungs - inhalation of allergens (pollen of plants, dust) leads to
reduction of smooth muscles of the bronchi and mucus
hypersecretion, resulting in acute obstruction respiratory
truct and asphyxia (allergic bronchial asthma).
Intestine - oral entrance of allergen (Nuts, shellfish, crabs)
causes muscle contraction and fluid secretion, which is
manifested in the form of spastic abdominal pain and
diarrhea (Allergic gastroenteritis).
Allergic dermatitis
Bronchial asthma
 II type hypersensitivity reaction
(antibodydependent)
Appearance of antibodies to own tissues,
which bind to the normal or damaged target
cells and cause their phagocytosis or lysis
There are 3 mechanisms of type ІІ reaction
development:
1. Complement-depended reaction
2. Ab-depended cellular cytotoxicity
3. Ab-mediated dysfunction of cells
1. Complement-depended reaction
2 mechanisms of development
1. Direct lysis:
IgM or IgG + АG (on the sufece of the cell)
↓
Complemen atactivation
↓
Activetion of membrane-attacking complex
↓
Cell death
2. Opsonisation (relief):
Аb (or complement component С3в)
+
Cellular membrane
↓
Phagocytosis of the cell

More often the targets are blood cells

 These reactions occur at:

1. Blood transfusion reaction Переливанні

несумісної крові,
2. Erythroblastosis fetalis,
3. Autoimmune hemolytic anemia,
agranulocytosis, thrombocytopenia
4. leucopenia drug-induced
 2. Antibody-depended cellular
cytotoxicity
Is not accompanied by complement fixation,
Causes cooperation of leucocytes.
E. g. tumor cells, parasytes
 3. Antibody-mediated dysfunction
of cells
Аb against receptors on the cellular surface
disturb their functioning wherein do not cause
their damage or inflammation development.

E.g. Graves’ diseases, myasthenia gravis,

male sterility
 III type hypersensitivity reaction
They are caused by presence of immune
complexes in the blood (circulating immune
complexes – CIC) or outside the vessels (IC in
situ).
CIC cause damage when penetrating vascular
wall or filtering structures.
2 types of reaction:
systemic (IC are formed in the blood and
deposit in organs, leading to their
inflammation);
focal – Arthus reaction.
 1. Systemic immune-complex disease
Acute serum sickness – occur as a result of
repeated injection of high doses of foreign
serum for passive immunization (antitetanic
serum etc.)

More often CIC deposit on:

Renal glomeruli;
Joints;
Skin;
Heart;
Serous membranes;
Small blood vessels.
 2. Focal IC-reaction (Arthus reaction)
Occurs as:
• Acute IC-vasculitis;
• Focal necrosis of tissues.
Arthus reaction develops in several hours.
Peak reaction in 4-10 hours after injection (zone
of swelling with hemorrhage due to vessel
rupture with following thrombosis).
 IV type hypersensitivity reaction
(cell-mediated cytotoxicity)
Is caused by speciefic sensitized T-lymphcytes.
Types:
1. Classic delated hypersensitivity reactions are caused by CD 4
+ Т-killers (e.g. granulomatous inflammation – TB, typhoid
fever etc.; Tuberculin reaction – Mantoux test, immune
response at contact of the skin with chemicals – dermatitis)

2. Direct cellular cytotoxicity – mediated by CD 8 and Т-killers

(e.g. immune response to intracellular pathogens – viruses,
tumor cells, transplant rejection).
Contact eczema
Contact dermatitis
 TRANSPLANT REJECTION.
Host organism recognizes transplant tissue as foreign.
HLA – antigens are responsible for rejection. This is very
complicated process, when there are changes in cellular
immunity and appearance of circulating Ab.
1. T-lymphocytes- mediated reactions.Recipient’s lymphocytes
+ HLA-antigens of donor. Main important Ag – dendritic cells
of donor.
2. Reactions caused by Ab formation. Very acute rejection – in
recipient’s blood there are Ab against donor.
Transplantation → IC formation → Deposition of IC in
endothelium → Complement fixation → Arthus reaction
Transplanted kidney Rejection
Transplantational vasculitis
 AUTOIMMUNE DISEASES
• Diseases which appear due to reaction
of autoantibodies and sensitized
lymphocytes against antigens of own
tissues.
 PATHOGENESIS OF AUTOIMMUNE DISEASES
• Predisposing factors (HLA genes, hormonal
background, genetically determined features
of target cells);
• Initial factors (viral and bacterial infections,
influence of chemical and physical factors on
the immune system and target organs);
• Contributory factors (immune system
dysfunction, Т-supressor activity).
Major histocompatibility complex - MHC - number of
genes main function of which is immune recognition.
• Т-calls are available to bind with Ag only if it is on
the surface of the other cell in complex with MHC
molecule
• MHC includes 1, 2, 3 classes of markers. In
pathogenesis of autoimmune diseases class 2 is
more important. Class 2 MHC markers are also
called HLA-Dr. There are a lot of autoimmune
diseases , which are connected with genetic
disturbances of HLA-Dr system. That is why HLA
genes predisposing factors in the pathogenesis of
autoimmune diseases.
 Classification
• 1 Group – Organ specific diseases.
Characterised by damage of physiologic barriers of
organs and tissues which have no contact with
the cells of immune system or they were formed
during ontogenesis after complete formation of
immune tolerance (lens of the eye, thyroid gland,
nervous tissue, adrenal glands, testes).
E.G. autoimmune goiter (Hasimoto's disease) ,
encephalomyelitis, autoimmune orchitis, etc.
Hasimoto's disease
 2 Group. Organ nonspecific diseases
• Primary disturbances in the
immune system causing the loss of
ability to distinguish "own" and
"foreign" antigens.
• E.g. Systemic lupus erithematosis,
rheumatic arthritis, scleroderma,
dermatomiositis, TPP, etc.
Rheumatic arthritis
SLE
Antinuclear Ab
GBM-disease (Goodpasture syndrome) -
production of autoAb to basal membranes of glomeruli
and lungs. Clinically: pulmonary bleeding and
glomerulonephritis
Antimembranous Ab
 Diseases with autoimmune
disturbances
• Autoimmunization is responsible not for
the beginning but the progress of the
disease as autoimmune antibodies
appear during the disease.
• It is observed in glomerulonephritis,
hepatitis, chronic gastritis, burn disease,
rheumatism, liver cirrhosis.
 IMMUNE DEFICIENCY SYNDROMES

All immune deficiencies are divided into

2 groups:
• primary, congenital immune
deficiencies
• secondary, acquired immune
deficiencies
• Primary IDS – genetically
determined states in which there
are disturbances of specific
immunity (T-cell, B-cell, or
combined Т+В-cell) and/or
nonspecific immunity
(agranulocytosis)
• T-cell T-cell deficiencies manifest
themselves by agenesis, hypoplasia
of the thymus and T-dependent
zones of the immune system and
occur as frequent recurrent
infections with severe clinical course
• E.g. Di George syndrome
• B-cell deficiencies.
• B-zones in the peripheral lymphatic
organs are absent. Immunoglobulins (one
or all of them) synthesis is absent.
E.g. Bruton's syndrome; isolated
deficiency of Ig A.
 Combined syndromes - insufficiency of
cellular and humoral immunity (T- B-cell)
• Hypoplasia of thymus and peripheral
lymphatic tissue.
It is inherited according to autosome-
recessive type.
E.g. Glanzmann-Riniker syndrome
(agammaglobulinemia of swiss type);
Viscott-Oldrich syndrome
 Secondary deficiencies occur after
complete development of the immune
system
• Some of them are caused by
immunosuppresive therapy (e.g. tumors,
autoimmune diseases, reumatic disease etc.)
or radiation, chronic infections, aging etc.
• HIV-infecton
 CHANGES OF LYMPHOID TISSUE AT
ANTIGEN STIMULATION
• In the thymus, different stages of
accidental transformation are observed.
• In the bone marrow the first hyperplasia
of B- lymphocytes are observed, then it
becomes empty, as a result of increased
transition of lymphocytes.
 Accidental thymus transformation
(involution)
• That is reduction of thymus in the size
and mass due to thymocyte migration to
the peripheral immune organs and
blood as well as due to their
appoptosis.
Normal thymus
Stages in ATT according to
T. Ivanovskaya (1976)
Stage 1 - "holey
clearing" –
accumulation of
lymphocytes
around the
macrophages. It
occurs in the
cortex.
• Stage 2 – migration
of the lymphocytes
from the cortex to
the medullar
substance. The
boundary between
the layers is either
poorly seen or not
seen at all.
• Stage 3 - "layer
inversion", when
cortex layer looks
like light, but vice
verse medullar
layer looks like
dark, as a result
migration of the
lymphocytes from
the cortex to the
medullar
substance.
• Stage 4 - Reduction in the lymphocyte amount in the
both layers with reticular stroma growth.
• Stage 5 - collapse of the lobe of the thymus and
sclerosis and lobe atrophy.
 Peripheral lymphoid organs
• First, T-zones and B-zone hyperplasia
occurs. Macrophages and plasmatic cells
appear as well as their blasts producing
immunoglobulins.
Follicle hyperplasia due to antigenic
stimulation
• Vascular
endothelium is
swollen, there
are
lymphocytes in
the lumen.
• After that both T
and B-zones
become empty. T-
zone is
characterized by
"holey"
appearance. In B-
zone density of the
cells decreases. The
lymphocytes either
die or circulate in
the blood.
• Reticuloepithelium hyperplasia and lympho-
plasmocyte infiltration occur in the interstitial
tissue of the kidneys, pancreas, intestines, liver,
muscles.