Introduction to

Immunology
History and Overview
Dr. Barasa AK
 Outline
• History of Immunology

• Concepts of the Immune Response

• Failure/Challenges to the development of healthy

immune responses
 Overview of the Immune System
• Protection of multicellular organisms from pathogens

• Diverse potential pathogens – tiny intracellular viruses to

large parasitic worms

• Requires a range of recognition & destruction mechanisms

• Complicated & dynamic network of cells, molecules &

pathways
Historical Perspectives of
Immunology
 Concept of Immunity
• Observation that individuals who had recovered from
certain infectious diseases were thereafter protected
from the disease

• Latin term immunis meaning “exempt”

• Immunity – a state of protection from infectious disease

Early Vaccination Studies
• Deliberate induction of immunity

• 15th Century – Chinese &Turks

• Attempts to prevent smallpox
• Dried crusts from smallpox
pustules inhaled or inserted into
small cuts in the skin
(variolation)

Kuby Immunology, 7e
 Early Vaccination Studies
• 1718; Lady Mary Montagu (wife of British ambassador
to Constantinople)

• Observed the positive effects of variolation

• Had it performed on her children

 Early Vaccination Studies
• 1798; English physician, Edward Jenner
• Milkmaids who had contracted cowpox were
subsequently immune to the more severe smallpox
• Reasoned that inoculating fluid from a cowpox pustule
into people would be protective
• Inoculated an 8-yr old boy & later infected him with
smallpox
• Technique spread throughout Europe
 Early Vaccination Studies
• Louis Pasteur
• Grew the bacterium that causes fowl cholera in culture
• Confirmed this by injecting it into chicken, that then
developed fatal cholera
• Reinjection with an old bacterial culture – the chickens
became sick but recovered
• Grew a fresh culture & injected a mix of previously
injected chicken and unexposed birds
 Early Vaccination Studies
• Only the fresh chickens died

• Aging had weakened the virulence of the pathogen

• A weakened/attenuated strain could be administered to

provide immunity against a disease

• He called this attenuated strain a vaccine (Latin vacca =

cow)
 Early Vaccination Studies
• 1881; Pasteur
• Vaccinated a group of sheep with Bacillus anthracis that
were attenuated by heating

• Challenged vaccinated & unvaccinated sheep with a

virulent culture of the bacteria

• Vaccinated sheep lived and unvaccinated ones died

 Early Vaccination Studies
• 1885; Pasteur administered his 1st vaccine to a young
boy who had been repeatedly bitten by a rabid dog

• Series of attenuated rabies virus preparations

• The boy lived; later became a caretaker at the Pasteur

Institute (1887)
 Vaccination
• The study of immunology is linked to the discovery of
vaccines
• Vaccination has aided in improving mortality rates
worldwide, esp among young children
• Measles, Mumps, Rubella, Polio, Tetanus…..
• Still a major challenge for some pathogens – malaria,
AIDS
• 1977 - last known case of naturally acquired smallpox
(Somalia)
 Vaccination
• Herd immunity – as a critical mass of people acquire
protective immunity through vaccination or infection, this
decreases the number of individuals who can harbor or
spread an infectious agent

• Significantly reduces the chances that a susceptible

person will become infected
Immunology is about more than just vaccines and
infectious disease

Immune response can be manipulated to boost, inhibit or

redirect the specific efforts of immune cells, in Rx of
autoimmune disease, allergy and other disorders
 Mechanisms of Immunity
• Pasteur showed that vaccination worked, but did not
understand the mechanisms
• 1883; Elie Metchnikoff demonstrated that cells
contribute to immunity
Observed that certain wbc (phagocytes) ingested
microorganisms & other foreign material
• 1890; Emil von Behring & Shibasaburo Kitasato, 1890
Demonstrated that serum from animals previously immunized
with diphtheria could transfer the immune state to
unimmunized animals
 Humoral Immunity
Soluble mediators of immunity
• Various researchers in the early 1900s helped
characterize the active immune component in serum
• Could neutralize or precipitate toxins; could agglutinate
bacteria
• The component was named antitoxin, precipitin, agglutinin
• 1930s; Elin Kabat - a fraction of serum, gamma globulin
(now immunoglobulin) was responsible for all these
activities (antibodies)
• Body fluids were then known as humors
 Humoral Immunity
• Antiserum – the antibody-containing serum fraction
from a pathogen-exposed individual (horses) was given
to patients suffering from diphtheria and tetanus

• Current therapies that rely on transfer of

immunoglobulins to protect susceptible individuals:
• Snake antivenom (immune serum containing Abs against
snake venom) to treat bite victims
 Humoral Immunity
Passive immunity
• Short-lived and limited – cells that produce the Abs are
not transferred

Active immunity - administration of a vaccine or natural

infection (production of one’s own immunity)
 Cell-Mediated Immunity
• 1940s; Merrill Chase (Rockefeller Institute) - conferred
immunity against TB by transferring wbc between
guinea pigs
• 1950s - lymphocyte was identified as the cell type
responsible for both cellular & humoral immunity
• Bruce Glick, (Mississippi State University), experiments
in chicken – 2 types of lymphocytes: T lymphocytes (T
cells), derived from the thymus, & B lymphocytes (B
cells), derived from the bursa of Fabricious in birds
Cellular immunity is imparted by T cells

Antibodies produced by B cells confer humoral immunity

Both are needed for a complete response against

most pathogens
The Immune System Recognizes Foreign
Substances
• Antigen – substance that elicits a specific response by B or T
cells
• 1900s; Jules Bordet (Pasteur Institute) – nonpathogenic
substances (rbc from other species) can serve as antigens
Serum from an animas that had been inoculated with noninfectious but
otherwise foreign (nonself) material would react with the injected material
in a specific manner
• Karl Landsteiner et al – injecting an animal with almost any
nonself organic chemical could induce production of Abs that
would bind specifically to the chemical
Outline for the humoral and cellular branches of the immune system

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Concepts of the Mammalian
Immune Response
 Pathogens
• Disease-causing organisms

• Pathogenesis – the process by which they induce

illness in the host

• Viruses, fungi, parasites, bacteria

Major categories of microorganisms causing human disease

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 Pathogens
The immune system exploits some shared characteristics
that are common to groups of pathogens, but not to the
host, for recognition & destruction
 Pathogens
The same pathogen can be treated differently depending
on the context/microenvironment in which it is
encountered
• Some areas of the body e.g. CNS are “off limits” for the
immune system (the immune response can cause more
harm than the pathogen)
• Some foreign compounds that enter via the GIT e.g.
commensal microbes, are tolerated by the immune
system; however if they enter the bloodstream, they are
treated aggressively
 Pathogens
• Immune pathways do not become engaged until the
foreign organisms first breach the physical barriers of
the body – skin, mucous membranes

• Other barriers – acidity of stomach, vagina, perspiration

(some microorganisms cannot survive in the low pH)
 The Immune Response
The cells and molecules that become activated in a given
immune response depend on

• The chemical structures present on the pathogen

• Whether it resides inside or outside of host cells

• The location of the response

 The Immune Response
• Pathogen recognition involves an interaction between
the foreign organism & a recognition molecule or
molecules expressed by host cells (membrane-bound)

• Can also be soluble receptors or secreted recognition

molecules
 The Immune Response
• Ligands for recognition molecules include whole
pathogens, antigenic fragments of pathogens, or
products secreted by pathogens

• Outcome of binding is an intracellular or extracellular

cascade of events that leads to labeling and destruction
of the pathogen – The Immune Response
 The Immune Response
• E.g. Viruses cause intracellular infection
• CTLs must be able to detect changes that occur in a
host cell after it becomes infected by virus
• Recognition molecules inside the cells bind to viral
proteins present in the cytosol & initiate events that alert
the CTLs to the presence of an invader
• The virally-infected cells must be killed so as to
eradicate the pathogen
• Can cause disruption to normal function; e.g. in HIV
 Pathogen Recognition Molecules
• Pathogen-associated molecular patterns (PAMPs) –
chemical structures that characterize whole groups of
pathogens
• Not typically found in mammals
• E.g. polysaccharide coat on encapsulated bacteria

• Recognized by the immune system – Pattern recognition

receptors (PRRs) on wbc
• Recognize sugar residues and other foreign structures

• A cascade of events then labels the target pathogen for

destruction
 Pathogen Recognition Molecules
• PRRs are conserved, germline-encoded recognition
molecules; first line of defense

• Pathogens evolve to express unique structures that

avoid host detection
 Pathogen Recognition Molecules
• Generation of diversity – each B and T cell expresses
many copies of one unique recognition molecule

• Resulting in a population with the potential to respond to

virtually any antigen

• Occurs by rearrangement and editing of the genomic

DNA that encodes the antigen receptors expressed by
B and T cells
 Generation of
diversity and
clonal selection

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 Tolerance
• The immune system must avoid accidentally
recognizing and destroying host tissues

• Principle that relies on self/nonself discrimination

• To establish tolerance, the antigen receptors on

developing B and T cells must first pass a test of
unresponsiveness against host structures
 Tolerance
• Downside of robust self-tolerance is that the immune
system frequently ignores cancerous cells that arise in
the body, as long as these cells continue to express self
structures that that immune system has been trained to
ignore

• Dysfunctional tolerance – autoimmune diseases

 Innate Immunity
• In-built cellular and molecular mechanisms encoded in
the germline
• Primitive
• Aimed at preventing infection or quickly eliminating
common invaders
• Physical and chemical barriers
• PRRs
• Complement – serum proteins that bind common pathogen-
associated structures and initiate a cascade of labeling and
destruction events
 Adaptive Immunity
• B and T lymphocytes
• Takes some time to be activated (5-6 days)
• Antigen-specific
• Evolves in real time in response to infection, and adapts
to better recognize, eliminate and remember the
invading pathogen
• Second line of defense
 Adaptive Immunity
• Goal of vaccination against infectious disease is to elicit
the development of specific & long-lived adaptive
responses

• So that the vaccinated individual will be protected in

future, when they encounter the actual pathogen
Adapted from Patton KT, Thibodeau GA: Anthony’s textbook of anatomy & physiology, ed 201, St. Louis, Elsevier, 2013
• Innate and adaptive immunity work together
• The 2 systems must be able to communicate with one
another
• Achieved by cell-cell contact and soluble messengers –
Cytokines
• Cytokines bind to receptors on responding cells & signal
them to perform new functions, e.g. synthesis of other
soluble factors, or differentiation to a new cell type

• Chemokines – cytokines that have chemotactic activity

(recruit specific cells to a site)
Immunologic memory – ability of the immune system to
respond more swiftly and with greater efficiency during a
second exposure to the same pathogen
• 1st exposure with foreign Ag – adaptive immunity
undergoes a primary immune response
Key lymphocytes that will be used to eradicate the pathogen
are clonally selected
• Subsequent exposure with the same Ag - secondary
response
• Memory cells (kin of B and T cells trained during the primary
response) are re-enlisted to fight again
Comparison of innate and adaptive immunity

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Kuby Immunology, 7e
The Good, Bad and Ugly of
the Immune system
Failures and challenges to the development of healthy immune responses
 Dysfunctional (Inappropriate) Immune
Responses
• The healthy immune response involves a balance
between immune aggression & immune suppression
pathways

• Improper regulation of the immune response:

• Attacks something it shouldn’t
• or fails to attack something it should
 Dysfunctional (Inappropriate) Immune
Responses
• Hypersensitivity – exaggerated/overzealous attacks on
common benign but foreign antigens; e.g. allergy

• Autoimmune disease – erroneous targeting of self-

proteins or tissues by immune cells

• Immune deficiency – insufficiency of the immune

response to protect against infectious agents
 Challenges of Transplantation
• The immune system will attack and reject a transplanted
organ (or cells, or tissue) that is nonself or not a genetic
macth
• Even when it is a lifesaving Rx

• Transplant rejection responses can be suppressed by

immune inhibitory drugs;
• Which also suppress general immune function, leaving
a host susceptible to infections
 Cancer (Malignancy) and the Immune
Response
• Occurs in host cells, when they begin to divide out of
control

• Self-tolerance mechanisms can inhibit the development

of an immune response, making detection and
eradication of cancerous cells challenging
 Cancer (Malignancy) and the Immune
Response
• Many tumour cells express unique or developmentally
inappropriate proteins
• This makes them potential targets for immune cell
recognition and elimination
• As well as targets for therapeutic intervention

• The immune system actively participates in the

detection and control of cancer in the body