Download Type I Hypersensitivity

Autoimmunity and Hypersensitivity (5/5)
2016
C.K.Shieh
§ The flip side of immunodeficiency is autoimmunity, which means attack of our
own body by the same immune system that is supposed to protect us.
Autoimmunity can happen in many organs and with many different mechanisms.
This complex process of autoimmunity has actually been found to be involved in a
variety of diseases.
Type I Hypersensitivity:
Immediate; in allergy, atopy, and anaphylaxis
Mast Cells and IgE:
Mast cells are big cells with numerous intracellular granules.
surface of mast cells and binds to IgE with high affinity.
Most patients with allergy have high IgE levels.
FcRI is expressed on the
Hereditary Factor in Allergy
People with positive family history have much higher chance of allergic diseases.
Regulation of IgE Responses:
For a B cell to differentiate into an IgE producing cells, IL4, IL13 and IL10, the so called
Th2 cytokines, play very important roles. T cell help is necessary.
Regulation of Mast Cells and the Effector Molecules
In addition to histamine, which is important for the immediate effects of mast cell
degranulation, other effector molecules including performed protein mediators and newly
synthesized lipid mediators are important. Many of them cause leukocyte recruitment
and are responsible for late phase response. Among them, leukotrienes, also known as
SRS-A (slow reactive substance of anaphylaxis), are products of arachidonic acid from
plasma membrane through the enzyme 5-lipoxygenase.
Late-phase Reaction in Type I Hypersensitivity
A stronger inflammatory response 4-8 hours after the initial stimulation. Leukocyte
trafficking is required, especially the accumulation of eosinophils. Evidences showed
that T cells themselves are part of the effector cells in late phase reaction in allergic
responses.
Eosinophils: the Major Effector Cells
Eosinophils, probably the major effector cells against parasites, cause major damages to
respiratory epithelial cells in the late phase and chronic allergy.
Type II Hypersensitivity: Ab-dependent Cytotoxicity
Even though antibodies by themselves are not very potent in damaging mammalian cells,
phagocytes enhance the type II hypersensitivity through interacting with the target cells
with Fc and complement receptors. Some antibodies can block or enhance critical
functions of biological molecules and lead to diseases without direct cell damages.
(examples: myasthenia gravis, Graves’ disease, pernicious anemia etc.)
RBC are major targets of type II hypersensitivity.
Rh antigen.
The targets include ABO antigen and
ABO antigens are carbohydrate antigens and induce “natural” IgM antibody. RhD is a
peptide antigen and often causes hemolytic disease of the newborn in RhD(-) mothers.
Coombs’ Test for anti-RBC Antibodies (please note the spelling)
Direct Coombs’ test: testing Ab already bound to patients’ RBC.
Indirect Coombs’ test: testing anti-RBC Ab in patients’ serum.
*The same Dr. Coombs proposed the categorization of 4 types of hypersensitivity and
Coombs’ test for anti-RBC antibodies.
Type III Hypersensitivity: Immune Complex Disease
In normal conditions, small amount of immune complexes are cleared by RBC in
cooperation with complements. Complement receptors (CR1) on RBC are effective in
picking up the immune complexes and deliver them to the liver to be cleared. Without
RBC, complements can solubilize small amount of immune complexes.
Immune complexes in the circulation will accumulate in the blood vessels of kidney,
joints, etc. and cause tissue damages.
A typical skin appearance of immune complex accumulation: Arthus reaction
Type IV Hypersensitivity: cell mediated immune responses
Sensitization and Elicitation Phases of Type IV Hypersensitivity
Langerhans cells and keratinocytes both are active participants in the induction phase of
type IV hypersensitivity.
Leukocyte trafficking of:
1. antigen presentation cells, 2. sensitized lymphocytes, and 3. recruited inflammatory
cells are important for the type IV immune responses.
Typical type IV responses:
Contact dermatitis
Tuberculin (PPD) induced skin response
Granuloma reaction to bacteria and chemicals.
Mononuclear cells involved in type IV hypersensitivity
Langerhans’ cells and macrophages are the high sensitivity APCs while epithelial cells
are generally inefficient APCs.
CD4+ cells with the Th1 phenotypes are the main lymphocyte population that appear in
the site of delayed type hypersensitivity. CD8+ cells, plasma cells and other
mononuclear cells are recruited later in chronic inflammation.
Epitheloid cells are macrophages chronically stimulated with cytokines including IFNγ and TNF. The name of epitheloid cells is due to the regular arrangement of these
cells that are similar to epithelial cells. They are aligned around the necrotic
inflammatory tissues in the centers of granulomas in order to fend off the infections.
Regarding skin tests:
Although different antigens have been assigned to different kind of skin reactions (e.g.
poison ivy induces delayed type skin reaction), a single antigen preparation may induce
multiple modes of skin responses that reflect different immune mechanisms. After
subcutaneous injection of a house dust preparation, immediate type reaction of wheal and
flare appears in minutes. A late phase reaction of type I hypersensitivity presenting with
swelling and itch may be apparent after 6 hours. An indurated and painful skin reaction
(representing type IV reaction or Arthus reaction (type III)) may be found after 2-3 days.
This may be due to the fact that different components in the injected antigen elicit
different modes of immunity.
Coombs and Gell’s classification of hypersensitivity