Download Adverse Immune Reactions and Immune Deficiencies

Dental Microbiology #211
IMMUNOLOGY
Lecture 6
Adverse Immune Reactions and
Immune Deficiencies
Topics
• Hypersensitivity reactions
• IgE-mediated hypersensitivity (Allergy)
• T cell-mediated reactions (Delayed-type
hypersensitivity)
• Autoimmune disorders
• Inherited and acquired immunodeficiency
disorders
• Impact on the oral cavity
Hypersensitivity (Allergy)
Definition:
Altered capacity of the body to react to a
foreign substance
The hypersensitivity states or allergies can be
divided into four categories:
Type
Type
Type
Type
I (IgE antibody-mediated)
II (IgG and IgM-mediated)
III (Immune complex-mediated)
IV (T cell-mediated)
Over 30% of individuals in the western
hemisphere have the tendency to produce IgEand suffer from IgE-mediated reactions. They
are called atopic individuals.
The atopic state is influenced by both genetic and
environmental factors.
The prevalence of atopic allergy and bronchial
asthma is affected by air pollution and exposure
to infectious diseases of the respiratory tract
Type I (IgE-mediated hypersensitivity
reactions)
There are certain antigens and routes of Ag
exposure that favour IgE Ab production
Antigens that evoke IgE responses are
collectively called allergens
The symptomatology is different depending on
whether the Ag is injected, inhaled or ingested
i.e. depending on the tissue where the
pharmacologic mediators of allergy i.e histamine
and serotonin are released (the target tissue) .
IgE-mediated reactions Fig 1
The IgE molecule Fig 2
Properties of IgE
IgE is present in low concentrations in the plasma
(<50 nannograms/ml)
Has a very potent biological effect: The Fc
segment of IgE binds with extremely high affinity
to an Fc receptor, called Fc,RI, on mast cells
and basophils.
Basophils are circulating polymorphonuclear
leukocytes. Mast cells reside in tissues
IgE has a half life of only two days in the plasma
but over 30 days when bound to a basophil or mast
cell surface.
Mediator release Fig 3
The biological effector
mechanism is triggered
when mast cell- (or
basophil-) bound IgE
molecules are cross-linked
by multivalent Ag .The
cross-linking induces
membrane modifications
resulting in the release of
granules containing
powerful pharmacologic
mediators such as
histamine and serotonin
Allergens
Most allergens are relatively small molecular
weight soluble proteins carried on desiccated
particles (pollen, dander, dried animal
saliva, house mite faeces, etc) which become
released from the particles, and penetrate
the respiratory or the gastro-intestinal
mucosa, depending on whether they are airborne or ingested.
House-dust Mites Fig 4
Fecal pellets
Consequences of mediator release Fig 5
Two major pathological
consequences:
contraction of smooth
muscles and increase in
vascular permeability.
All symptoms of IgEmediated allergic
reactions can be
explained based on
these two effects
Oral Allergy Syndrome
In the oral cavity a specific condition called Oral Allergy
Syndrome appears when an allergen (from foods or
drugs) makes contact with the oral cavity in sensitive
patients.
This syndrome is characterized by a rapid swelling of
the lips, tongue, gums, palate and pharynx.
Early and Late phases
An IgE allergic reaction is divided into an immediate
response (seconds to minutes) and a late-phase response
(8-10 hr).
IgE-mediated reactions have also been termed
Immediate-type hypersensitivity reactions.
The intradermal injection of a minute amount of allergen
into an allergic (atopic) individual gives rise to a local
reaction called cutaneous anaphylaxis and characterized
by the immediate appearance of a blister full with
histamine called a wheal, and redness around it called
erythema or flare
The Wheal and Flare, and the Latephase responses Fig 6
Immediate: appearance of
a blister containing
histamine called a wheal,
surrounded by redness
called erythema or flare
Late: Only erythema
Systemic anaphylaxis
Allergen given in high doses and reaching the
circulation, or given intravenously, triggers the
sudden release of large quantities of mediators
from the mast cells, and by the basophils in the
circulation, and may causes a generalized or
systemic reaction called systemic anaphylaxis or
anaphylactic shock.
These reactions can be fatal: insect venoms or
drugs (antibiotics, sulphonamides or even foods)
Dentists beware!!
Anaphylactic shock to local anaesthetics such as
lidocaine or novocaine although rare, are
encountered in dental practice
Treatment
Allergy can be treated:
a) by inhibiting IgE production through immune
deviation, called also desensitization
therapy or
b) by interfering with the release of mediators
or with their pharmacologic effects, such as
administration of anti-histamines and topical
steroids (Fluticasone propionate), or of
drugs that prevent mast cell/basophil
degranulation (cromolyn sodium).
c) Epinephrine injection (against anaphylactic
shock)
Type-II Hypersensitivities
Triggered by IgG or IgM Ab directed against
cells and tissues. These Ab activate the
complement cascade which in turn induces
target cell death.
E.g. IgG or IgM Antibodies against red blood
cells  Haemolytic anemia
Type-III Hypersensitivities
Soluble Antigen reacting with soluble Ab in the
circulation activate the complement cascade
leading to powerful inflammatory reactions due to
the release of anaphylatoxins.
E.g. glomerulonephritis (the immune complexes
are deposited on the glomerular basement
membrane of the kidney)
Type-IV Hypersensitivities
Due to the activation of Th-1 cells. The typical type-IV
reaction is called also delayed-type hypersensitivity
(DTH)
The intradermal administration of antigen recognized by
an effector CD4+ Th-1 cell  local cutaneous reaction.
“delayed”: takes 12-24 hr to appear.
The aspect of the lesion is different from the wheal and
flare of IgE.
Typical examples of DTH reactions are cutaneous
reactions to tuberculin in individuals that were in previous
contact with tubercle bacilli (Mycobacterium
tuberculosis), and reactions to poison ivy
DTH Reaction to Poison Ivy Fig 7
Autoimmune diseases
Chronic inflammatory conditions that arise as a result of
either Ab- or T cell-mediated responses to self-antigens
(auto-antigens).
Typical examples:
Juvenile Diabetes: Target tissue: Beta islets (produce
insulin) of the pancreas
Multiple Sclerosis. Target tissue: CNS white matter
(Myelin)
Systemic Lupus Erythematosus (SLE): anti-DNA Ab.
Target tissue: Kidney, Joints, Leukocytes
Graves disease. Target tissue: Thyroid gland.
Rheumatoid arthritis. Target tissue (joints).
Immune deficiencies
Occur when one or more components of the
immune system are defective.
Immune defects can be inherited or acquired.
The immune defects can involve the T cell, the B
cell or both compartments of the immune system,
the Complement or the APC.
Inherited (Genetic) Immune defects
Genetic defects can occur in almost any molecule involved
in the immune response.
T cell defects:
DiGeorge syndrome: Failure of the thymus to be formed
(thymic aplasia).
Patients suffer from general susceptibility to infections
since the absence of T lymphocytes impacts also on the
ability of B cells to synthesize antibodies (see Lecture on
T cells)
Inherited B cell defects
X-linked agammaglobulinemia:
X-chromosome-linked inability to produce
B lymphocytes, leads to absence of Ig.
Patients suffer mainly from infectious
diseases with bacteria and viruses that
require antibodies for their disposal.
Mixed Immunodeficiencies
Inherited mixed T and B cell defects:
Severe combined immune deficiencies (SCID).
Patients suffer from total susceptibility to
infections since neither T nor B cells are
generated.
Inherited defects of phagocytic function.
Inherited defects of complement: Loss of
specific complement components. Inability to
form the MAC and/or to produce anaphylatoxins.
Acquired immune deficiencies.
Acquired immune deficiency syndrome (AIDS). The
immune response becomes defective as a result of
exposure to the Human Immunodeficiency Virus
(HIV).
The HIV infects selectively CD4+ T cells and
macrophages. The disease is usually lethal due to loss
of CD4+ T cells.
B cell and T cell tumours (myelomas and lymphomas).
The uncontrolled growth either B or T lymphocyte
tumours encroaches on the ability of normal T and B
cells to divide and perform their function.
Consequences of immunodeficiencies in
dental patients
Increased incidence of infections in the oral cavity, even
with organisms that are usually non-pathogenic such as
Candida species (candidiasis) in AIDS patients
Cancer patients undergoing chemotherapy, and with AIDS
Ulcerations
Xerostomia
Sialadenitis
Osteomyelitis
Papillary atrophy of the tongue
Herpes virus infections
Periodontal disease
Increased plaque formation.