Download Human immune system

Medical biology, microbiology,
virology, immunology department
Human immune system.
By as. E.V. Pokryshko
Structure of the immune
system
Lymphoid organs can be classified
into
primary (central) lymphoid organs
secondary (peripheral) lymphoid
organs
Structure of the immune system
Primary (central) lymphoid organs:
 thymus
 avian bursa of Fabricius (the
equivalent of it in mammals is bone
marrow)
 foetal liver (during embrionic
development)
Structure of the immune system
Secondary (peripheral) lymphoid organs:
 lymph nodes
 spleen
 mucosa-associated lymphoid tissues
ORIGIN OF IMMUNE CELLS
The capability of responding to
immunologic stimuli rests mainly with
lymphoid
cells.
During
embryonic
development,
blood
cell
precursors
originate mainly in the fetal liver and yolk
sac; in postnatal life, the stem cells reside
in the bone marrow. Stem cells
differentiate into cells of the erythroid,
myeloid, or lymphoid series. The latter
evolve
into
two
main
lymphocyte
populations: T cells and B cells. The ratio
of T cells to B cells is approximately 3:1.
Differentiation of stem cells into B cells and T cells.
This occurs in the bone marrow and thymus.
T cells
T cell precursors differentiate into
immunocompetent T cells within the thymus. Stem
cells lack antigen receptors and CD3, CD4, and CD8
molecules on their surface, but during passage
through the thymus they differentiate into T cells
that can express these glycoproteins. The stem
cells, which initially express neither CD4 nor CD8
(double-negatives), first differentiate to express
both CD4 and CD8 (double-positives) and then
proceed to express either CD4 or CD8. A doublepositive cell will differentiate into a CD4-positive
cell if it contacts a cell bearing class II MHC
proteins but will differentiate into a CD8-positive
cell if it contacts a cell bearing class I MHC
proteins.
Lymphoid progenitors migrate from the bone marrow
to
the thymus where they develop into mature T cells
Thymocytes are intimately associated with epithelial cells as they
develop in the thymus
B cells perform two important functions: (1) They
differentiate into plasma cells and produce antibodies,
and (2) they are antigen-presenting cells (APCs).
Origin. During embryogenesis, B cell precursors are
recognized first in the fetal liver. From there they
migrate to the bone marrow, which is their main
location during adult life. Unlike T cells, they do not
require the thymus for maturation. Pre-B cells lack
surface immunoglobulins and light chains but do have μ
heavy chains in the cytoplasm. The maturation of B
cells has two phases: the antigen-independent phase
consists of stem cells, pre-B cells, and B.cells, whereas
the antigen-dependent phase consists of the cells that
arise subsequent to the interaction of antigen with the
B cells, eg, activated B cells and plasma cells. B cells
display surface IgM, which serves as a receptor for
antigens.
Pre-B cells are found in the bone
marrow, whereas B cells circulate in the
blood stream. B cells constitute about 30%
of the recirculating pool of small
lymphocytes, and their life span is short,
ie. days or weeks. Within lymph nodes,
they are located in germinal centers;
within the spleen, they are found in the
white pulp. They are also found in the gutassociated lymphoid tissue, eg, Peyer's
patches.
T Cells
perform several important functions, which can be
divided into two main categories, namely, regulatory and effector.
The regulatory functions are mediated primarily by helper (CD4positive) T cells, which produce interleukins. For example, helper T
cells make (1) interleukin-4 (IL-4) and IL-5, which help B cells produce
antibodies; (2) IL-2, which activates CD4 and CD8 cells; and (3)
gamma interferon, which activates macrophages,
CD4 and CD8 Types of T Cells. Within the thymus, perhaps
within the outer cortical epithelial cells (nurse cells), T cell
progenitors differentiate under the influence of thymic hormones
(thymosins and thymopoietins) into T cell subpopulations. These cells
are characterized by certain surface glycoproteins, eg, CD3, CD4, and
CD8. All T cells have CD3 proteins on their surface in association
with antigen receptors (T cell receptor [see below]). The CD3 complex
of five transmembrane proteins is involved with transmitting, from
the outside of the cell to the inside, the information that the antigen
receptor is occupied. CD4 is a single transmembrane polypeptide
whereas CD8 consists of two transmembrane polypeptides.
T
Cells
perform several important
functions, which can be divided into two main
categories, namely, regulatory and effector.
The regulatory functions are mediated
primarily by helper (CD4-positive) T cells,
which produce interleukins. For example,
helper T cells make
(1) interleukin-4 (IL-4) and IL-5, which help B
cells produce antibodies;
(2) IL-2, which activates CD4 and CD8 cells;
and
(3) Gamma-interferon,
which
activates
macrophages, effect delayed hypersensitivity
(eg, limit infection by M tuberculosis).
These
functions
are
performed
by
2
subpopulations of CD4 cells: Th-1 cells help
activate cytotoxic T cells by producing IL-2 and
help initiate the delayed hypersensitivity response
by producing primarily IL-2 and gamma interferon,
whereas Th-2 cells perform the B cell helper
function by producing primarily IL-4 and IL-5. One
important regulator of the balance between Th-l
cells and Th-2 cells is interleukin-12 (IL-12), which
is produced by macrophages. IL-12 increases the
number of Th-1 cells, thereby enhancing host
defenses against organisms that are controlled by a
delayed
hypersensitivity
response.
Another
important regulator is gamma interferon which
inhibits the production of Th-2 cells. CD4 cells make
up about 65% of peripheral T cells and predominate
in the thymic medulla, tonsils, and blood.
CD 8 lymphocytes perform cytotoxic
functions; that is, they kill virus
infected, tumor, and allograft cells.
They kill by either of two mechanisms,
namely, the release of performs, which
destroy cell membranes, or the
induction of programmed cell death
(apoptosis).
CD 8 cells predominate in human
bone marrow and gut lymphoid tissue
and constitute about 35% of peripheral
T cells.
Types of T cells: After T cells are challenged by
antigens, the cells differentiate into one of several types
of functioning T cells
T Cell Receptor
(TCR) for antigen consists of
two polypeptides, alpha and beta ,which are
associated with CD3 proteins. TCR proteins are
similar to immunoglobulin heavy chains.
Note that each T cell has a unique T cell
receptor on its surface, which means that hundreds
of millions of different T cells exist in each person.
Activated T cells, like activated B cells, clonally
expand to yield large numbers of cells specific for
that antigen.
Although TCRs and immunoglobulins are
analogous in that they both interact with antigen in
a highly specific manner, the T cell receptor is
different in two important ways: (1) it has two
chains rather than four, and (2) it recognizes
antigen only, in conjunction with MHC proteins,
whereas immunoglobulins recognize free antigen.
Colorized SEM of a small T lymphocyte attacking
two large tumor cells