Immunopathology

..

IMMUNOPATHOLOGY
LERTLAKANA BHOOPAT, MD.
(Hon.),
FRCP., FRCPath.(AP&CP)
He who has health has hope; and
he who has hope has everything.

1.Cellular basis for the immune response

2.Various types of immunologic disorders
3.Immunopathologic mechanisms of hypersensitivity
and related clinical conditions
4.Immunopathologic and clinical correlation of
autoimmune diseases
5.Immunopathologic and clinical features of immune
deficiency
Suggested reading- Robbins: Pathologic Basis of Diseases, 7 th
edition

Cells
of
the Immune
System

1.

Lymphocytes

1.1. The thymic lymphocytes (Tcells)

- the brains of the immune
system.
- 60%-70% of circulating
lymphocytes.

(TH) cells

TH1
- important for
stimulating cell-mediat
ed immune responses
- synthesize IL-2 and
IFN-g.

TH2
- important in humoral
immunity
- suppress cellmediated immune res
ponses.

1.2. B
Lymphocytes
- Cells of B-cell lineage

comprise
10%-20% of circulating
lymphocytes.
- responsible for the
production of immunoglobl
ins.

-After exposure to antigen

convert from memory
B cells to plasma cells
secrete large amounts
of immunoglobulin.

2. Macrophages
- phagocytose soluble and
insoluble proteins and micr
obes.
- present antigen &
stimulate T cells to divid
e and mature.

3. Dendritic Cells and

Langerhans Cells
- rapidly being recognized as
extremely important cells in
cell-mediated immunity.

4. Natural Killer (NK)

Cells
- large granular
lymphocytes
- lyse a large variety of
tumor cell without requiri
ng prior sensitization.

Immune system

Two edged sword

- Protection
- Disorders of immune system

Organs involving Immune system

- peripheral blood
- lymph node
- bone marrow
- spleen
- liver

- MALT
gastrointestinal tract
respiratory tract
- thymus
- tonsil

Mechanism of immune system

1. Innate immunity
Present before infection
consists of epithelial barrier,
phagocytic cells, natural killer
cell & several plasma protein .

Mechanism of immune system

2. Adaptive immunity
Develops later after exposure
to microbes
Recognizing antigens
consists of lymphocytes and
their products including
antibodies.

Immune system disorders

1.
2.
3.
4.

Hypersensitivity reactions
Autoimmune diseases
Immunologic deficiency syndromes
Amyloidosis

Hypersensitivity reaction
- Immune system is very sensitive
to allergen which leads to
inflammation and tissue injury .
- 4 types , different in mechanism .

Immediate [ type 1 ] hypersensitivity

- occurring within minute after the
combination of an antigen with
antibody bound to mast cells in
individuals
- previously sensitized to the antigen.

Immediate [ type 1 ] hypersensitivity

- 2 phases
immediate response [5 30 min ]
vasodilation , vascular leakage ,
smooth muscle spasm , conjuctival
discharge, hay fever, bronchial
asthma , allergic gastroenteritis , edema ,
increase secretion of mucous lining GI
tract

Immediate [ type 1 ] hypersensitivity

Late phase [ 2 24 hours ]
infiltration of tissue with
eosinophils, basophils, neutrophils
monocytes, tissue destruction,
epithelial damage

Mechanism
1st antigen + T cell receptor
production of IgE antibodies fixed on
a mast cell
2nd antigen

mast cell + IgE

Release of primary & secondary

mediators
allergy

Clinical example
Anaphylaxis
- Vasodilation
- Vascular shock / hypotension
- Widespread edema
- Severe bronchospasm
- May have itching , hives (urticaria)
Causes:
foreign protein, hormone, enzymes,
drug [ aspirin , penicillin ]

Clinical example
Atopic allergy
- Eyes [ allergic conjuctivitis ]
- Nose [ allergic rhinitis ]
- Lungs [ bronchial asthma ]
- Skin [ atopic dermatitis ]
Causes:
environmental allergen, such as
pollen, animal, house dust, foods

Lung asthma

Bronchiolar
epithelium

Acute
inflammation

Mucous
plug
Chronic inflammation

Atopic dermatitis

WHAT ELSE IN TYPE 1?

-Urticaria
-Angioedema
-Dermographism
-Bee sting allergy

DIAGNOSIS

Triggers

Examples

Allergens

Pollen, dust mites, animal dander,

insects, mold

Substances that may cause allergic

reactions in sensitive individuals
Medications
Prescriptions and over-the-counter
drugs
Irritats
Substances in the air that may trigger
episodes
Health conditions
Changes in your own body that may
trigger episodes
Exercise
Emotional responses

Aspirin or other medications

Cigarette smoke, fireplace smoke,
aerosol sprays, perfume, household
and industrial chemicals, very cold
air, air pollution.
Infections, such as colds, flu, and
sinusitis. Hormonal changes
Physical exertion, especially during
cold or dry weather
Crying, laughing, stress

Diagnostic tests for

immediate hypersensitivity

Treatme
Whatntcauses
this boy
using the
inhaler?

Antibody Mediated [ type 2 ]

hypersensitivity
- Allergen = blood group antigen
- Antibodies directed toward antigens
present on cell surface or
extracellular matrix

3 Type of reactions

1. Opsonization and phagocytosis

- cell are coated [opsonized] with
molecule that attractive for
phagocytes
- phagocytosis of target cells
Clinical example : transfusion reaction,
erythroblastosis fetalis, autoimmune
hemolytic anemia, certain drug
reaction

2.Complement and Fc receptor

mediated inflammatation
- antibodies deposit in extracellular tissue
- cells bind to the deposited antibodies
via Fc receptor
- the deposited antibodies activate
complement that recruit neutrophils
and monocytes

3.Antibody Mediated Cellular

dysfunction
- antibody bind to target cell
receptor
- causing receptors dysfunction
without cell injury or inflammation
Clinical example : Myasthenia gravis,
Graves diseae

Immune complex Mediated

[ type 3 ] hypersensitivity
- Antigen + antibodies within circulation
[circulating immune complex]
- Deposited in vessel walls
- Produce tissue damage by
inflammation at the site of deposition
Clinical example : SLE, Polyarteritis
nodosa, Serum sickness, Reactive
arthritis, Acute glomerulonephritis,
Arthus reaction,

2 types
1. Systemic immune complex
- Example : Serum sickness, SLE
- 3 phases
Immune complex formation
Immune complex deposition
Immune complex Mediated inflammation
- The result of inflammatory is vasculitis,
glomerulonephritis, arthritis

Vasculitis Vasculitis

2. Local immune complex [ Arthus

reaction ]
- Local area of tissue necrosis
resulting from acute immune
complex vasculitis.
- Usually elicited in the skin
- Edema, severe hemorrage followed
by ulceration, fibrinoid necrosis

Fibrinoid necrosis

Cell Mediated [ type 4 ] hypersensitivity

- Initiated by antigen activated T
lymphocyte
- response to microbiologic agent
[ Mycobacterium tuberculosis , many
viruses, fungi, protozoa, parasites ]

2 forms
1. Delayed Type Hypersensitivity
- Mediated by CD 4+ T cells
- 48 72 hours after exposure
- Example: tuberculin test reaction
- Accumulation of mononuclear cells
around small veins and venules ,
producing a perivascular cuffing
- Increase microvascular permeability,
dermal edema, deposition of fibrin in
interstitium

- Fully developed lesion , the

lymphocyte cuffed venules show
endothelial hypertrophy, hyperplasia
- The perivascular lymphocytic
infiltrate is replace by macrophage
- Aggregation of epitheloid cells ,
surrounded by lymphocytes
granuloma called granulomatous
inflammation

Tuberculin skin test

Perivascular T-cell infiltrate

Skin, hypersensitivity
lesion
epidermis

dermis

2. T cell Mediated cytotoxicity

- Mediated by CD 8 + T cell
(cytotoxic T lymphocyte [ CTLs ] )
- CTLs directed against cell surface
antigens.
- Example: graft rejection

Cell Mediated [ type 4 ] hypersensitivity

- Skin sensitivity to chemical agents
are also instance of cell mediated
reaction (Contact dermatitis).