Applications of Immunology

Chapter 18

Objectives
Know some terms
Immunization, vaccination, vaccine, etc

Explain why vaccination works

Compare and contrast different
vaccine types
Know some serological tests

Adaptive Immunity

Vaccination and Immunization

Terms often used interchangeably
Vaccination
Process of introducing vaccine into the body
Route of administration may be oral,
subcutaneous or intramuscular
Immunization
Result obtained when vaccine stimulates
immunity
Vaccines induce Abs and activated immune
cells to protect host from future infection

Booster Doses
Repeated vaccinations for the same diseases
Allow body to build up defence to particular
level
Schedule for infant and childhood
immunizations includes booster doses for
tetanus, diphtheria, whooping cough and polio
- Immunization begins at infancy
- Boosters start in kindergarten
- Adults need booster doses against tetanus
every ten years
- Booster tetanus toxoid also given
following any deep injury

Primary and Secondary Immune

Response to an Ag
IgM appears first and IgG follows and provide
longer-term immunity
Greater immune response following repeated
exposure(s) to the same Ag

Fig. 17.16

Types of Vaccines
Vaccines
Preparation of microbial antigens (Ags) used to
induce protective immunity
4 major types
Whole cells (live attenuated or inactivatedkilled)
Acellular or subunit (toxoid, recombinant
vaccine)
Conjugated (capsule + protein)- Haemophilus
influenzae type b vaccine
DNA or nucleic acid

Whole Cell Vaccines

Attenuated (live but avirulent):
longer term, w/o booster, effective, closely mimic actual
infection
Viral vaccines: Measles, rubella, polio (Sabin),
chickenpox
Bacterial vaccines: TB (BCG) and typhoid
What are the disadvantages?
Inactivated/killed: (inactivatedviruses; killed-bacteria)
Heat or chemical killing/inactivation (chemicals: formalin
or phenol). Less effective, required boosters.
Killed by heat,
Viral vaccines: Rabies (original), polio (Salk), influenza
Bacterial vaccine: Whooping cough (pertussis)
vaccine, cholera, pneumococcal pneumonia

Acellular or Subunit Vaccines

Antigenic fragments of a pathogen that best stimulates an immune
response
Capsular polysaccharide (part of capsule)
Surface antigenic proteins
Toxoids (inactivated toxin)
Recombinant:
Subunit vaccines that are produced by genetic modification
techniques
E.g. hepatitis B virus vaccine
Hepatisis B surface antigen (HBsAg)

Acellular or Subunit Vaccines

Conjugated Vaccines
Capsular polysaccharides elicit poor
immune responses
T-independent Ags do not effectively stimulate the
immune system especially in children < 24 months.

Conjugated vaccines covalently attach antigen to

carrier protein (from same organism)
This conferring immunological properties on carrier
protein (can activate B-cells)
Example:
Hib vaccine (Haemophilias influenzae type b) combined
with DT toxoids
Menengicocal vaccine (Neisseria menengitidis)
Pneumococcal vaccine (Streptococcus pneumoniae)

DNA Vaccines
DNA directly introduced into host cell
DNA fragment is expressed (protein produced)
host immune system (humoral and cellular)
responds to foreign proteins produced
Advantages

DNA is artificial and purity can be assured

Expressed for extended times with good immunological memory
Several genes can be mixed and injected as one
DNA sequences can be produced cheaply
Not for non-protein Ags

Approved in animals but not yet in humans

Protects horses from West Nile virus and salmon from viral
disease

DNA Vaccines

Part of gene encoding

pathogens protein is
introduced into the body
Inside the cell, this
protein (fragment) is
produced it exists the
cells and stimulates the
immune system

Multivalent Vaccines
Individual vaccines often combined
Reduces number of injections children
are subjected to.
Diphtheria (D) and acellular Pertussis
and Tetanus toxoids (T) vaccine DaPT
Salk polio vaccine added to above
DaPTpolio vaccine
Pentavalent vaccine - DaPT-polio-Hib
(with Haemophilus influenzae type b) has
been adopted in Canada

Adjuvants
Any nontoxic materials (chemical
additives) that prolongs antigen
interaction with immune cells
Increase the effectiveness of a vaccine
Several types are available
Aluminum salts, phosphates, oil-andwater emulsion
Multivalent DPT or DPT-polio vaccine
onto aluminum salts

Vaccines Used to Prevent Bacterial Diseases

Disease
Diphtheria

Vaccine
Purified diphtheria toxoid

Meningococcal
meningitis
Pertussis (whooping
cough)
Pneumococcal
pneumonia
Tetanus

Purified polysaccharide from

Neisseria meningitidis
Inactivated toxin plus acellular
fragments of Bordetella pertussis
Purified polysaccharide from
seven strains of Streptococcus
pneumoniae
Purified tetanus toxoid

Haemophilus
influenzae type b
meningitis

Polysaccharide from Haemophilus

influenzae type b conjugated with
protein to enhance effectiveness

Vaccines Used to Prevent Viral Diseases

Disease
Influenza
Measles

Vaccine
Injected vaccine: inactivated virus
(Nasally administered: attenuated
virus)
Attenuated virus

Mumps

Attenuated virus

Rubella

Attenuated virus

Chickenpox

Attenuated virus

Poliomyelitis

Inactivated virus (Salk) (IPV)

Attenuated virus (Sabin) (OPV)

Vaccines Used to Prevent Viral Diseases

Disease

Vaccine

Rabies

Inactivated virus

Hepatitis B

Antigenic fragments of virus

Hepatitis A

Inactivated virus

Smallpox

Live vaccinia virus

Herpes zoster

Attenuated virus

Human papillomavirus

Antigenic fragments of virus

Advantages:

Easy to administer
(Save the lives of
3-5 million
children who die
each year from
diseases like
bacterial diarrhea)

Easily harvested in
large quantities

No refrigeration
or expiry date

Transgenic Plants - Engineered to

Produce Vaccines

Qs & As

Some diseases such as diphtheria and tetanus are rare

in countries like Canada, why are vaccination against
these diseases still required?
Why are annual vaccinations against influenza required
whereas only one or two vaccinations over the course
of ones life may be required for some diseases?
Why is there need for more than one vaccinations of
infants/children against diseases such as diphtheria,
tetanus, polio and whooping cough (pertussis)?

The following is for your

information only.

Monoclonal Antibodies
Monoclonal antibodies:
Uniform
Highly specific
Produced readily
Useful in diagnostics
Bacteria pathogens
Pregnancy tests
Treatment of diseases
Leukemia
Rheumatoid arthritis
Asthma

Fig. 18.2

Diagnostic Immunology

Antiserum is specific for

bacterium and protein
recognition and is used in
diagnostic microbiology &
medicine
Slide agglutination test,
enzyme-linked
immunosorbent assay
(ELISA), direct
fluorescent-antibody test
Monoclonal vs polyclonal Abs

Fig. 18.11

Figure 18.11 Fluorescent-antibody (FA) techniques.

Group A
streptococci from
patients throat

Fluorescent dyelabeled
antibodies to group A
streptococci

Fluorescent
streptococci

Reactions in a positive direct fluorescent-antibody test

T. pallidum from
laboratory stock

Specific antibodies
in serum of patient

Antibodies binding
to T. pallidum

Reactions in a positive indirect fluorescent-antibody test

Fluorescent dyelabeled
anti-human immune
serum globulin
(will react with
any immunoglobulin)

Fluorescent spirochetes
(see Figure 3.6b)

Enzyme-Linked Immunosorbent Assay

Direct ELISA to detect Ags &
indirect ELISA to detect Abs
Use of microtiter plate
E.g. Measurement of drugs using
direct ELISA (A):
Anti-drug Abs are absorbed to well
Patients urine is added to well
Drug is captured by Abs
Wells are rinsed
Enzyme-linked Abs are added to
form a sandwich
Add a substrate for the linked
enzyme to produce a color

ELISA (Example)
Pregnancy test
Detects human chorionic gonadotropin (hCG) hormone in
urine of pregnant women

Fig. 18.13

Reactions in Neutralization Tests

Immune Disorders
C. 19

Self-Tolerance
The human immune system is capable of
recognizing a minimum of 1015 Ags
Body doesn't make Ab or CTL against self
Clonal deletion (B cells) and thymic selection
(T cells)
Process of destroying B and T cells that
react to self antigens
Happens at the immature lymphocyte stage

Autoimmune Diseases
Clonal deletion and thymic selection usually
ensures self-tolerance
Autoimmunity responses result from loss of
self-tolerance

May or may not be associated with disease

About 30% of population will have autoimmune lymphocytes by
age 65 (but not exhibit disease symptoms)
Can also be induced by infectious organisms and drugs

Disease results when autoimmune lymphocytes

damage tissue components
Autoimmune diseases more common in women
(75%)

Cytoxic Autoimmune Reactions

Antibodies react against cell
surface antigens
Graves disease
Antibodies against thyroidstimulating hormone receptor
Stimulate production of
thyroid hormone
hyperthyroidism
Thyroid gland greatly
enlarged and markedly
bulging, staring eyes

Immune Complex Autoimmune Reactions

Abs form complexes that are
deposited in tissues/organs
Systemic lupus erythematosus
Produce Abs that complex with
own cells, DNA, histones,
ribosomes
Complexes deposited in blood
vessels and kidney glomeruli
Rheumatoid arthritis
- Immune complexes of IgM, IgG and
complement are deposited in joints
- Cause severe damage to the
cartilage and bone of the joint

Cell Mediated Autoimmune Reactions

T-cells attack specific cells/tissues
Type I diabetes (Insulin dependent
diabetes)
T-cells attack the pancreatic -cells
Results in destruction of -cells and
loss of insulin production
Multiple sclerosis
T-cells attack myelin protein of nerves
Results in demyelination of axons
that leads to fatigue, weakness and
may eventually lead to paralysis

Immune Deficiencies
Congenital:
Due to defective or missing
genes
Selective IgA
immunodeficiency
Severe combined
immunodeficiency
Acquired:
Develop during an
individual's life, due to
drugs, cancers, and
infections
Artificial:
Immunosuppression drugs
Natural: HIV infections