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Cells & Organs of The Immune System, Cellular Immunity

1. The immune system is composed of organs and tissues like the thymus, bone marrow, spleen, lymph nodes, and cells like macrophages, neutrophils, B cells and T cells. 2. Cell-mediated immunity involves T cells and other cells that attack infected cells or tumors. Humoral immunity involves B cells that produce antibodies. 3. T cells mature in the thymus and B cells mature in the bone marrow. They circulate and help fight pathogens. Antigen presenting cells display pieces of pathogens to activate T cells and B cells.

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0% found this document useful (0 votes)
22 views53 pages

Cells & Organs of The Immune System, Cellular Immunity

1. The immune system is composed of organs and tissues like the thymus, bone marrow, spleen, lymph nodes, and cells like macrophages, neutrophils, B cells and T cells. 2. Cell-mediated immunity involves T cells and other cells that attack infected cells or tumors. Humoral immunity involves B cells that produce antibodies. 3. T cells mature in the thymus and B cells mature in the bone marrow. They circulate and help fight pathogens. Antigen presenting cells display pieces of pathogens to activate T cells and B cells.

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frenchatici
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© © All Rights Reserved
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Cells of the immune system &

Cell-Mediated Immunity

Dr. Bushra Tanzem


MBBS, MD (Virology)
Associate Professor & Head
Department of Microbiology
Ad-Din Akij
Medical College, Khulna
https://microbenotes.com/lymphatic-system-organs/

Organization of the Immune System


Immune System composed of
1. Organs & tissues:
I. Primary:
i. Thymus
ii. Bone marrow
II. Secondary
i. Spleen
ii. Lymph nodes
iii. Lymph vessels
iv. Tonsils
v. Adenoids
vi. Appendix
vii. Peyer’s patches
viii. Liver
ix. Skin
2. Cells
3. Proteins
Function of the immune system
mediated by
Cell mediated immunity Humoral immunity
(by WBC) (by Soluble proteins)
o Innate: o Innate
– Granulocytes (neutrophil,
eosinophil, – Complement
basophil)
– Macrophages/Monocytes – Interferon
– Mast cells – Lysozyme
– Natural killer (NK) cells
– Defensins
o Acquired (Lymphocytes &
others) – Transferrin
– Helper T cells, – Lactoferrin
– cytotoxic T cells
– B cells
– Macrophages /APCs o Acquired:
– Dendritic cells
– Natural killer (NK) cells – Antibody
Cells of the Immune System
• Cells of the immune response are
organized into tissues and organs.
• Origin of cells of the immune
system:
• all the cells are arise from the
hemapoietic stem cell.
• Platelets are released into the
circulation.
• Granulocytes and monocytes pass from
the circulation into the tissues.
• Mast cells are evidenced in all tissues.
• B cells mature in the primary lymphoid
organs (bone marrow...). T cells
mature in the
thymus (primary lymphoid organs).
Lymphocytes leave primary
lymphoid organs and recirculate
through secondary
lymphoid tissues.
• Dendritic cells act as antigen-presenting
Cells involved in cell-mediated
immunity
1. Macrophages/Monocytes
2. Polymorphonuclear Neutrophil
3. Eosinophil
4. Basophil
5. Mast cells
6. Dendritic cells
7. Natural killer (NK) cells
8. Helper T cells,
9. cytotoxic T cells
10. B cells
• Both B and T lymphocytes originate in the bone
marrow but only B lymphocytes mature there; T
lymphocytes migrate to the thymus to undergo their
maturation.

• Thus B lymphocytes are so-called because they are


bone marrow derived, and T lymphocytes because
they are thymus derived.

• They then migrate to guard the peripheral tissues,


circulating in the blood and in a specialized system
of vessels called the lymphatic system.
Function of the cells of the immune system:
• The innate responses use phagocytic cells (neutrophils, monocytes, and
macrophages), cells which release inflammatory mediators (basophils, mast
cells, and eosinophils), and natural killer cells. The molecular components of
the innate responses comprise complement, acute-phase
proteins, and cytokines such as the interferons.
• Acquired responses involve the proliferation of antigen-specific B and T cells,
occurring when their surface receptors bind to the antigen. Specialized cells
(antigen-presenting cells) display the antigen to T lymphocytes and
collaborate with them in the response to the antigen.
• B cells secrete immunoglobulins (antigen specific antibodies) responsible for
eliminating extracellular microorganisms or foreign agents. Innate and
acquired responses usually work together.
• Major Histocompatibility Complex (MHC): this gene complex was first
identified when it was observed that histocompatibility depended on the
donor and recipient sharing the same haplotype. The
molecules which determine graft rejection are a
limited group: Class I and Class II of cell-surface structures. The
molecules which present antigens to T cells are mostly encoded within the
MHC. All nucleated cells of the body express MHC Class I. By contrast,
MHC Class II molecules are used by antigen presenting
cells to present antigens to helper T cells, so cells expressing Class II are
smaller in numbers than those expressing Class I.
• Antigen presenting cells, in a lymphoid organ, include macrophages,
dendritic cells and B-cells.

• Mononuclear phagocytes: most important group of long-lived
phagocytic cells. These cells are bone marrow-derived and
their function is to engulf particles,
internalize them and destroy them.
• Dendritic cells which are found in the T-cell areas of lymph node
and spleen are the most effective cells for the initial activation
of naive T-cells.
• B-cells: bone marrow-derived. Each B cell is genetically
programmed to encode a surface receptor specific for a particular
antigen. Upon recognition of the antigen, B cells multiply and
differentiate into plasma cells, which produce large amounts of
the receptor molecule in a soluble form that
can be secreted (antibody).
The germinal centre: with the initiation of the acquired immune response,
germinal centres form in the secondary lymphoid tissues, where all the antigen-
specific and antigen-presenting cells can interact.
• Effector cells: T-cells and B lymphocytes.
• T cells: there are several types of T cells with a variety of
functions. They originate from bone marrow stem cells and
require further differentiation in the thymus where they migrate.
T cell maturation requires a number of cell interactions:
• T cells express in an orderly fashion certain markers or cell
surface proteins. The nomenclature used to refer to cell surface
molecules, characterized on the basis of their reactivity to
monoclonal antibodies, follows the CD (for "cluster of
differentiation") numbering. The CD4+ T cells, cytokine-secreting
helper cells can be divided into two major types:
• Type I helper T cells TH1 which secrete Interleukin (IL) 2 and
interferon (IFN) g.
• Type II helper T cells TH2 which secrete IL4 and 5.
• The production of cytokines by TH1 facilitates cell-mediated
immunity (activation of macrophages and T-cell mediated
cytotoxicity). TH2 cells help B cells produce antibodies.
Class II MHC on antigen presenting cells interact with CD4 on T
cells. Peptides which bind to MHC Class II come from proteins
which have been internalized by the cell and then degraded.
CD8+ T cells play a role in the elimination of virally infected cells. The infected cell marks
itself as a target for the cytotoxic T cell by displaying peptides derived from intracellular
viral protein on its surface. Viral proteins are bound to peptide-binding regions of class I
MHC molecules. Peptides which bind to MHC Class I molecules come from proteins
synthesized within the cell (which are broken down) and transported to the endoplasmic
reticulum.

B cells: the earliest cells which develop are called B1 cells; they express CD5 cell-surface
molecule and are the source of "natural antibodies", which are IgM antibodies and are
frequently polyreactive (recognize different antigens, pathogens and autoantigens). Natural
antibodies have a relative low affinity. Most B cells lack the CD5 molecule, they develop
later and are called B2 cells. Mature B2 cells coexpress IgM and IgD antibodies on their cell
surface. The genes encoding B-cell receptors undergo a process of somatic hypermutation;
the final stages of differentiation of B2 cells into antibody secreting plasma cells occurs
within the germinal centres of secondary lymphoid tissues.
• To elicit a strong antibody response, B cells require:
• Antigen
• T cells for direct contact (usually TH2 cells)
• Soluble cytokines (e.g. IL4 + IL13, INF-γ or IL10)
• Certain adhesion molecules

• Clonal selection involves the proliferation of cells which


recognize a specific antigen: each B cell is programmed to
make just one antibody specificity, located on its surface as
an antigen receptor. Antigen binds to only those B cells with
the appropriate surface receptor; these cells are stimulated
to proliferate and mature into antibody producing cells.
https://www.medicine.mcgill.ca/physio/vlab/im
mun/backg.htm
Functions of Antibody

• The primary function of the antibody is to bind the antigen; the antibody
directs specificity towards the antigen. By doing do, it also arms the killer
cells and activates complement, processes that eliminate foreign organisms,
which the antibody by itself cannot do. Of the different classes of antibodies,
two will be discussed briefly:
• IgM class: is the predominant antibody (it is the first to appear) in primary
immune responses and is associated with the immune responses to
antigenically complex, blood -borne agents. Once bound to the antigen, it is a
powerful activator of the classical pathway complement: a single molecule of
bound IgM is able to initiate the cascade because of the adjacent positioning
of the Fc regions.
• IgG class: is the most important class of immunoglobulin in secondary
immune responses
• The exposure to foreign antigen yields a biphasic response. The first phase is
associated with production of IgM, followed by production of IgG. The second
phase is characterized by a reduction of IgM followed by an increase of IgG.
The antigen will select and expand a clone of effector B cells which will
develop into plasma cells and produce antibodies.
• Complement system
• The complement system consists of about 20+
serum molecules (some of them being
proteases) constituting nearly 10% of the
total serum proteins and forming
one of the major defence systems of the
body. The complement system is
activated by the Ag-Ab complex. The
principle functions are the initiation of:
• chemotactic factors: polymorphs and macrophages have
specific receptors for small complement fragments
generated during complement activation. The fragments
diffuse away from the site of activation and stimulate
chemotaxis, the way chemokines do.
• vasodilation factors: some of the protein fragments of the
complement system (C5a) causes degranulation of mast cells
and basophils with release of histamine and other vasoactive
mediators. Consequently, there are indirect effects on blood
vessels, vasodilation and increased permeability of
capillaries.
• factors that increase phagocytosis: phagocytic cells carrying
receptors for the complement components are then able to
bind to the foreign particle (opsonization), and this triggers
phagocytosis and cell activation.
• membrane attack complex: the final step in complement
activation brings about the assembly of a membrane
attack complex, which can insert itself into lipid bilayers,
causing the lysis of the foreign body.
• The basic unit composed of B zones and T zones
are located within the cortex of the LN and the
white pulp of the spleen. Some MALTs, such
as tonsils and Peyer's patches
(PPs), are clusters of follicles
associated with T zones in the
interfollicular area.
• In addition to follicles, a significant proportion of
splenic B cells is located in 'marginal zones'
(MZs), which surround lymphoid follicles and
T- cell areas in spleen. MZs are
absent in peripheral lymph
nodes and Peyer's patches.
• B cells are primarily clustered in structures called
lymphoid follicles, whereas T cells are found
mainly in the paracortex.
• within the lymph node due to the
compartmentalization of the lymph nodes. The T
lymphocytes are present within the paracortex
lobules, and B lymphocytes are situated within
the cortex lobule.

• majority of T cells in the human body are likely
found within lymphoid tissues (bone marrow, spleen,
tonsils, and an estimated 500-700 lymph nodes) with
large numbers also present in mucosal sites (lungs, small
and large intestines) and skin, with estimates of 2–3% of
the total T cell complement found in human peripheral
blood
• B lymphocytes can be found in primary lymphoid tissues,
such as the bone marrow and ileal Peyer's patches (a
primary lymphoid tissue in some species because it is the
site of B lymphocyte development, rather than the bone
marrow), and in secondary lymphoid tissues, such as the
spleen, lymph nodes, tonsils, and Peyer's ...
• B lymphocytes can be found in primary lymphoid tissues, such as the bone
marrow and ileal Peyer's patches (a primary lymphoid tissue in some
species because it is the site of B lymphocyte development, rather than
the bone marrow), and in secondary lymphoid
tissues, such as the spleen, lymph nodes, tonsils, and Peyer's patches.
Within secondary lymphoid tissues, B
lymphocytes are aggregated in the form of distinct lymphoid
follicles, which on activation expand to form prominent pale regions
called germinal centers (Fig. 5-9). This anatomic localization, similar
to T lymphocytes in the PALS and paracortex, is
the result of elaboration of chemokines for which the B lymphocyte has
receptors. The antigen receptor of the B lymphocyte is the
membrane-bound immunoglobulin. After the
antigen-independent phase of development, B lymphocytes
express IgM and IgD on their surface, which signifies a mature B
lymphocyte. In the antigen-dependent phase, antigen-activated mature
B lymphocytes differentiate into IgM-secreting
plasma cells or switch to another antibody isotype.
Antigen-Presenting Cells
1. Macrophage
2. Dendritic cells
3. B cells
Important Cells of cell-mediated immunity
• Important cells of cell-mediated immunity
1. Macrophages,
– Phagocytosis bacteria & Present the antigen to T cells;
2. Helper T cells,
– Participate in antigen recognition and in regulation
(helper and suppressor) functions
3. Natural killer (NK) cells
– Kill virus-infected cells and cancer cells & Produce
gamma interferon that activates
macrophages to kill ingested bacteria
4. cytotoxic T cells
– Kill virus-infected & tumor cells with or without
antibody.

 Macrophages & helper T cells produce cytokines that activate


helper and cytotoxic T cells, leading to the killing of the pathogen
or tumor cell.
Role of Adjuvants & Lipids in
Establishing Cell-Mediated Reactivity
• Weak antigens or simple chemicals do not to elicit cell-
mediated hypersensitivity, but they elicit immunity when
given as a mixture with an adjuvant.

• The role of the adjuvant is to enhance the uptake of the


antigen by antigen-presenting cells, e.g., macrophages, to
stimulate the expression of co-stimulators, such as B7, and
to enhance the production of cytokines, such as IL-12, that
promotes the development of Th-1 cells.

• A common experimental adjuvant is a mixture of mineral


oil, lanolin, and killed mycobacteria (Freund's adjuvant),
which stimulates the formation of local granulomas.
Macrophages
Functions Mechanisms
1. Phagocytosis  Ingestion and killing of microbes
phagolysosomes.
in
 Killing caused by reactive oxygen
intermediates such as superoxides,
reactive nitrogen intermediates such as
nitric oxide, and lysosomal enzymes
such as proteases, nucleases, and
lysozyme.
2. Antigen presentation  Presentation of antigen in association
with
class II MHC proteins to CD4-
positive helper T cells.
 Also displays B7 protein, which acts
as a
costimulator of helper T cells.
Polymorphonuclear Neutrophils
• Have cytoplasmic granules (containing lysosomes) that stain a pale pink (neutral) color with
Wright stain.

• Functions:
1. Phagocytosis
• Lysosomes contain a variety of degradative enzymes which have bactericidal
action.
• Important for innate host defenses, & severe bacterial infections occur in low in
number (neutropenia) or are deficient in function, as in chronic
granulomatous disease.
2. Opsonization:
• Neutrophils have receptors for IgG on their surface, so IgG is the only
immunoglobulin that opsonizes, i.e., makes bacteria more easily
phagocytosed.
3. Tissue damage:
• The positive edge of the sword of neutrophil is their powerful microbicidal activity,
but the negative edge is the tissue damage caused by the release of
degradative enzymes. An excellent example of the latter is the
damage to the glomeruli in acute poststreptococcal
glomerulonephritis. The damage is caused by enzymes released

Eosinophils
Eosinophils are WBC with cytoplasmic granules stained red in Wright stain.
• The growth and differentiation of eosinophils is stimulated by interleukin-5.
• Role of eosinophils in types of diseases:
1. Parasitic diseases
– Eosinophil count elevated by nematodes. Important defense against migratory larvae
of nematodes, Strongyloides & Trichinella. They attach to the surface of the
larvae and discharge the contents of their granules, which in
turn damages the cuticle of the larvae. Attachment to
the larvae is mediated by receptors on the eosinophil surface for
the Fc portion of the heavy chain of IgG and IgE.
– Diseases caused by protozoa are typically not characterized by eosinophilia.
2. Hypersensitivity diseases
– Eosinophil count elevated in allergic conditions, such as, asthma and serum sickness.
– Causes immediate hypersensitivity reactions because the granules of eosinophils
contain histaminase, an enzyme that degrades histamine.
– The granules of the eosinophils also contain leukotrienes and peroxidases, which can
damage tissue and cause inflammation.
– The granules also contain major basic protein that damages respiratory epithelium and
contributes to the pathogenesis of asthma.
3. Phagocytose bacteria: Weakly & not sufficient to protect against pyogenic bacterial
infections in neutropenic patients.
Basophils
• Basophils are WBC with cytoplasmic granules stain blue
in Wright stain.
• Basophils circulate in the bloodstream

• Functions: Immediate hypersensitivity reactions by


– Basophils & mast cells have receptors on their surface for the Fc
portion of the heavy chain of IgE.
– When adjacent IgE molecules are cross-linked by antigen,
immunologically active mediators, such as
histamine, and enzymes, such as peroxidases
and hydrolases, are released.
– These cause inflammation and, when produced in large amounts,
cause severe immediate hypersensitivity reactions such
as systemic anaphylaxis.
Mast Cells
• Fixed in tissue, especially under the skin and in the
mucosa of the RT & GIT.

• Functions: Immediate hypersensitivity reactions by


– Innate response to bacteria & viruses.
– The surface of mast cells contain Toll-like receptors that
recognize bacteria & viruses.
– Acts by releasing cytokines & enzymes from their granules that
mediate inflammation & attract neutrophils and dendritic
cells to the site of infection.
– The role of mast cells in inflammation has been demonstrated in
rheumatoid arthritis. These cells produce both
inflammatory cytokines and the enzymes that
degrade the cartilage in the joints.
Dendritic Cells
• "dendritic" named from long, narrow processes (that resemble
neuronal dendrites), which make them very efficient at
making contact with foreign material.
• Dendritic cells are primarily located under the skin & mucosa, e.g.,
Langerhans' cells in the skin.
• Dendritic cells migrate from their peripheral location under the skin
& mucosa to local lymph nodes, where they present antigen to
helper T cells.

• Functions:
– Antigen-presenting cells
• Express class II MHC proteins & present antigen to CD4-positive Th cells.
– Main inducers of the primary antibody response.
Follicular Dendritic Cells (FDCs)
• Similar appearance but different from dendritic cells
in their location & function.
• located in the B-cell–containing germinal centers of
the follicles in the spleen and lymph nodes.
• Do not present antigen to helper T cells because they
do not produce class II MHC proteins.
• Capture antigen–antibody complexes via Fc receptors
located on their surface. The antigen–antibody
complexes are then detected by activated B cells. The
antibody produced by these B cells undergoes affinity
maturation. (Affinity maturation is the improvement
in the affinity of an antibody for the antigen that
occurs upon repeated exposure to the antigen.)
• FDCs produce chemokines that attract B cells to
the follicles in the spleen and lymph nodes.
Natural Killer Cells
• Nature of NK Cells
– Large granular lymphocytes
– Thymus is not required for development
– Lack T-cell receptor, CD3 proteins, and surface IgM and IgD
– Normal numbers in severe combined immunodeficiency disease (SCID)
patients
– Activity not enhanced by prior exposure
– involved in both innate and adaptive immunity, active all the time, & travel
around our bodies looking for infection or disease that it needs to
fight.

• Function of NK Cells
– Kill virus-infected cells & cancer cells
– Killing is nonspecific & is not dependent on foreign antigen presentation by
class I or II MHC proteins
– Produce gamma interferon that activates macrophages to kill ingested
bacteria
T Cells
• T-cell subpopulations are characterized by certain surface
glycoproteins
– CD3
– CD4
– CD8

• All T cells have CD3 proteins on their surface in association with


antigen receptors (T-cell receptor, TCR)

• T cells are subdivided into two major categories namely, regulatory


and effector, on the basis of whether they have CD4 or CD8
proteins on their surface.

• Mature T cells have either CD4 or CD8 proteins but not both.
T Cells
• The regulatory functions are mediated primarily by helper
(CD4-positive) T cells & Suppressor T cells
– Function of helper (CD4-positive) T cells produce interleukins
• Interleukin-4 (IL-4) and IL-5, which help B cells produce antibodies
• IL-2, which activates CD4 and CD8 cells
• Gamma interferon, activates macrophages, the main mediators of
delayed hypersensitivity against intracellular
organisms such as Mycobacterium tuberculosis.
• A subset of CD4 cells called Th-17 cells play an important role
in
mucosal immunity
– Function of Suppressor T cells
• Downregulate the immune response

• The effector functions are carried out by cytotoxic (CD8-


positive) T cells,
– kill virus-infected cells, tumor cells, and allografts.
Main Functions of Helper T Cells
Main Functions Cytokine That Mediates That
Function
Activates the antigen-specific helper T cell to IL-2
produce a clone of these cells
Activates cytotoxic T cells IL-2
Activates B cells IL-4 and IL-5
Activates macrophages Gamma interferon
Comparison of Th-1 Cells and Th-2 Cells
Property Th-1 Cells Th-2 Cells
Produces IL-2 and gamma interferon Yes No
Produces IL-4, IL-5, IL-6, and IL-10 No Yes
Enhances cell-mediated immunity and delayed Yes No
hypersensitivity primarily
Enhances antibody production primarily No Yes
Stimulated by IL-12 Yes No
Stimulated by IL-4 No Yes
B Cells
• During embryogenesis, B-cell precursors are
recognized first in the fetal liver. From there
they migrate to the bone marrow,
which is their main location during adult life.
• B-cells live mostly in our lymph nodes and
spleen.

• B cells perform two important functions:


– (1) they differentiate into plasma cells and
produce antibodies and
– (2) they can present antigen to helper T cells.
Comparison of T Cells and B Cell

Feature T Cells B Cells


Antigen receptors on surface Yes Yes
Antigen receptor recognizes only processed peptides in Yes No
association with MHC protein
Antigen receptor recognizes whole, unprocessed proteins No Yes
and has no requirement for presentation by MHC protein
IgM on surface No Yes
CD3 proteins on surface Yes No
Clonal expansion after contact with specific antigen Yes Yes
Immunoglobulin synthesis No Yes
Regulator of antibody synthesis Yes No
IL-2, IL-4, IL-5, and gamma interferon synthesis Yes No
Effector of cell-mediated immunity Yes No
Maturation in thymus Yes No
Maturation in bursa or its equivalent No Yes
Memory T & B Cells
• respond rapidly and vigorously for many years after the
initial exposure to a microbe or other foreign material. This
memory response to a specific antigen is due to several
features:
1. many memory cells are produced, so that the secondary
response is greater than the primary response, in which very
few cells respond;
2. memory cells live for many years or have the capacity to
reproduce themselves;
3. memory cells are activated by smaller amounts of antigen and
require less costimulation than do naïve, unactivated T cells;
and
4. activated memory cells produce greater amounts of interleukins
than do naïve T cells when they are first activated.
Origin of T and B cells
• Stem cells in the bone
marrow (or fetal liver)
are
the precursors of both T
and
B lymphocytes.

• Stem cells differentiate into


T cells in the thymus,
whereas they
differentiate
into B cells in the bone
marrow.

• Within the thymus, T cells


become either CD4-
positive
(helper) cells or CD8-
positive (cytotoxic)
cells.

• B cells can differentiate into


plasma cells that
produce
large amounts of
 Development of T
cells.

 Note the positive and


negative selection
that occurs in the
thymus.
• B-cells live mostly in our lymph nodes and
spleen.
• T-cells also found in lymph nodes, spleen &
lymphatic system but in smaller numbers.
Cell Surface Proteins that Play an Important Role in the Immune Response
Type of Cells Surface Proteins

Helper T cells CD4, TCR, CD28

Cytotoxic T cells CD8, TCR


B cells IgM, B7
Macrophages Class II
MHC
Natural killer
cells Receptors
for class I
MHC
All cells other than mature red cells Class I MHC
Cell-Mediated Immunity: Introduction

• Humoral (antibody-mediated immunity) is an


important host defense against
– Many bacterial (especially intracellular infections such
as tuberculosis)
– Viral infections

• Cell-mediated immunity is important in defense


against
– fungi, parasites, and tumors and in the rejection
of organ transplants.
– many bacterial infections
Decreased cell mediated immunity

• Clinical situations in which its suppression (by


immunosuppressive drugs or disease, e.g.,
AIDS) results in
– Overwhelming infections
– Tumors
Tests for Evaluation of Cell-Mediated
Immunity
• In Vivo Tests for Lymphoid Cell Competence (Skin Tests)

– Skin Tests for the Presence of Delayed-Type Hypersensitivity


• Most normal persons respond with delayed-type reactions to skin test
antigens of Candida, streptokinase–streptodornase, or mumps
virus because of past exposure to these antigens.
• Absence of reactions to several of these skin tests suggests impairment of
cell-mediated immunity.

– Skin Tests for the Ability to Develop Delayed-Type Hypersensitivity


• Most normal persons readily develop reactivity to simple chemicals (e.g.,
dinitrochlorobenzene [DNCB]) applied to their skin in lipid
solvents. When the same chemical is applied to the same area
7 to 14 days later, they respond with a delayed-type skin reaction.
• Immunocompromised persons with incompetent cell-mediated immunity
fail to develop such delayed-type hypersensitivity.
Tests for Evaluation of Cell-Mediated
Immunity
• In Vitro Tests for Lymphoid Cell Competence
– Lymphocyte Blast Transformation
• When sensitized T lymphocytes are exposed to the specific antigen,
they transform into large blast cells with greatly increased
DNA synthesis, as measured by incorporation of tritiated
thymidine. This specific effect involves relatively few
cells. A larger number of T cells undergo
nonspecific blast transformation when exposed to certain
mitogens. The mitogens phytohemagglutinin and concanavalin A are
plant extracts that stimulate T cells specifically. (Bacterial
endotoxin, a lipopolysaccharide, stimulates B cells
specifically.)
– Macrophage Migration Inhibitory Factor
• Macrophage migration inhibitory factor is elaborated by cultured T
cells when exposed to the antigen to which they are
sensitized. Its effect can be measured by observing
the reduced migration of macrophages in the presence of the
factor compared with the level in
controls.
Tests for Evaluation of Cell-Mediated
Immunity
• In Vitro Tests for Lymphoid Cell Competence
– Enumeration of T Cells, B Cells, and Subpopulations
• The number of each type of cell can be counted by use of a machine
called a fluorescence-activated cell sorter (FACS). In this
approach, cells are labeled with monoclonal antibody tagged with a
fluorescent dye, such as fluorescein or rhodamine.
Single cells are passed through a laser
light beam, and the number of cells that fluoresce is registered.
• B cells (and plasma cells) making different classes of antibodies can be
detected by using monoclonal antibodies against the
various heavy chains. The total number of B cells can
be counted by using fluorescein-labeled antibody against all
immunoglobulin classes. Specific monoclonal antibodies directed
against T-cell markers permit the
enumeration of T-cells, CD4 helper cells, CD8 suppressor cells, and
others. The normal ratio of CD4 to CD8 cells is 1.5 or
greater, whereas in some immunodeficiencies (e.g., AIDS)
it is less than 1.
Cell-Mediated Immunity
• In the following example, a bacterium, e.g., Mycobacterium
tuberculosis, enters the body and is ingested by a
macrophage.
• The bacterium is broken down, and fragments of it called antigens
or epitopes appear on the surface of the macrophage in
association with class II major histocompatibility
complex (MHC) proteins.
• The antigen–class II MHC protein complex interacts with an
antigen-specific receptor on the surface of a helper T
lymphocyte.
• Activation and clonal proliferation of this antigen-specific helper T
cell occur as a result of the production of interleukins, the most
important of which are interleukin-1 (produced by macrophages)
and interleukin-2 (produced by lymphocytes).
• These activated helper T cells, aided by activated macrophages,
mediate one important component of cellular immunity, i.e.,
a delayed hypersensitivity reaction
specifically against M. tuberculosis.
Cell-Mediated Immunity
• Cytotoxic (cytolytic) T lymphocytes are also specific effectors of
the cellular immune response, particularly against virus-infected
cells.
• In this example, a virus, e.g., influenza virus, is inhaled and
infects a cell of the respiratory tract.
• Viral envelope glycoproteins appear on the surface of the infected
cell in association with class I MHC proteins.
• A cytotoxic T cell binds via its antigen-specific receptor to the viral
antigen–class I MHC protein complex and is stimulated to grow
into a clone of cells by interleukin-2 produced
by helper T cells.
• These cytotoxic T cells specifically kill influenza virus–infected
cells (and not cells infected by other viruses) by recognizing
viral antigen–class I MHC protein
complexes on the cell surface and releasing
perforins that destroy the membrane of the infected cell.
Overview of the process by
which cell-mediated
immunity and antibody-
mediated immunity are
induced by exposure to a
virus.
Induction of cell-mediated immunity and antibody against a viral infection.

Right: Virus released by an infected cell is ingested and processed by an antigen-presenting


cell (APC), e.g., a macrophage. The viral epitope is presented in association with a class II
MHC protein to the virus-specific T-cell receptor (TCR) on the CD4 cell. The macrophage
makes IL-1, which helps activate the CD4 cell. The activated CD4 cell makes interleukins
(e.g., IL-2, which activates the CD8 cell to attack the virus-infected cell, and IL-4 and IL-5,
which activate the B cell to produce antibody). The specificity of the cytotoxic response
mounted by the CD8 cell is provided by its TCR, which recognizes the viral epitope
presented by the virus-infected cell in association with a class I MHC protein.
Induction of cell-mediated immunity and antibody against a viral infection.

Left: Virus released by an infected cell interacts with the antigen receptor (IgM
monomer) specific for that virus located on the surface of a B cell. The virus is
internalized, and the viral proteins are broken down into small peptides. B cells (as well as
macrophages) can present viral epitopes in association with class II MHC proteins and
activate CD4 cells. The CD4-positive helper cell produces IL-4 and IL-5, which induce
the B cell to differentiate into a plasma cell that produces antibody specifically against
this virus.

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