T cells are involved in the cell-mediated immune response, whereas B cells are part of the humoral

immune response.
Cell-Mediated Immunity
 Recall that the T cells are involved in the cell-mediated immune response.
 T cells encompass a heterogeneous population of cells with each T cell playing a specialized role
in immune defense, ensuring a balanced and effective response to pathogens and abnormal cells.
1. Helper T Cells (CD4+ T Cells)
 Function: Coordinate the immune response by secreting cytokines that activate other immune cells
(e.g., B cells, macrophages, and cytotoxic T cells).
 Subtypes:
a. Th1 Cells – Activate macrophages and promote cell-mediated immunity against intracellular
pathogens.
b. Th2 Cells – Stimulate B cells to produce antibodies, important for defense against extracellular
pathogens.
c. Th17 Cells – Involved in inflammation and defense against fungal and bacterial infections.
d. T Follicular Helper (Tfh) Cells – Assist B cells in germinal centers to produce high-affinity
antibodies.
2. Cytotoxic T Cells (CD8+ T Cells)
 Function: Directly kill virus-infected, cancerous, or damaged cells by releasing perforins and
granzymes, leading to apoptosis (cell death).
3. Regulatory T Cells (Tregs, CD4+CD25+ T Cells)
 Function: Suppress excessive immune responses and maintain immune tolerance, preventing
autoimmune diseases.
4. Memory T Cells
 Function: Provide long-term immunity by "remembering" previous infections for a faster response
upon re-exposure.
 Subtypes:
a. Central Memory T Cells (Tcm) – Reside in lymphoid organs and can rapidly expand when
needed.
b. Effector Memory T Cells (Tem) – Circulate in the bloodstream and tissues, ready to act
quickly.
5. Gamma Delta (γδ) T Cells
 Function: Bridge innate and adaptive immunity by responding rapidly to infections, especially in
mucosal and epithelial tissues.
6. Natural Killer T Cells (NKT Cells)
 Function: Recognize lipid antigens presented by CD1d molecules and contribute to immune
regulation, inflammation, and anti-tumor responses.
T Cell Activation
 Naïve T cells can express one of two different molecules, CD4 or CD8, on their surface and are
accordingly classified as CD4+ or CD8+ cells.
 These molecules are important because they regulate how a T cell will interact with and respond
to an APC.
+
 Naïve CD4 cells bind APCs via their antigen-embedded MHC II molecules and are stimulated to
become helper T (TH) lymphocytes, cells that go on to stimulate B cells (or cytotoxic T cells)
directly or secrete cytokines to inform more and various target cells about the pathogenic threat.
+
 In contrast, CD8 cells engage antigen-embedded MHC I molecules on APCs and are stimulated
to become cytotoxic T lymphocytes (CTLs), which directly kill infected cells by apoptosis and
emit cytokines to amplify the immune response.
 The two populations of T cells have different mechanisms of immune protection, but both
bind MHC molecules via their antigen receptors called T cell receptors (TCRs).
 The CD4 or CD8 surface molecules differentiate whether the TCR will engage an MHC II or an
MHC I molecule. Because they assist in binding specificity, the CD4 and CD8 molecules are
described as coreceptors.
 Figure 50.3.4: Naïve CD4+ T cells engage MHC II molecules on antigen-presenting cells (APCs) and
become activated. Clones of the activated helper T cell, in turn, activate B cells and CD8+ T cells,
which become cytotoxic T cells. Cytotoxic T cells kill infected cells.
 Considering the innumerable possible antigens that an individual will be exposed to during a
lifetime.
 The mammalian adaptive immune system is adept in responding appropriately to each antigen.
 Mammals have an enormous diversity of T cell populations, resulting from the diversity of
TCRs.

T cell Receptor (TCR)

 Each TCR consists of two polypeptide chains that span the T cell membrane, as illustrated in
diagram below.
 A T cell receptor spans the membrane and projects variable binding regions into the
extracellular space to bind processed antigens via MHC molecules on APCs.

 The chains are linked by a disulfide bridge.

 Each polypeptide chain is comprised of a constant domain and a variable domain: a domain, in
this sense, is a specific region of a protein that may be regulatory or structural.
 The intracellular domain is involved in intracellular signaling.
 A single T cell will express thousands of identical copies of one specific TCR variant on its cell
surface.
 The specificity of the adaptive immune system occurs because it synthesizes millions of different
T cell populations, each expressing a TCR that differs in its variable domain. This TCR diversity
is achieved by the mutation and recombination of genes that encode these receptors in stem cell
precursors of T cells.
 The binding between an antigen-displaying MHC molecule and a complementary TCR “match”
indicates that the adaptive immune system needs to activate and produce that specific T cell
because its structure is appropriate to recognize and destroy the invading pathogen.

Helper T Lymphocytes
 The TH lymphocytes function indirectly to identify potential pathogens for other cells of the
immune system.
 These cells are important for extracellular infections, such as those caused by certain bacteria,
helminths, and protozoa.
 TH lymphocytes recognize specific antigens displayed in the MHC II complexes of APCs.
 There are two major populations of TH cells: TH1 and TH2.
 Whether a TH1 or a TH2 immune response develops depends on the specific types of cytokines
secreted by cells of the innate immune system, which in turn depends on the nature of the
invading pathogen.
 TH1 cells secrete cytokines to enhance the activities of cytotoxic T cells, as well as
macrophages.
 The TH1-mediated response involves macrophages and is associated with inflammation.
 When intracellular infection like M. tuberculosis occurs, macrophages stimulate naïve T cells to
become TH1 cells.
 These stimulated T cells secrete specific cytokines that send feedback to the macrophage to
stimulate its digestive capabilities and allow it to destroy the colonizing M. tuberculosis.
 In the same manner, TH1-activated macrophages are activated to ingest and kill tumor cells.
 TH2 cells stimulate naïve B cells to destroy foreign invaders via antibody secretion.
 In summary; TH1 responses are directed toward intracellular invaders while TH2 responses are
aimed at those that are extracellular.

Humoral adaptive immunity

 This mechanism is primarily driven by B cell lymphocytes a type of immune cell that produces
antibodies after the detection of a specific antigen.
 It’s also called antibody-mediated immunity as antibody production is one of the notable features of
this immunity
 These responses are mediated by antibodies secreted by plasma cells, which arise from activated B-cells. They
constitute major form of protection against bacteria and viruses.

B cell types
a) Plasmablast
A short-lived, proliferating antibody-secreting cell arising from B cell differentiation. Plasmablasts are
generated early in an infection and their antibodies tend to have a weaker affinity towards their target antigen
compared to plasma cell. Plasmablasts can result from T cell-independent activation of B cells or the
extrafollicular response from T cell-dependent activation of B cells.
b) Plasma cell
A long-lived, non-proliferating antibody-secreting cell arising from B cell differentiation.[1] There is evidence
 that B cells first differentiate into a plasmablast-like cell, then differentiate into a plasma cell. Plasma cells are
generated later in an infection and, compared to plasmablasts, have antibodies with a higher affinity towards
their target antigen due to affinity maturation in the germinal center (GC) and produce more antibodies.
Plasma cells typically result from the germinal center reaction from T cell-dependent activation of B cells,
though they can also result from T cell-independent activation of B cells.[23]
c) Lymphoplasmacytoid cell
A cell with a mixture of B lymphocyte and plasma cell morphological features that is thought to be closely
related to or a subtype of plasma cells. This cell type is found in pre-malignant and malignant plasma cell
dyscrasias that are associated with the secretion of IgM monoclonal proteins; these dyscrasias include IgM
monoclonal gammopathy of undetermined significance and Waldenström's macroglobulinemia.
d) Memory B cell
Dormant B cell arising from B cell differentiation.[1] Their function is to circulate through the body and
initiate a stronger, more rapid antibody response (known as the anamnestic secondary antibody response) if
they detect the antigen that had activated their parent B cell (memory B cells and their parent B cells share the
same BCR, thus they detect the same antigen). Memory B cells can be generated from T cell-dependent
activation through both the extrafollicular response and the germinal center reaction as well as from T cell-
independent activation of B1 cells.
e) B-2 cell
Follicular (FO) B cell (also known as a B-2 cell)
Most common type of B cell and, when not circulating through the blood, is found mainly in the lymphoid
follicles of secondary lymphoid organs (SLOs). They are responsible for generating the majority of high-
affinity antibodies during an infection.
f) Marginal-zone (MZ) B cell
Found mainly in the marginal zone of the spleen and serves as a first line of defense against blood-borne
pathogens, as the marginal zone receives large amounts of blood from the general circulation. They can
undergo both T cell-independent and T cell-dependent activation, but preferentially undergo T cell-
independent activation.[16]
g) B-1 cell
Arises from a developmental pathway different from FO B cells and MZ B cells. In mice, they predominantly
populate the peritoneal cavity and pleural cavity, generate natural antibodies (antibodies produced without
infection), defend against mucosal pathogens, and primarily exhibit T cell-independent activation. A true
homologue of mouse B-1 cells has not been discovered in humans, though various cell populations similar to
B-1 cells have been described.
h) Regulatory B (Breg) cell
An immunosuppressive B cell type that stops the expansion of pathogenic, pro-inflammatory lymphocytes
through the secretion of IL-10, IL-35, and TGF-β. Also, it promotes the generation of regulatory T (Treg)
cells by directly interacting with T cells to skew their differentiation towards Tregs. No common Breg cell
identity has been described and many Breg cell subsets sharing regulatory functions have been found in both
mice and humans. It is currently unknown if Breg cell subsets are developmentally linked and how exactly
differentiation into a Breg cell occurs. There is evidence showing that nearly all B cell types can differentiate
into a Breg cell through mechanisms involving inflammatory signals and BCR recognition.