IMMUNITY

&
VACCINATION
 IMMUNE SYSTEM

• The immune system has evolved to protect the host from pathogens
while minimizing damage to self tissue.
• The immune system not only protects against infection, but also
influences healing and governs the responses that can lead to
autoimmune diseases.
• Immune defenses are normally categorized into the innate immune
response, which provides immediate protection against an invading
pathogen, and the adaptive or acquired immune response, which
takes more time to develop but confers exquisite specificity and long-
lasting protection
 The innate immune system

• Innate defences against infection include anatomical barriers, phagocytic

cells, soluble molecules, such as complement and acute phase proteins,
and natural killer cells.

• The innate immune system recognizes generic microbial structures present

on non-mammalian tissue and can be mobilized within minutes.
 Constitutive barriers to infection
• The tightly packed, highly keratinized cells of the skin constantly undergo
renewal and replacement, which physically limits colonization by
microorganisms.

• Microbial growth is inhibited by physiological factors, such as low pH and low

oxygen tension, and sebaceous glands secrete hydrophobic oils that further
repel water and microorganisms.

• Sweat also contains lysozyme, an enzyme that destroys the structural integrity
of bacterial cell walls; ammonia, which has antibacterial properties; and several
antimicrobial peptides such as defensins.

• Similarly, the mucous membranes of the respiratory, gastrointestinal and

genitourinary tract provide a constitutive barrier to infection. Secreted mucus
acts as a physical barrier to trap invading pathogens.
• Within the respiratory tract, cilia directly trap pathogens and contribute to
removal of mucus, assisted by physical maneuvers, such as sneezing and
coughing.

• In the gastrointestinal tract, hydrochloric acid and salivary amylase

chemically destroy bacteria, while normal peristalsis and induced vomiting
or diarrhea assist clearance of invading organisms.
 Phagocytes
• Phagocytes (‘eating cells’) are specialized cells which ingest and kill microorganisms,
scavenge cellular and infectious debris, and produce inflammatory molecules which
regulate other components of the immune system.

• They include neutrophils, monocytes and macrophages, and are particularly important
for defences against bacterial and fungal infections.

• While phagocytes can recognise microorganisms through pattern recognition

receptors alone, engulfment of microorganisms is greatly enhanced by opsonisation.

• Opsonins include acute phase proteins such as C-reactive protein (CRP), antibodies
and complement.

• They bind both to the pathogen and to phagocyte receptors, acting as a bridge
between the two to facilitate phagocytosis
Neutrophils

• Neutrophils, also known as polymorphonuclear leucocytes, are

derived from the bone marrow.

• They are short-lived cells with a half-life of 6 hours in the blood

stream, and are produced at the rate of approximately cells daily.

• Their functions are to kill microorganisms directly, facilitate the rapid

transit of cells through tissues, and non-specifically amplify the
immune response.
 Monocytes and macrophages
• Monocytes are the precursors of tissue macrophages. They are produced in
the bone marrow and constitute about 5% of leucocytes in the circulation.
• From the blood stream, they migrate to peripheral tissues, where they
differentiate into tissue macrophages and reside for long periods.
• Specialized populations of tissue macrophages include Kupffer cells in the
liver, alveolar macrophages in the lung, mesangial cells in the kidney, and
microglial cells in the brain.
• Macrophages are capable of phagocytosis and killing of microorganisms but
also play an important role in the amplification and regulation of the
inflammatory response.
• They are particularly important in tissue surveillance, monitoring their
immediate surroundings for signs of tissue damage or invading organisms.
Cytokines

• Cytokines are small soluble proteins that act as multipurpose chemical

messengers.

• They are produced by cells involved in immune responses

• any of a number of substances, such as interferon, interleukin, and growth

factors, which are secreted by certain cells of the immune system and have
an effect on other cells.
•Functions of macrophages
• Initiation and amplification of the inflammatory response
• Stimulation of the acute phase response
• Activation of vascular endothelium
• Stimulation of neutrophil maturation and chemotaxis
• Stimulation of monocyte chemotaxis
• Killing of microorganisms
• Phagocytosis
• Microbial killing through oxidative and non-oxidative mechanisms
• Clearance, resolution and repair
• Scavenging of necrotic and apoptotic cells
• Clearance of toxins and other inorganic debris
• Wound healing and scar formation (interleukin (IL)-1, platelet-derived growth
factor, fibroblast growth factor)
COMPLEMENT SYSTEM
• The complement system is a group of more than 20 tightly regulated,
functionally linked proteins that act to promote inflammation and
eliminate invading pathogens.

• Complement proteins are produced in the liver and are present in the
circulation as inactive molecules. When triggered, they enzymatically
activate other proteins in a rapidly amplified biological cascade
analogous to the coagulation cascade
• Mast cells and basophils

• Mast cells and basophils are bone marrow-derived cells which play a central role in
allergic disorders.

• Mast cells reside predominantly in tissues exposed to the external environment, such as
the skin and gut,
• while basophils are located in the circulation and are recruited into tissues in response
to inflammation.

• Mast cells and basophils express IgE receptors on their cell surface.

• On encounter with specific antigen, the cell is triggered to release preformed mediators
and synthesis additional mediators, including leukotrienes, prostaglandins and cytokines.

• These trigger an inflammatory cascade which increases local blood flow and vascular
permeability, stimulates smooth muscle contraction, and increases secretion at mucosal
surfaces.
• Natural killer cells

• Natural killer (NK) cells are large granular lymphocytes which play a
major role in defense against tumors and viruses.

• NK cells express a variety of cell surface receptors. Some recognise

stress signals, while others recognise the absence of human leucocyte
antigen (HLA) molecules on cell surfaces

• NK cells can also be activated by binding of antigen–antibody

complexes to surface receptors.
 Humoral immunity
• B lymphocytes

• These specialised cells arise in the bone marrow.

• Mature B lymphocytes (also known as B cells) are found in bone marrow,

lymphoid tissue, spleen and, to a lesser extent, the blood stream.

• Encounters with antigen usually occur within lymph nodes,

• These cells differentiate into either long lived memory cells, which reside
in the lymph nodes, or plasma cells, which produce antibody.
• Immunoglobulins
• Immunoglobulins (Ig) are soluble proteins made up of two heavy and
two light chains.

• The heavy chain determines the antibody class or isotype, i.e. IgG,
IgA, IgM, IgE or IgD.

• When a previously unstimulated B lymphocyte is activated by antigen,

the first antibody to be produced is IgM, which appears in the serum
after 5–10 days.

• Depending on additional stimuli provided by T lymphocytes, other

antibody classes (IgG, IgA and IgE) are produced 1–2 weeks later.
• IgG
• Distributed equally between blood and extracellular fluid, and transported
across placenta
• IgG2 is the predominant antibody produced against polysaccharides

• IgA
• Highly effective at neutralizing toxins
• Particularly important at mucosal surfaces

• IgM
• Highly effective at agglutinating pathogens

• IgE
• Mostly bound to mast cells, basophils and eosinophils
• Important in allergic disease and defences against parasite infection
Cellular immunity
• T lymphocytes (also known as T cells) mediate cellular immunity and
are important for defense against viruses, fungi and intracellular
bacteria
 Active immunity

• Active immunity (the power to resist infections on your own) develops from
• 1. A clinical infection (as in measles)
• 2. A subclinical infection
• 3. Vaccination.

• The first time an antigen is encountered in life, the immune system of the
individual spends sometime figuring what it is up against, and then mounts a
feeble immune response by producing a small titer of predominantly IgM
antibodies. This is primary response which lasts only as long the antigen
lasts in blood
• However, the second time that particular antigen is encountered, the
immune system recognizes it instantly (due to immune memory, a
property of cell mediated immunity) and produces a plethora of
predominantly IgG antibodies for a much longer period, which is
known as secondary response. This is what give the individual
immunity to a previously exposed agent
Passive immunity
• Passive immunity (lending somebody else's antibodies) is acquired by:
• 1. Passive immunization (injection of ready made antibodies).
• 2. Maternal IgG transfer through placenta, which persists in child up
to 6 months.
• 3. Maternal IgA transfer through milk.
• Passive immunity is
• 1. Rapid
• 2. Temporary
• 3. Bereft (lack) of immune memory
• 4. Expensive (vaccines are cheaper than antibodies).
Herd immunity
• It is the level of resistance of a community to a disease.
• It is built up by
• 1. Clinical/ subclinical infections
• 2. Immunization of individuals
• 3. Herd structure (hosts, vectors, reservoirs, environment).
• When swine influenza first hit the world, it spread like wildfire. With time
however, as our herd immunity has grown, it is turning more and more
benign.

• Before the advent of sanitary latrines, we used to have herd immunity

against poliomyelitis, as most kids acquired a subclinical infection during
childhood which gave immunity. However, with sanitary systems taking
over, most kids are nowadays protected from the virus, and when they
encounter it, they often develop clinical disease.
 Vaccines
• Vaccines are antigens to induce specific active immunity against a
disease.

• Live attenuated vaccines

Live attenuated vaccines (LAV) are prepared by attenuation of live
organisms by heat, subculture (BCG, OPV, MMR).
Live vaccines are more potent because the organisms multiply in body,
express all the antigens of that particular organism and often leave a
residual immunity after they have been excreted by the body (i.e.
mucosa immunity provided by oral polio vaccine).
• ALL LIVE VACCINES ARE CONTRAINDICATED IN IMMUNODEFICIENT AND
PREGNANCY.
• Also, there must remain a gap of AT LEAST 3 WEEKS between
administering a live vaccine and any other vaccine.
CONT…
• Live vaccines are single dose (except polio, which is given thrice
because seroconversion occurs one strain at a time). Because live
vaccines contain living organisms, they require a stringent cold chain.
• Killed vaccines
Killed vaccines: Organisms killed by heat/chemical methods
(typhoid, pertussis, HAV, influenza, cholera, plague) may also induce
active immunity, because they still retain the antigens.

Killed vaccines are:

• Safer than live vaccines (the organisms are already dead)
• Less potent
• Require booster doses
• Cannot be given orally (they'll be readily digested by enzymes).
• Subunit vaccines
Subunit vaccines/cellular fractions/toxoids are particular
proteins from the agent which, after detoxication, may be used for
immunization (HBsAg, meningococcal cell wall antigen, Haemophilus
influenzae B capsule, diphtheria and tetanus toxoids).

• Adjuvants
• An adjuvant is a compound that are added to potentate a vaccine
(they produce a local granuloma to retain the antigen and decelerate
its release) i.e. aluminium phosphate, aluminium hydroxide, water in
oil.
Freeze dried vaccines

• Freeze drying (also known as lyophilization or cryodesiccation) is a

dehydration process typically used to preserve a perishable material
or make the material more convenient for transport.
• Freeze-drying works by freezing the material and then reducing the
surrounding pressure and adding enough heat to allow the frozen
water in the material to sublime directly from the solid phase to the
gas phase.
• Freeze dried vaccines (BCG, measles, yellow fever) are powdered
vaccines prepared in such a way as to increase shelf life of vaccine.
They are reconstituted in a suitable liquid (BCG in saline, Measles in
double filtered pyrogen free water.
Immunoglobulins
• Normal human Ig
• They are antibody rich plasma fractions obtained from a pool of at least
100 donors.
• Such ‘passive immunization’ has been devised for measles (for highly
susceptible individuals) and HAV (for travelers).
• Because normal human Ig contains many other antibodies other than the
one wanted, live vaccines given within 12 weeks of normal human Ig will
get inactivated by those immunoglobulins. On the contrary, normal human
Ig may be given after 2 weeks of a live vaccine.
• Specific human Ig
• It is made from plasma of single convalescents patients, and contains
antibodies at least in fi ve fold concentration. Such Ig’s have been devised
for chickenpox, rabies, HAV, HBV, rubella, tetanus, Rh-isoimmunization.
They are more specific, concentrated for intramuscular use and do not
interfere with live vaccines.
• Specific human Ig
• It is made from plasma of single convalescents patients, and contains antibodies at least in
five fold concentration. Such Ig’s have been devised for chickenpox, rabies, HAV, HBV,
rubella, tetanus, Rh-isoimmunization.
• They are more specific, concentrated for intramuscular use and do not interfere with live
vaccines.
• Adverse reactions to immunoglobulins
• 1. Local—Pain and sterile abscess.
• 2. Systemic—Flushing, flank pain, rigor, dyspnea, shock, urticaria, arthralgia, fever, diarrhea.
• The ‘ cold chain’
• It is the combination of machines, personnel and procedure responsible for storing vaccines
at recommended temperature (0–8°C) from production to use.
• Arranging the vaccines by heat sensitivity, we have OPV > Measles > Pertussis and mumps >
Hepatitis B > DPT > DT > BCG > DPT > TT.
• The T series vaccines and hepatitis B vaccine are also ‘freeze sensitive’ and should never be
exposed to subzero temperatures.
• What to do with vials that have been opened but not used?

• In 1995, WHO recommended a changed global policy on the use of opened vials
of vaccine as follows.
• 1. Opened vials of OPV, DPT, DT, TT and hepatitis B vaccines may be used in
subsequent immunization sessions until a new shipment of vaccine arrives,
provided that each of the following 3 conditions are met
• • The expiry date has not passed
• • The vaccines are stored under appropriate conditions (0 to +8°C)
• • Opened vials of vaccine which have been taken out of the health facility for
immunization activities (e.g. outreach, National Immunization Days) are discarded
at the end of the day.
• 2. Opened vials of measles, yellow fever and BCG vaccines must be discarded
within six hours.
• 3. An opened vial must be discarded immediately if sterile procedures have not
been fully observed, or there is even a suspicion that the opened vial has been
contaminated, or there is visible evidence of contamination, such as a change in
appearance, floating particles
 Cold chain Equipments
• Walk in cold rooms. A cold room where people walk in and get the vaccine

• Deep freezers. Deep freezers create sub zero temperatures. They are suitable
• 1. to store for vaccines > 3 months
• 2. to make ice packs which are used in vaccine carriers.
• The deep freezer should be placed in a well ventilated room at least 10–20 cm from
the wall, and should not tilt on any side (should be perfectly horizontal).
• The power switch should be TAPED in the on position so that nobody can turn them
off accidentally.
• Its temperature should be recorded every morning and evening. The lid of the deep
freezer should be LOCKED when not in use.
• The device should be cleaned when ice has grown 4–6 mm thick over the inner walls
• After defrosting, clean the freezer and make it dry before loading vaccines again.
• Cold boxes. Cold boxes, packed with ice packs, are used for regional
transportation of vaccines.
• Vaccine carriers. These are packed with 4 fully frozen ice packs on the
day of vaccination.
• They can maintain the vaccine for 48 hours in 2–8° if not opened
• Ice packs. They are filled with salt free water (salt reduces freezing
point of water) up to a preset mark (if we fill up to the brink, water
will expand when frozen and crack the pack) and frozen in a deep
freezer.
• In all these devices, the T series vaccine and hepatitis vaccine should
never be placed in direct contact with ice.
Vaccine vial monitor
• It is a heat sensitive label to monitor cumulative heat exposure. It consists of round
piece of blue material inside which lies a heat sensitive square of lighter hue. The
square changes to darker shades with
• 1. high temperature, short exposure or 2. lower temperature, long exposure or 3.
high temperature, long exposure
• The vaccine is usable only until the inner square is lighter than the outer circle.
• DT and TT vaccine shipping indicators
• This is another type of indicator, which travels with the vaccines from manufacturer
to central store and is included with each 3,000 doses of DT, DPT and TT procured
through UNICEF. This indicator has a temperature sensitive dot that irreversibly
change from silver-gray to black at temperatures above +48°C, temperatures which
may be reached if vaccines are left in the sun or in poorly ventilated places.
• The shake test
• Before administering a T series vaccine, it is a must to shake it and see a uniform
mixture; any granules indicate freezing at some point of time, and the vial is
discarded.
• WHO recommendation on vaccine storage temperatures
• To summarize, if you work,
• At the national level. Keep your vaccines for a maximum of 6 months
• • Store OPV, measles, and mumps vaccines at –15 to –25°C
• • Store hepatitis B, DPT, DT, TT and BCG at 0 to +8°C
• • Send vaccines to regions in insulated containers at 0 to +8°
• At the regional level. Keep your vaccines for a maximum of 3 months
• • Store OPV, measles, and mumps vaccines at –15 to –25°
• • Store hepatitis B, DPT, DT, TT and BCG at 0 to +8°
• • Send vaccines to districts in insulated containers at 0 to +8°
• At the district level. Keep your vaccines for a maximum of 1 month,
• • Store OPV, measles, and mumps vaccines at –15 to –25°C, if possible
• • Store hepatitis B, DPT, DT, TT and BCG at 0 to +8°C
• • Send vaccines to health facilities in insulated containers at 0 to +8°C
• At the health facility level. Keep all your vaccines for a maximum of 1 month:
• Store all vaccines at 0 to +8°C.
• A fully immunized child
• 1. has completed primary doses before 1 year
• 2. has taken vaccines at least at 4 weeks interval
• 3. has taken no vaccine before time
THANK YOU