PRESENTED TO: PRESENTED BY:
Mrs. Vinay Kumari Amandeep Kaur
Associate Professor Roll No. 1915703
Medical Surgical Nursing M.Sc. (N) 2nd Year
1. Introduction to immunity
2. Types of immunity
3. What is antigen and antibody
4. Type of antigens
5. Type of antibody
6. Antibody targets and functions
7. Antigen and antibody action/reaction
8. Non specific defences
9. Introduction to immunosuppressant
10. Classification of immunosuppressants
11. Organ transplant rejection
12. Mechanism of cyclosporine and tacrolimus
13. Mechanism of sirolimus and tacrolimus
14. Mechanism of mycophenolate
15. Action of immunosuppressants
16. Side effects immunosuppressants
INTRODUCTION TO IMMUNITY
Immunity is the resistance of an organism to
infection or disease.
Immunity is the state of sufficient biological
defences to avoid infection, disease, or other
unwanted biological invasion.”
In biology, immunity is the state of having
sufficient biological defences to
avoid infection, disease, or other unwanted
biological invasion. It is the capability of the
body to resist harmful microbes from entering it.
2. A. INNATE IMMUNITY
Innate immunity is non- specific. It is first lines of defence. They
defences include secretion of chemical signals, phagocytic activity,
antimicrobial substance and fever.
Neutrophils, Eosinophils, Mast cells, Monocytes, Macrophages,
Killer cell, Platelets
Innate immunity also comes in a protein chemical form, called
innate humoral immunity. If an antigen gets past these barriers, it is
attacked and destroyed by other parts of the immune system.
Cough reflex, Enzymes in tears and skin oils, Mucus (which
traps bacteria and small particles),Skin, Stomach acid
May be a foreign substance from the environment such as
chemicals, bacteria, viruses, or pollen. An antigen may also
be formed within the body, as with bacterial toxins or tissue
cells. An antigen is any substance that causes our immune
system to produce antibodies against it.
Also known as an immunoglobulin (Ig), is a large Y-
shape protein produced by B cells that is used by
the immune system to identify and neutralize foreign
objects such as bacteria and viruses. The antibody
recognizes a unique part of the foreign target, called an
4. TYPE OFANTIGENS
1. Exogenous antigens
Exogenous antigens are antigens that have entered the
body from the outside, for example
by inhalation, ingestion, or injection.
2. Endogenous antigens
Endogenous antigens are antigens that have been
generated within previously normal cells as a result of
normal cell metabolism, or because of viral or
intracellular bacterial infection.
An autoantigen is usually a normal protein or complex of proteins
(and sometimes DNA or RNA) that is recognized by the immune
system of patients suffering from a specific autoimmune disease.
4. Tumour antigens or neoantigens
Those antigens that are presented by MHC I or MHC II molecules
on the surface of tumor cells. These antigens can sometimes be
presented by tumor cells and never by the normal ones. In this case,
they are called tumor-specific antigens (TSAs) and, in general,
result from a tumor-specific mutation.
Humoral immune response: The antigen (Ag) is
processed by macrophages or other antigen
presenting cells (APC), coupled with class II
major histocompatibility complex (MHC) and
presented to the CD4 helper T-cell which are
activated by interleukin-I (IL-1), proliferate and
secrete cytokines—these in turn promote
proliferation and differentiation of antigen
activated B cells into antibody (Ab) secreting
plasma cells. Antibodies finally bind and
inactivate the antigen.
In cell-mediated immunity—foreign antigen is
processed and presented to CD4 helper T cell
which elaborate IL-2 and other cytokines that in
turn stimulate proliferation and maturation of
precursor cytotoxic lymphocytes (CTL) that
have been activated by antigen presented with
class I MHC. The mature CTL (Killer cells)
recognize cells carrying the antigen and lyse
Immunosuppressant drugs are a class of drugs that suppress
or reduce the strength of the body’s immune system. They are
also called anti-rejection drugs. One of the primary uses of
immunosuppressant drugs is to lower the body’s ability to reject
a transplanted organ, such as a liver, heart or kidney.
Almost everyone who receives an organ transplant has to take
immunosuppressant drugs. The body recognizes a transplanted
organ as a foreign mass. This triggers a response by the body’s
immune system to attack it.
By weakening the immune system, immunosuppressant drugs
decrease the body’s reaction to the foreign organ. The drugs allow
the transplanted organ to remain healthy and free from damage
Immunosuppressant drugs also are used to treat autoimmune
diseases such as lupus. An autoimmune disorder is a disease
process in which the body attacks its own tissue. Lupus results
from just such a misdirected activity of the body’s own immune
system. By suppressing this reaction, immunosuppressant drugs
can help control the impact of the disease on the body.
These are drugs which inhibit cellular /humoral or both
immune response and have their major use in organ
transplantation and autoimmune diseases. The drugs are:
1. Calcineurin inhibitors
2. m-TOR inhibitors
3. Antiproliferative drugs (Cytotoxic drugs)
5. Biological agents
(Specific T-cell inhibitors)
It is a cyclic polypeptide with 11 amino acids,
obtained from a fungus and introduced in 1977 as a
highly selective immunosuppressant which has
markedly increased the success of organ
It profoundly and selectively inhibits T lymphocyte
proliferation, IL-2 and other cytokine production as
well as response of inducer T cells to IL-1, without any
effect on suppressor T-cells. Lymphocytes are arrested
in G0 or G1 phase.
Cyclosporine, tacrolimus and sirolimus inhibit
antigen stimulated activation and proliferation of
helper T cells as well as expression of IL-2 and other
cytokines by them.
Cyclosporine binds to an intracellular protein
‘Cyclophilin’ and this complex inhibits Ca2+
Calmodulin (Ca2+-CAM) activated phosphatase
Cyclosporine binds to an intracellular protein ‘Cyclophilin’ and
this complex inhibits Ca2+-Calmodulin (Ca2+-CAM) activated
classification Dose and route Uses Side effects
10–15 mg/kg/day with
milk or fruit juice till 1–2
reduced to maintenance
Of 2–6 mg/kg/day.
Therapy may be started
with 3–5 mg/kg
I. V. Infusion.
Rise in BP,
Cyclosporine is most active when administered before
antigen exposure, but can, in addition, suppress the responses of
primed helper T cells; hence useful in autoimmune diseases as
Cyclosporine selectively suppresses cellmediated
immunity (CMI), prevents graft rejection and yet leaves the
recipient with enough immune activity to combat bacterial
infection. Unlike cytotoxic immunosuppressants, it is free of
toxic effects on bone marrow and RE system. Humoral immunity
Cyclosporine is the most effective drug for prevention
and treatment of graft rejection reaction.
It is routinely used in renal, hepatic, cardiac, bone marrow
and other transplantations. For induction
it is started orally 12 hours before the transplant and
continued for as long as needed.
When graft rejection has started, it can be given i.v.,
because oral bioavailability is low, dependent on presence of
bile and is highly variable.
Blood level monitoring is required for effective therapy.
It is concentrated in WBCs and RBCs,
metabolized in liver by CYP3A4 and excrete in
The plasma t½ is biphasic 4–6 hr and 12–18 hr.
Cyclosporine can interact with a large number of
All nephrotoxic drugs like aminoglycosides,
vancomycin, amphotericin B and NSAIDs enhance its
By depressing renal function, it can reduce excretion
of many drugs. Phenytoin, phenobarbitone, rifampin
and other enzyme inducers lower its blood levels so
that transplant rejection may result.
This immunosuppressant is chemically different
from cyclosporine, but has the same mechanism of
action, and is ~100 times more potent.
It binds to a different cytoplasmic immunophilin
protein labelled ‘FK 506 binding protein (FKBP)’,
but the subsequent steps are the same, i.e.
inhibition of helper T cells via calcineurin.
classification Dose and route Uses Side effects
0.05–0.1 mg/kg BD oral (for
0.1–0.2 mg/kg BD (for liver
It can also be given i.v. (no
i.v. preparation is available in
Rise in BP,
Tacrolimus is administered orally as well as by
Oral absorption is variable and decreased by
It is metabolized by CYP3A4 and excreted in
bile with a t½ of 12 hour.
Therapeutic application, clinical efficacy as well
as toxicity profile are similar to cyclosporine.
2. m-TOR inhibitors
This new and potent immunosuppressant is a macrolide
antibiotic (like tacrolimus), which was earlier named
It binds to the same immunophillin FKBP as tacrolimus, but
the sirolimus-FKBP complex inhibits another kinase called
‘mammalian target of rapamycin’ (mTOR), and does not interact
The mTOR is an important link in the cascade of signalling
pathways which lead to proliferation and differentiation of T-
cells activated by IL-2 and other cytokines.
Sirolimus arrests the immune response at a later stage than
Sirolimus also binds to FKBP, but this complex acts at a later stage. It
binds to and inhibits a kinase termed m-TOR (mammalian target of
rapamycin) which is a key factor for progression of cell proliferation.
Sirolimus is absorbed orally, but fatty meal reduces
It is extensively metabolized, mainly by CYP3A4, so
that systemic bioavailability is only 15–20%.
Elimination occurs primarily by the biliary route; the
t½ is ~60 hours.
Inhibitors and inducers of CYP3A4 significantly alter
its blood level, which needs to be monitored.
Cyclosporine shares the same isoenzyme and raises
the blood level of sirolimus.
For prophylaxis and therapy of graft rejection
reaction, sirolimus can be used alone, but is generally
combined with lower dose of cyclosporine/tacrolimus
and/or corticosteroids and mycophenolate mofetil.
The latter combination avoids use of a calcineurin
inhibitor, and is particularly suitable for patients
developing renal toxicity with cyclosporine.
Sirolimus is effective in some steroid refractory
cases, and has been used in stem cell transplant as well.
However, it is not recommended for liver transplant.
Sirolimus coated stents are being used to reduce the
incidence of coronary artery restenosis, by inhibiting
endothelial proliferation at the site.
It is similar to sirolimus in mechanism,
clinical efficacy, doses, toxicity and drug
interactions, but is better absorbed orally and has
more consistent bioavailability.
The t½ is shorter (~40 hours) so that steady
state levels can be reached earlier.
It is a purine antimetabolite which has more marked
immunosuppressant than antitumour action.
The basis for this difference is not clear, but may be
due to its selective uptake into immune cells and
intracellular conversion to the active metabolite 6-
mercaptopurine, which then undergoes further
transformations to inhibit de novo purine synthesis and
damage to DNA.
It selectively affects differentiation and function of T
cells and inhibits cytolytic lymphocytes; CMI is primarily
The most important application of azathioprine is
prevention of renal and other graft rejection, but it is less
effective than cyclosporine; generally combined with it or
used in patients developing cyclosporine toxicity.
Relatively lower doses (1–2 mg/kg/day) are used in
progressive rheumatoid arthritis and it is frequently
employed for maintening remission in inflammatory bowel
It may be an alternative to long-term steroids in some
other autoimmune diseases as well. It is not combined with
Methotrexate. Dose: 50–150 mg/day; orally
This folate antagonist is a potent immunosuppressant
which markedly depresses cytokine production and cellular
immunity, and has antiinflammatory property.
It has been used as a first line drug in many
autoimmune diseases like rapidly progressing rheumatoid
arthritis, severe psoriasis, pemphigus, myasthenia gravis,
uveitis, chronic active hepatitis.
Low dose Mtx maintenance therapy is relatively well
This cytotoxic drug has more marked effect on B cells
and humoral immunity compared to that on T cells and CMI.
It has been particularly utilized in bone marrow
transplantation in which a short course with high dose is
In other organ transplants it is employed only as a
In rheumatoid arthritis, it is rarely used, only when
systemic manifestations are marked.
Low doses are occasionally employed for maintenance
therapy in pemphigus, systemic lupus erythematosus and
idiopathic thrombocytopenic purpura.
It has relatively weak immunosuppressant
action which is sometimes utilized in autoimmune
diseases and transplant maintenance regimens.
e). Mycophenolate mofetil (MMF)
It is a newer immunosuppressant; prodrug of
mycophenolic acid which selectively inhibits inosine
monophosphate dehydrogenase, an enzyme essential
for denovo synthesis of guanosine nucleotides in the T
and B cells (these cells, unlike others, do not have the
purine salvage pathway).
Lymphocyte proliferation, antibody production and
CMI are inhibited.
As ‘add on’ drug to cyclosporine
+glucocorticoid in renal transplantation, it has been
found as good or even superior to azathioprine, but
should not be combined with azathioprine.
It can help to reduce the dose of cyclosporine
and thus its toxicity. MMF + glucocorticoid +
sirolimus is a non-nephrotoxic combination that is
utilized in patients developing renal toxicity with
MMF is rapidly absorbed orally and quickly
converted to the active metabolite mycophenolic
This is then slowly inactivated by glucuronidation
with a t½ of ~ 16 hours.
The glucuronide is excreted in urine.
Name of drug classification Dose and route Uses Side effects
1.0 g bd oral;
250, 500 mg tab/cap.
Glucocorticoids have potent immunosuppressant and
anti-inflammatory action, inhibit several components of the
They particularly inhibit MHC expression and
activation/proliferation of T lymphocytes.
Expression of several IL and other cytokine genes is
regulated by corticosteroids and production of adhesion
molecules is depressed.
Accordingly, they have marked effect on CMI but
little effect on humoral immunity.
Name of drug Classification Dose and route Uses Side effects
-initial dose: 0.75
mg to 9 mg orally
-initial dose: 0.5
mg to 9 mg IV or
IM per day in
every 12 hours
the amount of
Name of drug Classification Dose and route Uses Side effects
5 to 60 mg orally
the amount of
The corticosteroids are widely employed as
companion drug to cyclosporine or other
immunosuppressants in various organ transplants.
In case graft rejection sets in—large doses of
corticoids I.V. are employed for short periods.
They are used in practically all cases of severe
autoimmune diseases, especially during exacerbation.
These are biotechnologically produced
recombinant proteins or polyclonal/monoclonal
antibodies directed to cytokines or lymphocyte
surface antigens which play a key role in immune
They are important recent additions, mostly as
supplementary/reserve drugs for severe and
refractory cases of autoimmune diseases and graft
versus host reaction.
TNFα is secreted by activated macrophages and
other immune cells to act on TNF receptors (TNFR1,
TNFR2) which are located on the surface of neutrophils,
fibroblasts, endothelial cells as well as found in free
soluble form in serum and serous fluids.
TNFα amplifies immune inflammation by releasing
other cytokines and enzymes like collagenases and
The TNFα inhibitors are mainly used in
autoimmune diseases, and are briefly described with
disease modifying drugs for rheumatoid arthritis.
This fusion protein of human TNF receptor and Fc
portion of human IgG1 neutralizes both TNFα and TNFβ.
It prevents activation of macrophages and T-cells
during immune reaction.
It is used mostly in combination with Mtx in
rheumatoid arthritis patients who fail to respond adequately
to the latter.
It is also approved for severe/refractory ankylosing
spondylitis, polyarticular idiopathic juvenile arthritis and
IL-1 receptor antagonist
Stimulated macrophages and other
mononuclear cells elaborate IL-1 which activates
helper T-cells and induces production of other ILs,
An endogenous IL-1 receptor antagonist has
been isolated and several of its recombinant variants
have been produced for clinical use.
This recombinant human IL-1 receptor
antagonist prevents IL-1 binding to its receptor and
has been approved for use in refractory rheumatoid
arthritis not controlled by conventional DMARDs.
Anakinra along with continued Mtx has been
used alone as well as added to TNFα antagonists,
because its clinical efficacy as monotherapy appears
to be lower.
IL-2 receptor antagonist
The CD-25 molecule is expressed on the surface
of immunologically activated, but not resting T-cells.
It acts as a high affinity receptor for IL-2 through
which cell proliferation and differentiation are
promoted. Some anti CD-25 antibodies have been
developed as IL-2 receptor antagonist to specifically
arrest the activated T-cells.
It is a highly humanized chimeric monoclonal
anti CD-25 antibody which binds to and acts as IL-2
Combined with glucocorticoids, calcineurin
antagonists and/or azathioprine/MMF, it is used to
prevent renal and other transplant rejection reaction.
The plasma t½ of daclizumab is long (3 weeks),
and it has also been used in combination regimens for
maintenance of graft.
It is a murine monoclonal artibody against the
CD3 glycoprotein expressed near to the T cell receptor
on helper T cells.
Binding of muromonab CD3 to the CD3 antigen
obstructs approach of the MHCIIantigen complex to the
Consequently, antigen recognition is interfered,
and participation of T-cells in the immune response is
Muromonab CD3 is the oldest (developed in the
1980s) monoclonal antibody that is still occasionally
Induction therapy of organ transplantation is
infrequent now, since better alternatives are available.
It has also been used to deplete T cells from the
donor bone marrow before transplantation.
Occasionally aseptic meningitis,
life-threatening pulmonary edema,
Seizures and a shock-like state
Antithymocyte globulin (ATG)
It is a polyclonal antibody purified from horse or
rabbit immunized with human thymic lymphocytes which
contains antibodies against many CD antigens as well as
It binds to T lymphocytes and depletes them. It is a
potent immunosuppressant and has been used primarily
to suppress acute allograft rejection episodes, especially
in steroid resistant cases, by combining with other
immunosuppressants, including steroids.
It can also be used in induction regimens, but
this has the potential to produce serum sickness or
LYMPHOGLOBULIN (equine) 100 mg/vial inj.; 10
THYMOGLOBULIN (rabbit) 25 mg/vial inj.; 1.5
ATG 100 mg inj; 200 mg I.V./day.
Anti-D immune globulin
It is human IgG having a high titer of antibodies
against Rh (D) antigen.
It binds the Rho antigens and does not allow them to
induce antibody formation in Rh negative individuals.
It is used for prevention of postpartum/post-abortion
formation of antibodies in Rho-D negative, DU negative
women who have delivered or aborted an Rho-D positive,
DU positive baby/foetus.
Administered within 72 hours of delivery/ abortion,
such treatment prevents Rh haemolytic disease in future
It has also been given at 28th week of pregnancy.
Dose: 250–350 μg I.M. of freez dried preparation.
RHESUMAN, RHOGAM, IMOGAM 300 μg per
Higher doses (1000–2000 μg) are needed for
Rh negative recipients of inadvertantly administered
Rh positive blood. It should never be given to the
infant or to Rho-D positive, DU positive individuals.
■ Obtain a health history including allergies, drug
history, and possible drug interactions.
■ Assess for presence of metastatic cancer, active
infection, renal or liver disease and pregnancy.
■ Assess skin integrity; specifically look for lesions
and skin color.
■ Obtain results of laboratory work including complete
blood count (CBC), electrolytes, and liver enzymes.
■ Obtain vital signs, especially temperature and blood
Potential Nursing Diagnoses
■ Risk for Infection, related to depressed immune
response secondary to drug
■ Risk for Injury, related to thrombocytopenia
secondary to drug
■ Assess renal function. (Drugs cause nephrotoxicity in
many clients because of physiological changes in the
kidneys such as micro-calcifications and interstitial
■ Monitor liver function tests. (Drugs increase the risk
for liver toxicity.)
■ Watch for signs and symptoms of infection,
including elevated temperature. (There is an increased
risk of infection owing to immune suppression.)
■ Monitor vital signs, especially temperature and
blood pressure. (Drugs may cause hypertension,
especially in clients with kidney transplants.)
■ Monitor for hirsutism, leukopenia, gingival
hyperplasia, gynecomastia, sinusitis, and
hyperkalemia. (These are common side effects.)
■ Avoid permitting client to ingest grapefruit juice.
(Grapefruit juice increases cyclosporine levels 50%
Client Education/Discharge Planning
Advise client to:
■ Keep accurate record of urine output, Report
significant reduction in urine flow.
■ Instruct client about the importance of regular
■ Wash hands thoroughly and frequently, Avoid
crowds and people with infection.
■ Monitor blood pressure and temperature,
ensuring proper use of home equipment.
■ Keep all appointments with healthcare provider.
■ Take medication with food to decrease GI upset.
■ Instruct client regarding a healthy diet that
avoids excessive fats and sugars.
Mosbey’s drug guide for nurses. Edition:-9th . P.-198-203.
Medications , How do analgesics work on pain? , Craig C.
Freudenrich and Discovery Fit & Health , Retrieved August 02,
Analgesics Research & Articles, Analgesics, Retrieved August