Effector

Mechanisms of
T- cell mediated
immunity
 • Host defense in which T lymphocytes
A recap of T serve as effector cells is called cell-
mediated immunity.
cells and Cell- • Cell-mediated immune responses begin
Mediated with the activation of naive T cells which
then proliferate and differentiate into
Immunity effector cells.
• These effector T cells then migrate to sites
of infection, and function to eliminate the
microbes.
 Types of effector cells

Regulatory T cells
Helper T cells
• essential for the
Cytotoxic T cells
maintenance of immune • help other leukocytes in
tolerance • destroy virus-infected
immunologic processes, cells and tumor cells,
• Main role: stop T cell- including maturation of
mediated immune and are also implicated
B cells into plasma cells in transplant rejection
response at the end of and memory B cells
an immune reaction
 Types of T CD8 + cytotoxic T CD4 + helper T
lymphocytes cells secrete
cell-mediated (CTLs) kill any
infected cell
cytokines that
recruit and
immune containing
microbial proteins
activate other
leukocytes to
reactions in the cytosol,
eliminating cellular phagocytose
reservoirs of (ingest) and
infection destroy microbes
 Cell-
mediated
immunity
•A, Effector T cells of the CD4 + Th1
and Th17 subsets recognize microbial
antigens and secrete cytokines that
recruit leukocytes (inflammation) and
activate phagocytes to kill the microbes.
Effector cells of the Th2 subset (not
shown) function in the eradication of
infections by helminthic parasites.
•B, CD8 + cytotoxic T lymphocytes
(CTLs) kill infected cells with microbes
in the cytoplasm. CD8 + T cells also
produce cytokines that induce
inflammation and activate macrophages
(not shown).
Steps of • Naive T cells are stimulated by microbial antigens in
peripheral (secondary) lymphoid organs, giving rise to

T cell- effector T cells

• The differentiated effector T cells then migrate to the site
of infection
mediated • Phagocytes at these sites that have ingested the microbes
into intracellular vesicles display peptide fragments of

immune microbial proteins bound to cell surface class II MHC

molecules for recognition by CD4 + effector T cells
• Peptide antigens derived from microbial proteins in the
reactions cytosol of infected cells are displayed by class I MHC
molecules for recognition by CD8 + effector T cells
Subsets of CD4 +
Helper T Cells
Distinguished by
Cytokine Profiles

• A naive CD4 + T cell may differentiate into subsets that produce different cytokines that
recruit and activate different cell types and combat different types of infections in host
defense. These subsets also are involved in various kinds of inflammatory diseases.
• The table summarizes the major differences among Th1, Th2, and Th17 subsets of
helper T cells.
Function of Th 1 Cells
• The Th1 subset is induced by microbes that
are ingested and activate phagocytes while
stimulating phagocyte-mediated killing of
ingested microbes.
• Th1 cells, act through CD40-ligand and IFN-γ
and increase the ability of macrophages to kill
phagocytosed microbes
• Activation of macrophages by Th 1
lymphocytes through a process called classical
macrophage activation.
 • T cells belong to the Th1 subset, they express CD40-ligand (CD40L, or CD154) and secrete IFN-γ.
• Binding of CD40L to CD40 on macrophages functions together with IFN-γ binding to its receptor on
the same macrophages to trigger biochemical signaling pathways that lead to the activation of several

Classical activation •
transcription factors.
These transcription factors induce the expression of genes that encode lysosomal proteases and enzymes
that stimulate the synthesis of reactive oxygen species and nitric oxide, all of which are potent
destroyers of microbes. The net result of CD40-mediated and IFN-γ–mediated activation is that
macrophages become strongly microbicidal and can destroy most ingested microbes.
 Function of Th 2
Cells
• Th2 cells produce the cytokines
interleukin-4 (IL-4), IL-5, and IL-13.
IL-4 (and IL-13) act on B cells to
stimulate production mainly of IgE
antibodies, which bind to mast cells
o Help for antibody production
may be provided by Tfh cells
that produce Th2 cytokines and
reside in lymphoid organs, and
not by classical Th2 cells
• IL-5 activates eosinophils, a response
that is important in the destruction of
helminths.
• Th2 cytokines inhibit classical
macrophage activation and stimulate
the alternative pathway of
macrophage activation
Classical and
alternative
macrophage
activation

• Classically activated (M1) macrophages are induced by microbial products

binding to TLRs and cytokines, particularly interferon-γ (IFN-γ), and are
microbicidal and proinflammatory. Alternatively activated (M2)
macrophages are induced by (IL-4) and IL-13 and are important in tissue
repair and fibrosis.
 • Main function: to stimulate the recruitment of
neutrophils and, to a lesser extent, monocytes, thus
inducing the inflammation that accompanies many T
cell–mediated adaptive immune responses
• IL-17 secreted by Th17 cells stimulates the production of
chemokines from other cells, and these chemokines are
responsible for leukocyte recruitment.
Function of • Th17 cells also stimulate the production of antimicrobial
substances, called defensins, that function like locally
Th 17 Cells produced endogenous antibiotics.
• IL-22 produced by Th17 cells helps to maintain the
integrity of epithelial barriers and may promote repair of
damaged epithelia.
• These reactions of Th17 cells are critical for defense
against fungal and bacterial infections.
 Function of CD 8+
Cells
• CTLs recognize class I MHC–
associated peptides of cytoplasmic
microbes in infected cells and form
tight adhesions (conjugates) with
these cells.
• Adhesion molecules such as integrins
stabilize the binding of the CTLs to
infected cells (not shown).
• The CTLs are activated to release
(exocytose) their granule contents
(perforin and granzymes) toward the
infected cell.
• Granzymes are delivered to the
cytosol of the target cell by a
perforin- dependent mechanism.
Granzymes then induce apoptosis.
 Although we have described the effector
functions of CD4 + T cells and CD8 + T cells
separately, these types of T lymphocytes may
function cooperatively to destroy intracellular
microbes. If microbes are phagocytosed and
remain sequestered in macrophage vesicles,
Keep in mind! CD4 + T cells may be adequate to eradicate
these infections by secreting IFN-γ and
activating the microbicidal mechanisms of the
macrophages. If the microbes are able to
escape from vesicles into the cytoplasm,
however, they become insusceptible to T cell–
mediated macrophage activation, and their
elimination requires killing of the infected
cells by CD8 + CTLs.
Bibliography

Abbas, A.K., H., L.A.H. and Pillai, S. (2017) Cellular and molecular immunology. Elsevier.
Effector T cells - cell types - knowledge base (no date) PluriSelect USA. Available at:
https://www.pluriselect.com/pl/knowledge-base/cell-types/effector-t-cells.html (Accessed: November 7,
2022).
“Immunobiology: The immune system in health and disease” (1995) Choice Reviews Online, 32(07).
Available at: https://doi.org/10.5860/choice.32-3876.
Marketing, M. (2022) Different types of T cells and their functions, Akadeum Life Sciences. Available at:
https://www.akadeum.com/blog/different-types-of-t-cells/ (Accessed: November 7, 2022).
Ngwaga, T., Chauhan, D. and Shames, S.R. (2021) “Mechanisms of effector-mediated immunity revealed by
the accidental human pathogen legionella pneumophila,” Frontiers in Cellular and Infection
Microbiology, 10. Available at: https://doi.org/10.3389/fcimb.2020.593823.
Thank you for your attention!