The document discusses various aspects of the immune system and drugs that impact immunity. It describes the components of the immune system including lymphocytes, cellular and humoral immunity. There are two types of immunity: active and passive. Immunosuppressants discussed include corticosteroids, cyclophosphamide, azathioprine and methotrexate which act on different phases of the immune response. Immunostimulants covered are BCG vaccine, levamisole, corynebacterium parvum and tilorone which enhance the immune system.

1. Presented by:
KINJAN MEHTA
Sem.- VII

2.  What is IMMUNITY?
 The word immunity is derived from the
Latin word immunes which means “exempt
from”.
 Immunity is usually defined as a state of
relative resistance to an infection.
 Substances capable of stimulating immune
mechanism are called as antigens.

3.  Components of immune system:
 Lymphocytes.
 Cellular immunity.
 Humoral immunity.
 Immunoglobulin.
 Lymph nodes.
 Spleen.
 Thymus.

4.  There are 2 types of immunity:
 Active immunity.
 Passive immunity.

5.  Theimportant components of immune
system include:
Granulocytes
Complement synthesis and antibody
formation
Cellular immunity
Mucocutaneous barriers

6.  NEUTROPHILS are synthesized from
GRANULOCYTES, as the total
granulocyte count falls below 1000 cells
/mm3, the rate of bacterial infection
increases.
 The common org. affecting this are
E.coli, Pseudomonas
aeruginosa, Klebsiella, Pneumonia and
stapylococcus aureus.
 The chances of fungal viral and protozal
infection is also very high.

7.  When the defect in this system is there the
increase in infection rate is seen.
 Such effects usually occur through the
chronic treatment with chemotherapeutic
agents.

8.  Itprovides protection against fungal
bacterial, viral and protozal infections.
 Certain drugs, neoplastic diseases and
organ transplantation procedures
paralyzes cellular immunity.

9.  They prohibit pathogenic organisms to
take entry into the internal vital organs.
 However these barriers are damaged by a
no. of medical devices, procedures, or
chemotherapy.
 This leads to easy access of pathogens to
the internal organs resulting into infectious
state.

10.  (A) ANTI-HISTAMINIC AGENTS:
 Histamine- binding lymphocytes have
immunosuppressive activities.
 By inhibiting their activation , antihistaminic
agents improve cell mediated immune
response.

11.  IT is the non-narcotic analgesic agent that
relives pain sensation b inhibiting
prostaglandin biosynthesis.
 This leads to significant improvement in
the functioning of t-lymphocytes.
 Useful in coccidiomycosis and
mycobacterial infections.

12.  Chemically it is the complex of inosine and
an organic salt.
 It enhances t-cell proliferation,
phagocyotsis and chemo taxis through
unknown mechanism.
 Initially it was found as an anti-viral agent.

13.  IT improves chemotactic responses and
immune mechanisms in patients with
diseases associated with
immunodeficiency.
 It probably acts by inducing the release of
c-GMP.

14.  Onlytwo lymphokines known as IL-1, IL-2
were found to stimulate the patient
immunity.

15.  These are the polypeptides isolated from
the epithelial cells of thymus gland.
 They induce formation of mature T- cells
by unknown mechanism.
 This are given usually in saline i.m. in
doses between 0.5mg/kg and 1.0 mg/kg
/day for 2-3 weeks and then reduced to 1-3
doses per week.

16.  Thisis low molecular weight peptide (m.w.
less than 6000 Daltons) isolated from
blood leucocytes of the patient with
delayed hypersensitivity. it has stimulant
effect of cell mediated immunity. it may be
used in treatment of immunodeficiency
syndrome like chronic mucotaneius
candidacies, in treatment of recurrent
herpes simplex conditions

17.  Various phases of immune responses
include:
 (1) antigen reorganisation and/processing.
 (2) amplification.
 (3) antibody formation and
 (4) immune effectors responses.

18.  Depending upon the suppressant and
stimulate effects exerted by these drugs on
immune system they are categorized as:
 (1) IMMUNOSUPPRESSANTS
 (2) IMMUNO ENHANCERS.

19. Phases of immune Suppressants Enhancers
response
Antigen recognisation Corticosteriods. BCG vaccine.
and processing Cyclophosphamide C. Parvum
cytimun Tetramisole
Amplification. L- Asparaginase Concanavalin A.
Corticosteroids. Tetramisole.
Cyclophosphamide.
Cytimum.
5-fluorouracil
Antibody formation Corticosteroids. Lipopolysaccaride.
Cyclophosphamide Tetramisole.
Cyclosporin A
cytimun

20. Phases of immune Suppressants. enhancers.
response
Immune affector Corticosteroids C. parvum.
response Cylcophosphamide tetramisole
Cyclosporin A
Cytarabine
Cytimun
Methotrexate.

21.  During organ transplantation, certain
complex antigens or allograts activate the
cytotoxic lymphocytes. Their activation
results to the development of cellular
immunity rejects organ transplants.
 Immunosuppressive agent beneficial
effects in such condition suppressing the
cellular immunity.

22.  Most of these agents are primarily used as
anti- neoplastic agents.
 On the basis of the mechanism of action,
immunosuppressant can be classified as:

23. Alkylating
corticosteroids antimetabolites
agents
Antibodies and
antibiotics enzymes miscellaneous
agents

24.  Examples:
Betamethasone ,
dexamethasone. triamcinolone
Prednisolone,
hydrocortisone
methylprednisolone
paramethasone

25.  They all possess anti allergic and anti-
inflammatory and immunosuppressive
activities.
 T- lymphocytes are most susceptible to the
action of corticosteroids resulting into
lymphopenia.
 They also effect humoral immune
responses by inhibiting antibody synthesis.

26.  Adverse effect:
 High doses cause Osteoporosis,
hyperglycemia, ulcer formation and
increased susceptibility for fungal
infections .
 DOSE: 2-10 mg/kg per day for few weeks.
 Adverse effect can be reduced by usig
combination of other cytotoxic agents and
lowering the dose.

27.  This kill components of immune response
of body.
 They give immunosuppressive action to
the rapidly proliferation cells in the marrow
and exert cytotoxic effects to the
lymphocytes by alkylating their nucleic
acid.
 EXAMPLES:
CYLCOPHOSPHAMIDE,CYTIMUN.

28.  CYCLOPHOSPHAMIDE:
 It is a nitrogen mustard and have broad
spectrum of antineoplastic and immune
suppressive activities.
 More effective suppressor of humoral
immune mechanisms.
 It exerts cyotoxic action on both T-cells and
B-cells.
 DOSE: 2 mg/kg per day.

29.  Usuallyused in combination with
corticosteroids in treatment of several
autoimmune diseases, including
Wegener’s granulomatosis. Childhood
nephrosis, idiopathic thrombocytopenia
purpura and severe rheumatoid arthrititis.

30.  CYTIMUM:
 It is analog of cylophosphamide having
better therapeutic index.
 It is specifically effective against B-cells.

31.  These drugs act by exerting cyotoxic
effects on rapidly proliferating cells like
those of bone marrow, myeloid
tissues, gonadal tissues and g.i. tract.
 METHOTREXATE, 6-
MERCAPTOPURINE, AND
AZATHIOPRINE are extensively studied
drugs which are more toxic to S-phase
when DNA synthesis is occurring.

32.  AZATHIOPRINE:
 It is imidazole derivative of 6-
mercaptopurine having anti-rheumatic
activity along with cytotoxic effect.
 It is orally effective and having plasma half
life of about 16 hours.
 It is the most effective suppressant of
phase-II of immune responses.

33.  Xanthine oxidase enzyme converts much of
the drug in liver and RBC to 6-thiouric
acid, thioionisic acid and various other
metabolized.
 Thioinosic acid competitively inhibit synthesis
of inosinic acid. This result in inhibition of
DNA synthesis. thus upon the metabolized
activation, this suppresses both mediated and
humoral immune responses and depresses
antibody proliferative responses.

34.  AZATHIOPRINE is used orally in the
treatment of acute glomerunephritis,
systemic lupus erythematosus,
temporalcranial arteritis.
 It is also used in management of organ
transplantation and delay hypersentizing
reactions.
 DOSE: 2-5 mg/kg per day.

35.  METHOTREXATE:
 It is an orally active folic acid analog having anti
neoplastic and antipsoratic and mild immune
suppressant activity.
 It has a plasma half-life 7.2-9.0 hours.
 It acts by inhibiting folate metabolism and affects
phase-II of immune responses.
 It is used to treat severe psorasis,
dermatomcosotis and rheumatoid arthritis and also
used in organ transplantation procedure.
 Other drug include chlorambucil, mercaptopurine,
thioguanine, azarbine, cytarabine.

36.  CYCLOSPORIN A is he example for this
having immunosuppressive. It is the cyclic
activity and is isolated from the soil fungus,
Tolypolacadofium inflatum.
 It spefically inhibit generation of effectors
T-lymphocytes without expressing effect of
suppressor lymphocytes and B-cells
activity.
 It impairs proflirative response of T-cells
of antigens.

37.  Once T-cells are stimulated by antigens
they synthesized interculin -2 that’s start
growth promoting effects on T-
lymphocytes.
 Cyclosporine has low activity profile.
 A.E.: gumhypertropy, tremor.
Neurasthesia, depressive psychosis and
benign breast tumours'.
 It has plasma half life of 10-27 hours.

38.  USED in organ transplantation in patients
having liver, kidney, pancreas disorder and
heart transplantation.
 It also expands its effects in the treatment
of immune diseases of rheumatic arthritis.
 DOSE: adult oral dose is 10-20 mg/kg per
day.
 i.v. 50 mg diluted intranasal saline may be
given by slow infusion.

39.  L-ASPARAGINASE is the drug of choice
in treatment of acute lymphoblastic
leukaemia.
 It has half life of about 11-23 hours.
 this enzyme is usually given i.v. or i.m.
 When combined with methotrexate it
lowers down the adverse effect and
intensifies its activity.

40. EXAMPLE: ANTITHYMOCYTE GLOBULIN (ATG)
 ATG is used alone or in combination with
azathioprine and corticosteroids in the
prevention of the renal allograft rejection in
the dose of 1-5 mg/kg per day.
 However in some patients , allergic
reactions has been reported to occur to
leading to serum sickness and nephritis.

41.  (A) ADENOSINE DEAMINASE
INHIBOTORS;
 Examples are erythro-9-(2-hydroxy-3-
nonyl) adenine hydrochloride and 2-
deoxy- coformycin.(pentastatin).
 Former one have effect on T-lympohcytes
while pentastatin is used as antimetabolite.

42.  (B) BREDININ:
 It is an imidazole nucleoside having
antimetabolite antineoplastic activity and is
used as an immunosuppressant in human
kidney transplantation.
 (C) CYCLOIMMUNE:
 It is analog of cyclosporine, undergoing
clinical trials and showing activity for organ
transplantation.

43.  (D) NIRIDAZOLE:
 It is an orally active nitrothiazole derivative
having anthelmintic activity, anti bacterial
and immunosuppressive activities.
 It is used to suppress cell- mediated
immunity response.

44.  This category of the drugs is used to
overcome immunodeficiency or
immunosupreesion arising as a result of
either inherited or acquired disorders of
immune system.
 Examples of inherited disorders:
Agammaglobulinemia and Severe combined
immune deficiency syndrome (SCIDS).
 Causes: chemotherapy. Radiation or viral
infection may cause immunosupreesion.

45.  Examples of this category include :
 (a) BCG Vaccine:
 It is used as immunological enhancer to
stimulate intact immune system (i.e. a non-
specific immunoenhancer.) of the body.
 BCG and its methanol extracted residue
(MER) contain muramyl dipeptide as an
active immunostimulant ingredient.

46.  T-lymphocytes are principle target cells for the action
of BCG vaccine.
 It causes stimulation of macrophage function,
phagocytic activity, lysosomal enzyme activity and
chemotaxis mechanisms .
 It induces the production of lymphocyte-activity factor
resulting of phase I of immune response.
 Because of its activity against tumour antigen it is
beneficial in treatment of lung and breast cancer, acute
lympholytic and myelogeneous leukaemia.
 It is available as unlyophilized, live or killed lyophilized
form.
 Administration as oral, i.v., i.p., i.d. , intralesional.

47.  Levamisole is orally active S(-) isomer of
tetramisole. It is used as immunostimulant in the
therapy of certain infections, r.a., and
immunosuppressive conditions
 It mainly acts by raising c-GMP levels through
interaction with thymopoietien receptor sites. this
leads to decrease in metabolic inactivation of c-
GMP accompanied with increased breakdown of c-
AMP. The increase in c-GMP level induces
lymphocyte proliferation and augmentation of
chemotactic responses.
 This reflects into increased antibody
production, lymphokine production, increased
phagocytosis.

48.  Tetramisole is used in treatment of:
 (1)certain chronic and recurrent bacterial
infections
 (2) certain diseases with immunodeficiency
like chronic granulomatous syndrome,
job’s syndrme etc.
 (3) autoimmune diseases like r.a., crohn’s
disease, SLE.

49.  OTHERS ARE:
 Corynebacterium parvum
 Tilorone
 Inosiplex
 Lipopolysaccharides
 Dialyzable leukocyte extract