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LECTURE # 5
CELLULAR BASIS OF THE IMMUNE
RESPONSE
Fayyaz Ahmad
UIMLT
Immunology
3/26/2024 Immunology I 1
Learning outlines
• Origin of Immune Cells
• T Cells
• CD4 & CD8 Types of T Cells
3/26/2024 Immunology I 2
Origin of immune cells
A)In embryonic life
Blood cell precursors originate mainly in the fetal liver and
yolk sac;
B)In postnatal life
• the stem cells reside in the bone marrow , differentiate
into cells of the erythroid, myeloid, or lymphoid series.
Lymphoid series evolve into two main lymphocyte
populations:
• T cells
• B cell.
The ratio of T cells to B cells is approximately 3:1
3/26/2024 Immunology I 3
Origin of Immune cell
3/26/2024 Immunology I 4
Origin of T and B cell
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
antibodies (immunoglobulins).
Dotted lines indicate interactions
mediated by interleukins.
3/26/2024 Immunology I 5
T lymphocytes
• T cells constitute 65–80% of the recirculating pool of small
lymphocytes.
• Within lymph nodes, they are located in the inner,
subcortical region, not in the germinal centers. (B cells
make up most of the remainder of the pool of small
lymphocytes and are found primarily in the germinal
centers of lymph nodes.)
• The life span of T cells is long: months or years.
• All are CD3+
• Performs various functions,which can be devided into
• Regulatory (CD4+)
• Effector (CD8+)
CD=cluster of differentiation ,
Cell membrane molecules that are used to classify leuk-
ocytes into subsets.
3/26/2024 Immunology I 6
Sites of T lymphocytes cell formation and
maturation
3/26/2024 Immunology I 7
Lymph node
• Within lymph nodes, T
cells are located in the
subcortical region, not in
the germinal centers.
• B cells make up most of
the remainder of the pool
of small lymphocytes
and are found primarily
in the germinal centers
of lymph nodes.
3/26/2024 Immunology I 8
Thymus:
• Is a lymphoid organ in the upper anterior thorax just
above the heart.
• It contains immature T cells (thymocytes), which are
embedded in a network of epithelial cells (thymic stroma).
These elements form:
• Cortex
• Medulla
3/26/2024 Immunology I 9
• T-cell precursors differentiate into immunocompetent T
cells within the thymus.
• Prior to entering the thymus, stem cells lack antigen
receptors and lack CD3, CD4, and CD8 proteins on their
surface.
• During passage through the thymus they differentiate into
T cells that can express both antigen receptors and the
various CD proteins.
3/26/2024 Immunology I 10
The cellular organization of the thymus
3/26/2024 Immunology I 11
Figure 7-8
3/26/2024 Immunology I 12
3/26/2024 Immunology I 13
• During their passage through the thymus, each double-
positive T cell synthesizes a different, highly specific
antigen receptor called the T-cell receptor (TCR).
• The rearrangement of the variable, diversity, and joining
genes that encode the receptor occurs early in T-cell
differentiation and accounts for the remarkable ability of T
cells to recognize millions of different antigens.
3/26/2024 Immunology I 14
T cell development in GALT
• Some T lymphocytes, perhaps as much as 40% of the
total, do not develop in the thymus but rather in the "gut-
associated lymphoid tissue" (GALT).
• These intraepithelial lymphocytes (IELs) are thought to
provide protection against intestinal pathogens.
• Their antigen receptors and surface proteins are different
from those of thymus-derived lymphocytes.
• IELs cannot substitute for thymus-derived lymphocytes
because patients with DiGeorge's syndrome who lack a
thymus are profoundly immunodeficient and have multiple
infections.
3/26/2024 Immunology I 15
Natural killer cells
• Natural killer (NK) cells are large granular lymphocytes
that do not pass through the thymus, do not have an
antigen receptor, and do not bear CD4 or CD8 proteins.
• They recognize and kill target cells, such as virus-infected
cells and tumor cells, without the requirement that the
antigens be presented in association with class I or class
II MHC proteins.
• Rather, NK cells target those cells to be killed by detecting
that they do not display class I MHC proteins on the cell
surface.
• This detection process is effective because many cells
lose their ability to synthesize class I MHC proteins after
they have been infected by a virus.
3/26/2024 Immunology I 16
Cell Surface Proteins that Play an
Important Role in the Immune Response
Type of Cells Surface Proteins
Helper T cells CD4, TCR,2 CD28
Cytotoxic T cells CD8, TCR
B cells IgM, B7
Macrophages3 Class II MHC
Natural killer cells Receptors for class I MHC
All cells other than mature red cells4 Class I MHC
3/26/2024 Immunology I 17
CD4 & CD8 Types of T Cells
• Within the thymus, perhaps within the outer cortical
epithelial cells (nurse cells), T-cell progenitors differentiate
under the influence of thymic hormones (thymosins and
thymopoietins) into T-cell subpopulations.
• These cells are characterized by certain surface
glycoproteins, e.g., CD3, CD4, and CD8.
• All T cells have CD3 proteins on their surface in
association with antigen receptors(TCR).
CD3:
The CD3 complex of five transmembrane proteins is
involved with transmitting, from the outside of the cell to the
inside, the information that the antigen receptor is
occupied.
3/26/2024 Immunology I 18
• One of the CD3 transmembrane proteins, the zeta chain,
is linked to a tyrosine kinase called fyn, which is involved
with signal transduction.
CD4:
• is a single transmembrane polypeptide,
CD8:
• consists of two transmembrane polypeptides.
• CD4 & CD8 may signal via tyrosine kinase (the lck
kinase) also.
3/26/2024 Immunology I 19
Types of T lymphocytes
• T cells are subdivided into two major categories 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.
3/26/2024 Immunology I 20
CD4+ T cell (Helper T cell)
CD4 lymphocytes perform the following helper functions:
• (1) they help B cells develop into antibody-producing
plasma cells
• (2) they help CD8 T cells to become activated cytotoxic T
cells
• (3) they help macrophages effect delayed hypersensitivity
(e.g., limit infection by M. tuberculosis).
3/26/2024 Immunology I 21
Helper T cell
3/26/2024 Immunology I 22
Main Functions of Helper T Cells
Main Functions
Cytokine That Mediates That
Function
Activates the antigen-specific helper T
cell to produce a clone of these cells
IL-2
Activates cytotoxic T cells IL-2
Activates B cells IL-4 and IL-5
Activates macrophages Gamma interferon
3/26/2024 Immunology I 23
The origin of Th-1 and Th-2 cells
Th-1 cells.
• Microorganisms are ingested by macrophages and IL-12
is produced. IL-12 induces naïve Th-0 cells to become Th-
1 cells that produce gamma interferon and IL-2. These
interleukins activate macrophages and cytotoxic T cells,
respectively, and cell-mediated immunity occurs.
Th-2 cells
• Microorganisms are ingested by an unknown type of cell
and IL-4 is produced. IL-4 induces naïve Th-0 cells to
become Th-2 cells that produce IL-4 and IL-5. These
interleukins activate B cells to become plasma cells and
antibodies are produced.
3/26/2024 Immunology I 24
The origin of Th-1 and Th-2 cells
3/26/2024 Immunology I 25
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
hypersensitivity primarily
Yes No
Enhances antibody
production primarily
No Yes
Stimulated by IL-12 Yes No
Stimulated by IL-4 No Yes
3/26/2024 Immunology I 26
Subtypes of Helper T cells
3/26/2024 Immunology I 27
CD8+ T lymphocyte
Perform cytotoxic functions
Kill
• Virus infected cells
• Tumor cells
• Allograt
Killing two mechanisms,
1.the release of perforins,
which destroy cell membranes,
2.the induction of programmed cell death (apoptosis).
CD8 cells predominate in human bone marrow and gut
lymphoid tissue and constitute about 35% of peripheral T
cells.
3/26/2024 Immunology I 28

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WEHH IMMDADA Cellular Immunity AND ALL THE

  • 1. LECTURE # 5 CELLULAR BASIS OF THE IMMUNE RESPONSE Fayyaz Ahmad UIMLT Immunology 3/26/2024 Immunology I 1
  • 2. Learning outlines • Origin of Immune Cells • T Cells • CD4 & CD8 Types of T Cells 3/26/2024 Immunology I 2
  • 3. Origin of immune cells A)In embryonic life Blood cell precursors originate mainly in the fetal liver and yolk sac; B)In postnatal life • the stem cells reside in the bone marrow , differentiate into cells of the erythroid, myeloid, or lymphoid series. Lymphoid series evolve into two main lymphocyte populations: • T cells • B cell. The ratio of T cells to B cells is approximately 3:1 3/26/2024 Immunology I 3
  • 4. Origin of Immune cell 3/26/2024 Immunology I 4
  • 5. Origin of T and B cell 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 antibodies (immunoglobulins). Dotted lines indicate interactions mediated by interleukins. 3/26/2024 Immunology I 5
  • 6. T lymphocytes • T cells constitute 65–80% of the recirculating pool of small lymphocytes. • Within lymph nodes, they are located in the inner, subcortical region, not in the germinal centers. (B cells make up most of the remainder of the pool of small lymphocytes and are found primarily in the germinal centers of lymph nodes.) • The life span of T cells is long: months or years. • All are CD3+ • Performs various functions,which can be devided into • Regulatory (CD4+) • Effector (CD8+) CD=cluster of differentiation , Cell membrane molecules that are used to classify leuk- ocytes into subsets. 3/26/2024 Immunology I 6
  • 7. Sites of T lymphocytes cell formation and maturation 3/26/2024 Immunology I 7
  • 8. Lymph node • Within lymph nodes, T cells are located in the subcortical region, not in the germinal centers. • B cells make up most of the remainder of the pool of small lymphocytes and are found primarily in the germinal centers of lymph nodes. 3/26/2024 Immunology I 8
  • 9. Thymus: • Is a lymphoid organ in the upper anterior thorax just above the heart. • It contains immature T cells (thymocytes), which are embedded in a network of epithelial cells (thymic stroma). These elements form: • Cortex • Medulla 3/26/2024 Immunology I 9
  • 10. • T-cell precursors differentiate into immunocompetent T cells within the thymus. • Prior to entering the thymus, stem cells lack antigen receptors and lack CD3, CD4, and CD8 proteins on their surface. • During passage through the thymus they differentiate into T cells that can express both antigen receptors and the various CD proteins. 3/26/2024 Immunology I 10
  • 11. The cellular organization of the thymus 3/26/2024 Immunology I 11
  • 14. • During their passage through the thymus, each double- positive T cell synthesizes a different, highly specific antigen receptor called the T-cell receptor (TCR). • The rearrangement of the variable, diversity, and joining genes that encode the receptor occurs early in T-cell differentiation and accounts for the remarkable ability of T cells to recognize millions of different antigens. 3/26/2024 Immunology I 14
  • 15. T cell development in GALT • Some T lymphocytes, perhaps as much as 40% of the total, do not develop in the thymus but rather in the "gut- associated lymphoid tissue" (GALT). • These intraepithelial lymphocytes (IELs) are thought to provide protection against intestinal pathogens. • Their antigen receptors and surface proteins are different from those of thymus-derived lymphocytes. • IELs cannot substitute for thymus-derived lymphocytes because patients with DiGeorge's syndrome who lack a thymus are profoundly immunodeficient and have multiple infections. 3/26/2024 Immunology I 15
  • 16. Natural killer cells • Natural killer (NK) cells are large granular lymphocytes that do not pass through the thymus, do not have an antigen receptor, and do not bear CD4 or CD8 proteins. • They recognize and kill target cells, such as virus-infected cells and tumor cells, without the requirement that the antigens be presented in association with class I or class II MHC proteins. • Rather, NK cells target those cells to be killed by detecting that they do not display class I MHC proteins on the cell surface. • This detection process is effective because many cells lose their ability to synthesize class I MHC proteins after they have been infected by a virus. 3/26/2024 Immunology I 16
  • 17. Cell Surface Proteins that Play an Important Role in the Immune Response Type of Cells Surface Proteins Helper T cells CD4, TCR,2 CD28 Cytotoxic T cells CD8, TCR B cells IgM, B7 Macrophages3 Class II MHC Natural killer cells Receptors for class I MHC All cells other than mature red cells4 Class I MHC 3/26/2024 Immunology I 17
  • 18. CD4 & CD8 Types of T Cells • Within the thymus, perhaps within the outer cortical epithelial cells (nurse cells), T-cell progenitors differentiate under the influence of thymic hormones (thymosins and thymopoietins) into T-cell subpopulations. • These cells are characterized by certain surface glycoproteins, e.g., CD3, CD4, and CD8. • All T cells have CD3 proteins on their surface in association with antigen receptors(TCR). CD3: The CD3 complex of five transmembrane proteins is involved with transmitting, from the outside of the cell to the inside, the information that the antigen receptor is occupied. 3/26/2024 Immunology I 18
  • 19. • One of the CD3 transmembrane proteins, the zeta chain, is linked to a tyrosine kinase called fyn, which is involved with signal transduction. CD4: • is a single transmembrane polypeptide, CD8: • consists of two transmembrane polypeptides. • CD4 & CD8 may signal via tyrosine kinase (the lck kinase) also. 3/26/2024 Immunology I 19
  • 20. Types of T lymphocytes • T cells are subdivided into two major categories 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. 3/26/2024 Immunology I 20
  • 21. CD4+ T cell (Helper T cell) CD4 lymphocytes perform the following helper functions: • (1) they help B cells develop into antibody-producing plasma cells • (2) they help CD8 T cells to become activated cytotoxic T cells • (3) they help macrophages effect delayed hypersensitivity (e.g., limit infection by M. tuberculosis). 3/26/2024 Immunology I 21
  • 22. Helper T cell 3/26/2024 Immunology I 22
  • 23. Main Functions of Helper T Cells Main Functions Cytokine That Mediates That Function Activates the antigen-specific helper T cell to produce a clone of these cells IL-2 Activates cytotoxic T cells IL-2 Activates B cells IL-4 and IL-5 Activates macrophages Gamma interferon 3/26/2024 Immunology I 23
  • 24. The origin of Th-1 and Th-2 cells Th-1 cells. • Microorganisms are ingested by macrophages and IL-12 is produced. IL-12 induces naïve Th-0 cells to become Th- 1 cells that produce gamma interferon and IL-2. These interleukins activate macrophages and cytotoxic T cells, respectively, and cell-mediated immunity occurs. Th-2 cells • Microorganisms are ingested by an unknown type of cell and IL-4 is produced. IL-4 induces naïve Th-0 cells to become Th-2 cells that produce IL-4 and IL-5. These interleukins activate B cells to become plasma cells and antibodies are produced. 3/26/2024 Immunology I 24
  • 25. The origin of Th-1 and Th-2 cells 3/26/2024 Immunology I 25
  • 26. 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 hypersensitivity primarily Yes No Enhances antibody production primarily No Yes Stimulated by IL-12 Yes No Stimulated by IL-4 No Yes 3/26/2024 Immunology I 26
  • 27. Subtypes of Helper T cells 3/26/2024 Immunology I 27
  • 28. CD8+ T lymphocyte Perform cytotoxic functions Kill • Virus infected cells • Tumor cells • Allograt Killing two mechanisms, 1.the release of perforins, which destroy cell membranes, 2.the induction of programmed cell death (apoptosis). CD8 cells predominate in human bone marrow and gut lymphoid tissue and constitute about 35% of peripheral T cells. 3/26/2024 Immunology I 28