Lecture 7

Hypersensitivity

NORBEL A. TABO, RM, SM

 Learning Objectives
1. Name the four types of hypersensitivity reactions.
2. Cite six examples of allergens.
3. Outline the steps in hypersensitivity reactions.
4. Discuss the principles in autoimmune diseases.
5. Explain the concept of immuno-suppression
6. Discuss the principles of immunodiagnostic procedures.
 Overview of the Immune System
Immune System

Innate Adaptive
(Nonspecific) (Specific)

Anatomical Humoral Cellular Humoral Cell-mediated

Barriers Components Components Immunity Immunity
Immunopathology
 Allergy, hypersensitivity – an exaggerated,
misdirected expression of immune responses
 Involves the same types of immune reactions as
those at work in protective immunities.
 Autoimmunity – abnormal responses to self Ag
 Immunodeficiency – deficiency or loss of immunity
 Cancer – results from a lack of surveillance
Type I Hypersensitivity
 Atopy – any chronic local allergy such as
hay fever or asthma
 Anaphylaxis – a systemic, often explosive
reaction that involves airway obstruction
and circulatory collapse
Mechanism of Type I
 sensitizing dose – on first contact with allergen, specific B
cells form IgE which attaches to mast cells and basophils
 provocative dose - subsequent exposure with the same
allergen binds to the IgE-mast cell complex
 degranulation releases mediators with physiological effects
such as vasodilation and bronchoconstriction
 symptoms are rash, itching, redness, increased mucous
discharge, pain, swelling, and difficulty breathing
Role of Mast Cells & Basophils
 Mast cells are located in the connective tissue of
virtually all organs; high conc. in lungs, skin, GI
and genital tract
 Basophils circulate in blood, migrate into tissues
 each cell can bind 10,000-40,000 IgE
 cytoplasmic granules contain physiologically
active cytokines, histamine, etc
 cells degranulate when stimulated by allergen
Chemical mediators
Systemic Anaphylaxis
 Sudden respiratory and circulatory
disruption that can be fatal in a few
minutes
 Allergen and route are variable
 Bee stings, antibiotics or serum injection
Strategies for circumventing allergic
attacks
Blocking Ab
Type II Hypersensitivity
 Reactions that lyse foreign cells
 Involve antibodies, complement, leading to
lysis of foreign cells
 Transfusion reactions
 ABO blood groups
 Rh factor – hemolytic disease of the newborn
Type III Hypersensitivity
 A large quantity of soluble foreign Ag
stimulates Ab that produce small, soluble Ag-
Ab complexes
 Immune complexes become trapped in
tissues & incite a damaging inflammatory
response
 Arthus reaction – local reaction to series of
injected Ag to same body site
 Serum sickness – systemic disease
resulting from repeated injections of foreign
proteins
Autoimmunity
 In certain type I & II hypersensitivities, the immune system
has lost tolerance to self molecules and forms
autoantibodies and sensitized T cells against them.
 More common in females
 Disruption of function can be systemic or organic specific
 Systemic lupus erythematosus
 Rheumatoid arthritis
 Endocrine autoimmunities
 Myasthenia gravis
 Multiple sclerosis
Type IV Hypersensitivity
 Cell-mediated
 A delayed response to Ag involving activation of
and damage by T cells
 Delayed allergic response – skin response to
allergens – tuberculin skin test, contact dermititis
from plants, metals, cosmetics
 Graft rejection – reaction of cytotoxic T cells
directed against foreign cells of a grafted tissue;
involves recognition of foreign HLA
Immune Diseases
 Autoimmune diseases
• Immunologic tolerance and autoimmunity
• Specific diseases
 Primary immune deficiencies
• Basic concepts
• Specific diseases
Immunologic Tolerance
 “Tolerance” = unresponsiveness to an antigen
 “Self-tolerance” = unresponsiveness to one’s
own antigens
 In generating billions of B and T cells, some will
react against self antigens!
 There are two ways of muzzling these cells:
central tolerance and peripheral tolerance
Autoimmunity

 “Autoimmunity” = immune reaction against self

 Self-tolerance breaks down, causing disease
 Two main reasons for breakdown:
• Genes
• HLA-DR4: ↑ risk of rheumatoid arthritis
• HLA-B27: ↑ risk of ankylosing spondylitis
• Environmental triggers
• Expose hidden self-antigens
• Activate APCs
• Mimic self antigens
Lupus
Rheumatoid Arthritis
Sjögren Syndrome
 Oral changes in Sjögren
Syndrome

atrophic papillae, missing teeth and

angular cheilitis
deeply fissured multiple caries
epithelium
Scleroderma
 Immunodeficiency diseases
 Components of the immune response system are absent.
Deficiencies involve B and T cells, phagocytes, and
complement
 Primary immunodeficiency – genetically based congenital
lack of B-cell and/or T cell activity
 B cell defect – agammaglobulinemia – patient lacks
antibodies
 T cell defect – thymus is missing or abnormal
 Severe combined immunodeficiency - both limbs of
lymphocyte system are missing or defective; no adaptive
immune response
 Secondary (acquired) immune deficiency – due to damage
after birth (infections, drugs, radiation) AIDS
Types of serological tests
1. Agglutination tests
2. Double diffusion precipitation tests
3. Immunoelectrophoresis
4. Western blot tests
5. Complement fixation tests
6. Immunofluorescence testing
7. Immunoassays
Types of serological tests
1. Agglutination tests – Ab cross-links whole cell
Ag, forming complexes that settle out and
from visible clumps in the test chamber
 blood type, some bacterial & viral diseases
2. Double diffusion precipitation tests involve
the diffusion of Ags and Abs in a soft agar gel,
forming zones of precipitation where they
meet
3. Immunoelectrophoresis – migration of serum
proteins in gel is combined with precipitation
by Ab
4. Western blot test – separates Ag into bands.
After the gel is affixed to a blotter, it is reacted
with a test specimen and developed by
radioactivity or with dyes
5. Complement fixation tests detect lysins- Ab that
fix complement and can lyse target cells.
Involves mixing test Ag and Ab with complement
and then with sensitized sheep RBCs.
If complement is fixed by the Ag-Ab, the RBCs
remain intact and the test is positive.
If RBCs are hemolyzed, specific Ab are lacking and
the test is negative.
6. Immunofluorescence testing uses fluorescent
Ab either directly or indirectly to visualize cells
or cell aggregates that have reacted with the
FAbs
7. Immunoassays are highly sensitive tests for Ag
and Ab.
Radioimmunoassay –Ag or Abs are labeled with
radioactive isotopes and traced
Enzyme-linked immunosorbent assay (ELISA)
can detect unknown Ag or Ab by direct or
indirect means. A positive result is visualized
when a colored product is released by an
enzyme-substrate reaction.
 Tests can differentiate B cells from T cells and
their subtypes.
Other IDP
 Quellung reaction
 Skin testing