Exaggerated or misdirected

immune response
Results in tissue injury or other
pathophysiological changes
Occurs when an already sensitized
individual is re-exposed to the
same foreign substance
May be immediate or delayed
Ensuing tissue injury may be
caused by:
1. Release of vasoactive substances
2. Phagocytosis or lysis of cells
3. Activation of inflammatory &
cytolytic components of
complement system
4. Release of cytokines, proteolytic
enzymes and other mediators of
tissue injury or inflammation
 Type I Hypersensitivity

Immediate/Anaphylactic type
IgE-mediated
Occur within minutes
Provoked by re-exposure to the
same antigen (by contact,
inhalation, ingestion or injection)
Local or systemic
T
Y
P
E
I

Source:
Robbins
PATHOLOGIC BASIS
OF DISEASE 6th ed
 Type I Hypersensitivity

LOCAL ANAPHYLAXIS
• Atopy  genetically determined
predisposition to develop localized
anaphylactic reactions to inhaled or
ingested allergens
• (+) family history  chr. 5q31
• With higher serum IgE levels
compared to general population
 Type I Hypersensitivity

LOCAL ANAPHYLAXIS
Two phases:
1. Initial response
 Vasodilation, vascular leakage,
smooth muscle spasm or
glandular secretions
 5-30 min. after exposure 
subside in 60 minutes
 Type I Hypersensitivity

LOCAL ANAPHYLAXIS
Two phases:
2. Late-phase reaction
 2-8 hrs. later without additional
exposure to antigen
 More intense infiltration of
tissues with eosinophils,
neutrophils, basophils,
monocytes & CD4+ T cells
 With mucosal epithelial damage
 Type I Hypersensitivity

SYSTEMIC ANAPHYLAXIS
• Occur after administration of
heterologous proteins (e.g.
antisera), hormones, enzymes,
polysaccharides & drugs
• Exposure  itching, hives & skin
erythema  contraction of resp.
bronchioles + resp. distress
• (+) laryngeal edema
 Type I Hypersensitivity

CLINICAL EXAMPLES:
1.Atopic disorders
 Allergic rhinitis, hay fever,
asthma, atopic dermatitis,
urticaria

2.Anaphylaxis
 Type I Hypersensitivity

PRIMARY MEDIATORS:
1. BIOGENIC AMINES
 Histamine
 Adenosine – enhance mast cell
mediator release
2. CHEMOTACTIC MEDIATORS
3. ENZYMES – proteases, acid hydrolases
4. PROTEOGLYCANS – heparin,
chondroitin sulfate  package & store
other mediators in the granules
 Type I Hypersensitivity

SECONDARY MEDIATORS:
1. LEUKOTRIENES – LTC4 , LTD4  most
potent vasoactive & spasmogenic
agents known; LTB4 (chemotaxis)
2. PROSTAGLANDIN D2 – most abundant
in mast cells
3. PAF – release of histamine,
bronchospasm, inc. vasc. permeability,
vasodilation
4. CYTOKINES – e.g. TNF, IL-1, IL-3, IL-
4, IL-5, IL-6
 Type I Hypersensitivity

DIAGNOSIS:
1.History
2.Skin prick test – (+) wheal &
flare
3.Blood eosinophilia
4.RAST (Radioallergosorbent
assay)
 Type I Hypersensitivity

TREATMENT:
1.Anti-histamine – acts on first
phase only
2.Corticosteroids – late phase
reaction
3.Desensitization – to induce
tolerance; no IgE production 
deplete already bound IgE
 Type II Hypersensitivity

Mediated by antibodies directed

toward antigens present on the
surface of cells or other tissue
components
IgG and IgM
Antigenic determinants – intrinsic
or exogenous
 Type II Hypersensitivity

MECHANISMS:

Complement-Dependent Reactions
Antibody-Complement-mediated
lysis
Antibody (IgM/IgG) + antigen on
cell surface  (+) activation of
complement system  (+) MAC
 Type II Hypersensitivity

MECHANISMS:
Complement-Dependent Reactions

Source: Robbins PATHOLOGIC

BASIS OF DISEASE 6th ed.
 Type II Hypersensitivity

MECHANISMS:
Complement-Dependent Reactions
1. Transfusion reactions
2. Erythroblastosis fetalis
3. Autoimmune hemolytic anemia,
agranulocytosis, thrombocytopenia –
(+) antibodies vs own blood cells
4. Pemphigus vulgaris – Ab’s vs.
desmosomes
5. Drug reactions
 Type II Hypersensitivity

MECHANISMS:
Antibody-Dependent Cell-Mediated
Cytotoxicity (ADCC)
due to NK activity  non-sensitized
cells with Fc receptors
Ab + Ag  activation of NK cells 
bind to Fc fragment of IgG  cell
lysis without phagocytosis
Destruction of targets too large to be
phagocytosed (parasites, tumor
cells) + graft rejection
 Type II Hypersensitivity

MECHANISMS:
Antibody-Dependent Cell-Mediated
Cytotoxicity (ADCC)

Source: Robbins PATHOLOGIC BASIS OF DISEASE 6th ed.

 Type II Hypersensitivity
MECHANISMS:
Antibody-Mediated Cellular Dysfunction
• Antibodies directed against cell surface
receptors  impair or dysregulate
function

Source: Robbins PATHOLOGIC BASIS OF DISEASE 6th ed.

 Type II Hypersensitivity

MECHANISMS:
Antibody-Mediated Cellular Dysfunction
1. Myasthenia gravis – acetylcholine
receptors
2. Goodpasture’s syndrome – type IV
collagen
3. Pernicious anemia – intrinsic factor
4. Acute rheumatic fever – antibodies vs.
Streptococcal antigens cross-react with
heart
 Type III Hypersensitivity

Immune Complex Mediated

Formation of immune complexes in
circulation  deposit in various
tissues  trigger classical pathway
of complement activation
Produce damage as they localize
within blood vessel walls or when
trapped in filtering structures (e.g.
renal glomeruli)
 Type III Hypersensitivity

Source: Robbins
PATHOLOGIC BASIS
OF DISEASE 6th ed.
 Type III Hypersensitivity

Source: Robbins PATHOLOGIC BASIS OF DISEASE 6th ed.

 Type III Hypersensitivity

Source: Robbins PATHOLOGIC BASIS OF DISEASE 6th ed.

 Type III Hypersensitivity
Antigens Associated with Immune Complex
Disorders
ANTIGEN CLINICAL MANIFESTATION
EXOGENOUS
Infectious agents:
Bacteria: Y. enterocolitica Arthritis
Streptococci GN, Infective endocarditis
T. pallidum Glomerulonephritis
Viruses: Hep. B, CMV Polyarteritis nodosa
Parasites: Plasmodium Glomerulonephritis
Schistosoma
Fungi: Actinomycetes Farmer’s lung
ENDOGENOUS
Nuclear antigens SLE
Immunoglobulins Rheumatoid arthritis
Tumor antigens Glomerulonephritis
 Type III Hypersensitivity

SERUM SICKNESS
• Patient forms antibodies to xenogeneic
Ig administered during passive immune
therapy regimens

ARTHUS REACTION
• Seen when boosters are administered to
individuals who already possess high
antibody titers to vaccine molecules
• Localized area to tissue necrosis 
edema, hemorrhage, ulceration
• Develop over a few hours
 Type IV Hypersensitivity

Cell-mediated hypersensitivity
Initiated by sensitized T lymphocytes
Principal pattern of immunologic
response to intracellular
microbiologic agents (particularly
Mycobacterium tuberculosis) as well
as viruses, fungi, protozoa &
parasites
 Type IV Hypersensitivity

Two forms:
1.Delayed-type hypersensitivity
 Mediated by CD4 T cells
 1st exposure to Ag  CD4 T cells +
class II MHC  differentiation of
naïve CD4 T cells to TH1 cells 
release of IL-12, IFN-, IL-2, TNF
& lymphotoxin
 Tuberculin skin test, contact
dermatitis, granulomatous
inflammation
 Type IV Hypersensitivity

Two forms:
2.T Cell-Mediated Cytotoxicity
 Mediated by CD8+ T cells
 Sensitized CD8+ T cells kill
antigen-bearing target cells
 Graft rejection, virus infections,
tumor immunity
 Type IV Hypersensitivity

Two forms:
2.T Cell-Mediated Cytotoxicity
 Two mechanisms:
a)Perforin-granzyme-dependent
killing  cause perforation of
plasma membrane
b)Fas-FasL-dependent killing 
activation of apoptosis