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The immune system
There are certain sites where the cells of the
immune system are organised into specific structures.
 central lymphoid tissue: bone marrow, thymus
 peripheral lymphoid tissue: lymph nodes, spleen
Bone marrow: all the cells of the immune system are
derived from stem cells in the bone marrow. The bone
marrow is the site of origin of red blood cells, white cells
(including lymphocytes and macrophages) and platelets.
Thymus: in the thymus gland lymphoid cells undergo a
process of maturation and education prior to release into
the circulation. This process allows T cells to develop the
important attribute known as self tolerance.
Lymph nodes: Lymph nodes are small bean shaped
structures lying along the course of lymphatics. They are
aggregated in particular sites such as the neck, axillae,
groins and para-aortic region. Knowledge of the sites of
lymph nodes is important in physical examination of patients.
T cells and B cells are activated by foreign antigens mainly in
peripheral lymphoid organs, such as lymph nodes or the spleen.
Spleen: is located in the upper left quadrant of the abdomen.
It has two main functions acting as part of the immune system and as a filter
Cells of the Immune System
Cells destined to become immune cells, like all
blood cells, arise in the bone marrow from so-called
stem cells.
Some develop into myeloid cells, large white blood
cells known as phagocytes; phagocytes include
monocytes, macrophages, and neutrophils. Other
myeloid descendants become granule-containing
inflammatory cells such as eosinophils and
basophils.
Lymphoid precursors develop into the small white
blood cells called lymphocytes. The two major
classes of lymphocytes are B cells and T cells.
Lymphocytes produced within bone marrow
B cells: achieve immune-competence within
the bone marrow
T cells: achieve immune-competence in the thymus
Mature lymphocytes all have a similar appearance
B and T cells circulate in the blood and through
body tissues.
B cells give rise to plasma cells which secrete
immunoglobulins (antibodies).
T cells also respond to antigens they act by
• secreting lymphokines which act on other cells
involved in the IR (T4 receptors)
• causing lysis of infected cells (T8 receptors,
cytotoxic)
lymphocytes
B Cells: work by secreting soluble
substances known as antibodies.
Each B cell is programmed to make
one specific antibody.
When a B cell encounters its
triggering antigen (along with
various accessory cells), it gives rise
to many large plasma cells.
Each plasma cell is essentially a
factory for producing that one
specific antibody.
lymphocytes
T Cells: contribute to the immune defenses
in two major ways. Some help regulate the
complex workings of the immune system,
while others are cytotoxic and directly
contact infected cells and destroy them.
Chief among the regulatory T cells are
"helper/inducer" T cells. They are needed
to activate many immune cells, including B
cells and other T cells. Another subset of
regulatory T cells acts to turn off or
suppress immune cells.
Vedi filmato
Cytotoxic T cells help rid the body of cells
that have been infected by viruses as well as
cells that have been transformed by cancer.
They are also responsible for the rejection of
tissue and organ grafts.
myeloid cells,
Phagocytes and Granulocytes
Phagocytes are large white cells that can engulf
and digest foreign invaders.
They include monocytes, which circulate in the
blood, and macrophages, which are found in
tissues throughout the body.
Macrophages are versatile cells; they act as
scavengers, they secrete a wide variety of
powerful chemicals, and they play an essential
role in activating T cells.
Neutrophils cells circulate in the blood but move
into tissues where they are needed. Neutrophils
are not only phagocytes but also granulocytes:
they contain granules filled with potent
chemicals. These chemicals, in addition to
destroying microorganisms, play a key role in
acute inflammatory reactions.
Other types of granulocytes are eosinophils and
basophils. Mast cells are granule-containing
cells in tissue.
Antigen Receptors
Both B cells and T cells carry receptor molecules that
allow them to recognize and respond to specific targets.
The B cell's antigen-specific receptor recognizes antigen
in its natural state.
A T cell can recognize an antigen only after the antigen is
processed and presented to it by a so-called antigenpresenting cell, in combination with a special type of cell
marker.
The T4 T cell's receptor looks for an antigen that has been
broken down by an immune system cell such as a
macrophage or a B cell and combined with a marker,
known as a class II protein, carried by immune cells.
The T8 T cell's receptor recognizes an antigen fragment
produced within the cell, combined with a class I
protein; class I proteins are found on virtually all body
cells.
Vedi filmato
Activation of B Cells to Make Antibody
The B cell uses its receptor to bind a matching
antigen, which it proceeds to engulf and
process.
Then it combines a fragment of antigen with
its special marker, the class II protein.
This combination of antigen and marker is
recognized and bound by a T cell carrying a
matching receptor.
The binding activates the T cell, which then
releases lymphokines—interleukins—that
transform the B cell into an antibodysecreting plasma cell
Activation of T Cells: Helper and ...
After an antigen-presenting cell such as a macrophage has
ingested and processed an antigen, it presents the antigen
fragment, along with a class II marker protein, to a matching
helper T cell with a T4 receptor.
The binding prompts the macrophage to release interleukins that
allow the T cell to mature.
... Cytotoxic
A cytotoxic T cell recognizes antigens,
such as virus proteins produced within a
cell, in combination with a class I selfmarker protein. With the cooperation of a
helper T cell, the cytotoxic T cell matures.
When the mature cytotoxic T cell
encounters its specific target antigen
combined with a class I marker protein-for
instance, on a body cell that has been
infected with a virus-it is ready to attack
and kill the target cell.
Antigen: a molecule able to react with the ensuing antibody or T cell receptor.
Antigens that succeed in invading the blood stream are intercepted in the spleen
Lymphocytes respond to presented antigens by the production of antibodies
(by B cells) or lymphokines (by T and B cells).
Immunogenicity: the ability of a molecule or molecular configuration (immunogen)
to induce an immune response
Haptens: antigens that are able to react, but unable to induce immune reaction, i.e.
they lack immunogenicity.
Macrophages and dendritic cells: derived from the bone marrow, have a variety of
functions in the immune response: phagocytosis, secretion of cytokines,
antigen presentation
The cells performing these various functions have differing microscopic appearances
but they are grouped together as the mononuclear phagocytic system. .
Humoral Immunity
It is offerred by antibodies
Antibodies (Immunoglobulins,
abbreviated Ig) are proteins of MW:
150,000 - 900,000 kd.
They are unique molecules, derived
from the 'immunoglobulin supergene'.
One end of the Ig binds to antigens
(the Fab portion, so called because it
is the fragment of the molecule which
is antigen binding), and the other end
which is crystallizable, and therefore
called Fc, is responsible for effector
functions:
Antibodies belong to a family of large protein molecules known as
immunoglobulins.
Scientists have identified nine chemically distinct classes of human
immunoglobulins, four kinds of IgG and two kinds of IgA, plus IgM, IgE, and
IgD.
Immunoglobulins G, D, and E are similar in appearance.
IgG, the major immunoglobulin in the blood, is also able to enter tissue spaces; it
works efficiently to coat microorganisms, speeding their uptake by other cells in
the immune system.
IgD is almost exclusively found inserted into the membrane of B cells, where it
somehow regulates the cell's activation.
IgE is normally present in only trace amounts, but it is responsible for the
symptoms of allergy
Each antibody is made up of
2 identical heavy chains
2 identical light chains
shaped to form a Y.
The sections that make up the tips of the
Y's arms vary greatly from one antibody to
another; this is called the variable region.
It is these unique contours in the antigenbinding site that allow the antibody to
recognize a matching antigen, much as a
lock matches a key.
The stem of the Y links the antibody to
other participants in the immune defenses.
This area is identical in all antibodies of
the same class—for instance, all IgEs—and
it's called the constant region.
The regions concerned with antigen binding are extremely variable, whereas other
regions of the molecule are relatively constant.
Thus each heavy and each light chain possesses a variable and a constant region. The
isotype of an Ig is determined by the constant region.
L chains are linked to H chains by disulphide (S-S) links.
Intrachain S-S links divide H and L chains into domains which are separately folded.
Thus, an IgG molecule contains
3 H chain domains: CH1, CH2
and CH3.
Between CH1 and CH2, there
are many cysteine and proline
residues.
This is known as the hinge
region and confers flexibility to
the Fab arms of the Ig molecule.
This is used when antibody
interacts with antigen.
Molecules with multiple antigenic determinants.
(A) A globular protein is shown with a number of different antigenic determinants.
Different regions of a polypeptide chain usually come together in the folded structure to
form each antigenic determinant on the surface of the protein.
(B) A polymeric structure is shown with many identical antigenic determinants.
Antibody-antigen interactions.
Because antibodies have two identical antigen-binding sites, they can cross-link
antigens. The types of antibody-antigen complexes that form depend on the
number of antigenic determinants on the antigen.
Here a single species of antibody (a monoclonal antibody) is shown binding to
antigens containing one, two, or three copies of a single type of antigenic
determinant. Antigens with two antigenic determinants can form small cyclic
complexes or linear chains with antibody, while antigens with three or more
antigenic determinants can form large three-dimensional lattices that readily
precipitate out of solution.
The hinge region of an antibody molecule.
Because of its flexibility, the hinge region
improves the efficiency of antigen binding
and cross-linking.