Penyebab penyakit hipersensitivitas

1. Autoimmunity. Failure of the normal mechanisms of self-tolerance

results in reactions against ones own cells and tissues that are
called autoimmunity.
The diseases caused by autoimmunity are
referred to as autoimmune diseases.
2. Reactions against microbes. Immune responses against microbial
antigens may cause disease if the reactions are excessive or the
microbes are unusually persistent.
Contoh :
- T cell responses against persistent microbes may give rise to
severe inflammation, sometimes with the formation of
granulomas; this is the cause of tissue injury in tuberculosis and
some other chronic infections.
If antibodies are produced against microbial antigens, the
antibodies may bind to the antigens to produce immune
complexes, which deposit in tissues and trigger inflammation.
- antibodies or T cells against a microbe may cross-react with a
host tissue. In some diseases involving the intestinal tract, called
inflammatory bowel disease, the immune response is directed
against commensal bacteria that normally reside in the gut and
cause no harm. Sometimes the disease-causing immune response
may be entirely normal, but in the process of eradicating the
infection, host tissues are injured.
3. Reactions against environmental antigens. Most healthy
individuals do not react against common, generally harmless
environmental substances, but almost 20% of the population is
abnormally responsive to one or more of these substances. These
individuals produce immunoglobulin E (IgE) antibodies that cause
allergic diseases.
Some individuals become sensitized to environmental antigens
and chemicals that contact the skin and develop T cell reactions that
lead to cytokine-mediated inflammation, resulting in contact sensitivity
The problem in hypersensitivity diseases is that the response
is triggered and maintained inappropriately. Because the stimuli for
these abnormal immune responses are difficult or impossible to
eliminate
(e.g.,
self
antigens,
commensal
microbes,
and
environmental antigens) and the immune system has many built-in
positive feedback loops (amplification mechanisms), once a pathologic
immune response starts, it is difficult to control or to terminate it

Klasifikasi Hipersensitivitas

1. Immediate Hypersensitivity : Type I hypersensitivity

Immediate hypersensitivity (type I hypersensitivity) caused by IgE
antibodies specific for environmental antigens and mast
cells. Immediate hypersensitivity diseases, commonly called allergic
or atopic disorders, are the prototypes of diseases caused by
activation of the TH 2 subset of helper T cells, in which the T
cells stimulate the production of IgE antibodies and
inflammation.
2. Antibodi mediated: Type II hypersensitivity
IgG and IgM antibodies can cause tissue injury by
activating
the
complement
system,
by
recruiting
inflammatory cells, and by interfering with normal cellular
functions. Some of these antibodies are specific for antigens of
particular cells or the extracellular matrix and are found either
attached to these cells or tissues or as unbound antibodies in the
circulation.
3. Immune complex mediated : Type III hypersensitivity
Other antibodies may form immune
complexes
in
the
circulation, and the complexes are subsequently deposited in
tissues, particularly in blood vessels, and cause injury.
4. T cell mediated : Type IV hypersensitivity
Tissue injury may be due to T lymphocytes that induce
inflammation or directly kill target cells.
Many hypersensitivity diseases are caused by the activation of T
H 1 or T H 17 subsets of helper T cells, which secrete cytokines
that promote inflammation, and the tissue injury is caused by the
recruited leukocytes, mainly neutrophils and macrophages. Helper
T cells also stimulate the production of antibodies that damage

tissues and induce inflammation. CTLs may also contribute to tissue

injury in some diseases.

Klasifikasi Penyakit Hipersensitivitas

1. Antibody-mediated diseases (Hipersensitivitas tipe II dan III)
Antibody-mediated diseases are produced either by :
- Antibodi berikatan dengan antigen pada sel- sel tertentu
atau jaringan ekstraseluler
- Kompleks antigen-antibodi yang terbentuk di sirkulasi pada
dinding pembuluh darah

Kasus :
Sebuah eksperimen alam kadang-kadang terlihat pada anak-anak
dari ibu yang menderita penyakit antibodi-mediated. Bayi-bayi ini
dapat lahir dengan manifestasi sementara penyakit tersebut karena
transplasental bagian dari antibodi.
Glossary :

Transplacental refers to the ability of a toxin or pathogen to cross

the physical and biological barriers of the placenta separating the
mother and fetus, to whom such substances may be dangerous.

Mekanisme Penyakit dimediasi antibodi

1. Penyakit Disebabkan oleh Antibodi Terhadap Sel tertentu dan
Antigen Jaringan (Hipersensitivitas Tipe II)
Antibodies against tissue antigens cause disease by 3 main
mechanisms:

Antibodies that bind to cell surface antigens may

directly opsonize cells, or they may activate the complement
system, resulting in the production of complement proteins that
opsonize cells. These opsonized cells are
phagocytosed and
destroyed by phagocytes that express receptors for the Fc
portions of IgG antibodies and receptors for complement proteins.
Contoh penyakit:
- Destruksi sel pada anemia hemolitik autoimun
- Autoimmune thrombocytopenic purpura
- Hemolysis pada reaksi transfusi

Antibodies deposited in tissues recruit neutrophils and

macrophages, which bind to the antibodies or to
attached complement proteins by IgG Fc and complement
receptors. These leukocytes are activated by signaling from the
receptors, particularly Fc receptors, and leukocyte products,
including lysosomal enzymes and reactive oxygen species, are
secreted and cause tissue injury. The mechanism of injury in
antibody-mediated glomerulonephritis and many other diseases is
inflammation and leukocyte activation.


Antibodi yang berikatan dengan reseptor sel normal atau
protein lain dapat mengganggu fungsi dari reseptor ini atau
protein dan menyebabkan penyakit tanpa peradangan atau
kerusakan jaringan. Kelainan fungsional antibodi-mediated adalah
penyebab penyakit Graves 'dan myasthenia gravis.