Innate (or natural) immunity: Non
specific defenses or barriers to infection
which are (in healthy people) always
Adaptive (or acquired) immunity: A
response that is directed toward a specific
pathogen and develops over time and has
“memory” (reactivity changes with repeated
Innate Immunity Components
o Barriers to infection e.g. skin
o Flushing mechanisms e.g. coughing,
Chemical responses e.g. lysozyme in
Cellular e.g. phagocytic cells (able to
engulf and ingest material)
Chemical – the humoral immune
response using antibodies
Cell mediated cells that are directed
by the immune response to attack an
o A series of molecules present in
serum, which interact with the
bacterial cell membranes and with
each other so that at completion they
punch a hole in the bacterial
o It is composed of a series of
reactions, which act as a cascade
with the product of one active on the
next in the chain.
o The products amplify the reaction,
increase permeability of blood
vessels and also act to attract cells to
the site of the reaction. The products
make the target more attractive to
phagocytosis by immune cells
o It can be activated by interaction of
one of the initial components with
bacterial cell surface substances
(“Lectin pathway”), bacterial
products (the “Alternative
pathway”), or by antibodies that have
bound to antigens (the “Classical
o There is a “recognition unit”, made
up of some of the initial components.
o The final product is the “membrane
Acute Phase Reactants
Substances that rapidly increase in
quantity in the body at the onset of
infection. An example is C reactive
protein. These may have antibacterial
properties or be involved in
sequestration of essential nutrients.
These are substances (IFN-,-,-) that
are produced by virally infected cells
which bind to receptors on other cells
and prompt them to produce antiviral
PMN, monocytes, macrophages, are part
of the innate system but have a role in
activating the specific system and when
activated become part of the specific
Cells found in the tissues that contain
granules that are rich in histamine and
inflammatory mediators. These are
released on stimulation by complement
products and IgE, promoting local
Antigens: molecules which stimulate an
Some antigens can only be
recognized after having been
processed by T cells.
“haptens” are substances which are
too small by themselves to elicit an
immune response but maydo so
when bound to a larger molecule.
Epitope: the molecular structure on an
antigen that the antibody interacts with.
An antigen may have many epitopes.
proteins produced by the body that bind
each molecule is “Y” shaped and has
two variable regions that bind to
antigens, and a “constant” (“Fc”) end
that binds to the host‟s receptors
Antigens may be on the surface of
organisms , they may be substances
in the serum, including toxins, or
viruses. An antibody may or may
not be able to neutralize the toxin or
Normally a mixture of antibodies of
a class is produced to different
epitopes of the antigen. This is a
A preparation of pure antibodies of a
single type, all directed at the same
epitope can be made; these are
The strength of the binding between
an antibody and an antigen is called
the affinity. It often increases with
second or more exposures to an
different types (“classes”) are
produced that have different
properties. These are IgM, IgG, IgA,
and the less plentiful IgE and IgD.
o This is the first antibody produced in
response to a first infection
o It occurs as 5 units that are attached,
and so is a big molecule that does not
get into tissue from blood or cross
o Complement binds to it very well
o IgG is the most plentiful
o It is produced after IgM in infection,
a process called class switching,
where the IgG antibody produced by
a cell has the same specificity for an
antigen as the IgM it replaces.
o It is produced predominately when
exposure to the agent occurs in a
second infection (boosting response).
o Its production is controlled by T
o It binds to complement (“fixes
complement”), attracts phagocytes,
and opsonizes well. It penetrates
tissue and crosses the placenta.
o Occurs as single or paired molecules
o Secretory IgA is found in secretions
(e.g. tears, saliva, respiratory
o Its production is controlled by T
o Activities are anti parasitic and
involved in hypersensitivity
o Found as a receptor on B cells cell
(neutrophils, PMN) white blood cells
able to phagocytose invaders. They are
the most common WBC, and are short
lived. They circulate in blood and enter
the tissues, gathering at the site of
infection. Pus is largely made up of
Eosinophils are white blood cells
(WBC) that are anti-parasitic. They
contain granules that stain red with the
dye eosin. They may also be increased
in hypersensitivity states (e.g.asthma).
Basophils are cells that are involved in
Mononuclear phagocytic system
o Monocytes are WBC that circulate
until stimulated to differentiate into
macrophages or one of a family of
phagocytic cells (dendritic cells)
found in various organs throughout
o Macrophages are larger and longe
lived than PMN and are found in the
tissues. They are able to:
Present the antigens to T
lymphocytes for development of
“Call for help” by secreting
Dendritic cells are phagocytic cells
descended from monocytes or the
lymphocyte cell lines, which are like
They are widely distributed in tissues
in an immature form
They are very good at presenting
antigen to T lymphocytes.
The immature form phagocytoses
antigen and then becomes mature,
stops its phagocytosis and goes to the
lymph node to deliver the antigen to
the T cells.
B Cells Differentiate in Bone
marrow in mammals.
Give rise to plasma cells, which are
antibody “factories” or to memory
cells, which circulate and are primed
to produce a specific antibody if they
come into contact with the
During development B cells are
produced that each recognizes a
specific antigen. There are so many
B cells, that a wide range of antigens
can be recognized.
When an antigen binds to
antibody on the surface of the
B cell, it stimulates the cell to
divide and to increase in
number (“clonal expansion”).
With clonal expansion,
mutations occur in the genes
controlling the antibody
region that binds to the
The antibodies produced vary
in their ability to bind and
those B cells that produce the
antibody that binds best are
stimulated to increase.
This causes the B cells that
best recognize an antigen to
increase in response to it, and
to improve the specificity of
the antibody produced.
T cells Develop in the
They control the immune
response by producing cytokines
They are able to directly kill
foreign tissue cells, virally
infected cells, or tumour cells.
They activate phagocytic cells to
destoy the organisms they have
Some develop into memory cells
(as do some B lymphocytes).
Generally T cells express CD-4
or CD-8 but some which are
specialized for killing cells, NK
(Natural Killer) cells do not
There are different populations of T cells
that perform each of these functions.
CD 4 T cells, or “T helper
cells”, activate and control the
o They respond to the signals
of the cell presenting the
antigen and differentiate
either into TH1 cells that
promote a local response
with inflammation and is
good at handling
intracellular pathogens, e.g.
o or TH2 cells that promote
antibody production and
memory cells. This is a
systemic response that
happens later in the
infection than the TH1.
CD 8 cells or “suppressor T
cells” patrol looking for virally
infected cells, or tumours. When
they detect them they start to
divide and differentiate into
Cytotoxic T Lymphocytes and
are able to destroy the target
cells. CD 8 cells also can
suppress Helper T cell function
using inhibitory cytokines.
- Large granular lymphocytes
(Natural Killer cells) contain
granules of cytotoxic material,
which they use to kill virally
infected cells and tumor cells.
(These are similar but distinct from
CD-8 T cells).
o They have Fc receptors to allow
them to detect cells coated with
antibody, which they then
Communication between cells
Cytokines (most common types are
interleukins, also tumor necrosis factors etc.)
Substances produced by cells that
Bring about differentiation of
Cause activation of
phagocytic cells and
Influence cell mediated
responses and antibody
They are usually produced in
They may act on different cells
T lymphocytes are an important
o Antigens must be presented to T cells for
them to act upon them.
o An important role is played by the Major
Histocompatibility Complex Class1 and
Class II molecules (MHC I, MHC II).
o MHC I is found on all cells and is
essential for recognition of “self”. They
are used in tissue typing to determine if
transplants will be compatible (HLA
o MHC II is found on monocytes,
macrophages, B cells, dendritic cells and
phagocytic cells related to macrophages
that are found in the tissues.
o Antigen is broken down into peptides by
the initial cell prior to presentation.
o The resulting short peptides are
presented associated with the MHC
o Antigen is presented with MHC I to CD
8 T cells
o Antigen is presented with MHC II to CD
4 T cells
o T cells recognise the peptides to be viral,
or bacterial debris and become activated,
producing ctokines to begin activity in
Anatomical Organization of the
Cells important in the immune system
originate in the bone marrow and some
develop in the thymus. These are the
primary lymphoid organs.
The lymphoid cell line gives rise to
The myeloid cell line give rise to white
blood cells (including PMN and
macrophages) as well as red blood cells
These cells can be identified based on
the receptors they express on their
surface. Each receptor is referred to by a
“CD” number, e.g. CD-4 is expressed
by T helper cells, CD-8 by T suppressor
cells. There are more than 200 CD
markers, and they are used to allow us to
determine the types of cells and their
Lymphocytes are based in the
secondary lymphoid organs
Lymph nodes (“glands”)
o These become swollen when
responding to infection because of
lymphocyte proliferation within
o They are strategically placed to
screen lymph draining from the
limbs (in the groin and axillae),
mouth and pharynx (groups
distributed in the neck), the gut
(groups distributed in the
retroperitoneum), and respiratory
pasages (hilum of the lungs and
around the trachea).
o Acts as a “super” lymph node
o Screen out old or infected blood
cells, encapsulated bacteria , and
Mucosa associated lymphoid tissue
(MALT) e.g. gut associated = GALT;
bronchial associated = BALT. This
includes the peyer‟s patches in the gut,
tonsils, and appendix.
o These are rich in memory cells and
plasma cells and sample the flora and
watch for pathogens.
An Immune Response that occurs as an
exagerated or inappropriate form.
There are four mechanism which may
proceed simultaneously but which have
different time courses and effects.
Type 1 or Immediate
The cause of allergic asthma, hayfever,
eczema, peanut allergy, anaphylaxis
Person develops IgE antibodies to a
substance (Sensitization), e.g. pollen, a bee
sting or an antibiotic (mucous membrane
exposure may favour IgE production)
Subsequently, on re-exposure, antigen reacts
with IgE bound to mast cells, causing
degranulation of the mast cells and release
of vasoactive substances.
Anaphylaxis occurs when the release is
more general, and results in an increase in
smooth muscle contraction, increased
vascular permeability, and a fall in blood
pressure, and may lead to respiratory or
circulatory collapse and are life threatening.
The initial reaction occurs within an hour
but a late reaction takes place after 4-12
Type 2 or Antibody Mediated
o The cause of transfusion reactions,
haemolytic disease of the newborn, and
some automimmune disease.
o Antibodies are produced to a target which
can be foreign or from host tissue.
o Binding of the antibody causes activation
of cell mediated or complement mediated
causing destruction or damage to the
o The reaction onset is 8 hours, or chronic in
Type 3 or Immune Complex
The cause of serum sickness,
glomerulonephritis in endocarditis,
autoimmune disease like rheumatoid
A large quantity of soluble antigen in
plasma reacts with antibody and forms large
antigen-antibody complexes, overwhelming
the normal ability of red cells to take them
up for transport and removal in the liver.
These are trapped in capillaries (esp in the
kidney) and activate the complement
Basophils and platelets which all increase
vascular permeability. PMN are attracted
and are unable to phagocytose the immune
complexes and release granules of damaging
enzymes, causing local tissue damage.
The reaction may begin with 6 hours of
Type 4 or Delayed Type
o Seen in tuberculin skin tests, contact
dermatitis, granuloma formation
o Sensitization to an antigen occurs when
the antiogen is processed by a tissue
phagocytic cell and the antigen is
presented to T lymphocytes in the local
o On re-exposure, the T cells initiate a cell
mediated response using monocytes,
macrophages and lymphocytes, which
invade the area with the antigen..
o Antibodies are not involved in this
o The reaction occurs in 24-48 hours, but if
the reaction is chronic and the antigen
cannot be cleared, the area becomes
surrounded by macrophages with
lymphocytes and fibrosis occurs to form a
o Resulting from Therapy
o Cancer (especially hematological
o Infection e.g. HIV, an infection of
T cells and macrophages
o Pregnancy – mild, but sufficient to
increase the susceptibility to
malaria and TB for example.
o Neonates are relatively
immunodeficient because of
immaturity of the immune system
Deficiencies of components of the
immune system result in “gaps” in the
o May occur as a result of lack of any
of the complement components.
o Causes failure of the cascade
o Loss of early components result in
increased Staphylococcal, and
o Loss of late components results in
increased Neisseria infections
Defects in Phagocytic Cell Function
o These predispose to bacterial
o Inability to kill organisms that have
been ingested is typical of Chronic
Staphylococci and other catalase-
producing organisms tend to cause
o There are a variety of syndromes
where there is deficiency in the
lymphocyte including Subacute
Combined Immune Deficiency
(SCID) agroup of diseases in which
there are low antibody levels, and
lack of lymphoid tissue because of
failure of their development.
o These patients will present with
infections as the maternal immunity
transfered at birth wears off.
T cell deficiencies
o Tend to get infection with viruses,
especially herpes family,
intracellular bacteria, and fungi.
B Cell deficiencies
o Tend to get bacterial infections
Iatrogenic (Caused by treatment)
o Many of these agents affect
lymphocytes particularly. They act
by interfering with cell division and
therefore inhibit regeneration of cells
that have a rapid turn over e.g. PMN.
After treatment with these agents
often the numbers of PMN (and
other blood cells) will drop and may
remain depressed for 1-4 weeks
depending on the therapy, during
which time there is a greatly
increased risk of infection.
o Damp down inflammation by many
mechanisms including anti
macrophage and anti T lymphocyte
effects, and interruption in the
presentation of antigens and decrease
Commonly used agents include
cyclosporinA, tacrolimus and serolimus
which inhibit lymphocyte function. The
result is immunosuppression with a
predisposition to infections of T cell
Removal of the spleen may be required
because of trauma or as part of treatment for
malignancies, or other conditions. Rarely it
may be congenitally absent.
The spleen is the main site of production of
It removes circulating microorganisms,
immune complexes, and old blood cells.
Removal increases the risk of life
threatening infection with encapsulated
organisms including Streptococcus
pneumoniae, Haemophilus influenzae, and
Neisseria meningitidis, and also Salmonella
and other less common bacteria.
These infections can progress very rapidly
from health to death in <24 hours
Immunization is recommended to patients
who are going to undergo splenectomy to
S.pneumoniae, H. influenzae and N.
Sequence of Events in the
First Exposure - Initial Response
Microorganisms gain entry through a
breach in skin (the innate defense barrier).
Tissue based macrophages and dendritic
cells phagocytose some bacteria and process
the antigens to present to T cells in the local
Complement is activated by the antigens
on the suface of the organisms and a
membrane attack complex is formed which
punches holes in the bacterial cell
membrane, killing some of the organisms.
Inflammatory mediators, e.g. histamine,
tumor necrosis factor (TNF-), are
released from cells that increase vascular
permeability, and blood flow. The site will
begin to appear red, swollen, warm to touch,
and painful. These are the classic signs of
The Arrival of PMN
Complement components diffuse out
from the site of infection and attract PMN
that are patrolling in the blood.
The PMN will migrate to the site of
The PMN begin to “roll” along the
endothelial lining of the blood vessels and
bind more closely to it as they are attracted
and activated by the inflammatory signals.
They penetrate the endothelium and enter
the tissues (“Diapedesis”).
The PMN phagocytose the organisms
which, once inside the cell, are killed in a
“phagocytic vacuole” by an “oxidative
burst” resulting from fusion with granules
that contain reactive oxygen radicals
(hydrogen peroxide) generated within the
The accumulating PMN form pus.
Activation of the Specific Response
The activation of T cells in the lymph
nodes causes proliferation of lymphocytes
and the lymph node becomes enlarged and
often tender. T cells are activated and
defend against intracellular organisms, B
cells are activated and develop into plasma
cells producing antibody after 5-7 days.
Initially IgM is produced and then with class
switching the antibody changes to IgG.
In the lymph node the T cells activate
macrophages so they become more effective
at killing the organisms, by producing more
reactive sustances to fuse to the phagocytic
vacuoles, and these arrive at the site of
infection after 1-3 days.
Antibody binding to the organism
promotes phagocytosis (opsonization) and
activates complement. Initially this occurs
in the blood with IgM, later in the tissues
If organisms have spilled into the
blood, macrophages in the spleen clear
A more severe infection will result in
the production of cytokines that cause
fever, and the production of acute phase
reactants. The bone marrow produces
more PMN and the WBC becomes
Memory cells are generated that are
long lived and are able to respond to
reexposure by generating antibody
(especially IgG) rapidly.
As the infection subsides T cells
suppress the immune response and
conditions return to normal, but there
may be residual tissue damage
manifested by fibrosis and scarring.
If the infection is chronic the site
may be infiltrated with macrophages and
lymphocytes, forming a granuloma,
which is walled off by fibroblasts.
If the infection is caused by a virus,
interferon is produced locally at the site of
infection. Interferon results in inhibition of
viral replication, it “warns” adjoining cells
and renders them resistant to infection,
activates the immune system, and the host
experiences a feeling of malaise with muscle
aches and fever.
Fever inhibits many viruses that are
unable to multiply at raised temperatures.
Macrophages phagocytose virus and
debris of cells killed by virus and present the
antigens to the T cells to activate the specific
NK cells may be activated by interferon
to eliminate infected cells.
The presence of memory cells
enables a more rapid and vigorous
response when antigens are presented by
macrophages or dendritic cells.
Antibody, predominately IgG is
more rapidly produced.
Infection maybe extinguished before
the host becomes aware of any
symptoms of it.
Evasion of the Immune Response
Bacteria may evade the immune response
Destroying complement components
e.g. Gp A Streptococci
Destroying immunoglobulin e.g.
Neisseria may produce an IgA protease.
Preventing phagocytosis e.g.
Preventing intracellular killing after
Bacteria may prevent the phagocytic cell
from killing them e.g. M. tuberculosis
Bacteria can be transported inside cells
throughout the body. Activation of
macrophages results in the cell
becoming able to kill the organisms
Some bacteria are not killed by the usual
mechanism inside the cell phagocytic
vacuole e.g. Salmonella
Bacteria growing inside the cytoplasm of
cells are protected from antibody or
detection by the immune system.e.g.
Bacteria (or other organisms) may
change their surface antigens rapidly
The immune system generates a specific
response but it does not recognise the
This is the use of a specific immune response to
prevent or lessen the severity of disease
resulting from infection or the products of an
infection (e.g. toxins)
o The host receives antibody produced by
o Naturally occurring: the neonate receives
antibody transplacentally from the mother,
or in colostrum.
o Therapeutic: Antibody (immunoglobulin or
Ig) is given :
o To provide rapid protection after a
potential exposure to an agent e.g. after a
o To lessen the severity of ongoing disease
e.g. antibody given in necrotizing
o For individuals unable to produce
o This protection is short lived (2-3 months)
and has no long term protection is generated.
o Examples: Hepatitis B Ig, Varicella Zoster
Ig (VZIG), Rabies Ig, RSV can be either
hyperimmune Ig or monoclonal Ig
Active Immunization (= vaccination)
o The generation of immunity by
administering an antigen to elicit an immune
response in the host.
o Among the first types was Jenner‟s
administration of cowpox virus (vaccinia) to
Types of Active Immunization can be divided
Inactivated whole cell or subunit
o These use organisms which are limited in
their ability to cause disease but share
antigenicity with the virulent forms.
o Attenuated organsim are those that have
been repeatedly cultured in the lab until they
have lost their virulence properties.
o Administration need not be by injection, and
may mimic the natural route of infection.
o They have the advantage that they mimic a
natural infection and give long term
immunity, not needing booster doses.
The principle disadvantages are
They may be virulent for immunosuppressed
people or in pregnancy
They may revert to the virulent form during
the infection in the host
They must be handled properly to maintain
viability until they are used
Sabin polio vaccine this agent was used
to eradicate polio in the Western
hemisphere. It was cheap andd gave IgA
immunity in the gut. Rarely, however, it
reverted to the virulent form and so as
wild type polio disappeared the vaccine
became more dangerous than the risk of
acquiring the disease and so it was
replaced by the killed (Salk) polio
Measles/mumps/rubella vaccine (MMR)
is used routinely in childhood and has
been very successful in largely
eradicating these diseases in the
These include whole cell, and subunit
They are often given with a substance that
increases their immunogenicity (an
“adjuvant” e.g. alum)
They usually are:
Given by injection, and therefore they do not
give a local IgA response (mucosal
Require multiple doses
Give immunity that wanes over time, so that
reimmunization may be required.
They give an antibody response but not cell
Salk polio vaccine, hepatitis A vaccine,
These are made with purifed antigens
derived from the pathogen and which are
found to produce an effective immune
These vaccines aer less prone to side
efects than whole cell and are often very
effective but are expensive.
Examples are Hepatitis B vaccine where the
outer coating (surface antigen) is used.
Haemophilus influenzae type B,
pneumococcal, and meningococcal vaccines
are prepared from bacterial polysaccharde
capsular material. As this material is not
very immunogenic, it is now often bound to
a protein (“conjugated”) to increase its
These are inactivated toxins
Immunization protects from the action of
Multiple doses are given, with an
adjuvant to increase immunogenicity.
These have been very effective vaccines.
Examples are tetanus and diphtheria
• Federal recommendations from National
Advisory Committee on Immunizations
(NACI) with provincial implementation
(varies between provinces).
• Have greatly reduced childhood
morbidity and mortality
• Why do vaccine programs fail ?
– Many programs do not reach the target
– Missed opportunities by health-care
workers and care-givers
– Improper vaccine storage
– Misconception of vaccine benefits, side-
effects and contra-indications. The anti-
Current Vaccine Targets
• Measles / Mumps / Rubella
• Diptheria / Polio / Tetanus / Pertussis
• Haemophilus influenza type B
• Hepatitis B
• Streptococcus pneumoniae
• Neisseria meningitidis
Diptheria / Tetanus / Pertussis
• Diptheria toxoid, tetanus toxoid, and
acellular pertussis vaccine (DTaP)
• primary immunization at 2,4,6 months
with boosters at 18 months and 4-6 years.
• often combined in a pentavalent form
(contains 5 vaccines in one) with
poliovirus and haemophilus b vaccines
• acellular pertussis vaccine approved in
1997 in Canada for primary vaccine has
less adverse effects and better
• Diptheria toxoid and tetanus toxoid (Td
• given at 14-16 yrs of age with boosters
every 10 years
• less diptheria toxoid (to decrease adverse
• Available as inactivated (IPV, Salk) and
live oral (OPV, Sabin)
• OPV induces a natural immunity with
advantages of secretory-IgA production
but shedding through GI tract offers
opportunity for vaccine-associated
• Primary immunization at 2,4,6 mo. with
boosters at 18 mo. and 4-6 yrs.
• May no longer be necessary in future
decades if poliovirus infection is
• Oral polio vaccine no longer used in
North America due to growing
immunosuppressed population, and
vaccine-asssociated paralytic polio.
Haemophilus type B vaccine
• Haemophilus influenza type B was the
most common cause of bacterial
meningitis and epiglottitis in Canada
prior to 1995.
• The current vaccine consists of
Polysaccharide conjugated to a protein
(4 preparations exist).
• Conjugation to a protein activates T-cell
dependant immunity (immunogenic in
infants and improved memory)
• Hib vaccine can be given in conjunction
with DTaP and polio
• Adverse reactions: fever, local redness,
and swelling in < 5%
• Live-attenuated vaccine
• Primary immunization age 12-15 months
• 2nd dose recommended at 18 mo. or 4-6
yr s .
• Elimination of indigenous transmission:
• Adverse reactions: rash and fever 5-
• Contraindications: severe acute illness
or immunosuppression (Not egg allergy)
• Inactivated whole or split-virus vaccine
• Vaccine changed annually depending on
• Vaccine contains two influenza A strains
(H2N3-like, H1N1-like) and an influenza B
• Recommended yearly to high-risk
individuals and those capable of transmitting
influenza to those at high risk (i.e. health
High Risk Groups who need to be
vaccinated for influenza:
• Chronic cardiac or pulmonary disorders
• Residents of nursing homes and chronic care
• Age > 65 yrs.
• Chronic conditions such as: Diabetes
mellitus, cancer, immunosuppression, renal
disease, anemia, hemoglobinopathy, HIV
• Children and adolescents requiring long-
• Individuals infected at an earlier age
have greater risk of liver failure,
cirrhosis, and carcinoma
• Increasing cases in Canada throughout
• Purified HBsAg (recombinant or
• 3 doses at 0,1 and 6 months IM
• Schedule varies from province to
• Booster not recommended
• Seroconversion rates: 90-95% in
• Polysaccharide vaccine (23-valent) which
will induce immunity against 90% of
pneumonia strains of S. pneumoniae
Efficacy ~ 80% in healthy adults
Recommended to repeat vaccinations every 5
• Age > 65yrs.
• Asplenia, splenic dysfunction or sickle cell
• Cerebrospinal fluid leaks
• All „high-risk‟ persons who require
• Live attenuated virus vaccine
• Given at age 12 months.
• If given >12 yrs of age requires 2 doses
• Extremely safe with < 5% of children
developing several varicella lesions.
• Over 95% effective in preventing severe
• Has the potential to make varicella an
uncommon disease in North America
• Immunity can be conferred either through
natural infection, passively via
administration of antibody or through active
• Our current vaccine schedule has
dramatically altered childhood morbidity
• The immunogenicity of a vaccine depends
on multiple factors and can be enhanced by
adjuvants and hapten conjugates.