FACULTY OF HEALTH SCIENCES

DEPARTMENT OF MEDICAL LABORATORY SCIENCE

LECTURE NOTES ON CLINICAL IMMUNOLOGY (MLSH 4101) 2021/2022
Lecturer: Dr BISONG C. EBAI
Lecture 2: Adaptive immunity

Plan:

I. T- cells
II. B- cells
III. Passive and active immunity
IV. Antibody-mediated vs cell mediated immunity

Generalities:

Adaptive immunity develops when innate immunity is ineffective in eliminating

infectious agents and the infection is established. The primary functions of the
adaptive immune response are:

- the recognition of specific “non-self” antigens in the presence of “self” antigens;

- the generation of pathogen-specific immunologic effector pathways that eliminate
specific pathogens or pathogen-infected cells; and
- the development of an immunologic memory that can quickly eliminate a specific
pathogen should subsequent infections occur.
The cells of the adaptive immune system include: T cells, which are activated
through the action of antigen presenting cells (APCs), and B cells.
I. T cells and APCs

T cells derive from hematopoietic stem cells in bone marrow and, following
migration, mature in the thymus. These cells express a unique antigen-binding
receptor on their membrane, known as the T-cell receptor (TCR), and require the
action of APCs (usually dendritic cells, but also macrophages, B cells, fibroblasts
and epithelial cells) to recognize a specific antigen. The surfaces of APCs express
cell-surface proteins known as the major histocompatibility complex (MHC). MHC
are classified as either class I (also termed human leukocyte antigen [HLA] A, B
and C) which are found on all nucleated cells, or class II (also termed HLA, DP, DQ
and DR) which are found on only certain cells of the immune system, including
macrophages, dendritic cells and B cells. Class I MHC molecules present

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endogenous (intracellular) peptides while class II molecules present exogenous
(extracellular) peptides. The MHC protein displays fragments of antigens
(peptides) when a cell is infected with a pathogen or has phagocytosed foreign
proteins.

T cells are activated when they encounter an APC that has digested an antigen and
is displaying antigen fragments bound to its MHC molecules. The MHC-antigen
complex activates the TCR and the T cell secretes cytokines which further control
the immune response. This antigen presentation process stimulates T cells to
differentiate into either cytotoxic T cells (CD8+ cells) or T helper (Th) cells (CD4+
cells).

Cytotoxic T cells are primarily involved in the destruction of cells infected by

foreign agents. They are activated by the interaction of their TCR with peptide-
bound MHC class I molecules. Clonal expansion of cytotoxic T cells produce
effector cells which release perforin and granzyme (proteins that causes lysis of
target cells) and granulysin (a substance that induces apoptosis of target cells).

Upon resolution of the infection, most effector cells die and are cleared by
phagocytes. However, a few of these cells are retained as memory cells that can
quickly differentiate into effector cells upon subsequent encounters with the same
antigen.

T helper (Th) cells play an important role in establishing and maximizing the
immune response. These cells have no cytotoxic or phagocytic activity, and cannot
kill infected cells or clear pathogens. However, they “mediate” the immune
response by directing other cells to perform these tasks. Th cells are activated
through TCR recognition of antigen bound to class II MHC molecules. Once
activated, Th cells release cytokines that influence the activity of many cell types,
including the APCs that activate them. Two types of Th cell responses can be
induced by an APC: Th1 or Th2.

The Th1 response is characterized by the production of interferon-gamma (IFN-

g) which activates the bactericidal activities of macrophages, and other cytokines
that induce B cells to make opsonizing (coating) and neutralizing antibodies.

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The Th2 response is characterized by the release of cytokines (interleukin-4, 5
and 13) which are involved in the activation and/or recruitment of immunoglobulin
E (IgE) antibody-producing B cells, mast cells and eosinophils. As mentioned
earlier, mast cells and eosinophils are instrumental in the initiation of acute
inflammatory responses, such as those seen in parasitic infections, allergy and
asthma. IgE antibodies are also associated with allergic reactions. Therefore, an
imbalance of Th2 cytokine production is associated with the development of atopic
(allergic) conditions. Like cytotoxic T cells, most Th cells will die upon resolution of
infection, with a few remaining as Th memory cells.

A third type of T cell, known as the regulatory T cell (T reg), also plays a role in
the immune response. T reg cells limit and suppress the immune system and,
thereby, may function to control aberrant immune responses to self-antigens and
the development of autoimmune disease.

II. B cells

B cells arise from hematopoietic stem cells in the bone marrow and, following
maturation, leave the marrow expressing a unique antigen-binding receptor on
their membrane. Unlike T cells, B cells can recognize free antigen directly, without
the need for APCs. The principal function of B cells is the production of
antibodies against foreign antigens. When activated by foreign antigens, B
cells undergo proliferation and differentiate into antibody-secreting plasma
cells or memory B cells. Memory B cells are “long-lived” survivors of past
infection and continue to express antigen-binding receptors. These cells can be
called upon to respond quickly and eliminate an antigen upon re-exposure. Plasma
cells, on the other hand, do not express antigen-binding receptors. These are short-
lived cells that undergo apoptosis when the inciting agent that induced the
immune response is eliminated.

Given their function in antibody production, B cells play a major role in the
humoral or antibody-mediated immune response (as opposed to the cell-mediated
immune response, which is governed primarily by T cells).

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 III. Antibody-mediated vs. cell-mediated immunity

Antibody-mediated immunity is the branch of the acquired immune system that is

mediated by B-cell antibody production. The antibody-production pathway begins when
the B cell’s antigen-binding receptor recognizes and binds to antigen in its native form.
This in turn, attracts the assistance of Th cells which secrete cytokines that help the B
cell multiply and mature into antibody-secreting plasma cells. The secreted antibodies
bind to antigens on the surface of pathogens, flagging them for destruction through

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pathogen and toxin neutralization, classical complement activation, opsonin promotion of
phagocytosis and pathogen elimination. Upon elimination of the pathogen, the antigen-
antibody complexes are cleared by the complement cascade.

IV. Passive and active immunity

Acquired immunity is attained through either passive or active immunization. Passive

immunization refers to the transfer of active humoral immunity, in the form of “ready-
made” antibodies, from one individual to another. It can occur naturally by transplacental
transfer of maternal antibodies to the developing fetus, or it can be induced artificially by
injecting a recipient with exogenous antibodies targeted to a specific pathogen or toxin.

The latter is used when there is a high risk of infection and insufficient time for the body
to develop its own immune response, or to reduce the symptoms of chronic or
immunosuppressive diseases.

Active immunization refers to the production of antibodies against a specific agent after
exposure to the antigen. It can be acquired through either natural infection with a
microbe or through administration of a vaccine that can consist of attenuated (weakened)
pathogens or inactivated organisms.