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Dr. Samir Ayad

Immunity
Natural (non-specific) immunity:
Inherited & do not depend on previous exposure
(a) First line of defense: mechanical (skin), cilia in
trachea and bronchi, nasal and gastric secretions
(b) Second line of defense: lysozymes, complement
and phagocytic cells
Acquired (specific) immunity:
Specific response following exposure to a particular
antigen
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Dr. Samir Ayad

Essential features of immune system

- Specificity: for one particular antigen
- Diversity:

can recognize different antigens

- Memory:

to previous antigens, responsible

for rapid, higher and persistent
secondary immune response

- Recruitment:by releasing cytokines that recruit

& activate other defense mechanisms

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Dr. Samir Ayad

Harmful Immune Reactions

Immunopathology
Three groups of diseases:

(1)

Hypersensitivity (as anaphylaxis)

(2)

Autoimmune (as SLE)

(3)

immunologic deficiency (congenital or

acquired)
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Dr. Samir Ayad

Hypersensitivity
Allergy
- Abnormal exaggerated immune reactions resulting
in tissue injury
- Four types on the basis of mechanism of injury:
Type I:

immediate (anaphylactic)

Type II:

cytotoxic

Type III:

immune complex

Type IV:

cell-mediated hypersensitivity
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Dr. Samir Ayad

Type I: Immediate (Anaphylactic) Reaction

Mechanism:
- 1st exposure to allergen stimulates IgE binds to
mast cell and blood basophils
- On subsequent exposure, the allergen reacts with
the fixed AB degranulation of mast cells
release of histamine and others
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Dr. Samir Ayad

Activation of mast cell & the potent inflammatory mediators

released

Dr. Samir Ayad

Clinical Types:

(1) Atopy
Local form (affecting one organ) e.g. urticaria
(hives), allergic rhinitis, bronchial asthma
Response to ingested or inhaled environmental
allergens
Affects 10% of population
Strong familial predisposition

Dr. Samir Ayad

Bronchial asthma, high power

Numerous eosinophils are prominent.

Dr. Samir Ayad

(2) Anaphylaxis
- Systemic from release of vasoactive amines
into circulation e.g. peripheral circulatory failure,
shock, hypotension, even death
- Follows injection of allergens e.g. serum, drugs
(penicillin)

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Dr. Samir Ayad

Drug-induced urticaria: penicillin

Large, urticarial wheals on the face, neck, and trunk with
angiodema in the periorbital region.

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Dr. Samir Ayad

Type II: Cytotoxic Reaction

& Antibody-mediated Reaction
Mechanism:
Specific antibody (IgG or IgM) reacts with cell
membrane antigen, activates the complement
resulting in cell lysis

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Dr. Samir Ayad

Clinical types
1 Transfusion reaction due to blood incompatibility:

AB in recipient serum reacts against antigen on

transfused RBCs

Rh incompatibility:
2
Maternal AB to fetal RBC antigen (Rh) cross the
placenta (IgG)
Autoimmune hemolytic anemia:
3 Autoantibodies to RBCs
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Dr. Samir Ayad

Type II hypersensitivity.
Antibodyand
complement-mediated red
blood cell lysis due to
complement activation and
the formation of the C5b-9
membrane attack complex
(MAC).

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Dr. Samir Ayad

4 Myasthenia gravis:

Autoantibodies against acetylcholine receptors

at neuromuscular junction, compete with
acetylcholine for the acetylcholine receptors,
inhibiting synaptic transmission leading to
profound muscle weakness.
5 Graves disease:

Autoantibodies to thyroid stimulating hormone

receptors on follicular cells
stimulation of cells
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Dr. Samir Ayad

Noncytotoxic antireceptor antibodies in Graves disease and

myasthenia. The binding of the antibody to the TSH receptor
in Graves disease results in hyperthyroidism, whereas the
inhibition of synaptic transmission in myasthenia gravis leads
to profound muscle weakness.
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Dr. Samir Ayad

6 Goodpastures syndrome:

- Formation of AB (IgG) to antigens common

in glomeruli & pulmonary basement membranes
- AB reacts with basement membrane antigen
activates complement resulting in:
- Lung: hemorrhage, necrosis, fibrosis
- Kidney: glomerulonephritis, fibrosis, failure

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Dr. Samir Ayad

Antibody against glomerular basement membrane antigens in

Goodpasture disease. The binding of antibody to antigens of
basement membrane activates complement, thereby recruiting
polymorphonuclear leukocytes and provoking tissue injury.
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Dr. Samir Ayad

Type III: immune Complex Reaction

Mechanism:
- Reaction of AB (IgG or IgM) with antigen results
in the formation of soluble immune complexes
- deposition of immune complexes in various tissues
- Activation of complement acute inflammation
and tissue damage

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Dr. Samir Ayad

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Dr. Samir Ayad

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Dr. Samir Ayad

Arthus phenomenon
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Dr. Samir Ayad

Clinical types:
(1) Systemic form:
- serum sickness
- rheumatoid arthritis
- systemic lupus erythematosus
(2) Local form:
- pneumonitis that develops 6-8 hours after
inhalation of moldy hay (Farmers lung) or
moldy cheese (Cheese makers lung)
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Dr. Samir Ayad

One form of hypersensitivity pneumonitis is known as

farmer's lung because the farmer inhales thermophilic
actinomyces in moldy hay that set off the reaction.

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Dr. Samir Ayad

Lung, hypersensitivity pneumonitis, microscopic

This is an example of hypersensitivity pneumonitis that can
occur when there is an inhaled organic dust that produces a
localized type III hypersensitivity (Arthus) reaction from
antigen-antibody complexes. There are no major long-term
complications.

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Dr. Samir Ayad

Type IV: Cell Mediated Hypersensitivity

Type IV is mediated by T cells rather than antibodies
Mechanism:
Includes 2 types of reaction

1- DTH: Delayed-type hypersensitivity:

-

Reaction is mediated by CD4 cells (antigenspecific memory T cells)

2-T cell-mediated cytotoxicity:

Release of IL-2 for activation of CD8 and yinterferon for activation of macrophages
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Dr. Samir Ayad

Granulomas, which are

typical of type IV
hypersensitivity, consist
of epithelioid cells, giant
cells, and lymphocytes.

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Dr. Samir Ayad

Clinical types:
(1) contact dermatitis

(2) Killing of tumors and virus infected cells

(3) Transplant rejection

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Dr. Samir Ayad

Contact Dermatitis
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Dr. Samir Ayad

Contact Dermatitis
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Dr. Samir Ayad

Immune Mechanism of Tissue Injury

Summary:
Immune responses (humoral or cellular) to antigens
(exogenous or endogenous) cause tissue damaging
hypersensitivity reactions:

Type I: Humoral AB (IgE) binds to antigens,

releases vasoactive amines from mast cells &
blood basophils.
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Dr. Samir Ayad

Type II:

Humoral AB (IgG, IgM) binds to antigen on

cell surface, activates complement cell lysis

Type III: Humoral AB (IgG, IgM) binds to antigen

forming soluble immune complexes

activates complement attracts neutrophils

release of neutrophilic enzymes tissue

damage
Type IV: Antigen-specific CD4 memory cells

recruit & activate CD8 and macrophages

tissue damage
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Dr. Samir Ayad