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Prelim - Adaptive Immune Response

The document discusses the adaptive immune response. The adaptive response is faster, larger, more specific, and causes less self-damage than innate immunity. It involves T and B lymphocytes that provide specificity and memory. T cells mature in the thymus and regulate B cell responses and kill infected cells. B cells mature in bone marrow and produce antibodies. The adaptive response has phases of antigen recognition, lymphocyte activation, antigen elimination, contraction, and memory. T cell differentiation occurs through gene rearrangement in the thymus cortex and medulla, with selection removing self-reactive cells.

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0% found this document useful (0 votes)
32 views12 pages

Prelim - Adaptive Immune Response

The document discusses the adaptive immune response. The adaptive response is faster, larger, more specific, and causes less self-damage than innate immunity. It involves T and B lymphocytes that provide specificity and memory. T cells mature in the thymus and regulate B cell responses and kill infected cells. B cells mature in bone marrow and produce antibodies. The adaptive response has phases of antigen recognition, lymphocyte activation, antigen elimination, contraction, and memory. T cell differentiation occurs through gene rearrangement in the thymus cortex and medulla, with selection removing self-reactive cells.

Uploaded by

Justin Bellosa
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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TOPIC 3: ADAPTIVE IMMUNITY – ADAPTIVE IMMUNE RESPONSE

OUTLINE ADPTIVE IMMUNE RESPONSE

1. Faster
I. Introduction
2. Larger
II. Adaptive Immune response
a. Phases of Adaptive Response 3. More specific
III. T-cell Differentiation 4. Less damage to self
IV. T- cell activation and effector function
V. T-helper sub populations and function 1. Antigen Recognition
VI. B- cell expansion and differentiation
PHASES OF ADAPTIVE RESPONSE
VII. The role of T-cell in Adaptive Immune
Response 2. Lymphocyte Activation
VIII. The role of B-cell in adaptive Immune 3. Antigen Elimination
Response 4. Contraction (Homeostasis)
IX. Laboratory Identification of Lymphocytes 5. Memory

INTRODUCTION
Adaptive immune response:
- Host response to foreign agents that
depends on T and B lymphocytes and is
characterized by specificity, memory, and
recognition of self versus nonself.

Shortcomings of innate immunity:


 Non-specific- Similar pattern of response
for all pathogens
 Poor regulation- Control mechanisms are
poor or lacking
 Poor amplification- Response magnitude
same for all insults
 Lack of self discrimination- Harm to self
results for lack of specificity
 Short duration
 No memory

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ADAPTIVE IMMUNITY Differentiation of lymphocytes:
- A type of resistance characterized by: ● Appears to take place very early in fetal
• Specificity for each individual pathogen or development.
microbial agent ● Essential to the acquisition of
• The ability to remember a prior exposure immunocompetence by the time the infant is
• An increased response to that pathogen upon born.
repeated exposure
- A more tailored response; takes a longer time to Progenitors of T and B cells - appear in the FETAL
be activated, but more specific and longer lasting. LIVER (at 8 weeks of pregnancy)

LYMPHOCYTE LATER in fetal development:


- the key cell involved in the adaptive immune
response. Production of lymphocyte progenitors - shifts to the
BONE MARROW (now the primary producer of
2 main types of lymphocytes: hematopoietic cells at birth)

1. T cells

- mature in the thymus T-CELL DIFFERENTIATION


- serve a regulatory role by providing help to B cells
in responding to antigens as well as by killing virally T-CELLS
infected target cells - About 60% to 80% of circulating lymphocytes in
the peripheral blood; differentiated in the thymus.
2. B cells Lymphocyte precursors enter the thymus from the
bone marrow.
- mature in the bone marrow
- differentiate into plasma cells that produce
W/in the lobules of the thymus are 2 Main
antibodies.
Zones:
Immunologic memory - based on clonal
1. Outer cortex (OC)
selection, expansion, and differentiation of antigen-
specific T and B cells. Result: ability to respond with - early precursors
GREATER speed and intensity to a re-encounter with enter the thymus at the cortico-medullary junction
the same pathogen, protecting the host from and migrate to the OC.
reinfection. Note: Migration occurs in waves w/c is driven by
chemical messengers called chemokines.
B and T cells go through an elaborate maturation
process in 2. Inner medulla
which:
● Specificity is developed
Possible self-reactive cells are destroyed. ● Chemokines - a large family of cytokines that
have the ability to recruit specific
cells to a particular site.
● Appears to take place very early in fetal
development ● Thymocytes - they refer to precursors that are
committed to becoming T cells, once in the
thymus.

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● As thymocytes travel through the thymus,
there is an orderly TCR consists of two specific chains:
● rearrangement of the genes coding for the 1. alpha (α) chains
antigen receptor. 2. beta (β) chains
● At the same time, distinct surface markers Both contain variable regions that recognize specific
appear during specific stages of antigens.
development. ● These 2 chains occur in a complex with 6 other
chains that are common to all T cells.
MATURATION - an elaborate process that ● CD3/TCR complex - the combination of the 8
takes place over a 3-week period as cells filter chains
through the cortex ● 6 chains of the nonspecific CD3 portion of
to the medulla. the complex - assist in signaling when an
antigen binds to the T cells.
Thymic stromal cells include: These chains occur in 3 pairs:
(all play a role in T-cell development) ● delta-epsilon (δ–ε) chain
● epithelial cells ● gamma-epsilon (γ–ε) chain
● macrophages ● a tau-tau (ζ–ζ) chain (in the cytoplasm of the
● fibroblasts cell)
● dendritic cells
● The α and β chains of the TCR - coded for by the
● Interaction with stromal cells under the selection of certain gene segments and deletion
influence of cytokines (esp. IL-7) = critical of others in a random fashion.
for growth and differentiation.

Significant selection process occurs as maturation Rearrangement:


takes place! This includes both:
o Positive selection 1. β chain coded for on chromosome 7 occurs first.
o Negative Selection 2. Then, the α chain coded for on
chromosome 14 is rearranged afterward.
An estimated 97% of the cortical cells die
intrathymically before becoming mature T cells! ● 3 different gene segments (V, D, & J) -
rearranged and combined with a constant region
to code for the β chain;
DOUBLE NEGATIVE STAGE
● 2 gene segments - combined with a constant
region for the β chain.
DOUBLE-NEGATIVE (DN) THYMOCYTES - refer ● The appearance of a functional α chain on the
to early thymocytes lacking CD4 and CD8 markers, cell surface sends a signal to suppress any
w/c are important to their later function further β chain gene rearrangements.
● Large DN thymocytes - actively proliferate in the
OC under the influence of IL-7. ALLELIC EXCLUSION - the selection of an allele
● Rearrangement of the genes that code for the on 1 chromosome only.
antigen receptor (aka T-cell receptor (TCR)) ● Pre-TRC Receptor - formed by the
begins at this stage combination of the β chain with the rest of CD3
forms.
This random gene rearrangement - builds in the ● Appearance of the β chain also triggers the
diversity that allows T cells to respond to the myriads thymocyte to become CD4–positive (CD4+) and
of different antigens that the body might encounter CD8–positive (CD8+).
in a lifetime.

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● MHC RESTRICTION - selection of thymocytes
10% of thymocytes: that will only interact with the MHC antigens
found on host cells.
● Any thymocytes that have either a very low or a
● Rearrange and express two other chains—
very high affinity for self-MHC antigens = DIE by
● gamma (γ) and delta (δ)—when there is NOT a
apoptosis.
productive rearrangement of DNA coding for a β
● NEGATIVE SELECTION (NS) - second
chain.
selection process taking place among the
● They proceed on a different developmental
surviving DP T cells, in the corticomedullary
pathway, remain NEGATIVE for both CD4 and
region and the medulla of the thymus
CD8.
Note: Medullary epithelial cells express a
● As mature T cells, they appear to represent the
dominant T-cell population in the skin, intestinal
wide variety of self-antigens
● Strong reactions with self-peptides other than
epithelium, and pulmonary epithelium. (Tasks
MHC antigens TRIGGERS apopotosis.
include wound healing and protection of the
epithelium)
CLONAL DELETION - process of elimination of
● Capable of recognizing antigens WITHOUT being
clones of T cells that would be capable of an
presented by MHC proteins (to represent as an
autoimmune response.
important bridge between innate & adaptive
Note: Only 1% to 3% of the DP thymocytes in the
immunity)
cortex survive!

DOUBLE- POSITIVE STAGE T-CELL ACTIVATION AND EFFECTOR


- the 2nd stage FUNCTION
Clonal expansion and memory
DOUBLE-POSITIVE (DP) THYMOCYTES • IL-2 induce T-cell proliferation
- when thymocytes express BOTH CD4 and CD8 •Expansion of antigen-specific T-cell begin
antigens O Effector Cells = ACTIVE
● Young DP thymocytes begin to rearrange the O Memory Cells = LONG LIFE SPAN
genes coding for the α chain. Note: Clones increase more than 100k fold; doubling
● When the CD3-αβ receptor complex time: 6hrs
(TCR) is complete and expressed on the cell surface,
a positive selection process takes place.

POSITIVE SELECTION
● Allows only DP cells with functional TCR
receptors to survive.
● T cells must recognize foreign antigen in
association with class I or class II MHC MATURE T-CELLS
molecules. ● Survivors of selection exhibit only one type of
● When thymocytes bind to self-MHC antigens in marker, either CD4 or CD8 (may depend on
the cortex by means of the newly formed TCR which MHC protein the cell interacts with, how
receptors, an enzyme cascade involving a group strongly they react, and to which cytokines they
of enzymes called kinases is activated. are exposed).
● Enzyme activity causes changes in cell shape ● CD4+ T cells - recognize antigen along with
and motility that lead to increased cell survival. class II MHC protein; mainly T helper cells
● CD8+ T cells - interact with antigen and class I
MHC proteins; cytotoxic T cells

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● the CD4 receptor are mainly T helper (Th) cells,
whereas the CD8+ population consists of ✔ Th17 Cells
cytotoxic T cells. -produce IL-17and IL-22 (both of these cytokines
Note: T cells 2/3 (CD4); 1/3 (CD8) can increase inflammation and joint destruction)
- associated with autoimmune diseases such as
SUBPOPULATION OF T-CELLS rheumatoid arthritis, multiple sclerosis, and
inflammatory bowel disease.

✔ Th1 Cells ● All single-positive T cells - spend approximately


12 days in
- produce IFN-γ, IL-2, and ● the medulla.
TNF-β w/c protect cells against ● Additional proliferation of carefully screened
intracellular pathogens by activating cytotoxic ● T cells occurs => then released from the thymus
lymphocytes to seed peripheral lymphoid organs =>
and macrophages. recirculate through the bloodstream and
peripheral organs approx. once every 12 to
✔ Th2 Cells ● 24hrs.
● RECIRCULATION - important for ensuring that T
- produce a variety of interleukins (IL-4, IL-5, IL-6, cells
IL-9, IL-10, & IL-13) ● make contact with antigen.
- Essential role: to HELP B cells produce antibodies ● Resting T cells - life span of up
against extracellular pathogens and to generally ● to several years in peripheral organs.
regulate B-cell activity.
When antigen recognition occurs in the secondary
✔ T regulatory (Treg) Cells lymphoid tissue:
● T lymphocytes are activated and differentiate
- possess the CD4 antigen and CD25 => functionally active small lymphocytes that
- comprise approximately 5% of all CD4+ T cells. produce cytokines.
-important role in SUPRESSING the immune Activities of specific cytokines:
response to self-antigens => inhibit proliferation of Assisting B cells in commencing
other T-cell populations by secreting inhibitory antibody production, eliminating tumor and other
cytokines and the response is antigen-specific. target cells, rejecting grafts, stimulating
hematopoiesis in the bone marrow, & initiating
2 OTHER T-CELL SUBPOPULATIONS: (based on delayed hypersensitivity allergic reactions (known as
the type of cytokines they produce) cell-mediated immunity)

✔ Th9 Cells

- produce IL-9; appear to have a proinflammatory


effect.
- may play a role at epithelial surfaces by warding
off fungi and extracellular bacteria.
- stimulate growth of hematopoietic cells (esp. mast
cells)
- thus, may promote autoimmune inflammation.

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STAGES IN CELL DIFFERENTIATION

Pro- B Cells

B cells – derived from hemtopoietic stem cell that


develops into an early lymphocyte progenitor in the
bone marrow.

 Remain and mature in the bone marrow itself


 Precursors go through developmental
B- CELL EXPANSON AND process that prepares them for their role in
DIFFERENTIATION antibody production and at the same time,
restricts the types of antigens to w/c any cell
can respond
● B-cell Clonal expansion Bone marrow stromal cells –form special niches
● Increase cytokine receptor where stem cells and B cell precursors reside.
● Migration out of lymphoid follicles for T-cell
interaction; Niches - keep B cell precursor localized in order to
● TH cell CD40 ligand (CD40L) bind with Bcell receive signals for differentiation.
CD40 receptor (CD40R) induces B cell
Variable regions- make each antibody molecule
proliferation and differentiation; CD40 and
specific for a certain antigen or group of antigens.
cytokines induces isotype switching (IgM
to IgG, IgE or IgA) Three phases of the developmental process:
1. Effector cells: Plasma Cells
1. Development of mature
2. Memory B cells
immunocompetent B cells
● Secretes low level IgM at early phase (Naïve
2. Activation of B cells by antigen
B-cells)
3. Differentiation of activated B cells into
IgM – in early infection plasma cells, w/c produce antibodies

IgG – later infection Antigen-independent phase – first phase of B-


cell development in the bone marrow, results to
mature B cells but not yet exposed to antigen

 can be divided according to formation of


distinct subpopulations: pro-B cells
(progenitor B cells), pre-B cells (precursor
B cells), immature B cells, and mature B
cells.
B cell progenitors – require direct contact w/
bone marrow stromal cells.

 Necessary transcription or growth factors


(produced in the microenvironment of bone

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marrow) to differentiate common lymphoid Surrogate light chain – consist of two short
precursors in to pro-B cells: polypeptide chains that are noncovalently associated
o E2A w/ each other, along w/ two shorter chains, Ig-α
o EBF (early B-cell factor) and Ig-β, w/c are signal-transducing subunits.
o IFR8 (Interferon regulatory
Pre-B cell receptor (pre-BCR) – formed by the
factors)
combination of two heavy chains along with Ig-α, Ig-
o PAX5 (paired bpx protein 5
β and surrogate light chain
1st step in the pro B-phase – the rearrangement
Pre-B cells expressing the μ heavy chains in
of genes that code for the heavy and light chains of
association w/ surrogate light chains survive and
an antibody molecule.
proceed to further differentiation.
 Rearrangement of the DNA is similar to the
Signaling through pre-B receptors formed
process that ccurs in T cells.
stimulates a bust of clonal expansion.
Chromosome 14 – heavy chains of antibody are
coded

 Takes place first in a random fashion


Apoptosis and B-cell development is halted
C-Kit – a receptor on the pro-B cell, interacts w/ a
when gene rearrangement does not work.
cell surface molecule called stem cell factor found on
stromal cells.

 The interaction triggers the activation


process
 DNA is cleaved randomly at certain possible
recombinatiom sites and
Deoxyribonucleotidyl transferase (TdT)
helps to join the pieces back together by
incorporating additional nucleotides in the
joining areas.

Chromosome 2 and 22 – light chains are coded.


Pre- B Cells

This stage begins when the synthesis of the


heavy chain part of the antibody molecule
occurs. Immature B Cells

μ chains – the first heavy chains synthesized, w/c ● Immature B cells are distinguished by
belongs to the class of IgM. complete IgM antibody molecules on the
cell surface.
 Accumulate in the cytoplasm
○ This indicates that rearrangement
 Can be expressed by Pre-B cells on the cell
of the genetic sequence coding for
surface, accompanied by surrogate light
chain molecule. light chains on either
chromosome 2 or 22 has taken
place by this time.

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○ Rearrangement commits a cell to ■
In other words, immature B
produce antibodies specific for cells that cannot recognize
particular antigens or groups of the self do not pass the
related antigens. negative selection.
○ IgM molecules thus serve as the ○ Thus, many B cells producing
receptor for antigen. antibody to self-antigens undergo
● Variable regions, which occur on both the cell death/apoptosis.
light and heavy chains, determine the ● It is estimated that more than 90% of B
antigen specificity. cells die in this manner without leaving the
● Preexisting diversity of receptors for antigen bone marrow.
- hallmark of the adaptive immune system. ● The elimination of B cells that bear self-
○ The capability to respond to a reactive receptors is known as central
specific antigen is built in before a B tolerance.
cell ever encounters an antigen. Immature B cells that survive this selection process
● Once surface immunoglobulins appear, µ leave the bone marrow and proceed to the
chains are no longer detectable in the spleen, where they become mature B cells.
cytoplasm. Mature B Cells
● Other surface proteins that appear on the
immature B cell include: ● Maturation is in the spleen, where they
○ CD21 become marginal zone B cells or follicular B
○ CD40 cells.
○ class II MHC molecules. ● Marginal B cells stay in the spleen for it
● CD21 acts as a receptor for a breakdown to respond quickly to any blood-borne
product of the complement component C3, pathogens they may come into contact
known as C3d. with.
● The presence of the CD21 receptor ● Follicular B cells migrate to lymph
enhances the likelihood of contact between nodes and other secondary organs.
B cells and antigens because antigens ○ Unlike marginal B cells staying in the
frequently become coated with complement spleen, follicular B cells are
fragments during the immune response. constantly recirculating
● CD40 and class II MHC are important for throughout the secondary lymphoid
interaction of B cells with T cells. organs.
● At this stage, there is evidence that self- ● In addition to IgM, all mature B cells
antigens give a negative signal to immature exhibit immunoglobulin D (IgD) on their
B cells. surface.
○ Immature B cells that tightly bind ○ Both IgM and IgD have the same
self-antigens through cross-linking of specificity for a particular antigen or
surface IgM molecules receive a group of antigens. These surface
signal to halt development, resulting immunoglobulins provide the
in arrested maturation and cell primary activating signal to B cells
death (negative selection). when contact with antigen takes
place.

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● IgD is not required for B-cell function but ● Plasma cells in other places DO NOT
may prolong the life span of mature B DIVIDE and, after several days of antibody
cells in the periphery. production, they die without further
○ Unless contact with antigen occurs, proliferation.
the life span of a mature B cell is
typically only a few days. THE ROLE OF T CELLS IN THE ADAPTIVE
● If, however, a B cell is stimulated by IMMUNE RESPONSE
antigen, it transforms to a blast stage that
eventually forms memory cells and  APCs (macrophages and dendritic cell)
antibody-secreting plasma cells. This - are first activated during the innate immune
process is known as the antigen- response through their pattern recognition
dependent phase of B-cell development. receptors.
 Class I MHC - presents antigen that is from
● The production of antibodies by plasma cells
intracellular pathogens such as viruses to
is called humoral immunity. CD8+ T cells.
 Class II MHC - presents antigen from
Plasma Cells extracellular pathogens such as bacteria
processed by a phagocytic cell to CD4+ T
● Plasma cells are spherical or ellipsoidal cells.
● Between 10 and 20 µm.  T cells - circulate continuously through the
● They are characterized by abundant bloodstream, lymph nodes, and
cytoplasmic immunoglobulin and little secondary lymphoid tissue; each naïve or
to no surface immunoglobulin. unstimulated T cell circulates from the lymph
nodes to the blood and back again within 12
● The nucleus is eccentric or oval with
to 24 hours; have either CD4 or CD8 on
heavily clumped chromatin that stains their cell surface.
darkly.  CD4+ T cells – also known as Th cells
● An abundant endoplasmic reticulum  CD8+ T cells – also called cytotoxic T
and a clear well-defined Golgi zone are cells (Tc)
present in the cytoplasm.
● Plasma cells represent the most fully ACTION OF HELPER CELLSS
differentiated lymphocyte
● MAIN FUNCTION: antibody production.  1st signal: CD4+ T cell encounters an
● They are not normally found in the blood; antigen along with a class II MHC molecule
rather, they are located in germinal and binds by using its antigen receptor. CD4
centers in the peripheral lymphoid acts as a co-receptor to stabilize binding.
organs or in the bone marrow.  2nd signal: binding of CD28 on the T cell
with CD80 and CD86 found on APCs.
○ In the bone marrow, plasma cells
 Within 1 to 2 days after antigen recognition
can survive in niches surrounded by has occurred, T lymphocytes are
stromal cells. transformed into large activated blast cells
○ Stromal cells provide chemical that are characterized by polyribosome-
stimulation by cytokines, which filled cytoplasm.
allow plasma cells to be long-lived  The two main subsets of Th cells, Th1 and
and continually produce antibodies. Th2, secrete different types of cytokines and
affect different classes of cells.

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o Th1 subset - secretes IL-2, usually within 30 minutes of
interferon-gamma (IFN-γ) and TNF- contact.
β, which are responsible for the  Granules within cytotoxic T cells contain two
activation of cytotoxic T lymphocytes different types of toxins: granzymes and
and macrophages. perforins.
o Th2 cells - secrete interleukins that  Granzymes - are a class of enzymes called
regulate B-cell activity. serine proteases; enter through the pores;
 Most antigens encountered in the body are do not directly break down DNA , but they
so-called T-dependent antigens, meaning activate a nuclease that destroys the target
that T-cell help is required in order for B cells cell DNA as well as any viral DNA that may
to respond to antigen. be contained inside it; also activate enzymes
 T memory cells - arise early in the course in the target cell that disrupt the cell’s
of an immune response; may arise mitochondria.
independently from effector cells or they may  Perforins - are pore-forming proteins that
arise as soon as the original T cell is insert themselves into the target cell
stimulated. membrane; insert themselves into the target
o Have a higher affinity for antigen cell membrane and polymerize, forming
than unstimulated T cells pores in the membrane.
o Able to proliferate sooner than naïve
T cells, express a broader array of THE ROLE OF B CELLS IN THE ADAPTIVE
cytokines, and appear to persist for IMMUNE RESPONSE
years.

Antigen-dependent activation of B cells takes place


ACTION OF CYTOTOXIC CELLS in the primary follicles of peripheral lymphoid tissue.
 Follicular dendritic cells - present antigen
T cells that bear the CD8 marker have a different to B cells and thus play a key role in the
role to play than that of the Th cells. immune response.

 Cytotoxic T cells - recognize antigen in RESPONSE TO T-DEPENDENT ANTIGENS


association with class I MHC complexes; act
as a primary defense against intracellular  When B cells respond to T-dependent
pathogens such as viruses, as well as other antigens, the B cells require two signals to be
altered host cells such as tumor cells that activated.
exhibit new antigens; bind to altered host o 1st: occurs when antigen binds to
cells by using the TCR receptor for antigen membrane immunoglobulin receptors
and by CD8, which recognizes class I MHC on the B-cell surface and cross-links
molecules. them. Cross-linking leads to
 Cytotoxic T cells can kill target cells in two activation of intracellular signalling
major ways: pathways that allow stimulated B
o Once antigen recognition occurs, the cells to interact with T cells.
cytotoxic T cells either release the o 2nd: provided by Th cells themselves,
contents of granules that damage the which bind to the B cell both through
cell or they bind to the host cell and, its antigen receptor and through
using intracellular signalling, induce CD40 on the B cell and CD40L on the
apoptosis. activated Th cell. The bound T cell
o In either case, the target cell is then delivers cytokines and other
induced to undergo apoptosis, signals to fully activate the B cell.

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 CD25 - found on both activated T and B cells
and which acts as a receptor for IL-2.
LABORATORY IDENTIFICATION OF
 IL-2 - a growth factor produced by T cells.
LYMPHOCYTES
 Daughter cells of proliferating B cells -
either migrates into the T-cell zone in lymph
nodes and differentiates into plasma cells Identification of lymphocytes as either T cells or B
that secrete IgM in about 4 days or they cells - useful in diagnosis of any of the following
enter B-cell follicles to form germinal centers. states:
 B cells - undergo further differentiation ● Malignancies such as leukemias and
under the influence of follicular Th cells. The lymphomas
CD40 on B cells must interact with CD40L on ● Immunodeficiency diseases involving either
Th cells in order for germinal center T or B cells or both; and acquired
formation to occur. immunodeficiency disease (AIDS).
 Memory cells - are progeny of B cells that
have been exposed to antigen; they are In some immunodeficiency diseases (X-linked
characterized by a long life span and a rapid hypogammaglobulinemia):
response to second exposure to the ● B cells are frequently absent
triggering antigen; they are similar in In severe combined immunodeficiency disease
appearance to unstimulated B cells, but they (SCID):
remain in an activated state for months or ● Both T and B cells are either absent or
years, ready to respond to the initial antigen. present in very low
 CD27 - is used as a marker to identify numbers.
memory cells because they are similar in
appearance to mature B cells. Assays for CD4+ T cells - useful in evaluating the
stage of infection; because HIV infects and
RESPONSE TO T-INDEPENDENT ANTIGENS progressively kills CD4+ T cells

Laboratory analysis - usually involves


 T-independent antigens - antigens
distinguishing the following lymphocyte subsets:
that are able to elicit antibody formation
● T cytotoxic cells (CD8)
in the absence of T cells. Such antigens
● Th cells (CD4)
are able to interact with multiple
● B cells
immunoglobulin receptors on a B cell to
cross-link them and induce proliferation
Cell Flow Cytometry
and antibody production.
- GOLD standard for testing
o Examples of these include: plant
- an automated system for identifying cells based on
lectins, polymerized proteins with
the scattering of light as cells in a stream of fluid
repeating molecular patterns, and
flow in a single file by a laser beam.
lipopolysaccharides found in
- Able to segregate lymphocytes into subsets using
bacterial cell walls.
a technique that relies on labeled monoclonal
These antigens produce IgM only because the
antibodies against specific surface anti-
induction of memory cells does not occur to any gens.
great extent. ● Monoclonal antibodies - highly specific
antibodies.
Some of the more common antigens tested for:
o CD2,
o CD3, CD4, and CD8 on T cells

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o CD19, CD20, CD22, and surface
immunoglobulin on B cells
● Fluorescent antibodies - used to screen for
subpopulations, such as B cells, Th cells, and T
cytotoxic cells.
● Each antibody has a different fluorescent tag.
● Some point-of-care testing has been developed
using either fluorescent or antibody-labeled
beads => measure the CD4 count and reported
as a percentage of the total T-cell count.

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