CHILDHOOD IMMUNIZATION

I. INTRODUCTION
Immunization is one of the most cost effective health interventions
known to mankind. It is also true that immunization is the most successful,
single, child survival strategy. Immunization schedules are the basic framework
for the delivery of vaccines to individuals as well as the community as whole.
Prevention of disease is one of the most important goals in childcare. During
infancy and childhood, preventive measures against certain infectious diseases
are available. One of the most dramatic advances in pediatrics has been the
decline of infectious diseases during 20thcentury because of the widespread use
of immunization for preventable diseases. Immunization recommendation
changes because of advances in the field of immunology. 80% of the infants and
children are now immunized and preventing the spread of infectious diseases.
Before any immunizations are undertaken the parents should be questioned
regarding present and past immunization status and past responses of
immunizations. The parents should be fully informed concerning the reasons for
immunizations. They should also be informed of possible side effects and
adverse reactions. A record of immunization should be kept by the health
professionals as well as the parents for future reference.

II. DEFINITIONS
a) Immunity: Immunity is the function of the body that provides
protection against infectious diseases.
- SURJITH SINGH
b) Immunization: Immunization is a process whereby a person is
made immune or resistant to an infectious disease, typically by
the administration of a vaccine.
- WHO
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a c) Vaccine: Vaccines are immuno- biological substances which
produce specific protection against a given disease by
stimulates active production of protective antibody and other
immune mechanisms.

PATHOPHYSIOLOGY OF IMMUNIZATION

IMMUNITY
-MANOJ YADAV

c) Vaccination: The procedure for giving the vaccine to a person

called vaccination.

-Jacob and Singh

Immunity is the function of the body that provides protection against

infectious diseases. The cells and molecules responsible for providing
immunity comprise the immune system. This system plays an
important role in autoimmune diseases and helps to fight against
malignancy. There are two types of immunity they are innate and
acquired immunity.
 1. TYPES OF IMMUNITY

Basic defence mechanisms are of two types: non-specific (innate) and specific
(adaptive). Both are equally important for the survival of the human being. Both
are interdependent in the ultimate goal of getting rid of what is ‘foreign’.

 Innate immunity (Non-specific Immunity)

It is also known as innate or non-adaptive immunity. It is present in every

normal individual since birth and does not need prior exposure to the organism
nor is it specific against an individual organism. This is the oldest type of
immunity in evolution which helps the body control invading organism before
specific immune response is mounted and also helps the specific immune
response to augment its efficacy by acting as the final effector pathway. The
innate immunity occurs with in a short period when a person exposed to any
type of infection. It includes natural mechanical barriers such as skin
integument and mucosal linings, chemical barriers such as gastric acidity and
gut enzymes classical and alternate pathways of compliment systems, cytokines,
chemokines and interferon α, β, and γ, and the cells like macrophages,
neutrophils, dendritic cells, natural killer cells. The complement system is again
divided into two pathways, the classical and the alternate path way both acting
through a cascade of more than 19 proteins. Complements help in initiating the
inflammation and in sustaining the specific immune response and ultimate
killing of the organism.

 Acquired immunity (Specific Immunity)

It can be divided into natural versus acquired, passive versus active and humoral
versus cellular. This occurs in the transplacental transfer of immunoglobulin
which offers protection to the newborn for a temporary period of time, it is not
fully active at birth and develops gradually after birth on repeated exposure to
the microbes in the surroundings. The most important cells of this arm include
the B lymphocytes, T lymphocytes, and their various subsets. On activation by
an antigen, the B cells proliferate and get converted to plasma cells, which, in
turn, produce antibodies. For effective production of antibodies B cells needs
the T cells which produced in the liver in fetal life and mature in bone marrows
in the humans. Besides its role as helper cells to induce better antibody
production by the B cells, the T cells are the most important cytotoxic cells ,
which helps in preventing invasion by and clearing of intracellular pathogens.
HUMORAL IMMUNE RESPONSE

The antibodies consist of heavy chains and light chains. There are two types of
light chains, lambda and kappa chains; whereas, there are five different types of
heavy chains which identify the five types of immunoglobulins; lgG, lgM, IgA,
IgD and IgE. In this lgG, lgM, and IgA are protective against pathogens. The
IgE type may play a role against parasites and is also involved in allergies.

The B cells have immunoglobulin surface receptor, which binds with the
appropriate antigen present on the infective pathogen. The antigen and the
receptor complex are internalized and the antigen is processed within the cell.

During acute infection, IgM antibodies appear within few days and the presence
of IgM indicates recent infection. The lgM response is usually seen in Primary
response, is short lived and the titers of the antibodies are lower. The IgG
response usually picks up along with the IgM or after a few days and lasts for a
very long time. The IgA response depends upon the route and the type of
infection. Serum IgA is seen in organisms that invade from mucosa; whereas
surface IgA is classically seen with localized mucosal infections such as in
cholera.

CELL-MEDIATED IMMUNITY

This type of immunity is transferable by the lymphocytes and not antibodies and
is mediated via T cells. They are called T cells as they mature in the cells.
Though called cell mediated immunity, it often involves the role of soluble
chemicals called cytokines, which are secreted and react upon T cells
themselves besides the B cells and macrophages.

The T cell lymphocyte is a very important cell in the immune response. It has T
cell receptor (TCR) with α and β chains, which binds with the antigen processed
and expressed on the antigen-presenting cell along with the MHC class I or II
antigens. It also has receptors for co-stimulatory factor and for the various
cytokines and chemokines released in the surrounding. It has many subsets,
which carry out different functions. These cells are in circulation and in the
lymphatic vessels. There are two essential types of T cells depending on the CD
molecules expressed on the surface of the T cell, CD4+T and CDS+ T cells. The
CD4+ T cells react cells MHC II on the APC, while CD8+ T cells react with the
MHC I. The CD4+ T cells are called T helper cells and CDS+ T cells are also
called cytotoxic T cells.
The CD4+ T cells are of two subtypes: Thl and Th2 cells. The Th2 cell response
is the major factor for the stimulation of B cells, and for the switch in the
production from IgM to other immuno-globulins, which occurs in role presence
of IL4. The Toi cells are responsible for the delayed hypersensitivity reaction
and occur in the presence of interleukin-12 (IL-12) and IL-18. Besides this, the
types of cytokines produced by Th1 and Th2 cells are also different. The CDB+
T cells recognize and target the infected cells in the body and hence, are called
cytotoxic T lymphocytes. This was first demonstrated with virus-infected cells
and later on with cells infected with bacteria as well as parasites.

PASSIVE IMMUNITY

Passive immunity is specific immunity which, is transferred passively to the

recipient. It gives readymade immunoglobulins, which help fight infection
immediately. However, it is for a temporary period and it wanes after a few
weeks to a few months depending upon the half-life of the transferred
immunoglobulins. Besides the natural transplacental passive transfer of the
immunoglobulins in the newborn, the other examples of the passive immunity
are infusing immunoglobulins in the person to protect him for a specific disease.

 Transplacental Passive Immunity

Immunoglobulins are transferred predominantly in the last trimester and are

mainly of IgG type. This means that at birth, the child will have similar type of
antibody pattern as the mother. This protects the child for the first few months
till the time that he develops his own immunity after repeated exposure to
various antigens after birth. The half-life and hence the protection offered will
depend on the half-life of the specific antibody, e.g. the antibody against
poliomyelitis does not protect for more than 4-6 weeks ( the time of starting the
polio vaccination in the baby), whereas the anti-measles antibody protects the
child till 6-9 months (the reason for delaying the measles vaccine till 9 months).
Not only does the passive immunity protect the newborn/infant against the
specific diseases, it also interferes with the immune response to the concerned
vaccine if given in the presence of maternal antibody
  Acquired passive immunity

Immunoglobulins can be passively transferred by giving immunoglobulin

preparation intramuscularly or intravenously. There are three types of
preparations,

1. Pooled human immunoglobulin preparation

2. Homologous humen hyperimmune globulin preparation
3. Heterologous human hyperimmune globulin preparation

1. Pooled Human lmmunoglobulins

This is prepared by Pooled Plasma from more than 100 healthy donors and
fractionation of this plasma to produce the final product, which is available as
intramuscular (IM) preparation as well as intravenous (IV) preparation. It is
used in many autoimmune disorders and passive prophylaxis for measles or
hepatitis A infection.

2. Homologous human hyperimmune Globulins

This is obtained by pooling plasma from specific donors who have high titers of
a specific antibody either due to repeated past natural exposure or due to
vaccination. This preparation serves to protect against a specific disease.

3. Heterologous Human Hyperimmune Globulins

It is obtained from animals mainly horse or rabbit who are hyperimmunized by

repeated vaccination against the concerned disease and then collecting plasma
which is fractionated to obtain pure product. Being an animal product it can lead
to severe allergic reactions including anaphylaxis, anaphylactoid reactions or
serum sickness.

ACTIVE IMMUNITY

Active immunity is developed by stimulating the immune system by antigens,

which can lead to specific humoral or cellular immune response or both. It can
happen in two ways, either by exposure to the wild pathogen naturally where
the immunity develops after the person suffers from the disease which has
chances of morbidity and even mortality or by exposure to the antigens given as
vaccines where the person has less morbidity and the person becomes immune
without much suffering. Not all natural diseases lead to protective immunity; in
naturally occurring tetanus or typhoid, repeated clinical courses are known
unless vaccination is done. However, most of the time natural disease leads to
strong protective immunity, which probably lasts lifelong, e.g. in measles or
varicella. Vaccination, on the other hand, is introduction of antigens with the
purpose of inducing immune response without leading to clinical diseases.

V. VACCINES

Vaccines can be live or inactivated and both can be bacterial or viral.

Live vaccines are attenuated live organisms, which have immunogenicity
without pathogenicity, Inactivated vaccines can kill the whole organism or a
fraction of it. Fractional vaccine also includes toxoids (Diphtheria or tetanus
toxoids) and subunit vaccine such as hepatitis B vaccine. They also include
proteins or polysaccharides, which again can be unconjugated (Vi typhoid
vaccine) or conjugated (Hib vaccine).

 Live Vaccines

These are pathogens, which are modified in such a way that they lose their
pathogenicity without altering their immunogenicity. Most live vaccines are
viral vaccines such as measles, MMR [( measles, mumps, and rubella ( German
measles)], varicella, and oral polio vaccine (OPV). Some bacterial vaccines too
are live vaccines such as Baccilus Calmette-Guerin (BCG) and oral Ty2Ia
typhoid vaccine. The pathogen is attenuated by serial passage of the wild type in
tissue cultures or animals. The live vaccine multiplies inside the body after
administration and stimulates the immune system. Injectable live vaccines thus
need only one dose for development of long-term immunity, e.g. measles or
MMR vaccine. The immunity is maintained subsequently, probably, by
subclinical infections. However, when such vaccine is used universally, it will
reduce or abolish the natural transmission leading to less chance of repeated
subclinical exposures. This may lead to waning immunity after many years and
may need artificial boosting, e.g. MMR where we now know that 2 dose are
required to maintain long-term protection. Live vaccines given orally such as
OPV or Ty2la typhoid vaccines need multiple doses to induce lasting immunity.
Another problem with live vaccines is side effects such as vaccine-induced
disease, e.g. OPV-induced paralysis, which occurs due to reversal of the
attenuated strain back to a virulent strains. Lastly, live vaccines are
contraindicated in immune compromised individuals as the organism can
replicate in such cases leading to disease. Attenuated and genetically modified
viruses are used as vectors to introduce other antigens.

 Inactivated vaccines (Killed vaccines)

Inactivated vaccines are either kill the whole organisms such as whole cell
typhoid vaccine or pertussis vaccine, or a fraction of it such as in acellular
pertussis vaccine, toxoids such as tetanus toxoid, subunit vaccine, e.g. surface
antigen of hepatitis B or polysaccharide such tetanus toxoid, subunit vaccine,
e.g. surface antigen of hepatitis B or polysaccharide such as pneumococcal
vaccine. As the vaccine does not replicate in the body, it does not lead to
clinical disease and is safe even in immune compromised host. 7 1he immune
response is not disturbed by the presence of previous antibodies; hence, these
vaccines can be started early in life, e.g. diphtheria, pertusis, and tetanus (DPT)
vaccination. The first dose usually does not lead to protection and only primes

The immune system subsequent doses lead to primary immune response, which
protects the individual for a short time. Subsequent repetition of doses leads to
boosting effect and long-term immunity. Hence, these vaccines need multiple
primary and booster dose.

1. BCG VACCINATION

History

Robert Koch discovered the tubercle bacillus.

1908-1921: The French scientists, Calmette and Guerin, began attenuating a

virulent strain of M. Bovis with a view to develop a vaccine against TB. After
231 subcultures over a period of 13 years, they were able to evolve a strain
known thereafter as ‘Bacillus Calmette-Guerin’ tor BCG). This strain was non-
virulent for humans but retained its capacity to induce an immune response.

1924: The bacillus was declared incapable of 14-reverting to virulent form by

Calmette.

1927: First human BCG vaccination.

1928: BCG strains were declared to be harmless to animals and man by the
League of Nations.
 1929-1930: The Lubeck tragedy- 72 children died from oral BCG preparation
contaminated with a virulent strain.

1939: Multiple puncture technique was developed.

1947: Scarification technique was developed

1948: Recognition of value of BCG came in 1948 when tuberculosis workers

from all over the world accepted it as a safe preventive measure. BCG
vaccination program in was started in 1948 in Madanpalle (Tamil Nadu) and in
the same year the BCG vaccine Laboratory was established in Madras Chennai).

1948-1974: WHO and UNICEF campaigns l. 5 billion vaccinations carried out

1948-1997: Yearly increase in BCG vaccination estimated approximately to be

50-100 million.

Types of vaccine

Liquid (fresh) vaccine and the freeze- dried vaccine are the two types of BCG
vaccine. Freeze-dried preparation is relatively a more stable preparation with
vastly superior keeping qualities. The present-day vaccines are distributed in
freeze-dried forms. The bacilli used for the vaccine production are derived from
the original Calmette strain of BCG.

Storage

This vaccine remains potent for 2 years, if store at -20°C. Undiluted vaccine
when stored at 2-4°C retains its potency for up to 6 months. When stored at 4-
8°C, it should be used within a week. Strict maintenance of cold chain is
essential. It should be wrapped in black paper/ cloth and supplied in dark
colored ampoules.

Reconstitution

Ampoules of freeze-dried vaccine are sealed under vacuum. They must be

opened carefully by gradually filling at the junction of the neck and the body of
the ampoule so that air does not rush in to cause spillage. Normal Saline is the
recommended diluents, as distilled water may cause irritation. The diluents can
be stored at room temperature, but it should be cooled immediately before use.
The reconstituted vaccine should be used within 4 hours. During this time, it
should be protected from light and heat. The left over products after a given
immunization session must be discarded.

Dosage

• O. l mg in 0.1 ml. Dose remains same for all ages. The currently available
BCG vaccine brand is prepared by Serum Institute of India

Age of vaccination

BCG vaccination should be administered at birth or soon thereafter.

Prevention of disease

Immunity against tuberculosis is mediated through complex cellular mechanism

in which macrophages and T lymphocytes have predominant role. Tuberculin
reactivity cannot be passively transmitted by injecting serum having antibodies
but by injecting cells from an immunized animal. BCG has a protective effect
against the severe forms of disease such as meningeal, military and
disseminated tuberculosis.

Administration

It should be injected intradermally using a ‘Tuberculin’ syringe. The syringe

and needle technique remains the most precise way of administering the desired
dose. It should be administered just above the insertion of deltoid muscle. If it is
injected too high, too anterior or too posterior, the chances of development of an
ipsilateral axillary lymphadenopathy are said to increase. A satisfactory
injection should produce a wheal 5 mm in diameter. Care must be taken to
avoid contamination with an antiseptic or detergent. Cleaning with sterile water
is enough. If alcohol swab is used to clean the skin, it must be allowed to
evaporate before the vaccine is administered.

Phenomena Seen after BCG Vaccination

Day 0: AboutS-8 mm of wheal develop over the site of injection, which gets
absorbed in 20-30 minutes; rubbing/hot fomentation at the injection site should
be avoided

2-3weeks: A papule develops at the site of vaccination

3-6 weeks: Papule increases slowly in size to reach a diameter of 4-8 mm

6-12 weeks: Papule subsides; a shallow ulcer may develop which may be
covered with a crust. This will heal within 6-12 weeks and will leave behind a
small scar, approximately 5 mm in diameter. Tuberculin positivity usually
develops within 6-8 weeks.

Complications with lntradermal BCG

Local and localized: swelling, pain at site, ulcer, abscess, regional

lymphadenitis, (non-sappuratiee and suppurative) and osteomyelitis.

Regional: Mesenteric adenitis, otitis, distant abscesses, hepatosplenomegaly

Disseminated: Distinctly unusual and is usually associated with severe

depression of cell-mediated immunity.

Post-BCG syndrome: Local chronic cutaneous lesions (e.g. keloids), acute

cutaneous eruption (e.g.erythema nodosum) and ocular lesions. BCG
lymphadenitis is the most common complication of BCG vaccination, occurring
in 0.1-4% of the vaccinated children.

Contraindications to BCG Vaccination

BCG should not be given in the following conditions

 Severe combined immunodeficiency

 Patients on prolonged immunosuppressant
 HIV-infected patients who are symptomatic or if CD41 is less than 25%

PENTAVALENT VACCINE

It is a 5 in 1 combination vaccine which includes diphtheria, pertussis, tetanus,

hepatitis B vaccine and hemophilus influenza B vaccine.

Diphtheria