CELLS OF THE IMMUNE SYSTEM

MLS 312
Overview of Immune system
The immune system
• all parts of the body that help in the recognition and destruction of
foreign materials such as
White blood cells:- phagocytes and lymphocytes; bone marrow;
lymph nodes; tonsils; thymus and the spleen.

Immunity is the body's ability to fight off foreign substances such as

viruses or bacteria by generating a specific immune response.
Antigens
• Antigens or immunogens are macromolecules that are foreign & elicit an
immune response in the body.
• Antigens can be
 proteins
 polysaccharides
 conjugates of lipids with
 proteins (lipoproteins) and
 polysaccharides (glycolipids).
• Not all Ags produce an immunogenic response, but all immunogens are
antigens.
• Most Ags are high mol wt substances.
• Low mol wt substances will also act as Ags if they bind to proteins or
carrier molecules in the body.
• The low mol wt (<5kd) compd is referred to as a hapten.

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Types of antigens
• Autoantigens are a person's own self antigens.
• Alloantigens are found in different members of the same species (e.g red
bld cell antigens A and B ).
• Heterophile antigens are identical Ags found in the cells of different
species.
• Endogenous antigens are generated within the cell, due to normal cell
metabolism or viral or intracellular bacterial infection.

• Exogenous antigens enter the body from the outside e.g. by inhalation,
ingestion, or injection.

• Allergens are Ags that cause an allergic reaction and the production of IgE.

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Two major subdivision of immune
system
• The immune system is composed of two major subdivisions, the
innate or nonspecific immune system and the adaptive or specific
immune system.

• Innate Immune response ( Anatomical Barriers to infections,humoral

barrier and cellular barriers )

• Adaptive Immune response ( Require time, antigen specific and

immunological memory)
Hematopioetic stem cell
All blood cells arise from a type of cell called the hematopioetic stem cell
(HSC) .It’s remarkable that every functionally specialized, mature blood cell
arise from an HSC.

Stem cells are cells that can differentiate into other cell types. They are
self- renewing, maintaining their population level by cell division .

Early in hematopoiesis, a multipotent stem cell differentiates along one

of two pathways, giving rise to either a :
1. Lymphoid progenitor cell, or a
2. Myeloid progenitor cell .
 Lymphoid progenitor cells:
give rise to B, T, and NK cells.

Myeloid progenitor cells:

generate progenitors of red blood cells (erythrocytes),
many of the various white blood cells (neutrophils,
eosinophils, basophils, monocytes, mast cells, dendritic
cells) ,and platelet-generating cells called megakaryocytes.
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Lymphoid Cells:
Lymphocytes constitute 20%–40% of the body’s white blood cells and 99% of
the cells in the lymph.
Lymphocytes are the central cells of the immune system, responsible for
adaptive immunity and the immunologic attributes of diversity, specificity,
memory, and self/nonself recognition.

The lymphocytes can be broadly subdivided into three populations:

*B cells, *T cells, and *natural killer cells—on the basis of function and cell-
membrane components.
Natural killer cells (NK cells) are large, granular lymphocytes that do not
express the set of surface markers typical of B or T cells.
B Lymphocytes (B cells)
• Mature B cells display of membrane-bound immunoglobulin
(antibody) molecules, which serve as receptor for Ag (BCR) .

• The binding of the Ag to the Ab causes the cell to divide rapidly; its
progeny differentiate into :

1. Plasma cells ,which produce the Ab in a form that can be

secreted and have little or no membrane-bound Ab. They are end-
stage cells and do not divide.

2.Memory B cells, which have a longer life span than naïve cells,
and they express the same membrane-bound Ab as their parent B
cell.
T-Lymphocytes (T-cell)
• It derive it litter designation from their site of
maturation in the thymus.

• During its maturation within the thymus, the T cell

comes to express on its membrane a unique Ag-
binding molecule called the T-cell receptor.

• TCR recognize Ag that is bound to cell membrane

proteins called major histocompatibility complex
(MHC).
• There are two well-defined subpopulations of T cells:
1. T-helper (T H) cells, and
2. T-cytotoxic (T C ) cells.
recently a third T-cell subpopulation,
3. T-regulatory ( T reg )cells .
T helper cells characterize by the presence of CD4 membrane
glycoproteins on their surfaces.
T cytotoxic cells express CD8 membrane glycoproteins on their
surfaces.
The ratio of T H to T C is about 2:1 in normal human peripheral blood,
but it may be significantly altered by immunodeficiency diseases,
autoimmune diseases, and other disorders .
NATURAL KILLER CELLS
NK cells play an important role in host defens against tumor cells and
against cells infected with some, though not all, viruses. These
cells, which constitute 5%–10% of lymphocytes in human
peripheral blood, do not express the membrane molecules and
receptors that distinguish T- and B-cell lineages.

NK cells express CD16, a membrane receptor for Fc region of IgG

molecule, they can attach to these antibodies and subsequently
destroy the targeted cells. This is an example of a process known as
antibody-dependent cell mediated cytotoxicity (ADCC).
Mononuclear Phagocytes
The mononuclear phagocytic system consists of monocytes circulating in the
blood and macrophages in the tissues.
• macrophage activity can be further enhanced by cytokines secreted by
activated TH cells,
One of the most potent activators of macrophages is interferon gamma(IFN-γ)
secreted by activated TH cells.
Activated macrophages also express higher levels of class II MHC molecules,
allowing them to function more effectively as antigen-presenting cells.

Activated macrophages secrete:

1. a collection of cytokines, such as interleukin 1 (IL-1), TNF-α and interleukin
6 (IL-6), that promote inflammatory responses.
2. Complement proteins.
3. The hydrolytic enzymes contained within the lysosomes of macrophages.
4. TNF-α, that can kill a variety of cells.
Macrophages are dispersed throughout the body. Some take up residence in
particular tissues, becoming fixed macrophages, whereas others remain
motile and are called free, or wandering, macrophages
Macrophage-like cells serve different functions in different tissues and are
named according to their tissue location:
1. Alveolar macrophages in the lung.
2. Histiocytes in connective tissues.
3. Kupffer cells in the liver.
4. Mesangial cells in the kidney.
Granulocytic Cells:
The granulocytes are classified as neutrophils, eosinophils, or basophils.
Neutrophils:
are produced by hematopoiesis in the bone marrow. In response to many
types of infections, the bone marrow releases more than the usual number
of neutrophils and these cells generally are the first to arrive at a site of
inflammation. The resulting transient increase in the number of circulating
neutrophils, called leukocytosis, is used medically as an indication of
infection.

Movement of circulating neutrophils into tissues, called extravasation,

takes several steps:
1. the cell first adheres to the vascular endothelium.
2. then penetrates the gap between adjacent endothelial cells lining the
vessel wall.
3. and finally penetrates the vascular basement membrane, moving out
into the tissue spaces.
Like macrophages, neutrophils are active phagocytic cells. Phagocytosis by
neutrophils is similar to that described for macrophages, except that the lytic
enzymes and bactericidal substances in neutrophils are contained within primary
and secondary granules.
Neutrophils are in fact much more likely than macrophages to kill ingested
microorganisms. Neutrophils exhibit a larger respiratory burst than macrophages
and consequently are able to generate more reactive oxygen intermediates
and reactive nitrogen intermediates.

Eosinophils
like neutrophils, are motile phagocytic cells that can migrate from the blood into
the tissue spaces. Their phagocytic role is significantly less important than that of
neutrophils, and it is thought that they play a role in the defense against parasitic
organisms
Basophils
are nonphagocytic granulocytes that function by releasing
pharmacologically active substances from their
cytoplasmic granules. These substances play a major role
in certain allergic responses.

Mast-cell
Mast-cell precursors, which are formed in the bone marrow by
hematopoiesis, are released into the blood as undifferentiated cells; they
do not differentiate until they leave the blood and enter the tissues. It
plays an important role in the development of allergies.
Dendritic cell (DC)
acquired its name because it is covered
with long membrane extensions giving it a
dendrite like projections.

Modulate Immune responses by

regulating T-cell activation,tolerance and
cytokine production

Four types of dendritic cells are known:

1. Langerhans cells.
2.Interstitial dendritic cells.
3. Myeloid cells.
4. Lymphoid dendritic cells. Each arises
from hematopoietic stem cells via
different pathways and in different
locations.
Assignment
1. Describe in detail various cells of immune system and their immune
functions.
2. Explain the process of antibody-dependent cell mediated cytotoxicity
(ADCC).
3. Highlight the major differences between Innate and Adaptive
immune response.
4. What are antigens and antibody