Maintenance of the Body
these intracellular pathogens, the cellular arm of adaptive im-
munity comes into play.
Check Your Understanding
Which class of antibody is most abundant in blood? Which is
secreted ﬁrst in a primary immune response? Which is most
abundant in secretions?
List four ways in which antibodies can bring about
destruction of a pathogen.
For answers, see Appendix H.
Cellular Immune Response
Deﬁne cellular immunity and describe the process of
activation and clonal selection of T cells.
Describe the roles of different types of T cells.
T cells are best suited for cell-to-cell interactions. When anti-
gens are presented to a T lymphocyte, they provoke a cellular
immune response. Some activated T cells directly kill body cells
infected by viruses or bacteria; abnormal or cancerous body
cells; and cells of infused or transplanted foreign tissues. Other
T cells release chemicals that regulate the immune response.
±e T cells that mediate cellular immunity are a diverse lot,
much more complex than B cells in both classiﬁcation and func-
tion. ±ere are two major populations of T cells based on which
of two structurally related
cell diﬀerentiation glycoproteins
CD4 or CD8—a mature T cell displays. ±e CD4 and CD8
glycoproteins are surface receptors but are distinct from the
T cell antigen receptors. ±ey play a role in interactions between
T cells and other cells.
When activated, CD4 and CD8 cells diﬀerentiate into the three
major kinds of
of cellular immunity
helper T cells
) that help acti-
vate B cells, other T cells, and macrophages, and direct the
adaptive immune response.
cytotoxic T cells
) that destroy any cells
in the body that harbor anything foreign.
Some CD4 cells become
regulatory T cells
), which mod-
erate the immune response.
Activated CD4 and CD8 cells can also become memory
T cells. We will provide details of T cells’ roles shortly. Note
that the names of the eﬀector cells (helper, cytotoxic, regulatory)
are reserved for
T cells, while naive T cells are simply
called CD4 or CD8 cells.
MHC Proteins and Antigen Presentation
Unlike B cells and antibodies, T cells cannot “see” either free
antigens or antigens that are in their natural state. T cells can
recognize and respond only to
fragments of protein
antigens displayed on surfaces of body cells (APCs and others).
Antigen presentation is necessary for both activation of naive
T cells and the normal functioning of eﬀector T cells. ±e cell
surface proteins on which antigens are presented to T cells are
called MHC proteins. As you might guess, we need to understand
how these critical players in antigen presentation work before we
can understand how T cells work. ±ere are two classes of MHC
proteins—class I MHC proteins and class II MHC proteins.
Class I MHC Proteins
Class I MHC proteins
are found on the surface of virtually
body cells except red blood cells. Each class I MHC protein
has a groove that holds an antigen—a protein fragment 8 or 9
amino acids long.
Where do these protein fragments come from? All antigens
displayed on class I MHC proteins are
fragments of proteins synthesized
inside the cell
. In a healthy
cell, endogenous antigens are all self-antigens, generally bits of
digested cellular proteins. But in an infected cell, endogenous
antigens may also include fragments of foreign antigens that are
synthesized within the infected cell but “belong to” the patho-
gen. In a cancerous cell, endogenous antigens can include al-
tered cancer proteins.
As proteases (protein-digesting enzymes) degrade cytoplas-
mic proteins as part of their natural recycling, a random sample
of the resulting protein fragments is transported into the endo-
plasmic reticulum. Inside the ER, these peptides bind to newly
synthesized class I MHC proteins. Transport vesicles then ex-
port the “loaded” class I MHC proteins to the cell surface.
Class I MHC proteins are crucial for both activating naive
CD8 cells and “informing” cytotoxic T cells that infectious mi-
croorganisms are hiding in body cells. Without them, viruses
and certain bacteria that thrive in cells could multiply unno-
ticed and unbothered.
When class I MHC proteins display fragments of our own
proteins (self-antigens), cytotoxic T cells passing by get the sig-
nal “Leave this cell alone, it’s ours!” and ignore them. But when
class I MHC proteins display foreign antigens, they “sound a
molecular alarm” that signals invasion. In this signaling, the
class I MHC proteins both (1) act as antigen holders and (2)
form the self part of the self-nonself complexes that cytotoxic T
cells must recognize in order to kill.
Class II MHC Proteins
Unlike the widely distributed class I MHC proteins, the second
type of MHC protein is less widespread.
Class II MHC pro-
are typically found
only on the surfaces of cells that present
antigens to CD4 cells
: dendritic cells, macrophages, and B cells.
Like their class I MHC counterparts, class II MHC proteins are
synthesized at the ER and bind to peptide fragments. However,
the peptides they bind are longer (14–17 amino acids) and come
the cell that
have been engulfed by the cell that displays them.
±e engulfed exogenous antigens are broken down by pro-
teases inside a phagolysosome. Vesicles from the ER containing
class II MHC proteins fuse with the phagolysosome, and the
antigen fragments bind to the groove of the MHC proteins. ±e
vesicle is then exported to the cell surface, where the class II
MHC protein displays its prize for CD4 cells to recognize.