Cell Mediated Immune Responses
Cell Mediated Immune Responses
Cell Mediated Immune Responses
PHYSIOLOGY OF IMMUNITY
involves the following series of events that culminate in B cell or T cell activation (or both ) and response
to the introduction of a foreign into the circulation :
processing of the foreign entity by a macrophage or B cell
recognition of this foreign entity by specific , preformed receptors on certain B cells and T cells
proliferation of these B cells and T cells , as stimulated by soluble signals(interleukins ) between
macrophages , B cells and T cells
blast transformation and a series of mitotic divisions leading to the generation (from B cells ) of plasma
cells that produce immunoglobulins and ( from T cells ) of sensitized T cells all capable of interacting
with the original foreign stimulus
T-dependent antigens
are proteins; they stimulate all
five classes of immunoglobulins
and can elicit an anamnestic
(secondary-booster) response
T-independent antigens
T cells
-mature in the thymus
-are involved in helpingB cells become antibody-producing plasma cells
-have specific receptors (T cell receptors) on their surface for antigen recognition
-are involved in cell mediated immunity
-participate in suppresion of the immune response
-are the predominant 95% lymphocytes in the circulation
-are found in the paracortical and interffolicular areas of the lymph nodes and spleen
The morphology of lymph nodes. A, This
schematic diagram shows the structural
organization and blood flow in a lymph node. B,
This light micrograph shows a cross section of a
lymph node with numerous follicles in the cortex,
some of which contain lightly stained central
areas (germinal centers), and the central medulla.
CD (cluster of differentiation) markers
arise on T cells during maturation in the thymus
appear on T cells in the following sequence:CD2(T11); CD3(T3); CD4(T4); CD8(T8)
CD2
is the earliest T cell marker
is the sheep red blood cell (SRBC) receptor
is present on virtually every peripheral T cell
CD3
is intimately associated with TCR
CD4
is present mainly on helper T cells
is involved in interaction with class II human leukocyte antigens (HLAs)
CD8
is present mainly on cytotoxic T cells
recognizes class I HLAs
Ontogeny of T cells
occurs as stem cells flow through the thymic cortex , into the medulla and then out into the general
circulation
begins in the thymic cortex with the appearance of CD2 , followed by appearance of CD3 (with TCR), then
with concomitant expression of CD4 and CD8
in the thymic medulla consists of a loss of marker to produce two populations of cells one CD2 +
,CD3+,TCR+, CD4+ (65%); and the other CD2+ ,CD3+,TCR+, CD8+ (35%)-that are then released into the
peripheral circulation
is the time when both positive selection and negative selection occur
The protein antigens of microbes are transported from the portals of entry
of the microbes to the same peripheral lymphoid organs through which naive
T cells recirculate
In these organs, the antigens are processed and displayed by MHC molecules
on dendritic cells, the antigen-presenting cells (APCs) that are the most
efficient stimulators of naive T cells
At the same time as the T cells are seeing antigen, they receive additional
signals in the form of microbial products or molecules expressed by APCs in
response to innate immune reactions to the microbes
Steps in the activation of T lymphocytes. Naive T cells recognize major histocompatibility complex (MHC)-
associated peptide antigens displayed on antigen-presenting cells (APCs) and other signals (not shown). The T cells
respond by producing cytokines, such as IL-2, and expressing receptors for these cytokines, leading to an autocrine
pathway of cell proliferation. The result is clonal expansion of the T cells. Some of the progeny differentiate into
effector cells, which serve various functions in cell-mediated immunity, and memory cells, which survive for long
periods. CTL, cytotoxic T lymphocyte; IL-2, interleukin-2; IL-2R, interleukin-2 receptor.
Role of Innate Immunity in Stimulating Adaptive Immune Responses
The TCR
recognizes antigens,
it is not able to transmit biochemical signals to the
interior of the cell.
is noncovalently associated with a complex of three
proteins that make up CD3 and with a homodimer of
another signaling protein called the chain
The molecules involved in the
effector functions of CD4+
helper T cells. CD4+ T cells that
have differentiated into
effector cells express CD40L
and secrete cytokines. CD40L
binds to CD40 on macrophages
or B lymphocytes, and cytokines
bind to their receptors on the
same cells. The combination of
signals delivered by CD40 and
cytokine receptors activates
macrophages in cell-mediated
immunity (A) and activates B
cells to produce antibodies in
humoral immune responses (B).
IL, interleukin.
The development and
characteristics of subsets of
CD4+ helper T lymphocytes.
A, A naive CD4+ T cell may
differentiate into subsets that
produce different cytokines and
perform different effector
functions.
B, The main differences between
TH1 and TH2 subsets of helper T
cells are summarized. Note that
many helper T cells are not readily
classified into these distinct and
polarized subsets. The chemokine
receptors are called CCR or CXCR
because they bind chemokines
classified into CC or CXC
chemokines based on whether key
cysteines are adjacent or
separated by one amino acid.
Different chemokine receptors
control the migration of different
types of cells. These, in
combination with the selectins,
determine whether TH1 or TH2
cells dominate in different
inflammatory reactions in various
tissues. GM-CSF, granulocyte-
macrophage colony-stimulating
factor; IFN, interferon; Ig,
immunoglobulin; IL, interleukin;
TNF, tumor necrosis factor.
The functions of TH1 cells. TH1 cells produce the
cytokine interferon- (IFN-), which activates
phagocytes to kill ingested microbes and stimulates
the production of antibodies that promote the
ingestion of microbes by the phagocytes. APC,
antigen-presenting cell
The functions of TH2 cells.
TH2 cells produce the cytokines
IL-4, which stimulates the
production of immunoglobulin E
(IgE) antibody, and IL-5, which
activates eosinophils. IgE
participates in the activation of
mast cells by protein antigens
and coats helminthes, and
eosinophils destroy the
helminthes
TH2 cells stimulate the
production of other antibody
isotypes that may neutralize
microbes and toxins but do not
opsonize microbes for
phagocytosis or activate
complement by the classical
pathway. APC, antigen-presenting
cell; IL, interleukin.
CONCLUSIONS
T lymphocytes are the cells of cell-mediated immunity, the arm of the adaptive immune system that
combats intracellular microbes, which may be microbes that are ingested by phagocytes and live within
these cells or microbes that infect nonphagocytic cells.
T cells use their antigen receptors to recognize peptide antigens displayed by MHC molecules on
antigen-presenting cells (which accounts for the specificity of the ensuing response) and polymorphic
residues of the MHC molecules (accounting for the MHC restriction of T cell responses)
Antigen recognition by the TCR triggers signals that are delivered to the interior of the cells by
molecules associated with the TCR (the CD3 and chains) and by the co-receptors, CD4 and CD8, which
recognize class II and class I MHC molecules, respectively
The binding of T cells to APCs is enhanced by adhesion molecules, notably the integrins, whose affinity
for their ligands is increased by chemokines produced in response to microbes and by antigen
recognition by the TCR.
CONCLUSIONS
CD4+ helper T cells may differentiate into subsets of effector cells that produce
restricted sets of cytokines and perform different functions
TH1 cells, which produce IFN-, activate phagocytes to eliminate ingested microbes,
and stimulate the production of opsonizing and complement-binding antibodies.
TH2 cells, which produce IL-4 and IL-5, stimulate IgE production and activate
eosinophils, which function mainly in defense against helminths.
TH17 cells, which produce IL-17, are implicated in several inflammatory diseases and
may play a role in defense against bacterial infections
CD8+ T cells recognize peptides of intracellular (cytoplasmic) protein antigens and may
require help from CD4+ T cells to differentiate into effector CTLs. The function of CTLs
is to kill cells producing cytoplasmic microbial antigens.