CHAPTER 6 1

DISEASES OF THE IMMUNE SYSTEM

HYPERSENSITIVITY AND AUTOIMMUNE DISORDERS
MECHANISMS OF HPERSENSITIVITY REACTIONS
o
o
o

o
o

Individuals who have been previously exposed to an antigen are said to be sensitized.
Hypersensitivity
repeat exposures to same antigen that triggers a pathologic reaction
excessive response to antigen
Important general features of hypersensitivity disorders:
a) both exogenous and endogenous antigens may elicit hypersensitivity reactions
b) development of hypersensitivity disease is often associated with the inheritance of
particular susceptibility genes
c) hypersensitivity reflects an imbalance between the effector mechanisms of immune
responses and te control mechanism that serve to normally limit such responses
Hypersensitivity dieseases are classified on the baiss of the immunologic mechanism that
mediates the disease
Main types are:
I.
IMMEDIATE HYPERSENSITIVITY (Type I )
immune response is mediated by
TH2 cells
IgE antibodies
mast cells
results in the release of
a) mediators that act on vessels and smooth muscle
b) pro inflammatory cytokines that recruit inflammatory cells
II.
ANTIBODY MEDIATED DISORDERS (Type II)
IgG and IgM antibodies participate directly in injury to cells by promoting their
phagocytosis or lysis
injury to tissues: inducing inflammation
Ab may also interfere with cellular functions and cause disease without tissue
injury
III.
IMMUNE COMPLEX-MEDIATED DISORDERS (Type III)
IgG and IgM antibodies bind antigens usually in the circulation
Ag-Ab complexes deposit on tissues and induce inflammation
Leukocytes that are recruited (neutrophils and monocytes) produce tissue
damage : release of lysosomal enzymes and generation of toxic free radicals
IV.
CELL MEDIATED IMMUNE DISORDERS (Type IV)
sensitized T lymphocytes (TH1 and TH17, CTLs) are the cause of the tissue
injury
TH2 cells - induce lesions; not considered as a form of Type IV
hypersensitivity

IMMEDIATE HYPERSENSITIVITY (TYPE I)

o
o
o

rapid immunologic reaction occurring within minutes after the combination of an antigen
with antibody bound to mast cells in individuals previously sensitized to the antigen
reaction is called Allergy; antigen that elicit an allergy is called Alergens
Type I hypersensitivity may occur as a systemic disorder or as a local reaction
Systemic Reaction
usually follows ingection of an antigen into a sensitized individual
Local reactions

CHAPTER 6 2
DISEASES OF THE IMMUNE SYSTEM
diverse; vary depending on the portal of entry of the allergen
take the form of localized cutaneous swelling, nasal and conjunctival
discharge, hay fever, bronchial asthma or allergic gastroenteritis
majoriy of Type I have two well-defined phases:
1. immediate or intial reaction
characterized by
a) vasodilation
b) vascular leakage and
c) smooth muscle spasm or glandular secretion. (depending on the
location)
usually becomes evident 5 to 30 minutes after exposure to an allergen
tend to subside in 60 minutes
2. late phase reaction
usually in allergic rhinitis and bronchial asthma
sets in 2 to 24 hours later withouth additional exposure to antigen
may last for several days
characterized by
a) infiltration of tissues with eosinophils, neutrophils, basophils,
monocytes and CD4+ T cells
b) tissue destruction : in the form of mucosal epithelial cell damage
-

o
o

Type I HSR are mediated by IgE antibody-dependent activation of mast cells and other
leukocytes
Mast Cells
bone marrow derived cells
widely distributed in the tissues
abundant near the blood vessels and nerves and in subepithelial tissues
have cytoplasmic membrane-bound granules that contain a variety of biologically
active mediators
granules also contain acidic proteoglycans that bind basic dyes (tolouidine blue)
mast cells and basophils are activatd by the cross linking of high affinity IgE Fc
receptor; MC may also be triggered byu tierh stimuli sucha as:
complement components C5a and C3a (anaphylatoxins)
other mast cell secretagogues:
chemokines (IL-8)
codein and morphine
adenosine
mellitin (bee venom)
physical Stimull
Basophils
similar to mast cells: presence of cell surface IgE Fc receptors and cytoplasmic
granules
not normally present in tissues; circulate in the blood in extremely small numbers
can be recruited to inflammatory sites
TH2 cells play a central role in the initiation and propagation of immediate hypersensitivity
reactions by stimulatinfg IgE production and promoting inflammation
PREFORMED MEDIATORS

mediators contained within mast cell granules are the first to be released.

CHAPTER 6 3
DISEASES OF THE IMMUNE SYSTEM
o

divided into 3
1. Vasoactive amines
most important mast cell-derived amine is histamine
Histamine causes intense smooth muscle contraction, increased vascular
permeability and increased mucus secretion by nasal, bronchial and gastric
glands
2. enzymes
contained in the granule matrix
include neutral protease (chymase, tryptase) and several acid hydrolase
-