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IMUNOPATOLOGI,

IMUNOTERAPI DAN
IMUNOMODULATOR
YUANDANI
IMUNOPATOLOGI
• Imunopatologi
ilmu yang mempelajari respon imun yang menyebabkan
penyakit

• Secara biologi, merujuk kepada kerusakan pada organisme


disebabkan respon imun
PENDAHULUAN
• Secara umum, sistem imun mampu mengenali jaringan tubuh
sebagai ‘self’ (tidak diserang) tetapi mengenali dan bereaksi
terhadap patogen
• Akan tetapi , respon imun kadang-kadang tidak
menguntungkan
• Gangguan atau malfungsi pada respon imun dapat
menyebabkan gangguan baik pada respon imun alamiah
maupun dapatan sehingga menyebabkan timbulnya penyakit.
Bentuk Gangguan Repon Imun
Imunodefisiensi
• Juga disebut inefektif respon imun.
• Bisa disebabkan kelainan genetik yang muncul sejak lahir atau
muncul kemudian, misalnya pada pasien AIDS (acquired
immunodeficiency syndrome)
• Gangguan dapat terjadi pada sel T, sel B , complement atau sel
fagosit.
HIpersensitivitas
• Kondisi dimana respon imun bereaksi berlebihan
atau tidak tepat terhadap senyawa yang tidak
berbahaya bagi tubuh.
• Misalnya: ketika terpapar terhadap makanan
Alergi
Autoimunitas
• Destruksi jaringan tubuh oleh respon imun yang tidak tepat
atau berlebihan.
• Dapat disebabkan oleh faktor genetik (human leukocyte
antigen (HLA)), faktor lingkungan seperti infeksi atau makanan
maupun obat.
IMUNOMODULATOR
• IMUNOMODULASI:
• Immunomodulation is the process of modifying an immune
response by administration of a drug or compound.

• IMUNOMODULATOR:
• Immunomodulators are substances which are used to modulate
components of immune system, including both innate and
adaptive arms of immune response and keeping them in a highly
prepared state for any threat it may encounter.
Immunostimulants
• Digunakan untuk meningkatkan sistem imun
• Dapat meningkatkan respon imun alamiah atau dapatan
• Pada individu sehat, agen imunostimulan bekerja sebagai
imunopotentiator dengan cara meningkatkan respon imun
sebagai profilaksis dan senyawa peningkat respon imun
• Pada individu dengan gangguan respon imun, agen
imunostimulan bekerja sebagai agen imunoterapi
• Imunostimulan digunakan pada pengobatan AIDS, kanker dan
penyakit infeksi
Contoh imunostimulan

• Recombinant proteins
• The two main types of cytokines that have been used to treat cancer are
interferons, which help the immune system to slow the growth of cancer
cells, and interleukins, which stimulate anti-cancer T-cells.
• Interferon to treat viral infection, such as hepatitis
• Leukimia has been proven highly responsive to therapy with cytokines such
as Interferon-α (IFN-α).
• Treatment with IFN-α is associated with a 90-95% response rate after having
the protocol for a year and supplanted with other even more effective drugs.
• Bacille-calmette guerin (BCG)
• This microbially derived drug has been used to treat carcinoma bladder in
USA, gastric and other cancers in Japan, and recurrent infections in Europe.
• However it poses considerable regulatory obstacles due to impurity,
unreliability, and adverse effect
• Levamisole
• The anthelmintic drug restores the function of lymphocytes (B
and T-cells), monocytes and macrophages. It has been used for
the treatment of colon cancer
• Monoclonal antibodies
• Monoclonal antibodies are agents, produced in the laboratory,
that bind to cancer cells. When cancer-destroying agents are
introduced into the body, they seek out the antibodies and kill
the cancer cells. Monoclonal antibody agents do not destroy
healthy cells.
• Rituximab (trade name = Rituxan®). Used to treat B-cell
lymphomas. The CD20 molecule to which it binds is present on
most B cells, healthy as well as malignant, but over the months
following treatment, new healthy B cells are formed from
precursors that do not have CD20 and thus were not destroyed by
the treatment.
Immunosuppressants
• Immunosuppressive agents are used to treat the diseases
which may occur through activation of the immune system
such as:
• inflammation,
• autoimmune disorders and
• rejection of transplanted organ
• Contoh imunosupressant
• Corticosteroids
• Corticosteroids serve as potent suppressors of the immune and inflammatory
system which include prednisone, hydrocortison and dexamethasone.
• They mediate their effects through interaction with intracellular steroid
receptor found in most cells of the body.
• Upon binding to the intracellular receptor, the complex enter into the cell
nucleus, then interacts with spesific transcription factors, furthermore they
regulate gene transcription (Elgert 2009).
• The resulting of immunosuppresion is due to the decrease in multiple
proinflammatory cytokine gene expression.
• Corticosteroids may also have direct inhibitory effect on many immune cells,
including macrophages, eosinophils, mast cells, T lymphocytes and epithelial
cells which lead to reduction in mediator synthesis as well as its release.
• Hence, downregulating all aspects of inflammation, starting from adhesion to
migration, phagocytosis and lastly to killing mechanism of phagocytes.
Corticosteroids also diminish the expression of class II MHC molecules
• Anti-proliferative drugs
• These drugs inhibit cell division, hence they can be
used in the chemotherapeutic treatment of malignant
diseases.
• However, many of them also play important role to the
delay and prevention of graft rejection by inhibiting
the lymphocytes proliferation in order to allow the
survival of lifesaving antigen.
• Examples: Cyclophosphamide, azathioprine,
methotrexate and 5-fluorouracil
• Microbial peptide
• Microbial peptide is the most widely used
immunosuppressant in anti-graft therapy, such as
cyclosporin A.
• Cyclosporin A inhibits transcription of the IL-2 gene by
blocking a late stage of the signal pathway started by T
cell receptor (TCR) engagement and thereby
suppresses T cell growth and differentiation.
• However the activity is reversible once the treatment
with cyclosposporin A is stopped (Elgert 2009).
• Antibiotics
• Some antibiotics such as actinomycin D, mitomycin C
and puromycin, have immunosuppresive activity.
• These antibiotics could inhibit DNA-directed synthesis
of RNA, DNA replication or protein synthesis (Elgert
2009).
• Antibody
• Monoclonal or polyclonal antibodies do not have the generalized
toxic effects that chemical immunosuppresants do because they
target spesific lymphocytes.
• CD3-muromonab is a murine monoclonal antibody that prevents
T cell activation and proliferation by binding the TCR complex,
which leads to T cell depletion.
• It is used to treat acute rejection of renal allograft, cardiac and
hepatic transplantation (Elgert 2009; Saroj et al. 2012).
IMUNOTERAPI
• IMUNOTERAPI:
• Immunotherapy is the "treatment of disease by inducing,
enhancing, or suppressing an immune response"

• activation immunotherapies
• Immunotherapies designed to elicit or amplify an immune
response are classified as,
• suppression immunotherapies.
immunotherapies that reduce or suppress
Activation immunotherapies
Cancer
• Cancer immunotherapy attempts to stimulate the immue
response to destroy tumors.
• Examples: the vaccine Bacillus Calmette-Guérin (BCG) is given
into the bladder through a catheter to stimulate a person’s
immune system to stop or delay bladder cancer coming back
or becoming invasive.
The challenges of immunotherapy
• There have been media reports of how immunotherapy is a
“miracle drug” and how it can cure cancer.
• Some people, especially with advanced melanoma, have had
encouraging outcomes.
• Because of these factors, people’s expectations can be high
when starting treatment
Will it work?
• The most challenging issue is that checkpoint immunotherapy
doesn’t work for everyone – only a small number of people
respond well to immunotherapy.
• The percentage is higher for some cancers such as melanoma.
• To make the benefits of immunotherapy available to more
people in the future, researchers are trying to understand why
some people respond better than others.
How long will it take to work?
• As most immunotherapy takes a while to work, people and
their families may experience anxiety waiting to see whether
they’ll respond to the treatment.
• And if it does work, some people are always wondering how
long immunotherapy will control the cancer or whether the
cancer will come back.
Side effects
• Not everyone will experience the same side effects, and some
people may have no side effects.
• The side effects can vary depending on the type of
immunotherapy you receive and how your body responds.
• Since your immune system takes care of your whole body,
immunotherapy can cause inflammation in any of the organs
in the body.
• This can mean that some people with an autoimmune disease
such as lupus or rheumatoid arthritis may find it difficult to
have immunotherapy safely.
• Side effects are likely to be more severe if you are taking a
combination of immunotherapy drugs or having
immunotherapy with other cancer treatments.
• Common side effects
• Dry irritated eyes – Could be inflammation of the eyes or
inflammation of the tear glands
• Pain in the joints – Could be a sign of inflammation of the joint
(arthralgia)
• Diarrhoea, bloody stools, abdominal pain and bloating – Could be
signs of inflammation of the bowel (colitis)
• Skin rashes on the body – Could be signs of dermatitis, which
makes skin itchy and appear red and bumpy
• Rare side effect
• Headache, change in vision – Could be signs of inflammation of
the pituitary gland (hypophysitis)
• Thyroid-related issues – Could be signs of the thyroid working too
fast (weight loss, feeling warm) or the thyroid working too slow
(weight gain, feeling cold)
• Shortness of breath and coughing – Could be signs of
inflammation of the lungs (pneumonitis)
• Yellowing of the eyes, severe abdominal pain and dark urine –
Could be signs of inflammation of the liver (hepatitis)
Managing the side effects of immunotherapy
• Side effects can sometimes begin within days of starting
treatment, but more commonly they occur weeks or even
months after starting treatment.
• In some rare cases, they can occur after treatment has ended.
• Moderate and severe side effects – These are often treated
with steroids such as prednisone.
• Severe side effects – In some cases, people may need to be
hospitalised or treated with high doses of steroids if side
effects are severe. Side effects often improve with treatment,
but sometimes they can be serious and people will be unable
to continue immunotherapy.
Suppression immunotherapies
Allergies
• Immunotherapy is used to treat allergies.
• While allergy treatments (such as antihistamine or
corticostreoids) treat allergic symptoms, immunotherapy can
reduce sensitivity to allergens, lessening its severity.
• Allergen immunotherapy, also known
as desensitization or hypo-sensitization, is a medical
treatment for some types of allergies.
• Immunotherapy may produce long-term benefits.
• Immunotherapy is partly effective in some people and
ineffective in others, but it offers allergy sufferers a chance to
reduce or stop their symptoms.
• The therapy is indicated for people who are extremely allergic
or who cannot avoid specific allergens.
• It is useful for environmental allergies, allergies to insect bites,
and asthma. Its benefit for food and medicinal allergies are
unclear and thus not recommended
• This therapy is particularly useful for people with allergic
rhinitis or asthma.
• The first dose contain tiny amounts of the allergen or antigen.
Dosages increase over time, as the person becomes
desensitized.
• Side effects during treatment are usually local and mild and
can usually be eliminated by adjusting the dosage. Anaphylaxis
has occurred on rare occasions and this is why treatment
should only be administered in a medical environment