HISTORICAL DEVELOPMENT OF IMMUNOLOGY

OUTLINE
I Historical Development of Immunology
A Definition of Terms
B Functions of the Immune System
C History
D Foundation of Immunology
E From Antibodies to Lymphocytes
F T Lymphocytes: From Function to Instruction
II IMMUNITY
A. Innate Immunity
B. Acquired Immunity
C. B cell Lymphopoiesis
D. T cell Lymphopoiesis
E. T Lymphocytes Antigen Receptor
F. Natural Killer Cell

HISTORICAL DEVELOPMENT OF IMMUNOLOGY o Allogenic organ/tissue transplant are organ

DEFINITION OF TERMS tissues that are harvested from another
individual
● Immunology
o Can be defined as the study of a host’s ▪ Example: A kidney organ recipient
reactions when foreign substances are (allogenic organ tissue)). It comes from
introduced into the body. another individual/organism that is of the
o A foreign substance that induces such same species of the donor and recipient
immune response is called an antigen. of the donor.
● Immunology as a science has its roots in the study of
immunity, the condition of being resistant to HISTORY
infection. 1500
● The Greeks have already contributed in the study of
● Serology is the study of blood serum and the immunology.
application of these components of immune system ● The Chinese developed the practice of
in the laboratory determination of diseases. VARIOLATION.
o “Inhaling powder made from smallpox scabs
FUNCTIONS OF THE IMMUNE SYSTEM in order to produce protection against this
● It functions to recognize, respond to, and destroy a dreaded disease.”
wide variety of invading organisms such as bacteria,
▪ Scabs – superficial of the healing wound
viruses, fungi, and parasites that otherwise would be
capable of promoting infection that is harmful to the ▪ The Chinese powderized it and they ad it
body. inhaled by the people to induce
● It also maintains surveillance over the appearance of protection against the smallpox disease.
new or foreign antigens on tumor cells and attempts ▪ It was proven deleterious, so later on, the
to destroy them while leaving unharmed the normal
practice was refined
(or self) antigens on healthy cells.
o The theory was that, if a healthy individual
o Immune surveillance is very important in
was exposed as a child or young adult, the
context of the ability of immune system to
effects of the disease would be minimized.
confer immunologic injury to the body.
However, this was not always the case.
● It is responsible for rejection of allogeneic
1700
organ/tissue transplant and graft-versus-host disease.

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● English country doctor Edward Jenner discovered
cross-immunity.
o Cross-immunity – you develop immunity in a
certain disease. In this case, smallpox after
being infected or exposed to a cowpox virus.
● He observed that milkmaids who were exposed to
cowpox had apparent immunity to smallpox, he
deliberately injected individuals with material from a
cowpox lesion and then exposed them to smallpox.
● He thus proved that immunity to cowpox had
apparent immunity to cowpox, a very mild disease,
provided protection against smallpox.
● This procedure of injecting cellular material became
known as vaccination, from vacca, the Latin word for
“cow.”
IMMUNITY (in early days)
● Robert Koch
o Anthrax vaccine
o Koch Postulate (Germ Theory)
▪ In every disease, there is causative agent
● Louis Pasteur
o Anthrax vaccine and rabies vaccine
o Experimented attenuated rabies vaccine
(specimen used: came from spinal cord)
▪ Child bitten by rabied dog, he deliberately
experimented (injected 12 to 18 attenuated
spinal cord specimen): nabuhay yung bata
o Invented chicken cholera vaccine; inoculated
some of the excreta of the chicken on a medium
and he did it in a manner that they are all
inoculum and compared it to new ones
FOUNDATION OF IMMUNOLOGY

● The field of immunology is not exclusive or separate

from other field of science.
● DIAGRAM: Overview of individuals that have bigger
contribution to immunology
o Different component of immune system that
confers immunity
o Cellular: cells (specifically, hematopoietic stem
cell lineage)
o Humoral: soluble substances responsible for
immunity (ex. Complement, Abs, etc.)
o In early period: notion: human immunity is
composed of innate immunity only (Elie and Jules
ELIE METCHNIKOFF (1845-1916)
period) ● Russian Biologist and immunologist
o As science evolved, new discoveries and ● Phagocytosis
breakthrough about immune system o He introduced rose thorns is the larvae of
starfish. At some time, Metchnikoff observed
▪ Another component of immune system:
that there are some motile cells that in
acquired
contact with rose thorns when he initially
o Innate and acquired immunity is complementary
observed the process of phagocytosis.
to one another
o His discovery paved to the concept of
They help each other
cellular component of immune system –
● Immunity can be innate and acquired (2 general
macrophages and, neutrophils having the
components)
ability to engulf foreign materials or antigens
or microbes in its attempt to protect the
ROBERT KOCH AND LOUIS PASTEUR body

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o Notion: Cells are responsible for the ● Physician
conference of immune system ● Known for his work regarding the body’s complement
● Nobel Prize 1908 which are proteins that when activated can affect
numerous biological reactions and are a part of the
NOTE: soluble humoral innate immunity of the body.
● Before Elie Metchnikoff, his superiors/predecessors o Complement pathway is composed of 3
were Louis Pasteur and Robert Koch. interdependent/interrelated – Classical,
● Louis Pasteur – known for his contribution to the Alternative, and Mannan
vaccination, specifically rabies vaccine and chicken o The complement is part of the innate
cholera vaccine humoral component of the immune system
● Robert Koch – known for his work in tuberculosis o Humoral – refer to soluble chemicals or
● Pasteur and Koch greatly contributed to germ theory mediators of immunity
of infection o Cellular – formed elements or cells
● These complements and its derivatives can augment
PAUL EHRLICH (1854-1915) phagocytotic activities of phagocytes, so they are
● Physician and immunologist activated through the antigen-antibody reaction
● Side chain theory classical pathway and direct binding of certain
● Nobel Prize 1908 specific compounds found in bacteria, viruses and
● Known for his contribution on humoral component of fungi through the alternative pathway.
the immune system ● Nobel Prize 1919
o He observed that the cell will elaborate or
expressed a side chain on its protoplasm in ALMROTH WRIGHT (1861-1947)
order to uptake or established contact with ● Bacteriologist and immunologist
antigen. Eventually, the chain that was ● Opsonization
present on the membrane of the cell later on o Proved that the humoral and cellular
was considered the antibody. component of the immune system is integral
● His theory debunked the notion that immunity is only or interrelated to each other
cellular, but rather he proved that there is also a o Augmentation process for phagocytosis
humoral component or soluble component of o Opsonins
immunity. ▪ substances or structures like antibody,
specifically IgG, or it could be a
EMIL BEHRING (1854-1917) complement fragment like C3b
● Physician, researcher, entrepreneur
▪ these are substances that opsonize,
● Known for Serum therapy together with Shibasaburu
meaning, they coat antigen so it could
Kitasato
be recognize better by the immune
● First individual to receive a Nobel Prize (Nobel Prize
system, particularly the cells that has the
1901)
ability of phagocytosis
● He solely authored research about the Diaphteria
toxin which is an example of a passive artificial ▪ humoral by characteristic and soluble;
immunization they help the phagocytes to recognize
antigens
SHIBASABURO KITASATO (1853-1931)
● Researcher CHARLES RICHET (1850-1935)
● Tetanus antiserum ● Physiologist
NOTE: ● Anaphylaxis
● Behring and Kitasato – colleagues; known for their o Severe form of hypersensitivity.
contributions in serum therapy. They work together to o Clinical definition: Anaphylaxis occur when a
develop tetanus antiserum. person exposed to an allergen would
eventually develop multisystem syndromes
that involved different systems of the body.
● Nobel Prize 1913
JULES BORDET (1870-1961)

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▪ Discovery: He mixed the serum of an

individual with a whole blood from
another
▪ He termed the antibodies agglutinin –
naturally occurring antibodies (anti A, B,
AB)
● He saw that a Type A individual whose blood was
mixed with a Type B individual, the red blood cells
agglutinated
● Nobel Prize 1930
● Plasma cells are responsible in producing antibodies

NIELS JERNE
FROM ANTIBODIES TO B LYMPHOCYTES ● 1911-1994
● Immunologist
● Idiotypic networks
● Nobel prize 1984

ASTRID FRAGRAEUS (1913-1997)

● Immunologist
● Discovered the plasma cells that produces
antibodies

MAX COOPER (1933-)

● Physician and Immunologist
● Discovered B lymphocytes
● Responsible for the chemical structure of the
antibodies together with Porter
RODNEY PORTER (1917-1985)
● Biochemist
● Responsible for the chemical structure of the
antibodies together with Cooper
● Noble Prize 1972

SUSUMU TONEGAWA (1939-)

● Molecular Biologist
● Responsible for the discovery of recombination
KARL LANDSTEINER (1868-1943) ● Noble Prize 1987
● Serologist
● He was responsible for the discovery of ABO blood GERALD EDELMAN (1929-2014)
group and 10 years later, also discovered the Resus ● Biochemist and Immunologist
blood group ● Also responsible for the recognition of the chemical
o ABO and Rh blood groups structure of antibodies
o ABO antigen is NOT only present in RBC, but
can also be found in platelets, WBCs, and CESAR MILSTEIN (1927-2002)
tissues
● Biochemist and Immunologist
o Rh antigen is only present in RBCs
● Responsible for the recognition of monoclonal
o Agglutinins
antibodies
● Nobel Prize 1984

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GEORGES KOHLER (1946-1995)

● Immunologist GEORGE D. SNELL (1903-1996)
● Also responsible for the recognition of monoclonal ● Geneticist
antibodies ● Major histocompatibility complex
● Nobel Prize 1984 ● Nobel Prize 1980

T LYMPHOCYTES: FROM FUNCTION TO INSTRUCTION JEAN DAUSSET (1916-2009)

● Geneticist and immunologist
● Major histocompatibility complex
● Nobel Prize 1980

BARUJ BENACERRAF (1920-2011)

● Geneticist
● Major histocompatibility complex
● Nobel Prize 1980

JAMES L. GOWANS (1924)

● Immunologist
● Lymphocyte recirculation

JACQUES MILLER (1931)

● Immunologist
● T Lymphocytes

PETER DOHERTY (1940)

● Veterinarian and immunologist
● Restriction of cellular immunity
● Nobel Prize 1996

ROLF ZINKERNAGEL (1944)

● Physician and immunologist
● Restriction of cellular immunity
● Nobel Prize 1996

CHARLES JANEWAY (1943-2003)

● Immunologist
FRANK MACFARLANE BURNET (1899-1985) ● Pattern recognition receptors
● Physician and Immunologist
● Responsible for the recognition of acquired immune JULES HOFFMAN (1941)
tolerance and the Clonal Selection Theory ● Biochemist and immunologist
o Immune Tolerance ● Molecular basis of innate immunity
● Nobel Prize 1960 ● Nobel Prize 2011

PETER BRIAN MEDAWAR (1915-1967) BRUCE BEUTLER (1957)

● Biologist and immunologist ● Immunologist and geneticist
● Acquired immune tolerance ● Molecular basis of innate immunity
● Nobel Prize 1960 ● Nobel Prize 2011
TASUKU HONJO (1942)
DAVID TALMAGE (1919-2014) ● Immunologist
● Physician and immunologist ● Checkpoint blockade for cancer therapy
● Clonal selection theory

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JAMES ALLISON (1948) ● Is the ability of the individual to resist infection by

● Immunologist means of naturally present body functions.
● Checkpoint blockade for cancer therapy ● These are considered nonadaptive or nonspecific
● Nobel Prize 2018 and are the same for all pathogens or foreign
substances to which one is exposed.
● No prior exposure is required, and the response does
RALPH STEINMAN (1943-2011)
not change with subsequent exposures.
● Immunologist
● Many of these mechanisms are subject to influence
● Dendritic cells (one of the antigens presenting cells of
by such factors as nutrition, age, fatigue, stress, and
the body)
genetic determinants.
o Located in skin, spleen, lymph nodes;
o Genetic determinants
phagocytose antigen or foreign matter;
process, package and present it to ▪ chromosomal disorders and anomalies
lymphocytes predisposes the certain individual to
● Nobel Prize 2011 infections
o Age
IMMUNITY ▪ Children: 3 yrs. younger and elderly: 70
● Immune system composes of innate and acquired yrs. Old; they have underdeveloped and
component that is integral and not functioning deteriorating immune system.
separately. They are interrelated to each other. ● After the physical contact, a part of the membrane
of the phagocyte will engulf the foreign antigen.
Then, it will be dislodged from the main membrane of
the phagocyte to form phagosome.
o The component of the phagosome is the
ingested antigen and the disintegrated part of
the membrane of the phagocyte.
● When the phagosome that encapsulates the antigen
and the lysosomal granules combine together, they
are called phagolysosome.
● In the digestion process, the degradation of antigen
into its elementary particles happen
o If an antigen is digested, the product will be
excreted. Some of them will be processed and
will be expressed in the surface of the
phagocyte.
o In the case of macrophages and dendritic
Table No. 1 Resistance Mechanism
cells, these processed digested matter will be
TYPE OF EXAMPLES presented to the lymphocyte. Particularly, the T
RESISTANCE lymphocyte.
Nonspecific ● Mucous membranes
(Innate) ● Phagocytic cells ● Cardinal signs of inflammation
● Enzymes in secretions o Redness (Rubor)
● Interferon o Swelling (tumour)
Specific (Acquired) o Heat (calor),
Naturally ● Placental transfer of o Pain (dolor)
antibody (passive) o Loss of function (functio laesa)
acquired
● Recovery from disease ● Infection- types of microorganisms invading the
(active) systems of the body
● Inflammation- the overall reaction of the body in
Artificially ● Administration of antitoxin
(passive) injury or infection.
acquired
● Vaccination (active)

INNATE IMMUNITY

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NOTE: macrophages, neutrophils, and other phagocytes B. OUTFLOWING OF CYTOPLASM to
have specialized and secondary granules or surround the antigen
lysosomal granules in their cytoplasm. ● Neutrophils and other cells are
capable of extending their
EXTERNAL DEFENSE SYSTEM cytoplasm to engulf the
● Microorganism is attempting to invade our body antigen.
● Skin (intact skin) ● After some time, the
o Physical barrier cytoplasm of the phagocyte
o Fatty acid secretions (sebum) would enclose to fully surround
the antigen
▪ Parasites can invade intact skin (e.g.
hookworm etc.)
C. PHAGOSOME
● Oral cavity
● Antigen plus cytoplasm of the
o Enzymes and antibodies in saliva
phagocytes
o Flow of saliva to throat
● Antigen is completely
o Epithelial cells and mucous layer
surrounded by a part of the
● Respiratory system (smokers are prone to pneumonia)
cell membrane
o Turbinations and hairs in nasal passage, which
help trap microbes
D. PHAGOLYSOSOME
o Mucous secretions containing enzymes and
● Cytoplasmic granules fuse
antibodies, which help inactivate microbes
with the membrane of the
o Ciliary beating, which moves mucous blanket up
phagosome, emptying the
to esophagus, where it is swallowed
contents into this
● Gastrointestinal system
membrane-bound space.
o Low pH of stomach
● Depending on the content of
▪ Because of gastric secretions, it sets low pH the lysosomal granules, several
(pH 1 to 2) types of reactions take place
o Enzymes and antibodies in secretions depending on the enzymes
o Peristalsis present in the granules.
● Eyes
o Lysozyme in tears E. DIGESTION
▪ Contains enzymes such as lysozyme ● Digestion of the antigen by
hydrolytic enzymes
o Flushing action of tears
● One notable Enzyme present
● Ears
in neutrophils are
o Antimicrobial properties of cerumen (tutuli)
myeloperoxidase producing
● Genitourinary system
hypochlorite that destroys the
o pH of vagina and mala urethra
antigen.
▪ Possesses normal flora
F. EXCRETION
o pH of urine ● Contents of phagolysosome
o Flushing action of urine are excreted outside by
exocytosis
INTERNAL DEFENSE SYSTEM/PHAGOCYTOSIS ● Along the process,
● Discovered by: Ellie Metchnikoff degradative products may
contain epitopes.
A. ADHERENCE: ● The epitope is specific to an
● Physical contact between the antibody.
phagocytic cell and the ● Epitope may be presented by
ANTIGEN occurs macrophage to the
● Aided by opsonins. lymphocyte
● Debris may also go to the
blood and will be filtered by
the spleen and lymohnide

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where , macrophage and o Mechanism responsible for vaccination.

lymphocytes are waiting for ● Characterized by specificity for each individual
binding pathogen, or microbial agent and has the ability to
remember a prior exposure, which results in an
INFLAMMATION increased response upon repeated exposure.
o Has humoral and cellular components
● Overall reaction of the body in response to injury
brought about by invading microorganisms or ▪ Humoral: soluble; example: antibodies.
trauma ▪ Cellular: T lymphocytes.
o Inflammation is not only brought about by o B cell has the ability to remember a prior
invading microorganism exposure, which results in an increased
● Inflammation is not the same as infection. response
o Inflammation could be brought about by injury or
▪ Anamnestic Immune Response
trauma
- Results to increased response during the
● “-itis” denotes inflammation.
second exposure
- Basis for vaccination

ACQUIRED IMMUNITY
● Specific/adaptive type of immunity. Anamnestic
response/does not forget.
o Through this, we are able to fight off
reinvading/ reinfection more efficiently.
o Less or mild manifestation.
LYMPHOID SYSTEM
PRIMARY LYMPHOID ORGANS
● bone marrow and the thymus.
o Primary lymphoid organs are site for
lymphocyte maturation and differentiation.
Specifically, b lymphocytes mature in the
bone marrow as t lymphocytes mature in the
thymus, but both of them are produced in
the bone marrow.
● BONE MARROW
o Site for general hematopoiesis
▪ Hematopoiesis starts as early as the fetal
stage
▪ T lymphocyte production starts as early
as 2 months/ 8 weeks during gestation.
o Situated at flat bones (vertebral discs, ileum,
skull)
● THYMUS
o organ located inferior to the thyroid and
anterior to the heart. An anterior mediastinal
structure. At birth, it weighs 30 grams and at
puberty weighs 35 grams. After puberty
during adulthood, it atrophies and still
functions up until 50-60 year of age. It
produces and supports the maturation of T
lymphocytes.
● Usually, lymph nodes are concentrated on the sites of
articulation between the limbs and the trunk. Special
association of this tissue is found in the Peyer’s
patches of the terminal ilium.
SECONDARY LYMPHOID ORGANS
● include spleen, lymph nodes, MALT
(Mucosa-associated lymphoid tissue).

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● Site where the mature and T and B lymphocyte o Same role with spleen,
further differentiate o Paracortex is t cell’s area. Cortex is the b cell
● SPLEEN area. Primary follicle and then the secondary
o site for the antigen antibody or antigen t cell follicle with germinal centers houses the b
b cell binding and proliferation. The spleen in
general serves as the organ of blood
filtration.
o An average adult having 5-6 liter of blood,
the spleen is perfused with that volume of
blood 4 times within 24 hours. By doing so,
the spleen cleanses or filter the blood of
foreign antigens and senescent or old
cellular elements of the body.
o It is the graveyard of the body.
o Someone who had been splenectomized is
prone to infection. Particularly, infection
caused by encapsulated microorganisms. lymphocytes.
***Illustration above is a structure of lymph node. A lymph
node is surrounded by a tough outer capsule. Right
underneath is the subscapular sinus, where lymph fluid
drains from afferent lymphatic vessels. The outer cortex
contains collections of B cells in primary follicles. When
stimulated by antigen, secondary follicles are formed. T
cells are found in the paracortical area. Fluid drains slowly
through sinusoids to the medullary region and out the
efferent lymphatic vessel to the thoracic duct.

● LYMPH NODES (contionuation)

o Kulani in Tagalog
o Distributed in body
▪ Rich areas: joints, articulation in between
the body and the lymph (singit)
o Filter lymph fluid or the fluid that came out
***Illustration above is the cross-section of the spleen from the blood vessel
showing organization of the lymphoid tissue. T cells
▪ There is the fluid that is able to leech out
surround arterioles in the PALS. B cells are just beyond
of the blood vessel into the interstitial
in follicles. When stimulated by antigens, the B cells
space. That fluid is called the lymph fluid
form germinal centers. The Lymphoid tissues is
referred to as the White Pulp. ▪ Lymph fluid goes back to the circulation
using the thoracic duct
o Primary follicle- contains b cells which are ▪ Before going back, it should be filtered
not stimulated or has not encountered a
from contaminants (done by lymph
specific antigen yet.
node)
o Germinal center- contains stimulated b cells.
o CORTEX OF LYMPH NODES
Banded with surface immunoglobulin a
specific antigen. ▪ The Follicle is situated in the cortex and
o Periarteriolar lymphoid sheath- composed of contains B cells
t cells. - Primary Follicle: contains unstimulated
o Marginal zone- composed of stimulated b mature B cells
cells. Follicular dendritic cells/ antigen ▪ Secondary Follicle: contains Germinal
presenting cell.
centers that contains stimulated B cells
- Stimulated: there is Ag and Ab binding
● LYMPH NODE
o PARACORTEX of LYMPH NODES

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▪ Contains T cells

Contains T cells
● Spleen filters the blood. The lymph node filters the
lymph fluid.
o Collection of fluid that was filtered or
ultra-filtered across the blood vessel wall.
Before it enters the blood circulation.

T CELL VS. B CELLS

Table No. 2 Comparison of T cell and B cell
T Cell B Cell
Develop in the thymus Develop in the bone
marrow
Found in the blood Found in bone marrow,
(60-80% of circulating spleen, lymph nodes
lymphocytes), the
thoracic duct fluid,
lymph nodes
Identified by rosette Identified by surface
formation with SRBCs immunoglobulin
End products of End product of
activation are activation is antibody
cytokines
Antigens include CD2, Antigens include CD19,
CD3, CD4, CD8 CD29, CD21, CD40,
MHC Class II
Located in Located in cortical
paracortical region of region of lymph nodes
lymph nodes
SRBC- Sheep red blood cell

● Cytokines
o Are soluble chemicals that serves as
mediator/effector of immune system
o Dictates hematopoiesis
● CD Markers
o Important in the identification of the cell
o Play an integral role in the immune response
mechanisms

HEMATOPOESIS

● Occurs in the bone marrow in adult

● 8 weeks (embryo)
o Start to create or produce lymphocytes

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o Lymphopoiesis o Occurs in the bone marrow where the
progenitor B cell, pre-B cell, and immature b
cell are found
o The cells other than the B cell (stromal cells,
epithelial cells) serve a nutritive function for
the maturation of B cell
B-CELL LYMPHOPOESIS ▪ The stromal cells secrete cytokines and
Table No. 3 Key Cell Surfaces Markers in Lymphocyte substances that instruct the stem cell to
Development differentiate and produce B cells
depending on the signaling of the body
Cell Name CD Markers
● The progenitor B cell, in its nucleus, the gene for the
Progenitor B cell CD19,TdT, CD79a, HLA-DR joint and diverse region of an immunoglobulin
Pre- B cell CD19, Tdt, CD10, CD20, rearranges.
cytoplasmic μ o Immunoglobulin is composed of a heavy
Naive mature B CD19, CD20, Bcl-2, Surface chain and a light chain
cell or Immature IgM o The gene of the heavy chain is first
B cell rearranged
● On a pre-B cell, the gene that codes for the variable
Germinal center CD19, CD20, CD10, Bcl-6
region of the immunoglobulin is also subjected to
B cell
rearrangement
Mature B cells CD19, CD20, CD21, CD22, o The rearrangement identifies the specificity
(peripheral CD24, CD38 of the immunoglobulin receptor of the B cell
blood cells) o The pre-B cell has a cytoplasmic µ
Plasma cells CD38, CD138, cytoplasmic Ig chain(heavy chain) for IgM
● The immature B cell has gene rearrangement for the
● Aka B cell production, happens in the bone marrow light chain
● Stages in B Cell Development ● Bone Marrow
o Progenitor B Cell o There is already a gene rearrangement
o Pre-B Cell
● What antibody class is found in a B cell as its receptor
o Naive Mature B Cell
▪ Aka inactivated mature B cell for an antigen?
o Germinal Center B cell o IgM
▪ Found in the secondary lymphoid organs ● IgD
o Mature B cell o Not involved in the antigen binding of the B
o Plasma Cells cell
o Prolongs the B cell in order for it to have a
longer life
● After coming out of the bone marrow, it travels to the
secondary lymphoid organs (spleen and lymph
nodes) through the blood
o Once the mature B cell has reached the
secondary lymphoid organs, where it can be
activated by being bound with specific
antigen, it can further differentiate into a
plasma cell and a memory B cell
● Plasma Cell
o It produces antibody specific to the antigen
that has activated the B cell prior.
o Dies in 6 weeks after serving as a cite of
antibody production
● Memory B cell
STAGES IN B CELL DEVELOPMENT o Confers the ability of the immune system for
● Antigen Independent B Cell Formation an amnestic response (secondary immune

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response) so they can survive in the system
for years
● Activated B cell
o It can be activated by T helper cell that has
bound in itself an antigen
● If Ag and Ab binding occurs, the mature B cell will
be activated.
● Depending on what it binds with, it will undergo
blast transformation whether as a:
o Plasma cell that Produces specific
antibody
o Some will transform as memory B cell
responsible for the anamnestic or
secondary immune response.
● Plasma cells are characterized by cytoplasmic
immunoglobulin
o First infection: IgM
o Succeeding: IgG
o Plasma cells can survive up to 6 weeks
o B cell will stay in system for years to come,
waiting for the second infection of the
same organism. That’s why manifestation
is milder that the first one.

Additional Notes!
T CELL LYMPHOPOESIS
STAGES IN B CELL DEVELOPMENT
ANTIGEN INDEPENDENT PHASE (BONE MARROW) Table No. 4 Summary of T Cell Maturation
● Stromal Cell in the BM secrets the necessary Stage Maturation CD Surface
cytokines, immune substances that influence the Events Markers
development of a b cell from a common
Pro-T Cell Migration from CD2, CD44
lymphoid progenitor
marrow to
● Early in the period of a progenitor B cell, there will
be a gene rearrangement that will occur inside
thymic cortex
the nucleus α/β Pre- T Migration from TdT, CD1, CD2,
o Differentiation: The Pre-B cell a cell thymic cortex to CD3, CD4, CD5,
cytoplasmic (m) heavy chain medulla, CD7, CD8
o This will be a part of the developing IgM elimination of
● Mature or naïve immature B cell will have genes self-recognizing T
that were rearranged for the light chain cells, α/β TCR
o Antibody has both heavy chain and light
arrangement (for
chain
T cells destined
o These are gens that rearrange according
to the specificity for the helper or
o Adoptive immune system is specific suppressor
● After some time, it will migrate from the bone subset)
marrow to the follicles of the secondary lymphoid γ/δ Pre- T Migration from TdT, CD1, CD2,
organs, bearing the IgM and IgD in its surface that cell thymic cortex to CD3, CD7
will act as a receptor for the antibody to react medulla,
with an antigen that it will encounter in the spleen
elimination of
and lymph node
self-recognizing T
o It will be bloodborne. That’s why
lymphocyte concentration is measured in
cells, γ/δ TCR
the blood arrangement (for
T cells destined
ANTIGEN DEPENDENT PHASE for the cytotoxic
● The mature B cell will go to the germinal centers or subset)
follicles

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Mature T Loss of the ability HELPER T: CD2, o Either CD4 or CD8 is present but not the both
Cell to make TdT, CD3, CD4, CD5, of them or there is none of them at all are
present.
circulation in CD7
● It already lost its ability to create TdT (Terminal
peripheral blood SUPPRESSOR T:
deoxyribonucleotide Transferase)
as helper, CD2, CD3, CD5,
o Hindi na makakaarrange ng CR. Meaning
suppressor, or CD7, CD8 specific na siya to a certain antigen
cytotoxic subset CYTOTOXIC T: Mature B cell
CD2, CD3, CD7 ● After the maturation in thymus, it will go to the spleen
and lymph nodes and waits for antigen the is being
● The formation of the T cell happens in the bone filtered by spleen and lymph nodes. When binds with
marrow specific antigen, the T cell will proliferate either T
o It travels to the thymus for maturation or helper cells or cytotoxic T cells depends on the
differentiation instruction/dictate of cytokines.
● The surface receptor of T cell is TCR (T cell receptor)
o The surface receptor of B cell is IgM
● In the thymus, the selection process occurs to
eliminate t cells that recognize our self-antigens
o IMMUNE TOLERANCE
o 97% will undergo apoptosis due to the
selection process
o This is to ensure immune tolerance against
self-antigens

PRO T CELL
● It has CD25 receptor of IL 2 (produce by the
macrophages which when bound to CD25 that is
present to Pro T cell will lead to further differentiation
of T cells to the different subtypes).

A/B PRE-T CELL

● Double Positive Stage
o TCR rearrangement (T-Cell receptor) of
genes that codes for TCR proteins
▪ Counter part of immunoglobulin of B cell
o Bears CD4 and CD8

Y/G PRE-T CELL

● Double Negative Stage
o Immune tolerance and Specificity
o 97% of the prothymocytes that was formed in
the bone marrow is eventually destroyed in
the thymus
o To eliminate self-recognizing T cells
o To avoid having T cells, later on, that
recognizes and destroys self-antigen

MATURE T CELL
● They can be a helper cells, suppressor or cytotoxic
subset depending on the kind of the invading
microorganism

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HISTORICAL DEVELOPMENT OF IMMUNOLOGY
● TCR CD4 binds antigen in context of MHC class I and
MHC class II partners with the antigen which is
presented to the T lymphocytes.
o Example: Extracellular microbes is
T LYMPHOCYTES ANTIGEN RECEPTOR phagocytize, the digestive product is one of
the antigens of the microbe and partners
● >95 % of T lymphocytes antigen receptor are made
with Class I. During the activation of T cells, it
of α and β subunits linked with the disulfide bonds to
binds to the CD8 receptor and then the
form a molecular heterodimer that resides on the
CD8+ T cells will bind with the one molecule
outer membrane of the cell in association with the
of the antigen.
CD3 molecular complex (CD3 is a pan-T cell marker)
● α~ and β-subunit TCR proteins have variable, joining
Additional Notes!
and constant regions (α also contains a diversity
region), with corresponding encoding regions in the ● Antigen was phagocytosed,
TCR gene that undergo rearrangement, resulting in
phagosome/endosome is formed, and then the
high specificity binding for a particular antigen.
antigen is digested.
● CD3 proteins assist transduction of the signal to the
● Epitope of the microorganisms was processed and
interior of the cell when an antigen binds to the TCR
is presented through the MHC antigen as a
on the lymphocytes surface.
receptor to the TCR receptor of the Cell. If binding
o Co-receptor restricts the activation of T cell
occurs, it will activate t-cell.
● A small percentage of T lymphocytes have a TCR
composed of γ- and δ-subunits that similarly interact ● T lymphocytes will proliferate into different t-
with CD3; these cells are generally found at the lymphocytes
mucosal surfaces of the gastrointestinal and o MHC class II: CD4 + TCR – TH Cells
respiratory tracts. ▪ Macrophage, neutrophil, activated B cell
o MHC class I: CD8 + TCR – Cytotoxic T cells
▪ Other somatic cells of the body

CD4+ HELPER/INDUCER T CELLS

● 60% of CD4+ cells
● Direct the functions of other cells of the immune
system by secreting cytokines that stimulate various
functions.
● Mechanism of antigen recognition: CD4+ T cells
recognizes antigen only in the context of MHC class II
antigens
● SUBPOPULATIONS: (depends on the proliferation of
T-cells)
a. Th1 cells which secret interleukin (IL)-2, TNF-β and
interferon (IFN)-γ, facilitate macrophage
activation, delayed-type hypersensitivity, and the
production of antibodies with opsonizing action.
It mediates an immune response against
intracellular pathogens.
▪ Tuberculosis (intracellular)- the
Notes: immunologic mechanism for injury is a
● Human Leukocyte Antigen or Major delayed type of hypersensitivity.
Histocompatibility Complex present in leukocytes.
▪ The Th1 cells influences the B cell by
Human leukocytes Class I (MHC I) antigens are found
secreting these substances to produce
in normal cells and almost all nucleated cells have
antibodies with opsonizing action. This is
MHC I while MHC II are rare to see in cells.
the mechanism/process that would kill
intracellular pathogens.

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HISTORICAL DEVELOPMENT OF IMMUNOLOGY
▪ Opsonin- needed to recognize the
intracellular pathogen
b. Th2 cells which secretes IL-4 and IL-5, direct
synthesis of other antibodies such as IgE and
activate eosinophils and are important in
defense against extracellular parasites.
i. Extracellular parasite: T. vaginalis
c. T regulatory (Treg) cells have surface markers for
CD4 and CD25 (IL-2 receptor). Induces regulatory
T (Treg) cells produce TGF-β, IL-10 and IL-35 are
involved in maintaining self-tolerance and
regulating immune responses.
d. Th17 cells produce IL-17, IL-21 and, IL-22 and
mediate immune responses against extracellular
bacteria and fungi.
● Intracellular pathogen: chlamydia, mycobacterium,
plasmodium spp.
e. Cannot be phagocytose because it is inside the
cell
Example:
● Plasmodium- infects the liver cells and RBC
o Cannot be phagocytose because it is inside
the cell
o The means that they can be recognized by the
immune system is through the spleen
CD8+ CYTOTOXIC/SUPPRESSOR T CELLS
● 30% of T cells
● Mechanism of antigen recognition: CD8 molecules
interact with MHC class I molecules.
● Can lyse/destroy the infected cell
f. Ex. Liver cell infected with Hepatitis B virus.
G. Direct cytotoxicity
H. Can directly kill the viral infected cell
Note:
● Normal ratio of CD4+ to CD8+ cells in the blood is
typically 2:1.
● CD4+ = 60% of CD3+ of the cells
● CD8+ = 30% of T cells
● NK = 10% (does not express/ possess a CD4/CD8
marker)
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NATURAL KILLER CELL (NK CELL)
● Part of natural/ innate component of immune system
but also an effector cell for the adaptive immune
system
● CD Marker: CD16 and CD56
o CD16- receptor for Antibody Dependent Cell
Cytotoxicity (ADCC)
TWO MECHANISM IN FIGHTING INFECTED CELLS:
● FIRST: One mechanism of NK cell cytotoxicity is
through the Antibody Dependent Cell Cytotoxicity
(ADCC)
o Direct cytotoxicity of the NK cell wherein CD
16 present is the receptor for the Fc fragment
of IgG acting as an opsonin facilitating
ADCC
o Normally, the NK cell does not kill a normal
cell
● SECOND: NK cell is activated or kills a virus infected
cell/ tumor cell because during infection or in the
conversion of a cell to becoming a tumor cell, if the
cell loses the expression of the class I major
histocompatibility complex antigen
o Normal cell- has class I MHC
o Virus infected cell/ Tumor cell- loses the
ability to express have MHC I
o MHC- dictates an inhibitory effect to the NK
cell
o In absence of Class I MHC, NK cells are
activated and exerts cytotoxic effect with
the mediators granzymes and perforins
▪ NK cells can directly destroy abnormal/
infected cells through cytotoxicity
through the molecules/ chemical
perforins and granzymes
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HISTORICAL DEVELOPMENT OF IMMUNOLOGY
▪ Perforins- these are soluble factors that
create perforations/leak in infected cells
so that the infected cells will lyse/burst REFERENCES
Figure B: Notes from the discussion by Prof. Jordan Callueng,
● If the cell is infected with virus, nawawala ang class I RMT, MD
MHC expression, leaving the activating receptor of
the NK cell to transduce the signal for the Cagayan State University PowerPoint presentation
proliferation and activation of NK cell, thus killing the
virus infected cell/ tumor cell
● All nucleated cells normally express the class I
antigen

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