Introduction to immune system:
•Immunity: The resistance offered by the host to the
harmfull effects of pathogenic microbial infection or any
foreign material is called as immunity.
•Immune response: the specific reactivity induced in a
host by an antigenic stimulus is known as the immune
response.
•Antigen: molecule from a pathogen or foreign
organism that provoke a specific immune response.
•Antibodies: (immunoglobulines) produced in response
to antigenic stimulus.
TYPES OF IMMUNITY:
•INNATE/NATURAL/NATIVE: Everyone is born with innate
(natural) immunity, a type of general protection.Many of the
germs that affect others don't harm us. Innate immunity also
includes the external barriers of the body, like the skin and
mucous membranes which in preventing diseases from entering
the body.
•ACQUIRED: Immunity that an organism develops during its
lifetime.
1. Active: Involves the lymphocytes production and develops as
people are exposed to diseases(Natural) or immunized
against diseases through vaccination(Artificial).
2. Passive: Immunity that is transferred in a ready-made
prepared form of antibodies to the recipients.
CELLULAR AND HUMORAL IMMUNITY:
WHAT ARE IMMUNOSUPPRESSANTS?:
•Agents used to dampen the immune response in
Organ transplantation and Autoimmune disease.
•These drugs have met with a high degree of
clinical success ,however, such therapies require
lifelong use and nonspecifically suppress the
entire immune system, exposing patients to
considerably higher risks of infection and cancer.
•Immunosupressive drugs have one meaning:
drugs that lowers body’s normal immune
response.
Allograft rejaction:
Allograft rejection is the recipient's immune response to
nonself antigens expressed by donor tissues. After
transplantation of organ allografts, there are two pathways
of antigen presentation. In the direct pathway, recipient T
cells react to intact allogeneic MHC molecules expressed
on the surface of donor cells. This pathway would activate
host CD4 or CD8 T cells. In contrast, donor MHC molecules
(and all other proteins) shed from the graft can be taken
up by host APCs and presented to recipient T cells in the
context of self-MHC molecules - the indirect pathway.
IMMUNOSUPPRESSIVE DRUGS:
Calcineurin inhibitors:
•cyclosporine,
•tacrolimus,
•Sirolimus (Antiproliferative).
Antiproliferative (Antimetabolite):
•azathioprine,
•mycophenolate(mofetil),
•methotrexate.
Antibodies:
•muromonab,
•alemtuzumab,
•antithymocyte globin.
Glucocorticoids:
•prednisolone.
Mechanism of action:
•Cyclosporine suppresses call mediated
immunity. After diffusing t-cell it binds to
cyclophilin (immunophilin) to form a
Adverse effects:
complex.
•Nephrotoxicity;
•This complex cause dephosphorylation of
•Hepatotoxicity;
NFATc (Nuclear Factor of Activated T-cells).
•viral infection;
•Thus NFATc cannot enter the nucleus for the
•Hypertention;
synthesis of cytokines-the primary stimulus
•hyperkalemia.
for increasing the no. of T-lymophocytes.
Therapeutic uses:
•kidney, liver, heart, and other organ
transplantation;
•rheumatoid arthritis;
•Psoriasis.
Mechanism of action:
•It has same action as cyclosporin.
•The differnce is that it binds to different
immunophilin,FKBP-12(FK-binding protein)
Adverse effects:
Therapeutic uses:
•Nephrotoxicity;
•Organ transplantation;
•Hyperglycemia;
•Topically in psoriasis and dermatitis.
•GIT disturbances;
•Hyperkalemia.
Mechanism of action:
•It binds to FKBP forming complex with m-TOR
(molecular target of rapamycin).
•Blocks the progression of activated T-cells from G1
Phase to S-phase of cell cycle.
•Thus inhibits the proliferation of activated T-calls.
Adverse effects:
Therapeutic uses:
•Hyperlipidemia;
prophylaxis of organ transplant rejection in
•Nausea;
combination with a calcineurin inhibitor
•Headache;
and glucocorticoids.
•Diarrhea;
•Leukopenia.
Mechanism of action of cyclosporin, tacrolimus and sirolimus.
Mechanism of action:
•Azathioprine is cleaved to 6-mercaptopurine, which
in turn is converted to additional metabolites 6-ThioIMP which is converted to 6-thio-GMP and finally to
6-thio-GTP, which is incorporated into DNA.
•Inhibition of purine synthesis impairs a variety of
lymphocyte functions.
Adverse effects:
Therapeutic uses:
•Leukopenia;
•Acute glomeruloneritis;
•Thrombocytopenia;
•Systemic lupus erythematosus;
•GI toxicity;
•Rheumatoid arthritis.
•Risk of infection.
Mechanism of action:
•It is the potent inhibitor of inosine
monophosphate dehdrogenase(IMP),crucial
for purine synthesis.
•Prevents the proliferation of T &B
lymphocytes.
Adverse effects:
Therapeutic uses:
•Nausea;
•Rheumatoid arthritis;
•Vomittig;
•In combination with prednisolone as
•Diarrhea;
alternative to cyclosporin and tacrolimus.
•Abdominal pain;
•Neutropenia.
Mechanism of action:
•Muromonab binds to CD3 receptor involved in
antigen recognition.
•Thus preventing subsequent antigen recognition.
•Administration of the antibody is followed rapid
depletion of T cells.
Adverse effects:
Therapeutic uses:
•Fever;
•Acute renal transplant rejection;
•Seizures;
•Steroid resistant rejection;
•Infection;
•to deplete donors T-cells prior to trasplantation.
•Cytokine release syndrome.
Mechanism of action:
•The mechanism is same as
muromonab the only difference is
that it exerts it action through
CD52 receptors.
Adverse effects:
•Cytokine release syndrome;
Therapeutic uses:
•Neutropenia;
•Leukemia;
•Anaemia.
•In combination with calcineurin
inhibitors and sirolimus.
Mechanism of action:
•It contains cytotoxic antibodies that bind to CD2, CD3, CD4,
CD8, CD11a, CD18, CD25, CD44 and CD45 on the surface of
human T lymphocytes .
•The antibodies deplete circulating lymphocytes and block
lymphocyte function
Adverse effects:
Therapeutic uses:
•glomerulonephritis
•Steroid resistant rejection;
•leukopenia
•In combination with calcineurin
•thrombocytopenia
inhibitors.
•hypotension
Mechanism of action:
•It interfers with the production of various cytokines
like IL-1,IL-2,interferons and TNF by inhibiting gene
transcription.
•Thus reduce the proliferation of T-cells.
Adverse effects:
Therapeutic uses:
•Hyperlipidemia;
•Haemopoietic stem cell transplantation;
•Hyperglycemia;
•Rheumatoid arthritis;
•Hypertention;
•Systemic lupus erythmatosus;
•Osteoporosis.
•Asthma.
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