Occasionally, the immune system responds inappropriately to the presence of
antigen. These responses are refered to as
hypersensitivities. There are
four different types of hypersensitivities that result from different
alterations of the immune system. These types are classified as:
- Type I: Immediate Hypersensitivity
- Type II: Cytotoxic Hypersensitivity
- Type III: Immune Complex Hypersensitivity
- Type IV: Delayed Hypersensitivity
This page will describe the four
types of hypersensitivity, giving examples of diseases that may result.
TYPE I HYPERSENSITIVITYType I or Immediate Hypersensitivity can be illustrated by considering the
following experiment:
- First, a guinea pig is injected intravenously with an antigen. For this
example, bovine serum albumin (BSA, a protein) will be used. After two weeks,
the same antigen will be reinjected into the same animal. Within a few
minutes, the animal begins to suffocate and dies by a process called
anaphylactic shock.
- Instead of reinjecting the immunized guinea pig, serum is transferred from
this pig to a "naive" (unimmunized) pig. When this second guinea pig is now
injected with BSA, it also dies of anaphylactic shock. However, if the second
pig is injected with a different antigen (e.g. egg white albumin), the pig
shows no reaction.
- If immune cells (T-cells and macrophages instead of serum) are transfered
from the immunized pig to a second pig, the result is very different;
injection of the second pig with BSA has no effect.
These results tell us that:
- The reaction elicited by antigen occurs very rapidly (hence the name
"immediate hypersensitivity").
- The hypersensitivity is mediated via serum-derived components (i.e.
antibody).
- The hypersensitivity is antigen-specific (as one might expect for an
antibody-mediated reaction).
The details of this reaction can be
summarized as follows (
click the image to animate):
- Initial introduction of antigen produces an antibody response. More
specifically, the type of antigen and the way in which it is administered
induce the synthesis of IgE antibody in particular.
- Immunoglobulin IgE binds very specifically to receptors on the surface of
mast cells, which remain circulating.
- Reintroduced antigen interacts with IgE on mast cells causing the cells to
degranulate and release large amounts of histamine, lipid mediators and
chemotactic factors that cause smooth muscle contraction, vasodilation,
increased vascular permeability, broncoconstriction and edema. These reactions
occur very suddenly, causing death.
Examples of Type I
hypersensitivities include allergies to penicillin, insect bites, molds, etc. A
person's sensitivity to these allergens can be tested by a cutaneous reaction.
If the specific antigen in question is injected intradermally and the patient is
sensitive, a specific reaction known as
wheal and flare can be observed
within 15 minutes. Individuals who are hypersensitive to such allergens must
avoid contact with large inocula to prevent anaphylactic shock.
TYPE II HYPERSENSITIVITY 
Type II or Cytotoxic Hypersensitivity also involves antibody-mediated reactions.
However, the immunoglobulin class (isotype) is generally IgG. In addition, this
process involves K-cells rather than mast cells. K-cells are, of course,
involved in antibody-dependent cell-mediated cytotoxicity (ADCC). Type II
hypersensitivity may also involve complement that binds to cell-bound antibody.
The difference here is that the antibodies are specific for (or able to
cross-react with) "self" antigens. When these circulating antibodies react with
a host cell surface, tissue damage may result.
Click the image
to animate the process.
There are many examples of Type II hypersensitivity. These include:
- Pemphigus: IgG antibodies that react with the intracellular
substance found between epidermal cells.
- Autoimmune hemolytic anemia (AHA): This disease is generally
inspired by a drug such as penicillin that becomes attached to the surface of
red blood cells (RBC) and acts as hapten for the production of antibody which
then binds the RBC surface leading to lysis of RBCs.
- Goodpasture's syndrome: Generally manifested as a
glomerulonephritis, IgG antibodies that react against glomerular basement
membrane surfaces can lead to kidney destruction.
TYPE III HYPERSENSITIVITY 
Type III or Immune Complex hypersensitivity involves circulating antibody that
reacts with free antigen. These circulating complexes can then become deposited
on tissues. Tissue deposition may lead to reaction with complement, causing
tissue damage. this type of hypersensitivity develops as a result of systematic
exposure to an antigen and is dependent on i) the type of antigen and antibody
and ii) the size of the resulting complex
(click here for
more information). More specifically, complexes that are too small remain in
circulation; complexes too large are removed by the glomerulus; intermediate
complexes may become lodged in the glomerulus leading to kidney damage.
Click the image to animate the process.
One example of a Type III hypersensitivity is
serum sickness, a
condition that may develop when a patient is injected with a large amount of
e.g. antitoxin that was produced in an animal. After about 10 days,
anti-antitoxin antibodies react with the antitoxin forming immune complexes that
deposit in tissues. Type III hypersensitivities can be ascertained by
intradermal injection of the antigen, followed by the observance of an "Arthus"
reaction (swelling and redness at site of injection) after a few hours.
TYPE IV HYPERSENSITIVITYType IV or Delayed Hypersensitivity can be illustrated by considering the
following experiment:
- First, a guinea pig is injected with a sub-lethal dose of Mycobacterium
tuberculosis (MT). Following recovery of the animal, injection of a lethal
dose of MT under the skin produces only erythema (redness) and induration
(hard spot) at the site of injection 1-2 days later.
- Instead of reinjecting the immunized guinea pig, serum is transfered from
this pig to a "naive" (unimmunized) pig. When this second guinea pig is now
injected with MT, it dies of the infection.
- If immune cells (T-cells and macrophages instead of serum) are transfered
from the immunized pig to a second pig, the result is very different;
injection of the second pig with MT causes only erythema and induration at the
site of injection 1-2 days later.
- In a separate experiment, if the immunized guinea pig is injected with a
lethal dose of Listeria monocytogenes (LM) instead of MT, it dies of
the infection. However, if the pig is simultaneously injected with both LM and
MT, it survives.
These results tell us that:
- The reaction elicited by antigen occurs relatively slowly (hence the name
"delayed hypersensitivity").
- The hypersensitivity is mediated via T-cells and macrophages.
- The hypersensitivity illustrates both antigen-specific (T-cell) and
antigen non-specific (macrophage) characteristics.
The details of this
reaction can be summarized as follows (
click the image to
animate):
- Initial introduction of antigen produces a cell-mediated response.
Mycobacterium tuberculosis is an intracellular pathogen and recovery
requires induction of specific T-cell clones with subsequent activation of
macrophages.
- Memory T-cells respond upon secondary injection of the specific (i.e. MT)
antigen, but not the non-specific (i.e. LM) antigen.
- Induction of the memory T-cells causes activation of macrophages and
destruction of both specific (MT) and non-specific (LM) microorganisms.
موضوع: Hypersensitivity 
الخميس 26 مارس - 19:35
