HYPERSENSITIVITY (ALLERGY)
Allergies
are a reaction to an antigen which is called an allergen. Allergens themselves
are not harmful and do not provoke a reaction in everyone. Some individuals
become sensitized to a particular allergen, which the immune systems of most of
the population ignore. The resulting reaction causes tissue damage which can be
anywhere from mildly annoying to miserable to fatal.
1. Type
I (anaphylactic) reactions—these can be the most severe and dangerous allergic
reactions. They occur when IgE
antibodies are formed against a particular allergen. These antibodies attach to
mast cells and basophils. When the allergen enters the body and comes in
contact with these antibodies, the chemical mediator histamine is rapidly
released from granules inside the basophils and mast cells. These cells also
produce and release other mediators such as leukotrienes and prostaglandins.
The chemical mediators cause increased permeability of capillaries, increased
secretion of mucus, smooth muscle contraction, etc.
a. Systemic anaphylaxis—very large amounts
of the chemical mediators are released and cause circulatory collapse and
constriction of air passages which may lead to death. Epinephrine can
counteract this.
b. Local anaphylaxis—less severe, less
release of mediators. Usually associated with ingested or inhaled antigens.
Effects include hives, asthma, hay fever, gastrointestinal upsets, etc.
Repeated
injections of tiny amounts of the
allergen may succeed in desensitization. IgG antibodies are formed, which block
the antigen by binding to it before it can reach the IgEs.
2. Type
II (cytotoxic reactions)—these are mediated by IgG or IgM antibodies and
complement. This type of reaction is directed toward cells, which are lysed or
damaged in other ways.
a. Blood groups—“wrong” type blood cells
given in a transfusion are an example of this type of reaction.
b. Drug-induced cytotoxic reactions—drug
molecules coat a blood cell or a platelet and the combination becomes
antigenic, resulting in destruction of the cell or platelet. Complement
proteins are involved.
Platelets attacked—thrombocytopenic
purpura
White blood cells
attacked—agranuloctosis
Red blood cells
attacked—hemolytic anemia
3. Type
III (immune complex) reactions---antigen-antibody complexes are deposited in
organs and cause inflammatory damage. Complement becomes activated and this
plus attraction and release of enzymes from neutrophils results in damage or
destruction of the cells in the area.
Glomerulonephritis is an example.
4. Type
IV (cell-mediated) reactions—also called delayed hypersensitivity reactions. T
cells are involved in this type instead of antibodies. T cells become
activated, release destructive cytokines, and attract macrophages to the area.
Cytotoxic T cells may also appear. This results in damage to cells in the
affected area. Contact dermatitis and poison ivy are examples. The skin test
for tuberculosis is based on this type of reaction. Purified protein components
of M. tuberculosis are injected. If the person has been previously exposed
to the organism, sensitized T cells will react.
In spite
of nature’s ways of preventing it, it is possible for one’s own immune system
to lose the ability to distinguish self or to choose not to respond to self.
The result is an attack on a tissue or tissues of the body.
1. Type
I Autoimmunity--antibodies made in response to a virus find proteins on body
cells that also react with the antibodies. Cells are destroyed.
2. Type
II (Cytotoxic) autoimmune reactions involve production of antibodies which
react to cell-surface antigens. Cells are not destroyed but other harmful
effects occur. Myasthenia gravis and Grave’s disease are examples.
3. Type
III ( Immune complex) autoimmune
reactions involve the deposition of immune complexes (antigen-antibody
complexes) which result in tissue damage. Examples are lupus and rheumatoid
arthritis.
4. Type
IV (Cell-mediated) autoimmune reactions involve attack by cytolytic T cells.
Examples are Hashimoto’s thyroiditis, multiple sclerosis, and Type I diabetes mellitus.
DISEASES & REACTIONS RELATED TO THE HUMAN
LEUKOCYTE ANTIGEN (HLA) COMPLEX
All
nucleated human cells bear on the surface of their plasma membranes special
protein complexes that are the thing the immune system uses to recognize self
(or non-self). These proteins are capable of acting as antigens, but the immune
system of the owner is supposed to recognize that these proteins and the cells
they are attached to are self, and not respond to them. These proteins are
known as MHC (major histocompatibility complex) proteins or HLA (human
leukocyte antigens). These proteins are found on cells other than leukocytes,
but leukocytes can be easily removed and classified, so that is the way this
name arose.
These
antigens are of major importance in tissue transplants. The ABO blood group and
the HLA antigens must be matched as closely as possible between donor and
recipient in an effort to prevent or minimize
the rejection of transplants. Certain HLA antigens may also be
associated with increased susceptibility to certain diseases. HLA typing is the
process used to identify the exact type of HLA antigens a person has.
To
determine the suitability of a transplant between two persons, the ABO group
must first match. Then HLA typing
further tests the chances of a successful transplant. Two main classes of HLAs
are tested and matched, Class I HLAs and Class II HLAs. Class I HLAs are found
on all cells in the body except RBC. Class II HLAs are found mostly on the
surface of specialized immune cells. Ideally, both will be a close match,
although they will not be identical unless an identical twin can act as the
donor.
1.
Privileged sites and tissues---this type of transplant normally is not rejected
and does not require matching because it does not stimulate an immune response.
a. Cornea
b. Brain---one day we might be able to transplant
nerves (but not yet)
c. Valves from pigs’ hearts
d. Pregnancy
2. Other
transplants
a. Autograft---some of your own tissue,
such as skin, is transplanted to another site on the body
b. Isograft---between identical twins
c.
Allograft---between two people who are
not identical twins
d. Xenograft---between different
species--disasters now but some day we may grow pigs with human-like MHC
proteins—transplanted tissue is called a xenotransplantation product.
3. Bone marrow
transplants---this procedure is used in several circumstances:
a. To give a person who cannot produce B
and T cells that ability
b. Leukemia patients
c. Metastasis of other cancers to the bone
marrow
The
patient’s own bone marrow is destroyed and the transplant is given to replace
it. Unfortunately, the new bone marrow sometimes produces immune cells that
begin to attack the tissues of the recipient. This is called graft-versus-host
disease. Use of umbilical cord blood,
which is rich in stem cells, may work better than transplanting bone marrow.
Persons
who have received a transplant that might involve rejection must be treated to
prevent that from happening. The major aim is to suppress cell-mediated
immunity. The drugs used have side effects, so the benefits of the transplant
must be weighed against the drawbacks.
1.
Congenital deficiencies---person is born without some component of the immune
system.
a. DiGeorge syndrome---no thymus
gland---no T cells---often fatal in infancy due to viral or fungal infections
b. Severe combined immunodeficiency (boy
in the bubble)---complete lack of the stem cells that produce both B and T
cells
2.
Acquired immune deficiencies---due to something that happens after birth
a. AIDS is the best known
b. Viruses, cancers, loss of the spleen,
etc. are other causes
Immunological
surveillance--the immune system constantly looks for abnormal cells, including
early cancers, and destroys them before they cause trouble. If this fails and a
tumor develops, the cancer cells may be evading the immune system by:
Immunotherapy
is treating cancer by means of the immune system. Possibilities: