OBAT DAN SISTEM

IMMUNE
KULIAH PAKAR
BLOK IMUNOLOGI
PPD UNISMA

ANTIGEN DARI LUAR

DARI DALAM TUBUH
PROTEIN ASING BAKTERI
PROTEIN DARI DALAM

ANTIGEN

+
ANTIBODY

MASUK KEDALAM TUBUH

MELALUI BERBAGAI ROUTE
MULUT, JALAN NAPAS INJEKSI

MENYEBABKAN DISINTESANYA
ANTI BODY OLEH SEL SEL
LIMPOSIT

DIKELUARKANNYA
MEDIATOR DARI SEL

REAKSI INFLAMASI

MEDIATOR MEDIATOR PADA REAKSI ALLERGI

MEDIATOR KIMIA YANG DIKELUARKAN OLEH SEL BASOPHIL

DAN SEL MAST
AG
IgE

PROTEIN DERIVED MEDIATOR

HISTAMIN , SEROTONIN
EOSINOPHIL CHEMOTACTIC FACTOR
NEUTROPIL CHEMOTACTIC FACTOR
BRADIKININ GENERATING FACTOR

LIPID DERIVED MEDIATOR

PROSTAGLANDINE
TROMBOXANE
LEUKOTRIENS
SEL MAST /SEL BASOPHIL

CONTOH EFEK HISTAMIN : SECRESI MUKUS, KONSTRIKSI BRONKUS

KONTRAKSI OTOT POLOS USUS
PELEBARAN PEMBULUH DARAH KAPILER
EFEK CEPAT 1-2 MENIT DAN EFEK HILANG
SETELAH 15 MENIT

REAKSI TIPE 1
ADA IgE SPESIFIK TERHADAP OBAT TERTENTU ATAU
BAGIAN DARI OBAT YANG DIKENAL SEBAGAI HAPTENE IgE
SPESIFIK
TERBENTUK SETELAH KONTAK PERTAMA DENGAN OBAT TERTENTU
PADA PAPARAN ULANG OAT AKAN BERIKATAN DENGAN IgE DIPER
MUKAAN MEMBRANE MAST SEL ATAU SEL BASOPHIL TERJADI
RELEASE MEDIATOR INFLAMASI SEPERTI HISTAMIN, SEROTONIN,
HEPARIN PROTEASE, LEUKOTRIENS TROMBOXANE DSB
REAKSI TIPE 1 INI MERUPAKAN IMMEDIATE HYPERSENSITIVITY ATAU
REAKSI ANAPHYLAKSIS . REAKSI TYPE 1 DAPAT MENGENAI 1
ORGAN
SEPERTI MUKOSA HIDUNG (RHINITIS) ACUT ASTMA, KULIT GASTRO
INTESTINAL ATAU DAPAT MENGENAI SELURUH ORGAN YANG
DIKENAL
SEBAGAI ANAPHILAKSIS

ASMA BRONHIALE

PENYEMPITAN BRONKUS YANG TERJADI BERULANG YANG DILANDASI

OLEH KKELAINAN INFLAMASI. PADA ASMA OK ALLERGI, ALLERGEN
YANG DIHISAP BERIKATAN DENGAN IgE PADA MAST SEL DAN SEL
BASOPIL . MENGHASILKAN REAKSI YANG MELIBATKAN SEL IMUNE
DAN DIKELUARKANNYA MEDIATOR INFLAMASI PADA INTERSTTIAL
SPACE YANG KEMUDIAN MEMPENGARUHI FUNGSI SEL PADA DINDING
JALAN NAPAS.

Asthma is associated with inflammation of the airway wall. Increased numbers

of various types of inflammatory cells, most notably eosinophils but also
basophils, mast cells, macrophages, and certain types of lymphocytes, can be
found in airway wall biopsies and in bronchoalveolar lavage fluid from asthmatic
patients. Inflammatory mediators and various cytokines also are increased in
the airways of asthmatic subjects compared with healthy control subjects. How
bronchial inflammation contributes to the asthmatic condition remains poorly
understood. Even asthmatics with normal baseline lung function and no recent
exacerbations of their asthma have increased numbers of inflammatory cells in
their airways. Conversely, many individuals allergic to inhaled allergens have
evidence of lower airway inflammation but suffer only from the symptoms of
allergic rhinitis. The basis for this inflammation is not entirely clear. Many
individuals with asthma are atopic and have clearly defined allergen exposures
that are partially or substantially responsible for their asthmatic inflammation.
Epidemiological studies show a strong correlation between increasing IgE levels
and the prevalence of asthma regardless of atopic status Nonallergic individuals
also can suffer from asthma, as is often seen in subjects in whom the onset of
disease is later in life.

Asthma is a common disorder, accounting in the United States for 1%

to 3% of all office visits, 500,000 hospital admissions per year, more
pediatric hospital admissions than any other single illness, and more
than 5000 deaths annually.

TERAPI ASMA DENGAN MENGGUNAAN OBAT UNTUK

MENGURANGI INFLAMASI PADA JALAN NAPAS,
(DENGAN OBAT ANTI INFLAMASI)
Mengurangi spasme bronkhus (bronkodilator) yaitu:
b adrenergic receptor agonists,
glucocorticoids,
leukotriene inhibitors,
chromones,
methylxanthines, and
inhibitors of immunoglobulin E (IgE).
DENGAN OBAT MENGENCERKAN DAHAK YANG BIASANYA
KENTAL PADA PENDRRITA ASMA

The drugs available for the treatment of asthma are targeted at inhibiting the inflammatory
responses and/or relaxing the bronchial smooth muscle. Letters denote the putative sites of
action for the various classes of drugs used in treating asthma. b, b2 adrenergic agonists; cs,
corticosteroids; l, leukotriene modifiers; m, muscarinic receptor antagonists; cr, cromolyn; t,
theophylline; aI, anti-IgE therapy. The sunburst (
) symbolizes an allergen.

Schematic representations of the disposition of inhaled drugs.

Inhalation therapy deposits asthma medications directly, but not exclusively, in
the lungs. Distribution of inhaled drug between lungs and esophagus depends
on particle size and efficiency of delivery to lungs. Most material, approximately
90%, will be swallowed and absorbed, entering the systemic circulation. Some
drug also will be absorbed from the lungs. Optimal particle size for deposition in
small airways is 1 to 5 mm.

REAKSI TIPE II
REAKSI ALLERGI INI ENYEBABKAN KERUSAKAN KAMATIAN
SEL HOST BIASANYA SEL DARAH. PADA AWALNYA OBAT
TERIKAT DENGAN KE SEL DARAH SEBAGAI HAPTENE MISALNYA
PADA PLATELET ATAU ERITROSIT.
ANTI BODI IgG ATAU IgM SPESIFIK UNTUK OBAT ATAU
KOMPONEN PERMUKAAN SEL YANG TELAH DIRUBAH OLEH OBAT
BERKATAN DAN TERJADI AWAL DARI KERUSAKAN SEL MISALNYA
KEHILANGAN INTEGRITAS MEMBRAN DAN SELANJUTNYA KEMATIAN SEL
KEMATIAN SEL JUGA TERJADI MELALUI PHAGOSITOSIS OLEH SEL
NETROPHIL MONOSIT ATAU MACROPHAGE SUATU PROSES YANG
DIKENAL SEBAGAI OPSONISASI ATAU TERJADI PERUSAKAN SEL
MELALUI ANTIBODI DEPENDENT CELLULAER CYTOTOXICITY.
SEL YANG TERLIBAT ANTARA LAIN ERYTROSIT, LEUKOSIT DAN
TROMBOSIT TERJADI HEMOLITIK ANAEMIA, AGRANULOCYTOSIS
ATAU TOBOSITOPENIA.

THE IMMUNE RESPONSE

The immune system evolved to discriminate self from nonself. Multicellular
organisms were faced with the problem of destroying infectious invaders
(microbes) or dysregulated self (tumors) while leaving normal cells intact.
These organisms responded by developing a robust array of receptormediated sensing and effector mechanisms broadly described as innate
and adaptive. Innate, or natural, immunity is primitive, does not require
priming, and is of relatively low affinity, but is broadly reactive. Adaptive, or
learned, immunity is antigen-specific, depends upon antigen exposure or
priming, and can be of very high affinity. The two arms of immunity work
closely together, with the innate immune system being most active early in
an immune response and adaptive immunity becoming progressively
dominant over time..

. The major effectors of innate immunity are complement, granulocytes,

monocytes/macrophages, natural killer cells, mast cells, and basophils. The
major effectors of adaptive immunity are B and T lymphocytes. B
lymphocytes make antibodies; T lymphocytes function as helper, cytolytic,
and regulatory (suppressor) cells. These cells are important in the normal
immune response to infection and tumors, but also mediate transplant
rejection and autoimmunity Immunoglobulins (antibodies) on the B
lymphocyte surface are receptors for a large variety of specific structural
conformations. In contrast, T lymphocytes recognize antigens as peptide
fragments in the context of self major histocompatibility complex (MHC)
antigens (called human leukocyte antigens [HLA] in human beings) on the
surface of antigen-presenting cells, such as dendritic cells, macrophages,
and other cell types expressing MHC class I (HLA-A, -B, and -C) and class
II antigens (HLA-DR, -DP, and -DQ) in human beings. Once activated by
specific antigen recognition via their respective clonally restricted cellsurface receptors, both B and T lymphocytes are triggered to differentiate
and divide, leading to release of soluble mediators (cytokines, lymphokines)
that perform as effectors and regulators of the immune response.

The impact of the immune system in human disease is enormous. Developing

vaccines against emerging infectious agents such as human immunodeficiency
virus (HIV) and Ebola virus is among the most critical challenges facing the
research community. Immune system-mediated diseases are significant medical
problems. Immunological diseases are growing at epidemic proportions that
require aggressive and innovative approaches to develop new treatments.
These diseases include a broad spectrum of autoimmune diseases such as
rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus, and
multiple sclerosis; solid tumors and hematologic malignancies; infectious
diseases; asthma; and various allergic conditions. Furthermore, one of the great
therapeutic opportunities for the treatment of many disorders is organ
transplantation. However, immune system-mediated graft rejection remains the
single greatest barrier to widespread use of this technology. An improved
understanding of the immune system has led to the development of new
therapies to treat immune system-mediated diseases.

IMMUNOSUPPRESSION
OBAT YANG MENEKAN SISTEMIMUNE BETUJUAN UNTUK
MENURUNKAN RESPON IMUNE PADA TRANSPLANTASI ORGAN
DAN PENYAKIT AUTOIMUNE.
PADA TRANSPLANTASI OAT IMMNOSUPRESIVE YANG DIGUNAKAN
ADLAH:
(1) glucocorticoids,
(2) calcineurin inhibitors,
(3) antiproliferative/antimetabolic agents, and
(4) biologics (antibodies).
OBAT INI BERMANFAAT PADA IMUNE REJECTION YANG ACUT PADA
TRANSPLANTASI ORGAN, DAN PENYAKIT AUTOIMUNE YANG
NAMUN PENGOBATAN INI SERING ALI DIBUTUHKAN PENGGUNAAN
YANG LAMA DAN DAPAT MENYEBABKAN PENEKANAN SELURUH
SISTEM IMUNE. SEHINGGA BERISIKO TERJADINYA INFEKSI DAN
KANKER
Efek samping calcineurin dan glukocortikoid adalah nefrotksik dan
diabetes

General Approach to Organ Transplantation Therapy

Organ transplant therapy is organized around five general principles.
The first principle is careful patient preparation and selection of the best
available ABO blood type-compatible HLA match for organ donation.
Second, a multitiered approach to immunosuppressive drug therapy,
similar to that in cancer chemotherapy, is employed. Several agents are used
simultaneously, each of which is directed at a different molecular target within the
allograft response Synergistic effects permit use of the various agents at relatively
low doses, thereby limiting specific toxicities while maximizing the
immunosuppressive effect.
The third principle is that greater immunosuppression is required to gain
early engraftment and/or to treat established rejection than to maintain long-term
immunosuppression. Therefore, intensive induction and lower-dose maintenance
drug protocols are employed.
Fourth, careful investigation of each episode of transplant dysfunction is
required, including evaluation for rejection, drug toxicity, and infection, keeping in
mind that these various problems can and often do coexist. Organ-specific
problems (e.g., obstruction in the case of kidney transplants) must also be
considered. The fifth principle, which is common to all drugs, is that a drug should
be reduced or withdrawn if its toxicity exceeds its benefit.

Biologic Induction Therapy. Induction therapy with polyclonal and

monoclonal antibodies (mAbs) has been an important component of
immunosuppression dating back to the 1960s, when Starzl and colleagues
demonstrated the beneficial effect of antilymphocyte globulin (ALG) in the
prophylaxis of rejection in renal transplant recipients. Over the past 40 years,
several polyclonal antilymphocyte preparations have been used in renal
transplantation; however, only 2 preparations are currently FDA approved:
lymphocyte immune globulin (ATGAM) and antithymocyte globulin
(THYMOGLOBULIN) Another important milestone in biologic therapy was the
development of mAbs and the introduction of the murine anti-CD3 mAb
(muromonab-CD3 or OKT3)

Maintenance Immunotherapy. The basic immunosuppressive protocols in

most transplant centers use multiple drugs simultaneously. Therapy typically
involves a calcineurin inhibitor, glucocorticoids, and mycophenolate mofetil (a
purine metabolism inhibitor; see below), each directed at a discrete site in Tcell activation Glucocorticoids, azathioprine, cyclosporine, tacrolimus,
mycophenolate mofetil, sirolimus, and various monoclonal and polyclonal
antibodies are all approved for use in transplantation. Glucocorticoid-free
regimens have achieved special prominence in recent successes in using
pancreatic islet transplants to treat patients with type I diabetes mellitus.
Protocols employing steroid withdrawal or steroid avoidance are being
evaluated in many transplant centers. Short-term results are good, but the
effects on long-term graft function are unknown Recent data suggest that
calcineurin inhibitors may shorten graft half-life by their nephrotoxic effects
Protocols under evaluation include calcineurin dose reduction or switching
from calcineurin to sirolimus-based immunosuppressive therapy at 3 to 4
months

Adrenocortical Steroids
The introduction of glucocorticoids as immunosuppressive drugs in the 1960s
played a key role in making organ transplantation possible. Their chemistry,
pharmacokinetics, and drug interactions are described in Chapter 59.
Prednisone, prednisolone, and other glucocorticoids are used alone and in
combination with other immunosuppressive agents for treatment of transplant
rejection and autoimmune disorders.
Mechanism of Action. The immunosuppressive effects of glucocorticoids have
long been known, but the specific mechanism(s) of their immunosuppressive
action remains somewhat elusive. Glucocorticoids lyse (in some species) and
induce the redistribution of lymphocytes, causing a rapid, transient decrease in
peripheral blood lymphocyte counts. To effect longer-term responses, steroids
bind to receptors inside cells; either these receptors, glucocorticoid-induced
proteins, or interacting proteins regulate the transcription of numerous other
genes Additionally, glucocorticoid-receptor complexes increase IkB expression,
thereby curtailing activation of NF-kB, which increases apoptosis of activated
cells Of central importance, key proinflammatory cytokines such as IL-1 and IL-6
are downregulated. T cells are inhibited from making IL-2 and proliferating. The
activation of cytotoxic T lymphocytes is inhibited. Neutrophils and monocytes
display poor chemotaxis and decreased lysosomal enzyme release. Therefore,
glucocorticoids have broad antiinflammatory effects on multiple components of
cellular immunity. In contrast, they have relatively little effect on humoral
immunity.

Calcineurin Inhibitors
Perhaps the most effective immunosuppressive drugs in routine use are the
calcineurin inhibitors, cyclosporine and tacrolimus, which target intracellular
signaling pathways induced as a consequence of T-cell-receptor activation
(Although they are structurally unrelated and bind to distinct, albeit related
molecular targets, they inhibit normal T-cell signal transduction essentially by
the same mechanism Cyclosporine and tacrolimus do not act per se as
immunosuppressive agents. Instead, these drugs bind to an immunophilin
(cyclophilin for cyclosporine or FKBP-12 for tacrolimus), resulting in subsequent
interaction with calcineurin to block its phosphatase activity. Calcineurincatalyzed dephosphorylation is required for movement of a component of the
nuclear factor of activated T lymphocytes (NFAT) into the nucleus NFAT, in turn,
is required to induce a number of cytokine genes, including that for interleukin-2
(IL-2), a prototypic T-cell growth and differentiation factor.

Cyclosporine. Chemistry. Cyclosporine (cyclosporin A), a cyclic polypeptide

consisting of 11 amino acids, is produced by the fungus species Beauveria
nivea. Of note, all amide nitrogens are either hydrogen bonded or methylated,
the single D-amino acid is at position 8, the methyl amide between residues 9
and 10 is in the cis configuration, and all other methyl amide moieties are in
the trans form Because cyclosporine is lipophilic and highly hydrophobic, it is
formulated for clinical administration using castor oil or other strategies to
ensure solubilization.

Mechanism of Action. Cyclosporine suppresses some humoral immunity, but

is more effective against T-cell-dependent immune mechanisms such as those
underlying transplant rejection and some forms of autoimmunity It
preferentially inhibits antigen-triggered signal transduction in T lymphocytes,
blunting expression of many lymphokines including IL-2, and the expression of
antiapoptotic proteins. Cyclosporine forms a complex with cyclophilin, a
cytoplasmic receptor protein present in target cells. This complex binds to
calcineurin, inhibiting Ca2+-stimulated dephosphorylation of the cytosolic
component of NFAT

Clinical indications for cyclosporine are kidney, liver, heart, and other organ
transplantation; rheumatoid arthritis; and psoriasis. Cyclosporine generally is
recognized as the agent that ushered in the modern era of organ
transplantation, increasing the rates of early engraftment, extending kidney graft
survival, and making cardiac and liver transplantation possible. Cyclosporine
usually is combined with other agents, especially glucocorticoids and either
azathioprine or mycophenolate mofetil, and most recently, sirolimus.

Tacrolimus. Tacrolimus (PROGRAF, FK506) is a macrolide antibiotic produced

by Streptomyces tsukubaensis

Mechanism of Action. Like cyclosporine, tacrolimus inhibits T-cell activation

by inhibiting calcineurin Tacrolimus binds to an intracellular protein, FK506binding protein-12 (FKBP-12), an immunophilin structurally related to
cyclophilin. A complex of tacrolimus-FKBP-12, Ca2+, calmodulin, and
calcineurin then forms, and calcineurin phosphatase activity is inhibited. As
described for cyclosporine and depicted in, the inhibition of phosphatase
activity prevents dephosphorylation and nuclear translocation of NFAT and
inhibits T-cell activation. Thus, although the intracellular receptors differ,
cyclosporine and tacrolimus target the same pathway for immunosuppression

TOLERANCE
Introduction
Immunosuppression has concomitant risks of opportunistic infections and
secondary tumors. Therefore, the ultimate goal of research on organ
transplantation and autoimmune diseases is to induce and maintain
immunologic tolerance, the active state of antigen-specific
nonresponsiveness Tolerance, if attainable, would represent a true cure for
conditions discussed above without the side effects of the various
immunosuppressive therapies. The calcineurin inhibitors prevent tolerance
induction in some, but not all, preclinical models In these same model
systems, sirolimus does not prevent tolerance and may even promote
tolerance induction Several other promising approaches are being evaluated
in clinical trials. Because they remain experimental, they are discussed only
briefly here.

IMMUNOSTIMULATION
General Principles

In contrast to immunosuppressive agents that inhibit the immune response in

transplant rejection and autoimmunity, a few immunostimulatory drugs have
been developed with applicability to infection, immunodeficiency, and cancer.
Problems with such drugs include systemic (generalized) effects at one
extreme or limited efficacy at the other.

Immunostimulants
Levamisole. Levamisole (ERGAMISOL) was synthesized originally as an
anthelmintic but appears to "restore" depressed immune function of B
lymphocytes, T lymphocytes, monocytes, and macrophages. Its only clinical
indication is as adjuvant therapy with 5-fluorouracil after surgical resection in
patients with Dukes' stage C colon cancer where it occasionally has been
associated with fatal agranulocytosis.

Thalidomide. Thalidomide (THALOMID) is best known for the severe, lifethreatening birth defects it caused when administered to pregnant women For
this reason, it is available only under a restricted distribution program and can be
prescribed only by specially licensed physicians who understand the risk of
teratogenicity if thalidomide is used during pregnancy. Thalidomide should never
be taken by women who are pregnant or who could become pregnant while
taking the drug. Nevertheless, it is indicated for the treatment of patients with
erythema nodosum leprosum and also is used in conditions such as multiple
myeloma. Its mechanism of action is unclear Reported immunologic effects vary
substantially under different conditions. For example, thalidomide has been
reported to decrease circulating TNF-a in patients with erythema nodosum
leprosum, but to increase it in patients who are HIV-seropositive Alternatively, it
has been suggested that the drug affects angiogenesis The anti-TNF-a effect
has led to its evaluation as a treatment for severe, refractory rheumatoid arthritis

Bacillus Calmette-Guerin (BCG). Live bacillus Calmette-Guerin (BCG;

TICE BCG, THERACYS) is an attenuated, live culture of the bacillus of
Calmette and Guerin strain of Mycobacterium bovis, that induces a
granulomatous reaction at the site of administration. By unclear mechanisms,
this preparation is active against tumors and is indicated for treatment and
prophylaxis of carcinoma in situ of the urinary bladder and for prophylaxis of
primary and recurrent stage Ta and/or T1 papillary tumors after transurethral
resection Adverse effects include hypersensitivity, shock, chills, fever,
malaise, and immune complex disease.

Recombinant Cytokines. Interferons. Although interferons (alpha, beta, and

gamma) initially were identified by their antiviral activity, these agents also have
important immunomodulatory activities The interferons bind to specific cell-surface
receptors that initiate a series of intracellular events: induction of certain enzymes,
inhibition of cell proliferation, and enhancement of immune activities, including
increased phagocytosis by macrophages and augmentation of specific cytotoxicity
by T lymphocytes
Recombinant interferon alfa-2b (IFN-alpha 2, INTRON A) is obtained from
Escherichia coli by recombinant expression. It is a member of a family of naturally
occurring small proteins with molecular weights of 15,000 to 27,600 daltons,
produced and secreted by cells in response to viral infections and other inducers.
Interferon alfa-2b is indicated in the treatment of a variety of tumors, including
hairy cell leukemia, malignant melanoma, follicular lymphoma, and AIDS-related
Kaposi's sarcoma, It also is indicated for infectious diseases, chronic hepatitis B,
and condylomata acuminata. In addition, it is supplied in combination with ribavirin
(REBETRON) for treatment of chronic hepatitis C in patients with compensated
liver function not treated previously with interferon alfa-2b or who have relapsed
after interferon alfa-2b therapy. Adverse experiences involving the cardiovascular
system (hypotension, arrhythmias, and rarely cardiomyopathy and myocardial
infarction) and CNS (depression, confusion) are less-frequent side effects.

Interleukin-2. Human recombinant interleukin-2 (aldesleukin, PROLEUKIN;

des-alanyl-1, serine-125 human IL-2) is produced by recombinant DNA
technology in E. coli This recombinant form differs from native IL-2 in that it
is not glycosylated, has no amino terminal alanine, and has a serine
substituted for the cysteine at amino acid 125 The potency of the
preparation is represented in International Units in a lymphocyte proliferation
assay such that 1.1 mg of recombinant IL-2 protein equals 18 million
International Units. Aldesleukin has the following in vitro biologic activities of
native IL-2: enhancement of lymphocyte proliferation and growth of IL-2dependent cell lines; enhancement of lymphocyte-mediated cytotoxicity and
killer cell activity; and induction of interferon-g activity In vivo administration
of aldesleukin in animals produces multiple immunologic effects in a dosedependent manner. Cellular immunity is profoundly activated with
lymphocytosis, eosinophilia, thrombocytopenia, and release of multiple
cytokines (e.g., TNF, IL-1, interferon-g). Aldesleukin is indicated for the
treatment of adults with metastatic renal cell carcinoma and melanoma.
Administration of aldesleukin has been associated with serious
cardiovascular toxicity resulting from capillary leak syndrome, which involves
loss of vascular tone and leak of plasma proteins and fluid into the
extravascular space. Hypotension, reduced organ perfusion, and death may
occur. An increased risk of disseminated infection due to impaired neutrophil
function also has been associated with aldesleukin treatment.

Immunization
Immunization may be active or passive. Active immunization involves
stimulation with an antigen to develop immunologic defenses against a future
exposure. Passive immunization involves administration of preformed
antibodies to an individual who is already exposed or is about to be exposed to
an antigen.
Vaccines. Active immunization, vaccination, involves administration of an
antigen as a whole, killed organism, attenuated (live) organism, or a specific
protein or peptide constituent of an organism. Booster doses often are required,
especially when killed (inactivated) organisms are used as the immunogen. In
the United States, vaccination has sharply curtailed or practically eliminated a
variety of major infections, including diphtheria, measles, mumps, pertussis,
rubella, tetanus, Haemophilus influenzae type b, and pneumococcus

Although most vaccines have targeted infectious diseases, a new generation of

vaccines may provide complete or limited protection from specific cancers or
autoimmune diseases Because T cells optimally are activated by peptides and
costimulatory ligands that both are present on antigen-presenting cells (APCs),
one approach for vaccination has consisted of immunizing patients with APCs
expressing a tumor antigen. The first generation of anticancer vaccines used
whole cancer cells or tumor-cell lysates as a source of antigen in combination
with various adjuvants, relying on host APCs to process and present tumorspecific antigens These anticancer vaccines resulted in occasional clinical
responses and are being tested in prospective clinical trials. Second generation
anticancer vaccines utilized specific APCs incubated ex vivo with antigen or
transduced to express antigen and subsequently reinfused into patients.

Immune Globulin. Passive immunization is indicated when an individual is

deficient in antibodies because of a congenital or acquired immunodeficiency,
when an individual with a high degree of risk is exposed to an agent and there is
inadequate time for active immunization (e.g., measles, rabies, hepatitis B), or
when a disease is already present but can be ameliorated by passive antibodies
(e.g., botulism, diphtheria, tetanus). Passive immunization may be provided by
several different products Nonspecific immunoglobulins or highly specific
immunoglobulins may be provided based upon the indication.
The protection provided usually lasts from 1 to 3 months. Immune globulin is
derived from pooled plasma of adults by an alcohol-fractionation procedure. It
contains largely IgG (95%) and is indicated for antibody-deficiency disorders,
exposure to infections such as hepatitis A and measles, and specific
immunologic diseases such as immune thrombocytopenic purpura and GuillainBarre syndrome In contrast, specific immune globulins ("hyperimmune") differ
from other immune globulin preparations in that donors are selected for high
titers of the desired antibodies. Specific immune globulin preparations are
available for hepatitis B, rabies, tetanus, varicella-zoster, cytomegalovirus, and
respiratory syncytial virus. Rho(D) immune globulin is a specific hyperimmune
globulin for prophylaxis against hemolytic disease of the newborn due to Rh
incompatibility between mother and fetus. All such plasma-derived products
carry the theoretical risk of transmission of infectious disease.