IMMUNE MODULATORS

Immune system protects the host from

invading substances, microorganisms and
aberrant native cells
It responds to injurious stimuli by variety of
receptor mediated sensing and effector
mechanisms which are broadly clarified as
innate and adaptive immune responses
 Innate immune response
Innate immune responses are primitive and is
the first line of defense
It is of relatively low affinity and does not
require priming
Major effects of innate immunity are
complement, granulocytes, monocytes/NKC,
mast cells and basophiles
Innate immune response includes
inflammation
Adaptive or acquired immune response
It is antigen specific, depends on earlier
exposure or priming and can be of very high
affinity
Major effectors of adaptive immunity are B and
T lymphocytes
B-lymphocytes produce antibodies
T-lymphocytes function as helper, cytotoxic and
regulatory (suppressor) cells
These cells are important for the normal
immune response against infection and tumors
and also mediates transplant rejection and
autoimmunity
The innate and adaptive immunity work closely
together
Innate immunity is most active early in the immune
response
Adaptive immunity becomes progressively
dominant over time
Immune system response to noxious stimuli
with retaining the capacity to differentiate self
from non-self, thus leaving the normal cells
unaffected by immune reaction i.e. tolerant to
self antigen
When immune system fails to differentiate self
from non-self, the autoimmune disorders occur
 Abnormal immune response
Hypersensitivity
Autoimmunity: occurs when body produces
immune responses against itself due to failure
to distinguish self tissues and cells from non-
self antigens
Type I DM
Systemic lupus erythematosus (SLE)
Rheumatoid arthritis (RA)
Rheumatic fever (RF)
Inflammatory bowel diseases (IBD)
Immunodificiency diseases
Results from inadequate function of immune
system
Consequences are
Increased susceptibility to infections
Prolonged duration and severity of infections
Malignancy
Immunodificient states can be
Congenital
Acquired e.g. AIDS
Immune modulations are being used in
Prevention of rejection of organ or tissues graft
Treatment of autoimmune diseases
Treatment of inflammatory conditions
Treatment of cancers
Immunodeficiency states
Drugs that modulate immune responses can
be classified as
Immunosuppressants
Immunostimulants
IMMUNOSUPPRESSIVE AGENTS
Immunosuppressive agents are used to
dampen the immune response
Major classes of immunosuppressive drugs
are
Calcineurin inhibitors
Antiproliferative agents/ Immunosuppressive
antimetabolites
Biological agents
Glucocorticoids
Sites of action of immunosuppressive agents
Immunosuppressive agents are being used in
Organ transplantation
Autoimmune diseases
Chronic inflammatory conditions

All the immunosuppressive agents increase

the risk of neoplasm and infections
 Calcineurin inhibitors
Calcineurin inhibitors are the agent that target
the signaling pathway of the activated T-cells

Calcineurin inhibitors includes

Cyclosporin (cyclosporine A)
Tacrolimus
Calcineurin is a cytoplasmic phosphatase that
is necessary for the activation a T cell specific
transcription factor, NF-AT which involves in
the synthesis of IL (e.g. IL-2) by activated T
cells

Calcineurin inhibitors act as effective

immunosuprresants by inhibiting proliferation
of activated T cells by interfering with the
synthesis of IL-2 and its signaling
 Cyclosporin
Cyclosporin is a lipophilic cyclic polypeptide
consisting 11 amino acids, is produced by soil
fungus

It preferentially affects the cell mediated

immunity rather than humoral immunity

Calcneurin in the presence of Ca2+ activates

NF-AT which involves in the synthesis of Ils
Cyclosporin binds and forms a complex with
cyclophyllin (an immunophyllin)
This complex binds with calcineurin and
inhibits its phosphatase activity
Inhibition of calcineurin activity prvrnt thr
movement of NF-AT into the neucleus and
interferes with the synthesis of IL-2, resulting
in inhibition of cytokine-driven activation and
proliferation of activated T cells
Cyclosporine also increases expression of TGF-
-2 stimulated T-cell
proliferation and generation of cytotoxic T
cells
 Antigen presenting cell Cell mediated
immune response
Signal 1 Signal 2
IL-2 receptor

IL-2
Tacrolimus Cyclosporine T Cell
receptor CD28
Ca2+ Signal 3
Inactive NFATc P
Cyclophilin +
IL-2 mTOR
Calcineurin P
Sirolimus
Active NFATc
FK-binding
proteins(FKBP)
CYTOPLASM
Active NFATc G0
M
NUCLEUS IL-2 gene G2 G1
S
IL-2 mRNA
IL-2 mRNA
Cell cycle
Pharmacokinetics
Cyclosporin can be administered intravenously or
orally
Drug is primarily metabolized by CYP450 3A
enzyme system.
Thus, has the propensity for drug interaction with
enzyme inducers and inhibitors.
Metabolites are excreted primarily via bile in the
faeces
Dosing is guided by signs of rejection renal or
other toxicity and close monitoring of blood
levels
Therapeutic uses
Organ transplantation including kidney, liver and
heart
Rheumatoid arthritis
Psoriasis
Ophthalmic preparations
Xerophthalmia
acute ocular syndrome
Endogenous Uveitis
Others: atopic dermatitis, IBD, nephrotic syndrome
Inhaled drug is being investigated in lung
transplantation
Adverse effects
Main AEs are
renal dysfunction
Hypertension
Others include
tremor
Hirsutism
Hyperlipidemia
gum hyperplasia
Hyperuricaemia which may worsens gout
Combination with glucocorticoid is
diabetogenic
 Tacrolimus
An immunosuppressive macrolide antibiotic
It is not chemically related to cyclosporin, but the
MOA are similar
Tacrolimus binds to another immunophyllin
FK binding protein (FKBP)
Like cyclosporin cyclophyllin complex tacrolimus
FKBP complex also inhibits the calcineurin
activity thereby inhibits T-cell activation
It is given orally and IV; dose is adjusted based on
plasma concentration
Like cyclosporin, it is metabolised by CYP450 in
the liver and has the risk of drug interaction
Drug and metabolites are mainly excreted in
faeces
Therapeutic Uses
Prevention of solid organ transplant rejection
Tacrolimus ointment can be used to treat
Atopic dermatitis
Psoriasis
Adverse effect
Similar to cyclosporin, but not adversely affect the
uric acid or LDL
glucose intolerance and diabetes mellitus are well-
recognized complications
Antiproliferative / antimetabolic agents
Sirolimus
Azathioprine
Mycophenolate Mofetil
Leflunomide
Thalidomide
Methotrexate*
Cytotoxic agents *
Cyclophosphamide and chlorambucil
Fingolimod
(*- will be done later with drugs used in rheumatoid arthritis and cancer
treatment)
 Sirolimus (Rapamycin)
It is a macrolyclic lactone produced by fungus
It binds with FK-BP, but does not affect the
calcineurin activity; instead the complex
inhibits a protein kinase known as mammalian
target of rapamycin (mTOR) - (see the figure above)
Which is a key enzyme in cell cycle progression
Inhibition of mTOR blocks cell cycle progression,
thus acts as an antiproliferative drug
Drug is available as oral preparation
Rapidly absorbed and metabolized by CYP450,
thus significant drug interaction can occur
Therapeutic uses
Prevention of rejection of solid organ
transplantation in combination with
glucocorticoids and calcineurin inhibitor
Incorporated in coronary stents to inhibit local cell
proliferation to reduce restenosis
Topically can be used to treat
Dermatological disorders
Uveoretinitis
AEs
Hypercholesteraemia and hypertriglyceridaemia
GI side effects
Head ache
Myelosuppression
Everolimus
Closely related to sirolimus with similar action
Main difference is the short t ½
Toxicity and interaction are similar to sirolimus
It has anticancer effect and is approved for a
variety of cancers (not for skin cancers)
Temsirolimus, another mTOR inhibitor is
specifically approved for renal cancer
 Azathioprine
It is a prodrug of 6-mercaptopurine (6-MP)
Following exposure to nucleophiles such as
glutathione, it is converted into 6-MP
6-MP further metabolized and the metabolites
inhibits de novo purine synthesis
Thereby inhibiting cell proliferation and impairs a
variety lymphocyte functions
Given orally, well absorbed; the metabolites are
mainly inactivated by XANTHINE OXIDASE and
metabolites are excreted in urine
Patients on allopurinol (a xanthine oxidase
inhibitor) requires dose reduction (up to 23%-
35% of normal dose)
Therapeutic uses
As an adjunct for prevention of organ transplant
rejection
Severe rheumatoid arthritis
AEs
Major side effect is bone marrow suppression
Others AEs includes
Increased susceptibility to infection
Hepatotoxicity
Alopecia
GI toxicity
Pancreatitis
Increased risk of neoplasm
Complete blood count and liver function must be
monitored in patients receiving azathioprine
 Mycophenolate Mofetil
It is a semisynthetic derivative of mycophenolic
acid (MPA)
It is a prodrug, rapidly converted into MPA
MPA is a selective, non-competitive reversible
inhibitor of inosine monophosphate
dehydrogenase, an important enzyme in de novo
guanine synthesis
B & T cells are HIGHLY DEPENDENT on this pathway
for cell proliferation, while other cells can utilize
salvage pathway
Thus, it selectively inhibits lymphocyte proliferation
and functions including antibody formation,
cellular adhesion and migration
Available as oral and IV preparations
Rapidly converted into MPA, which further
metabolized into inactive metabolites and
excreted mainly in urine
Therapeutic uses
Indicated for prophylaxis of transplant rejection in
combination with glucocorticoids and calcineurine
inhibitors, but NOT with azathioprine
Important AEs
GI AEs: nausea, vomiting, diarrhoea, abdominal pain
Myelosuppression
Teratogenicity (contraindicated in pregnancy)
 Leflunomide
It is a prodrug; active metabolite is an inhibitor
of pyrimidine synthesis
by inhibiting dihydro-orotate dehydrogenase
enzyme, which a mitochondrial enzyme required for
pyrimidine
thereby arrests the proliferation of activated T cells
Drug is orally active and currently drug is
approved for treatment of
RA
Psoriasis
Active metabolite, teriflunomide is approved for
relapsing-remitting multiple sclerosis
AEs
GI disturbances especially diarrhea
allergic reactions
alopecia, HT
Leukopenia
hepatotoxic and may cause fatal hepatitis in
pregnant women
Contraindications
Renal & hepatic impairment
Severe hyponatraemia
Immunodeficiency, serious infection
Pregnancy & breast feeding: 2 year gap between
stopping the drug and conception is recommended
 Thalidomide
Because of its teratogenicity SHOULD be
prescribed only by specially licensed
physicians who understand the risk of
teratogenicity
It inhibits angiogenesis and has anti-
inflammatory and immunomodulatory effects
Currently approved for the treatment of
Multiple myeloma
Erythema nodosum leprosum
 Fingolimod
Fingolimod, a new class of small molecules, S1P-
R agonists; it a prodrug
Sphingosine kinase 2 phosphorylates fingolimod; the
fingolimod-phosphate is a potent agonist at S1P-R
causes sequestration of host lymphocytes into the
lymph nodes and patches, diverting them
away from the circulation; thus, protecting lesions
and grafts from T-cell mediated attack
It is approved as a first-line therapy for multiple
sclerosis (MS)
AEs: reversible leucopenia and negative
chronotropic effect on heart
 Biological agents
Both polyclonal and monoclonal antibodies
(MABs) are being used as immunosuppressive
agents
Polyclonal antibodies
Antithymocyte antibodies
Monoclonal antibodies include
antibodies against surface proteins
anti-IL receptor antagonist
anti-TNF antibodies
 Antithymocyte antibodies
Antithymocyte immunoglobulins are purified
gamma-globulin from serum of rabbits or
horse, immunised with human lymphocytes
They are provided as sterile freeze-dried
product for IV use after reconstitution with
distilled water
They contains antibodies (Ab) against surface
antigens of human lymphocytes
They deplete circulating lymphocytes by direct
cytotoxicity and block lymphocyte function by
binding to cell surface molecules involved in
the regulation of cell function
Therapeutic uses
Acute renal transplant rejection in combination with
other immunosuppressive agents
Also can be used in acute rejection of other organ
transplants
Prophylaxis of transplant rejection
AEs
These are foreign proteins, thus can cause reaction
fever and chills with the potential for hypotension
could be minimized by premedication with corticosteroids,
paracetamol and antihistamine
Leukopenia and thrombocytopenia
Increased risk of infection and neoplasm
 Rho(D) Immunoglobulin
It contains IgG Abs against Rho(D) surface
antigen of RBC and from serum of human
donors purified
Rho(D) immunoglobulin (Ig) is administered to
prevent sensitization of Rh antigen in Rh
negative mother who is exposed to Rh (+)ve
blood at the time of
Delivery
Miscarriage
Ectopic pregnancy
Transplacental haemorrhage
If mother is sensitized, Ab against Rh antigen
can cross the placenta and cause haemolysis
in foetus- haemolytic disorder of newborn
Rho(D) Ig Ab response

get sensitized to Rh surface antigen of foetal

RBC
Drug is given within 24-72 hours after delivery
by IM route (t½ 21-29 days)
Therapeutic use: given to Rh negative mother
after
the delivery of Rh positive baby
amniocentesis, abortion or stillbirth
ectopic pregnancy
incompatible blood transfusion
AEs
Discomfort at injection site and low grade fever
Systemic reactions are rare
Myalgia, lethargy and anaphylaxis may occur
 Monoclonal antibodies
With the advent of hybridoma technology, it is
possible to produce unlimited amounts of a
single Abs of defined specificity
These monoclonal Abs have advantages over
polycolonal Abs
More specific
Chimeric or humanised Abs lack antigenicity
Prolonged half-lives
 Anti-TNF agents
TNF- is a pro inflammatory cytokine plays an
important role in macrophage activation and
eradication of intracellular bacterial and fungal
infections
It may play an important role in pathogenesis
of several immune-mediated diseases and
levated TNF- is seen in RA and Crohn disease
Anti-TNF agents are used chronic inflammatory
conditions
Infliximab
Etanecept
Adalimumab, etc.
 Infliximab
It is a human-mouse chimeric IgG1 MAB
Infliximab binds with high affinity to TNF-
prevents it from binding to its receptors
It is used in
RA in patients who do not respond to methotrexate
Drug is given as IV infusion; second and third and doses
are given at 2 and 6 weeks intervals respectively and
then at 8 weeks interval
co-prescription of methotrexate limit the development
of neutralizing antibodies
Other indications: ankylosing spondylitis (AS),
psoriasis and IBD
AEs: may cause infusion site reaction
Etanercept
Etanercept is a fusion protein that targets TNF-
contains ligand-binding portion of a human TNF-
receptor fused to the Fc portion of human IgG1
binds to TNF- its interaction with the
cell receptors
It is given as weekly subcutaneous injection
Approved for treatment of RA, polyarticular
juvenile idiopathic arthritis (children older than
4 years), AS and psoriasis
AEs: injection-site reactions is the common AE
occurs in about 1/3rd of patients
Adalimumab
It is a human IgG1, blocks TNF a from binding to
its receptor
Given as Sc. injection every other week (t ½ is 2
weeks) in combination with methotrexate
It is approve for the treatment of RA, AS & psoriasis
Newer anti-TNF-
Golimumab, human MAB given as Sc. Injection
monthly; is approved for the treatment of RA,
psoriatic arthritis, AS and ulcerative colitis
Certolizumab pegol is a humanized pegylated
antibody specific to TNF- for RA,
AS, psoriasis and Crohn disease in adults
Adverse Effects of anti-TNF agents
All anti-TNF agents increase the risk of
bacterial infections
macrophage-dependent infections
TB
Fungal and other opportunistic infections
Patents must be screened for latent or active
TB before stating anti-TNF agents
They may
increase the risk of skin cancer
exacerbate heart failure
cause alopecia, hypertrichosis and lichen planus
cause injection site reactions
 IL-1 receptor antagonists
IL-1 plays an important role in pathogenesis of
several inflammatory and autoimmune diseases
Few IL-1 receptor antagonists are approved for
clinical use
Anakinra: used fin RA, cryopyrin-associated periodic
syndromes (CAPS), neonatal-onset multisystem
inflammatory disease, systemic onset juvenile
inflammatory arthritis and severe gout
Canakinuma: used in CAPS and active systemic
juvenile idiopathic arthritis
Rilonacept is being evaluated for gout
 IL-2 receptor antagonists
Basiliximab and daclizumab are chimeric
mouse-human IgGI and humanized IgG1
respectively, that bind to IL-2 receptor
They act as IL-2 receptors antagonist by
blocking IL-2 from binding to activated
lymphocytes and causes immunosuppression
They are indicated for
prophylaxis of acute transplant rejection along
with other immunosuppressive agents
being investigated for the treatment of MS
 Other interleukin antagonists
Tocilizumab, a MAB binds with IL-6 receptor
approved for the treatment of rheumatoid
arthritis and systemic juvenile idiopathic
arthritis
Ustekinumab is a human IL-12 and IL-23
antagonist is approved for the treatment of
psoriasis and psoriatic arthritis
Secukinumab is a human anti-IL-17A
antagonist indicated for treatment of psoriasis,
psoriatic arthritis and AS
 Other immunosuppressive MABs
Abatacept
A recombinant fusion protein composed of
extracellular domain of T cells fused to human IgG Fc
portion; fusion protein blocks the activation of T cells
It is approved for patients with severe RA who have
failed other DMARDS
Omalizumab
An anti-IgE recombinant humanized MAB blocks the
binding of IgE to mast cells and basophils and
suppresses the type I allergic reaction
Approved for treatment of allergic asthma in adults
and adolescents who are refractory to inhaled
steroids
 Antitumor MABs
Some examples for antitumor MABs
Alemtuzumab: targeted against CD52 on normal
and malignant B and T lymphocytes
Bevacizumab: MAB against VEGF, thereby
inhibits angiogenesis in tumor
Rituximab: chimeric murine-human MAB binds
with CD20 on normal and malignant B
lymphocytes; used in lymphomas and also
approved for the use in RA and SLE
Transtuzumab: recombinant MAB binds with
HER/neu; used to treat HER-positive breast
cancer
MABs used to deliver isotopes & toxins to tumors
Ado-transtuzumab emtansine: transtuzumab is
linked to cytotoxic agent, mertansine; used to
treat HER-positive breast cancer previously
treateted with transtuzumab and taxanes
Arcitumomab: labeled with technetium 99m;
used for imaging in metastatic colorectal
carcinoma (immunoscintigraphy)
Ibritumomab tiuxetan: anti-CD20 murine MAB,
labeled with isotropic yttium or indium;
radiating isotope coupled to Ab provides
antitumor activity; used in non-
lymphomas
 Glucocorticoids
The immunosuppressive effect of cortisol is
widely applied in clinical practice
Glucocorticoids produce immunosuppressive
effects mainly by anti-inflammatory effects on
cellular immunity with relatively little effect on
humoral immunity
In the nucleolus by regulation of transcription of
genes thereby
Inhibit activation of NF- B
suppress formation of pro-inflammatory cytokines IL-2
and TNF- , thereby inhibit the proliferation of T-cells
In the circulation reduce the number of circulating
lymphocytes, eosinophils and monocytes
 Glucocorticoids are used in wide range of
conditions for their immunosuppressive and
ant-inflammatory properties s
Allergic reactions
asthma
Iodiopathic thrombocytopenic puprpura (ITP)
Immunosuppressive therapy for solid organ and
haemopoietic stem cell transplant patients

(Detail pharmacology, therapeutic applications and

adverse effect of corticosteroids will be discussed in
term 9)
 Clinical applications of immunosuppressive agents
Disease Immunosuppressive agents
Autoimmune diseases
ITP Prednisone, vincristine, occasionally
cyclophosphamide, mercaptopurine, or
azathioprine; commonly high dose gamma
globulin, plasma immunoadsorption or plasma
exchange
Autoimmune Prednisone, cyclophosphamide, chlorambucil,
hemolytic anemia mercaptopurine, azathioprine, high-dose
gamma globulin
Acute Prednisone, mercaptopurine,
glomerulonephritis cyclophosphamide
Autoreactive tissue Prednisone, cyclophosphamide, methotrexate,
disorders interferon- and azathioprine, cyclosporine,
infliximab, etanercept, adalimumab
Disease Immunosuppressive agents
Isoimmune disease
Hemolytic disease Rho(D) immune globulin
of newborn
Organ transplantation
Renal Cyclosporine, azathioprine, prednisone, ALG, OKT3,
tacrolimus, basiliximab, declizumab, sirolimus
Heart Cyclosporine, azathioprine, prednisone, ALG, OKT3,
tacrolimus, basiliximab, declizumab, sirolimus
Liver Cyclosporine, cyclophosphamide, prednisone,
methotrexate, ALG
Bone marrow Cyclosporine, cyclophosphamide, prednisone,
methotrexate, ALG
Prevention of cell proliferation
Coronary stents Sirolimus (impregnated stent)
IMMUNOSTIMULANTS
Few immunostimulatory drugs have been
developed for the use in
Infections
Immunodeficiency
Cancer
Problems with the immuno stimulants are
Systemic effects
Limited efficacy
 BCG Vaccine
It is a live attenuated vaccine for TB
By unclear mechanisms it is active against
tumors; indicated for
treatment and prophylaxis of cancer in situ of
urinary bladder as a bladder instillation
Prophylaxis for recurrent after treansurethiral
resection
AE
Hyper sensitivity reactions
Shock
Chill, fever, malaise
Immune complex disease
 Recombinant Cytokines
Interferons (alpha, beta and gamma) initially
identified for their antiviral activity, also have
immune modulatory activities by binding to
specific cell surface receptors
Induction of certain enzymes
Inhibition of cell proliferation
Augmentation of immune activities
Increased phagocytosis by macrophages
Augmentation of specific cytotoxicity by T cells
With the advent of genetic engineering,
recombinant interferons are produced for clinical
use
Interferon 2b
Recombinant 2b is obtained from E.coli
It is indicated in
variety of tumors: hairy cell leukaemia, malignant
melanoma, follicular lymphoma and AIDS related
sarcoma
infectious diseases
Chronic hepatitis B
Condylomata acuminata
Combination with ribovirin for treatment of chronic
hepatitis C
Adverse effects
Flue like symptoms
CVS: hypotension, arrhythmia, cardiomyopathy, MI
CNS effects: depression, confusion are less frequent
Inteferon Ia
It has antiviral and immunomodulatory
properties
Inteferon Ia is used in relapsing-remitting MS
AE
Flue like symptoms
Injection site reactions
Interferon -IB
It activates phagocytes and is indicated to reduce
the frequency and severity of serious infections
associated with chronic granulomatous disease
AEs: Fever, headache, rash fatigue, myalgia, GI
symptoms, weight loss and depression
Interleukin-2
Human recombinant IL-2, aldesleukin is
produced by recombinant DNA technology from
E.Coli; IL-2
enhances lymphocyte proliferation and growth of IL-2
dependent cell-lines and lymphocytes mediated
cytotoxicity and killer cell activity
induces interferon activity
It is indicated in adults with metastatic renal cell
carcinoma and melanoma
AEs
Drug is associated with severe CVS toxicity due to
capillary leak syndrome
Increased risk of disseminated infection due to
impaired neutrophil function
IMMUNIZATION
Immunization enhances or reinforces
immunological defense against foreign
substances
Immunization can be
Active
Passive
ACTIVE immunization involves stimulation
immune system with an antigen to develop
immunological defense against future exposure
PASSIVE immunization involves administration of
antisera or Abs to an individual who is already
exposed or is about to be exposed to an antigen
that can be inactivated by antisera or Ab
 Vaccines
Vaccines are antigenic substances used to induce
production of specific Ab by host (ACTIVE
immunization)
Vaccine can be
Killed organisms
Live attenuated organisms
Specific protein or peptide constituent of an organism
Toxoids
Bacterial polysaccharide: Meningococcal polysaccharide
vaccine, Pneumococcal vaccine, Typhoid Vi polysaccharide
vaccine
Booster are often given especially for killed
vaccines
Vaccines are primarily used to prevent infections
Combined vaccines
Combined vaccine provide protection against 2
or more diseases such as
Double antigen: DT (diphtheria and tetanus)
Triple antigen
DPT: diphtheria, pertussis, tetanus
Measles, mumps, rubella (MMR)
Pentavalent vaccine (diphtheria, pertussis, tetanus,
and hepatitis B and Haemophilus influenzae type b)
Toxoids
Toxoids are modified bacterial exotoxins that
lack toxicity while retain their antigenicity
Tetanus (fluid/adsorbed)
Diphtheria (adsorbed)
Adverse effect following immunization
(AEFI)
Any untoward medical occurrence which
follows immunization and which does not
necessarily have a causal relationship with the
use of vaccine
The AEs may be any unfavourable or
unintended sign, an abnormal laboratory
finding, a symptom or disease
(WHO)
 Vaccine vial monitor
A vaccine vial monitor (VVM)is a label
containing a heat sensitive material which
isplaced on a vaccine vial to register
cumulative heat exposure over time
Cumulative heat exposure over time cause the
inner square of the VVM darken gradually and
irreversibly
VVM
Reduces wastage
Ensure that children receive the good vaccine
(WHO)
 Passive immunization
It involves administration of preformed
antibodies as antisera or immunoglobulins
who is exposed to or about to be exposed to
the antigen
Indicated in
Congenital or acquired inmmunodeficiency state
Individual with high risk exposed to an antigen
Inadequate time for active immunization (e.g.
rabies)
Antisera are purified and concentrated
preparations of serum of horses that are
actively immunized;
Tetanus
Gas gangrene
Antirabies
Antisnake venom
Igs are separated from human gamma
globulins which carry Abs;
Nonspecific
Specific or hyperimmune
Nonspecific Igs
They contain largely IgG
Indicated in
Ab-deficiency disorders
Infections
Hepatitis A
Measles
Immunological diseases
Thrombocytopenic purpura
GB
 Hyperimmune IGs are derived from donor sera
with high titers of desired Ab and more
efficacious than corresponding antisera
Anthrax immune globulin
Botulism immune globulin
Cytomegalovirus immune globulin
Hepatitis B immune globulin,
Rho(D) immune globulin
Varicella zoster immune globulin
(For further information on immunization refer the learning
materials provided by Departments of Community and Family
Medicine, Microbiology and Paediatrics)
Intravenous immunoglobulin (IVIG)
It consists of IV polyclonal human Igs
No specific antigen is targeted
Indicated for
Replacement therapy for agammaglobimaemia and
immunodeficiency
Bacterial and viral infections
Autoimmune and inflammatory disorders
Thrombocytopenic purpura

Autoimmune skin, neuromuscular and neurological

diseases
END OF THE LESSON