MT021: IMMUNOLOGY & SEROLOGY

LESSON 4: ADAPTIVE IMMUNITY

2ND SEMESTER | S.Y. 2021-2022 TRANSCRIBED BY: GILLIAN J. HERCE – L3
LECTURER: MR. JAN ETHAN LOVENDINO, RMT, MSPH

TOPIC ᵜ once they enter, they migrate upward in the

SUBTOPIC
SUB-SUB TOPIC cortex and begin development of your T-cell
NOTES receptors
OUTLINE ᵜ from T cell precursor nagiging Double
‫؞‬ Adaptive Immune System negative/ DN
‫؞‬ T-cell Differentiation ᵜ then undergoes series of reax, maturation
‫؞‬ B-cell Differentiation sequences
‫؞‬ The Role of T-cells in the Adaptive Immune ᵜ from then, magdedevelop na siya ng T cell
Response receptor
‫؞‬ The Role of B-cells in the Adaptive Immune ᵜ t cell receptor consists of 2 specific chains:
Response º alpha & beta – recognize our antigen
‫؞‬ Study Guide
ADAPTIVE IMMUNE SYSTEM
Specificity for each individual pathogen or
ᵜ
microbial agent
ᵜ The ability to remember a prior exposure
ᵜ An increased response to that pathogen upon
repeated exposure
LYMPHOCYTES
ᵜ T cells
ᵜ B cells
Notes:
ᵜ T-cells and B-cells are primarily produced in
bone marrow however, has diff. maturation
site
ᵜ T-cell – maturation site: thymus
º Pinaka mataas na number of º has 2 regions:
circulating lymphocyte 60-80% º variable region (taas) – the one that
ᵜ B-cell – maturation site: bone marrow come in contact sa antigen
º Main function: to transform into º constant region – effector region,
plasma cell and produce antibodies nagsignal sa cell na meron naka
attach sa variable region
T-CELL DIFFERENTIATION º beta chain is the most important
ᵜ Lymphocyte precursors ->THYMUS->Thymocytes ▪ formation & rearrangement
ᵜ Interaction with stromal cells under the influence happens in
of cytokines, especially interleukin-7 (IL-7), is ▪ first thing to occur
critical for growth and differentiation ▪ appearance of alpha chain
ᵜ The CD2 (E rosette) marker is also known as means beta chain should not
Sheep RBC receptor (SRBC receptor) be produced. That’s why beta
ᵜ Pan T cell markers: CD2, CD3, CD5 and CD7 chain ang nauuna. Pag
Notes:
ᵜ IL-7 natapos na ang beta chain
º Major interleukin that stimulated the saka magoccur ang alpha
maturation of our lymphoid progenitor chain
º Lymphoid lineage helps with the ▪ in short, presence of a-chain
stimulations of T-cell suppresses the coding of b-
chain
DOUBLE-NEGATIVE STAGE Beta chain:
ᵜ Early thymocytes that lack CD4 and CD8 markers ᵜ important bcs the appearance of beta chain
ᵜ actively proliferate in the outer cortex under the triggers thymocyte to become CD4 & CD8
influence of IL-7 ᵜ appearance of b chains triggers thymocytes
ᵜ Rearrangement of the genes that code for T-cell to become double positive
receptor (TCR) begins at this stage
Notes: ᵜ lymphocyte that undergoes/ express b
chain to be double positive becomes our T
cells (either CD4/CD8)
*beta chain component is coded by chromosome 7
*alpha chain component is coded by chromosome 14
ᵜ other chain involved: (comes in pair)
º delta & epsilon
º gamma & epsilon
º tau & tau
ᵜ collectively (these 3 pairs), it is called CD3
(common in immature lymphocyte)
ᵜ as a whole (all 4 pairs), it is called CD3/TCR
complex
º found in immature/developing T cell –
called pre-TCR receptor
ᵜ corticomedullary junction – digdi nagaagi si T
lymphocyte precursor
 MT021: IMMUNOLOGY & SEROLOGY
LESSON 4: ADAPTIVE IMMUNITY
2ND SEMESTER | S.Y. 2021-2022 TRANSCRIBED BY: GILLIAN J. HERCE – L3
LECTURER: MR. JAN ETHAN LOVENDINO, RMT, MSPH

Double negative express gamma & delta instead of

b chain – has different development pathway that’s
why they remain CD4 negative & CD8 negative for
the rest of their life
ᵜ ini tong mga nagiging natural killer cells.
DOUBLE-POSITIVE STAGE
ᵜ expresses both CD4 and CD8 antigens
Notes:

Pag hindi pinatay magccause ng autoimmune

ᵜ
disease
ᵜ Same process sa positive selection pero this
time self-antigen ng involved instead na MHC
ᵜ CD4/CD8 binding to MHC class I/II is okay but if
the cell reacts to the self-antigen, it means it
doesn’t recognize the self.
ᵜ It will undergo clonal deletion via apoptosis
ᵜ Single positives that does not attack the self-
expresses CD4 & CD8
ᵜ
antigen will be permitted to exit the thymus –
has CD3/TCR complex
ᵜ
becoming the mature T cell
if CD3/TCR complex naexpress na totally,
ᵜ
“positive” because dapat may association between
double positive stage will undergo positive
T cell and MHC
selection.
“negative” because dapat walang reaction yung
POSITIVE SELECTION:
lymphocyte sa self-antigen
ᵜ double
SELF-REACTIVE CELLS
positive
ᵜ Positive selection is not perfect, meron mga
T cells
nakakalusot kahit na hindi dapat and it is
that
called self-reactive cells
have
ᵜ Dito papasok ang peripheral tolerance, which
TCR
ensures that self-reactive lymphocytes are
ᵜ capable
killed to prevent autoimmune disease
magbind
ᵜ The most important cell related to peripheral
sa MHC
tolerance is nTreg cell
class I/II
ᵜ Since it is capable of regulating the cells that
sa thymic epithelial cells
escaped
ᵜ sila ang binubuhay.
ᵜ Ways how nTreg regulates:
ᵜ Double + t cells that doesn’t bind with MHC
º Clonal anergy (main mechanism of
class I/II sila ang namamatay (apoptosis)
PT) & clonal deletion
ᵜ Double + that has strong bond to MHC also
º Clonal anergy – inactivates self-
dies
reactive cells so that they wont
ᵜ After positive selection, it will become single
respond to antigens, therefore not
positive, either CD4 or CD8
capable of reacting with self-antigen
ᵜ CD4- MHC class II
º Clonal deletion – ntreg cell triggers the
ᵜ CD8- MHC class I
cell to undergo apoptosis but ntreg
*capacity of our double + to recognize MHC class I/II
main function is clonal anergy kaya
is called MHC restriction.
konti lang ang kaya niyang patayin
* double + t cells that has TCR are exposed to cells in
ᵜ Transforming growth factor beta / TGF-beta
your cortex that has either MHC class I or MHC class
º Converts self-reactive T cells in the
II
periphery to become induced Treg/
iTreg (under peripheral tolerance)
In positive selection, not only CD4 & CD8 ang
napproduce, other cells are formed too which is MATURE T-CELLS
called ᵜ Mature, peripheral T cells have the CD2 (E
Regulatory t cells/ Treg cells (formerly known as rosette), CD3 (mature T cell), and CD4 or CD8
suppressor T cell. markers.
ᵜ Treg has 2 classifications: ᵜ CD4+ T cells (T helper or Th cells) recognize
º nTreg cell (Natural Treg) – produced antigen along with class II MHC protein
in thymus together with CD4 & CD8 ᵜ CD8+ T cells (cytotoxic T cells) interact with
iTreg cell (induced Treg) – produced in periphery antigen and class I MHC proteins.
Maturation doesn’t end in positive selection… T-HELPER CELLS
Notes:
NAGATIVE SELECTION
ᵜ APCs secretes specific polarizing cytokines
ᵜ these are the ones that survived positive (depending on the pathogen present) that
selection direct naïve CD4 Tcells to further differentiate
ᵜ aka: central tolerance
into:
ᵜ purpose: kill all single positive cells that react
ᵜ Th1 cells
to self-antigen
ᵜ Th2 cells
ᵜ MHC-self antigen reaction
 MT021: IMMUNOLOGY & SEROLOGY
LESSON 4: ADAPTIVE IMMUNITY
2ND SEMESTER | S.Y. 2021-2022 TRANSCRIBED BY: GILLIAN J. HERCE – L3
LECTURER: MR. JAN ETHAN LOVENDINO, RMT, MSPH

ᵜ T regulatory (Treg) cells ᵜ Differentiation of pro-B cells into pre-B cells occurs
ᵜ Th9 cells upon successful
ᵜ Th17 cells rearrangement
of heavy-chain
genes on one of
the number 14
chromosomes
Notes:
Requires direct contact with bone marrow
ᵜ
stromal cells for it to be differentiated
ᵜ Stem cell
º common lymphoid progenitor
º has CD34
º becomes pro B cell pag meron na
growth factors
ᵜ growth factor… esp IL-7 -> stimulates common
lymphoid progenitor
ᵜ the genes of progenitor B cells are now
Notes:
encoding for the chains of antibody molecules
Ex. Kung ang nasecrete na cytokine katong
ᵜ
C-Kit + Stem cell factor = ACTIVATION
specific na pathogen is IL-22, IFN-y, si CD4
ᵜ c-kit -> receptor found in progenitor b cell
magiging TH1. Then TH1 will secrete IFN-y &
ᵜ stem cell factor -> receptor/factor found in
TGF-beta
bone marrow stromal cell
*we can conclude that majority of the cells involved in
autoimmune disorders are CD4 coz ang tinatransform ᵜ activation -> direct contact is necessary for
activation
kang TGF-beta para maging induced is CD4
*differentiation of pro B cells into pre-B cells occurs
pag naencode na yung heavy chains sa chromosome
TH1 -> effective sa intracellular pathogen
14
TH2 -> effective sa extracellular pathogen
PRE-B CELLS
Treg cells (markers?) ᵜ (1) Characterized by the presence of
ᵜ CD4 CYTOPLASMIC µ chains
ᵜ CD25 ᵜ (2) may also express µ chains on the cell surface,
ᵜ FOXP3 accompanied by an
º Aka Scurfin unusual light chain
º Most important molecule called a
º Purpose: suppression of immune surrogate light chain.
response to self-antigen ᵜ (3) Ig-α and Ig-β, which
TH17: IL-17 – induced inflammation are signal-transducing
TH9: IL-9 – stimulates mast cell (allergic reactions) subunits
B-CELL DIFFERENTIATION ᵜ (1) + (2) + (3) = pre-BCR
Notes:
ᵜ BONE MARROW ᵜ Pag arranged na ang heavy chain genes
ᵜ B-cell precursors go through a developmental maeencode na yan ng chains na part ng
process that prepares them for their role in antibody which is cytoplasmic u chains
antibody production and, at the same time, ᵜ Indicating pre-B cell
restricts the types of antigens to which any one cell ᵜ Involved in IgM
can respond. ᵜ Signal transducing subunits – receive ng
3 PHASES: signals from the body/produced by other cells
ᵜ Development of mature immunocompetent B ᵜ Without surrogate light chain & Ig-a & Ig-b the
cells pre-B cell will undergo cellular arrest/
ᵜ Activation of B cells by antigen developmental arrest
ᵜ Differentiation of activated B cells into plasma ᵜ Only those who have this indicator may
cells, which produce antibodies continue to differentiation/ multiplication
ANTIGEN-INDEPENDENT PHASE ᵜ Only found in developing B cell
ᵜ Divided according to formation of several distinct ᵜ Without any expression of pre-BCR si pre-B
subpopulations: cell hindi siya magdidifferentiate into
º Pro-B cells – aka progenitor immature B cell
º Pre-B cells – aka precursor
º Immature B cells IMMATURE B CELLS
º Mature B cells ᵜ distinguished
PRO-B CELLS/ PROGENITOR B CELL by the
ᵜ E2A, EBF (early B-cell factor), interferon regulatory appearance
factor (IFR8), and paired box protein 5 (PAX5) of complete
interleukin-7 (IL-7) are necessary at this early IgM antibody
developmental stage. molecules on
ᵜ Heavy chains of antibody = CHROMOSOME 14 the cell
ᵜ Light chains = CHROMOSOME 2 and 22 surface
ᵜ C-Kit + Stem cell factor = ACTIVATION
 MT021: IMMUNOLOGY & SEROLOGY
LESSON 4: ADAPTIVE IMMUNITY
2ND SEMESTER | S.Y. 2021-2022 TRANSCRIBED BY: GILLIAN J. HERCE – L3
LECTURER: MR. JAN ETHAN LOVENDINO, RMT, MSPH

ᵜ Variable regions determine the specificity for ᵜ Commonly found in lymphoid organs/resides
antigen in bone marrow
ᵜ Pre-existing diversity of receptors for antigen is a ᵜ If ever mangapit bahay sinda, they are non-
hallmark of the adaptive immune system. dividing so they die without proliferating but
ᵜ surface proteins that appear on the immature B capable of producing antibodies but have
cell include CD21, CD40, and class II MHC shorter life span
molecules THE ROLE OF T-CELLS IN THE ADAPTIVE IMMUNE
* Central Tolerance – elimination of B cells that bear self- RESPONSE
reactive receptors in the marrow ᵜ Interaction between T cells and antigen presenting
Notes:
ᵜ complete means heavy & light chains are cells (APCs) is the initiating event in the adaptive
done. Therefore chromosome 2 & 22 are immune response.
Notes:
involved Tcell <-> APcs interaction is important, no
ᵜ
ᵜ IgM on the surface serves as a receptor for the interaction means useless ang T cells
antigens: the variable region of IgM ᵜ T cells can be found in lymphoid organ/lymph
ᵜ The capability to respond to an antigen is built nodes
before a B cell ever encounter an antigen. Action of Thelper Cell
Unlike in T cell receptor, it needs APCs to be ᵜ Without antigen presented T cell (CD4/8) will
activated not function at all
ᵜ CD21- most important ᵜ To induce transformation of t cell, interaction
º Receptor of C3 (C3 coats antigen) between the CD4 & TCR , antigen together with
º Presence of this enhances the the MHC class II is a must.
likelihood na yung contact between b ᵜ CD4 acts as a co receptor to stabilize the
cells and antigen is magooccur binding of TCR-antigen.
ᵜ B cells that are capable of producing ᵜ 2nd signal is provided by the binding og CD28
antibodies against self-antigen receives a on the t cell
signal to undergo apoptosis. This is through ᵜ Exposure of CD4 to antigen causes production
central tolerance of IL-2 receptor
MATURE B CELLS ᵜ CD25 which binds to IL-2 produced by the t-
ᵜ Characterized by cell to proliferate
the presence of THE ROLE OF B-CELLS IN THE ADAPTIVE IMMUNE
both IgM and IgD on RESPONSE
the cell surface ᵜ Antigen-dependent activation of B cells takes
ᵜ Marginal Zone B place in the primary follicles of peripheral
cells lymphoid tissue.
ᵜ Follicular B cells ᵜ Follicular dendritic cells present antigen to B cells
Notes:
ᵜ B cell that doesn’t react with self-antigen & and thus play a key role in the immune response.
survived central tolerance RESPONSE TO T-DEPENDENT ANTIGENS
ᵜ Presence of IgM & IgD
ᵜ IgD – is not required in the functioning of B cells
but prolongs the life span of the mature B cell
esp yung mga nasa periphery
ᵜ Categorized into 2
ᵜ Marginal zone B cells – remain in the spleen
and this is where they interact with pathogens
ᵜ Follicular zone B cells – migrate into the lymph
nodes and constantly circulate the secondary
lymphoid organ
*when a mature B cell come in contact with an antigen
it will transform into
ᵜ Plasma- produce antibodies
ᵜ Memory- memory of the antigen
ANTIGEN-DEPENDENT PHASE
ᵜ Plasma Cells
º characterized by the presence of
abundant cytoplasmic immunoglobulin
and little to no surface
immunoglobulin
º cartwheel or clock face
arrangement/appearance
º most fully differentiated
lymphocyte
º Main function is
antibody production RESPONSE TO T-INDEPENDENT ANTIGENS
Notes:
ᵜ Not normally found in blood
 MT021: IMMUNOLOGY & SEROLOGY
LESSON 4: ADAPTIVE IMMUNITY
2ND SEMESTER | S.Y. 2021-2022 TRANSCRIBED BY: GILLIAN J. HERCE – L3
LECTURER: MR. JAN ETHAN LOVENDINO, RMT, MSPH

ᵜ T-independent antigens can bind to B cells

through immunoglobulin receptors and trigger B-
cell transformation directly.
ᵜ Several antigen receptors must be cross-linked in
order to activate a B cell directly.
ᵜ Antigens can also be bound to B cells’ innate
immune receptors
such as TLRs.
ᵜ Typically, these
antigens produce
IgM only because the
induction of memory
cells does not occur
to any great extent.
STUDY GUIDE