Download UNIT 7: Immunology and Vaccinology

UNIT 7: Immunology and Vaccinology
Terminologies:
Antigen: an antigen is a substance that elicits a specific immune response when
introduced into the tissue of an animal. The response may consist of antibody
production, cell-mediated immunity, or immunologic tolerance.
Haptens: a hapten is a simple chemical or a portion of an antigen that cannot induce
in immune response, but can react demonstrably and specifically with an appropriate
antibody or cell.
Antibodies: an antibody is a modified blood globulin which is fored in response to an
antigenic stimulus. It is capable of combining specifically with the corresponding
antigen.
What is immunity?
Immunity is the resistance of animals to disease causing organisms. It is made
possible by the ability of the immune system to recognize foreign agents or tissues
and eliminate them. On encountering the same foreign agent again, the immune
system eliminates it more rapidly and effectively.
There are different types of immunity.
Active immunity develops in response to direct exposure to an infectious agent. This
can occur naturally by exposure (natural immunity) or artificially by the process of
vaccination (vaccine- induced immunity).
Passive immunity is the temporary immunity conferred on an animal when it receives
antibodies from another animal. In nature this occurs when new born animals absorb
antibodies from the colostrums of the mother. These antibodies are taken up into the
blood stream and are in the circulation for a few months. This gives the young animal
time to develop its own active immunity. In the case of some diseases the presence of
passive antibodies can suppress the formation of active immunity and this must be
taken into consideration when vaccinating young animals. Passive immunity can be
given artificially in the form of antisera or feeding colostrums to a new born animal.
The immune system:
The immune system is made up of specific types of cells which are found in various
organs.
Organs of immune system
The organ called thymus regulates the production and maturation of the lymphoid
cells which are produced in the bone marrow. The lymphoid cells circulate via the
lymphatic system to the spleen and the lymphnodes where they filter out any invading
organisms.
The immune cells
The immune or lymphoid cells are found in the circulation as well as in the organs
discussed above. They form the component in the blood known as the white blood
cells. The white blood cells consist of a number of different types of cells:
Neutrophils (pus cells): they move to the site where micro organisms invade the body,
engulf and destroy them with digestive enzymes. The neutrophils die in the process
and do not play any role in the memory of the immune system.
Macrophages: these are amoeba- like cells which take up micro organisms and break
them into small parts which they then “offer” to other white blood cells called
lymphocytes.
Lymphocytes: they respond to the fragments offered to them by macrophages. There
are two types, B lymphocytes and T lymphocytes.
Macrophages and lymphocytes are the cells which are involved in the process of
recognizing and remembering specific organisms.
The immune process
How does the immune process take place? It is a complex process but can be
simplified by distinguishing two different types of reaction, although both may occur
in response to a particular disease.
Let us look at the sequence of events if we inject bacteria under the skin of an animal.
1. Neutrophils and macrophages migrate to the site of injection, and engulf bacteria.
The bacteria taken up by bacteria are killed. The macrophages are carried to the
nearest lymph node where they break down the bacteria in to smaller particles and
then exhibit these on their cell surface.
2. Lymphocytes in the lymph node respond to these particles or antigens which are
offered. They can respond in two different ways.
3. Lymphocyte response: if T- lymphocytes respond to the antigen presented they
activate other lymphocytes called “killer cells “or cytotoxic lymphocytes which
kill the invading micro organisms by direct contact. This is called cellular
immunity. If B lymphocytes respond, they stimulate the production of antibody
from a set of lymphocytes called plasma cells. This is called humoral or antibodymediated immunity.
What is antibody and how does it work?
Antibodies are protein molecules which are arranged in a Y-shape. At the tip of each
branch of Y are sites which are able to recognise and attach to antigens or parts of
infectious agents. Antibody fights infections by binding to an infectious organism and
therefore immobilising it. This allows it to be caught and processed by macrophages.
Specific antibodies are produced for specific disease-causing organisms.
The memory of immune system
Animals become immune to disease causing organisms after an initial encounter
because their immune system has a “memory”.
The “memory” is in fact a set of lymphocytes which recognises a disease-causing
organism that has been encountered before. These memory cells may remain in an
animal’s body for the rest of its life.
Primary immune response
On exposure to a disease-causing organism for the first time, antibody or cellular
response is stimulated. The response gradually decreases with time.
Secondary immune response
When the animal is exposed to the same organism for a second time, the antibody or
cellular response that is activated is greater and more rapid because of the memory of
the immune system.
Primary and secondary antibody response can be demonstrated for both antibody and
cellular immunity.
Antibody-mediated immunity: with the first exposure to an antigen the antibody
response is slow and relatively weak while the second exposure is rapid and strong.
Cellular immunity: this can be demonstrated by tissue transplants. A skin graft from
mouse A to mouse B. Mouse B will be rejected eventually because the cells of its
immune system recognise that the tissue is foreign. If the transplant is repeated, the
rejection process will take place rapidly, as the immune system of mouse B has
“remembered the transplant from A.
Vaccinology
A vaccine is a preparation containing an infectious agent which when administered to
an animal will produce resistance to that specific agent. The animal is protected on a
subsequent exposure to the same organism. There are various types of vaccines.
1. Live vaccine: live vaccine usually contain a live micro organism which has been
weakened (attenuated) in some way, or a naturally occurring avirulent strain. Most
live vaccines are in a freeze-dried form. Freeze-dried vaccine is presented in the
form of a compact, dry pellet which must be mixed with sterile water before it can
be injected. In this form the micro organisms in the vaccine can be successfully
stored provided the vaccine is kept in a refrigerator and is not exposed to direct
sunlight.
2. Inactivated vaccines: there are three types of inactivated or non-living vaccines.
a. Killed vaccines: this is a vaccine made of micro organisms that have been
killed using chemicals or heat. Killed bacterial vaccines are sometimes
referred to as bacterins.
b. Toxoids: these are toxins made of bacterial toxins which have been
rendered non-toxic by chemical treatment.
c. Subunit vaccines: subunit vaccines contain only certain parts or structures
of a micro organism.
Inactivated vaccines are usually less effective inducers of immune response than live
vaccines and so they have chemicals added to them which improve the immune
reaction. These chemicals are called adjuvants. The adjuvants may be mineral oils or
potassium or aluminium salts. In some adjuvanted vaccines that have been standing
for a while sediment may settle out to the bottom of the vaccine bottle. Vaccines
containing adjuvants must be shaken well before use to mix all the components.
Vaccine and cold chain maintenance
The ‘cold chain’ is the system of transporting and storing vaccines within the
temperature range of 35°F (2°C) to 45°F (8°C). The cold chain begins when vaccine
is manufactured, moves through to the Dzongkhags distribution center and ends with
the local immunization provider at the time of administration.
Vaccine procurement and storage
Vaccines after production or import are stored in cold chain at a temperature range of
2-8ºC. All the vaccines are initially stored at the central store at Serbithang. The
vaccines are then distributed to different Dzongkhags according to the demand. The
Dzongkhag in turn distribute to Livestock Extension Centres (LECs) for vaccination.
During all this period from the manufacture to vaccination, cold chain has to be
maintained.
Essential equipment required to keep vaccines cold are:
1. refrigerator for storage,
2. Cold box for transport, ice packs to keep cool and separator for vaccine and ice
pack.
Placing vaccine in refrigerator
 Freezer sensitive vaccine in middle shelf.
 Diluents and emergency drugs in lower shelf
 Vaccine should be kept in refrigerator until just before administration.
 The vaccine should return into fridge after each dose.
Cold chain Management
Anyone handling vaccines is responsible for their potency, at each step in transport,
storage and administration of vaccines. Vaccines are delicate biological substances
that can become less effective or destroyed if they are:





Frozen
Allowed to get too hot
Exposed to direct sunlight or fluorescent light
Vaccines should be maintained within the recommended temperature range of
35°F (2°C) to 45°F (8°C). The loss of vaccine effectiveness is cumulative and
cannot be reversed.
Equipment for Transporting and Storing Vaccines
The essential cold chain equipment needed to transport and store vaccines within a
consistent safe temperature range include:
 A refrigerator for storing vaccines
 cold boxes for transporting and storing vaccines
 Ice packs to keep vaccines cool
 Material to separate ice packs from the vaccines when using cold boxes (e.g.
shredded paper, cardboard, bubble wrap or Styrofoam).
Refrigerators and Freezers
It is recommended that one refrigerator should be dedicated to store vaccines.
At least 50% of the space needs to be filled at all times to allow for adequate
circulation of cold air, and to stabilize the refrigerator temperature. [Vaccines should
be maintained with the recommended temperature range of 35°F (2°C) to 45°F (8°C)].
Maintenance of the vaccine refrigerator
Safe vaccines storage is possible with refrigerators if the following procedures or
modifications are carried out. Report breakdowns immediately so that repairs can be
made. Regularly check refrigerator seals to ensure cold air cannot leak out. If they are
brittle or torn arrange for replacement. Defrost refrigerators are required to prevent ice
build up which reduces efficiency. Ensure the area around (including behind and
under) the refrigerator is clean and dust free. Arrange for regular maintenance
inspections by the manufacturer or technician. Inspections may need to be more
frequent as the refrigerator ages.
Defrosting or Cleaning
When defrosting or cleaning the refrigerator, move the vaccines to second
refrigerator. This temporary storage refrigerator must also be monitored to ensure the
correct temperature 35°F (2°C) to 45°F (8°C) is maintained. If you don't have a
storage refrigerator, store the vaccines in a pre-cooler insulted container with
icepacks. Continue to monitor the temperature inside the container until the normal
vaccine refrigerator is ready for use again.
Power Failures
During a power failure of 4 hours or less, the refrigerator door should be kept closed.
If the power failure continues for more than 4 hours, store vaccines in an insulted
container containing ice packs. If power failures are a common occurrence vaccines
could be transferred to another site with power.
Maintaining and Monitoring Refrigerator Temperatures
The thermometer needs to measure the refrigerator temperature close to the vaccine
vials.
Choosing a thermometer to monitor the vaccine refrigerator:
Digital-type thermometers or mercury minimum-maximum thermometers are the
reliable and easiest to read.
Ordering Vaccines
Keep vaccine stock to a minimum by regularly ordering only the quantity of Vaccine
required for the period until the next scheduled delivery. At least 14-day supply of
vaccine should be avialable in the refrigerator when you are re-ordering. Storing
excess vaccines supplies in the refrigerator can increase the risk of wastage from
vaccines.
Equipment for Transporting Vaccines
A number of issues should be considered when choosing equipment to transport
vaccines. They should include:
Space required for the amount of vaccine transported
Number of icepacks needed to keep the vaccines at less than 50°F
The length of time in transit
How the cold box will be handled
Criteria for selecting a cold Box
It needs to be large enough to store vaccines and icepacks during transport
External surface material needs to be durable and robust
Lid needs to be tight fitting
Strong handles for carrying the cold box
Icepacks, Freezer Blocks, Ice Blocks
Icepacks are used to cool insulated containers or cold boxes. Icepacks are flat plastic
containers that are filled with water and frozen. Some commercial icepacks contain a
chemical product that ensures the icepack remains colder than 23°F (0°) longer than
water-filled icepacks.
Unpacking Vaccines after Transport
Unpack vaccines from the transport container and store them in their packaging
regardless of their bulkiness. Removing vaccines from the original packaging exposes
vaccines to room temperature and light. Check the temperature to ensure the vaccines
have not been exposed to temperatures above 35°F or below 32°F.
Placing Vaccines in Refrigerator
All freezer sensitive vaccines should be stored on the middle shelves Diluents and
emergency drugs can be stored on the lower shelves Vaccines should remain in the
refrigerator until immediately before they are administered. They should be returned
to the refrigerator immediately after drawing up each recommended dose.
Vaccine break downs
Some times in the field the disease outbreak occur soon after the vaccination and the
farmers lose faith in extension worker. Such a condition is called vaccine break down
but the cause could be many for example: break in cold chain, mishandling like
exposure to heat or light, some time due to the expiry of vaccine if not checked
properly at the time of procurement.
NOTE: Take all precaution to keep vaccine at a required temperature for better
protection of animal health.
How to use a vaccine
Vaccines may be available from different manufacturers for the same disease and the
directions for use of a specific vaccine must always be followed carefully. As the
directions for using a vaccine are changed from time to time vaccines should never be
purchased without the package inserts which contain the directions for use. It is
essential to read the package inserts with regard to the following important
information:
1. Storage: the vaccine must be stored at the recommended temperature. With the
exception of heart water and frozen red water vaccines, which are kept frozen on
dry ice or in liquid nitrogen, all other vaccines should not be frozen and are
usually stored at temperature range of 2-8º C. Freezing and thawing destroys
certain components in vaccines and therefore a vaccine which has been
accidentally frozen must be discarded. Fridges used for vaccine storage should be
checked regularly for efficient functioning. Maximum-minimum thermometers or
commercially available colour indicators can be used for this.
2. Dose: the dose recommended by the manufacturer has been determined by
extensive and expensive research. Reducing the dose to save vaccine will result in
toxic or allergic reactions.
3. Route: the route by which the vaccine is administered is very important and use of
the wrong route of vaccination may cause problems.
4. Age: the recommended age of vaccination is usually based on the age at which the
animal is exposed to or becomes susceptible to that particular disease.
5. Season: some diseases are seasonal and vaccination must be carried out before the
exposure period in order to be effective. Time must therefore be allowed for an
immune response to develop. It must be borne in mind that for some diseases
(e.g., blue tongue in sheep) a number of vaccinations must be given before the
animal is fully immune and sufficient time must be allowed for this.
Precautions when using vaccines:
1. Needle and syringe hygiene: needles and syringes used for vaccination must be
sterile. During outbreaks of disease a single needle must be used for each animal.
Using unsterilised needles and syringes can cause abscesses or generalised
infections. Syringes must be set aside for administering Brucella abortus vaccine
and only used for this purpose.
2. Exposure of vaccine to sunlight: the ultraviolet rays of the sun are damaging to all
infectious agents and it is therefore essential that live vaccines are kept out of
direct sunlight. All vaccines are degraded by heating and care must be taken to
keep vaccines cool during transport and use in the field. A cool bag containing
cool packs should be used for this purpose.
3. Mixing vaccines: different vaccines should not be mixed in the same syringe
unless the manufacturer states that this can be done. Vaccines must also not be
mixed in syringes with any other injectable preparations (vitamins, antibiotics,
dewormers, etc) as chemicals contained in the latter may damage the vaccine
components.
4. Vaccinating during outbreaks: vaccinating during outbreak is fraught with
problems and should be avoided by implementing a well-planned vaccination
program. Apart from the fact that animals may already be incubating disease when
they are vaccinated, immunity takes time to develop and animals may sometimes
be infected before they can develop immunity. Another consideration is that
diseases can be transmitted from animals incubating disease to healthy stock, by
inoculation needles. Needle transmission can occur with the following diseases:
lumpy skin disease, anthrax, black quarter, anaplasmosis, etc. It is essential a use a
separate needle for each animal during outbreaks of these diseases.
Vaccine failure
Vaccinating an animal does not necessarily protect it against disease. There are many
reasons why a vaccine may fail to give protection and they can be divided into
problems arising from:
1. the VACCINE itself
2. the ADMINISTRATION of the vaccine
3. the ANIMAL being inoculated
1. The Vaccine
a. Damage to vaccines: damage caused to a vaccine by exposing to heat, direct
sunlight, freezing or storage at room temperature for too long a time will result
in a failure of effective immunization.
b. Expired vaccines: Expired vaccines should never be used.
c. Wrong vaccine used due to wrong diagnosis: vaccines are often used without a
specific diagnosis being made. This usually happens when a vaccine is used
based on the occurrence of one single symptom.
d. Serotypes or strains not included in the vaccines: some micro organisms have
more than one type of the same organism. These different types are called
SEROTYPES. In some cases the different serotypes do not cross-protect
against each other and if a certain serotype is not included in a vaccine there
will be no protection.
e. Sub-standard vaccine: a poor quality vaccine may have been issued from the
manufacturer and if after eliminating all the other reasons for vaccine failure,
this is suspected, the company in question should be contacted.
2. Administration of vaccine
a. Antibiotics and live bacterial vaccines: live bacterial vaccines like anthrax,
salmonella, brucella must not be used simultaneously with antibiotics because
the bacteria will be killed off and no immune response will be produced.
b. Transmission of disease during vaccination: some diseases can be transmitted
during vaccination.
c. Vaccinating at the wrong age: in many cases there is an optimal age for
vaccination. Examples are pulpy kidney vaccine which does not stimulate
immunity before two months of age in lambs, and Rev. I vaccine used to
prevent brucellosis in rams does not give good protection if it is given after
weaning age.
d. Vaccinating too late: vaccinating animals during an outbreak will result in
animals becoming infected before immunity can develop.
e. Vaccinating during disease incubation: animals may sometimes be incubating
a disease at the time of vaccination, and it may appear that the vaccine has
failed to protect or that the vaccine itself has caused the disease.
f. Failure to give boosters: booster vaccinations for killed vaccines are essential
for the development of good immunity. The manufacturer will recommend
when the booster must be given.
g. Poor management: vaccines designed to prevent diseases of new born animals
are given to the mothers to raise the antibody level of the colostrums or the
“first milk”. If the new born animal does not receive colostrums for any
reason, the vaccine will not prevent disease.
h. The interaction of vaccines: live vaccines may interfere with each other, and
more than one live vaccine should not be administered at the same time unless
this is recommended by the manufacturer.
i. Wrong dose: too little vaccine may be given deliberately to save vaccine or by
accident if an automatic syringe is not calibrated correctly or is sticking, or if a
freeze-dried vaccine is diluted too much. Administering insufficient vaccine
will almost certainly result in poor immunity, or occasionally “sensitization”
which results in exacerbation of disease.
3. The animal being vaccinated
a. Animals in poor health: animals in poor health condition because of starvation,
vitamin or mineral deficiencies, heavy parasite infestations or chronic diseases
will not respond well to vaccination.
b. Passive immunity: the antibodies in the colostrums of a mother are transferred
to the new born animal and provide what is called PASSIVE or maternal
immunity. This protection declines after a few months. The young animal
must then develop its own active immunity. If certain vaccines are given to a
very young animal, the presence of passive immunity will prevent the
development of ACTIVE immunity. Therefore if a mother has been vaccinated
with vaccine A and the passive immunity is to last for 3 months, the best time
to vaccinate the young animal against A is roughly at 3 months of age.
c. Exposure to severe challenge: the vaccine immunity can be neutralized or
overwhelmed if there is massive exposure to an infectious agent.
d. Population response: in a population of animals, the ability to develop an
immune response follows follows a normal response curve. This means that
most of the individuals in a population have the ability to to develop adequate
immunity, while a small percentage develops poor immunity. Therefore in any
population not all animals will be solidly immune.
THE SIDE EFFECTS OF VACCINATION
Manufacturers of vaccines are required to do extensive safety testing before a product
can be sold for use in the field. In most cases vaccination is therefore an uneventful
procedure but some side effects can occur even with highly purified products. Some
of the side effects that can occur are discussed below.
1. allergic reactions: allergic reactions can be either immediate “shock” type
reactions or local reactions at the site of injection
2. Local non-allergic reactions: some vaccines contain substances (adjuvants) which
are included to improve the immune response. The adjuvants may produce
irritation and swelling at the site of injection which takes a few days to develop
and a few weeks to subside. This type of reaction when it occurs will be seen in a
large proportion of the vaccinated animals.
3. Other post-vaccination problems: other adverse responses to vaccination (e.g.,
abortion, drop in milk production, etc) can occur with certain vaccines.
4. Accidental injection of humans: this should be avoided because although most
veterinary vaccines are harmless to humans many can cause severe swelling and
pain at the site of injection.
Vaccination Schedule for Livestock
Vaccine
Species
Dosage
Route
Primary
Booster
Anthrax Spore
vaccine
(Locally
produced)
Cattle
buffalo
& yak.
Sheep,
goat &
pig
Cattle
buffalo
& yak.
Sheep,
goat &
pig
1 ml
s/c
3
months
Not
required
Revaccinatio
n
Annually in
March/ April
s/c
3
months
Not
required
Annually in
March/ April
Every 6
months in
April/may &
Aug/Sept.
Every 6
months
Black Quarter
Vaccine
(locally
produced)
0.5 ml
5 ml
2 ml
Haemorrhagic
septicaemia
(locally
produced)
FMD tri-valent
oil-adjuvant
Vaccine
(importedIndia)
Cattle &
buffalo
4 ml
s/c
3
months
6 months
Cattle
buffalo
& yak.
Sheep,
goat &
pig
2 ml
I/m
3-4
months
1 month
Neonatal
enterotoxicosis
vaccine
(Imported-UK)
Pigs
2 ml
i/m
Gilts &
sows
5-6
weeks
Every 6
months
Antirabies
vaccine
(importedIindia &
France)
Dogs &
cats
1 ml
s/c or
i/m
1 month
1 month
Classical
swine fever
vaccine
(locally
produced)
E.coli (oral )
Vaccine
(locally
produced)
Newcastle
Disease
thermostable
I2 vaccine
(locally
produced)
Pigs
1 ml
s/c
45-60
days
Not
required
Annually in
endemic
areas & once
in 2 years in
non-endemic
areas.
Annually
200 ml
mixed
with 1.5
kg feed.
1 drop
Orally
75 days
of
gestation
-
-
Eye
drop
All ages
3 months
Every 3
months
Pigs
(pregna
nt sows)
Poultry
1 ml
2
months
Remarks
Vaccination not required if there
has been no outbreak in a
particular area for three years
after the last outbreak.
Vaccinate animals upto 3 years of
age. In endemic areas healthy
adults may be vaccinated.
Primary vaccination should be
done when the calf reaches 3
months of age & not wait for
annual vaccination programme.
Vaccination to be carried out in
the risk areas only & prior to the
on set of monsoon and migration.
High risk & medium areas- twice
a year vaccination.
Low risk areas- annually.
In pigs, breeding stock should be
revaccinated at 6 months interval.
Vaccinated at least 21 days
before migration.
All the breeding stock present in
the farm may be vaccinated at the
same time. Avoid vaccination of
sows during two weeks prior to
farrowing.
-
May produce hypersensititve
reaction in animals.
Adrenaline/antihistamine should
be given immediately in such
reactions.
The vaccine should be given for 3
consecutive days starting from 75
days of gestation.
If primary vaccination is given
via drinking water, booster dose
should be given after 3 weeks and
then re-vaccination to be done
every after 3 months. Throough
eye-drop, onl;y re-vaccination to
be done every 3 months.
Poultry Vaccination Schedule in the Organised Farms
Age
Vaccine
Route
Dose
Remarks
Day 1
Mareks Disease
s/c
Life-long immunity
Day 3
IBD Intermediate Strain (first
dose)
Newcastle Disease B1 strain
Eye drop
0.2 ml /chick or as per
manufacturer’s instruction
0.03 ml or as per
manufacturer’s instruction
0.03 ml or as per
manufacturer’s instruction
Day 14
IBD intermediate strain
(2nd dose)
Day 28 or
30
IBD intermediate strain
(3rd dose)
Day 42
Fowl pox
Eye drop
or
drinking
water
Eye drop
or
drinking
water
i/m
Day 56
ND R2B strain (booster)
s/c or I/m
Day 98
Fowl pox (repeat)
i/m
Day 120
ND R2B strain
s/c or i/m
Day 7
Eye drop
0.03 ml or as per
manufacturer’s instruction
0.03 ml or as per
manufacturer’s instruction
0.02 ml or as per
manufacturer’s instruction
0.05 ml or as per
manufacturer’s instruction
0.02 ml or as per
manufacturer’s instruction
0.05 ml or as per
manufacturer’s instruction
In case the locally produced
I-2 ND vaccine is used it
has to be repeated every 3
months@ 1 drop eye drop