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Cells and organs of the immune system
Cells of the immune system
Bone marrow
T-cell
Lymphoid
Multipotent hemopoetic
Precursor
stem cells
B. Lymphocytes
Eosin
T-helper
cells
NK lymphocytes
myeloid precursor
RBC, mast cells, platelets
RBC, mast cells, platelets,
Dentriticcells,
cells,polymorphs
polymorphs,
Dentritic
eosinophils, basophils,
neutrophils, Monocytes,
macrophages
T-cytotoxic
cells ,Tsuppressor
cells
Circulation through blood,
lymph, secondary lymphoid
organs tissues
Organization of the immune system: An overview
All lymphoid cells originate in the bone marrow .The nature of the not
uncommitted lymphoid stem cell is not clear. An understanding of the
developmental pathways is important, not only to clarify the physiology of
the normal immune response but because some leukemia’s and
immunodeficiency states represent maturation arrest of cells in their early
stages of development.
Lymphoid progenitors destined to become T cells migrate from the bone
marrow into the cortex of the thymus. Under the influence of stromal cells
and Hassall’s corpuscles in the thymic cortex, further differentiation into
mature T cell occurs. The passage of T cells from the thymic cortex to
medulla is associated with the acquisition of characteristic surface
glycoprotein molecules so that medullary thymocytes eventually resemble
mature peripheral T cells. T- Cells.
T lymphocytes
• Originate in bone marrow
• Mature in thymus
• Enter circulation
FUNCTION
• Control the immune system
• Eliminate infection - e.g. virus, fungus
• Lymphocytes are a separate lineage (cf. myeloid), also derived from
stem cells.
• Multiple types: Both “innate” and “adaptive” populations (using
“pattern recognition receptors” vs “Ag-sp” receptors to sense their
environment .
• All originally derived from bone marrow,
develop/differentiate further in different locales
but
then
In contrast, B-cell development occurs in the bone marrow and is closely
dependent upon interaction between a surface glycoprotein on nonlymphoid stromal cells called stem-cell factor (SCF) and its receptor on Bcell precursors ,kit tyrosine kinase.
The thymus and the bone marrow are primary lymphoid organs. They
contain cells undergoing a process of maturation from stem cells to
antigen-sensitive (and antigen-restricted) cells. This process of maturation
in independent of antigenic stimulation within the animal. In contrast,
secondary lymphoid organs are those which contain antigen-reactive cells
in the process of recirculating through the body .They include the lymph
nodes, spleen and mucosal-associated lymphoid tissues. Antigenic
stimulation changes the relative proportions of the mature cell types in
secondary tissues. Peripheral T and B cells circulate in a definite pattern
through the secondary lymphoid organs. Most of the recirculating cells are
T cells and the complete cycle takes about 24h; some B cells, including
long-lived memory B cells, also recirculate. Lymphocyte circulation is
strongly influenced by adhesion molecules on the lymphocyte surface
which act as homing agents directing cells to their respective ligands on
high endothelial venules of lymph nodes and mucosal tissue.
B lymphocytes:
• Originate in bone marrow
• Mature in bursa (equivalent)
• Enter circulation
FUNCTION
• Become antibody producing “plasma” cells
• Absence - no antibody.
• Antigen presenting cells.
Cells and organs of the immune system:
1- Antigen presenting cells:
Monocytes ,macrophages, dendritic cells and B-cells.
2- Primary immune system organs :
Thymus gland(T-cells production) ,Bone marrow, and bursa fabricius(Bcells production).
3- Secondary lymphoid organs :
i- lymph node.
ii- Spleen .
Iii- Mucous associated lymphoid tissues :
• Mucosal associated lymphocytic tract (MaLT).
• Bronchial associated lymphocyte tissue (BALT).
Gastrointestinal associated lymphoid tissue (GALT).
Immune system – components:
• white cells - found in the blood, and tissues
proteins - also found in blood, and tissues
• organs - such as the spleen, tonsils
• circulatory system – blood, lymphatics
Dendritic
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Lymph node architecture is well adapted to its function. The lymphatic
network, which drains the extra vascular spaces in the tissues, is connected
to the lymph nodes by lymphatic vessels; these penetrate the lymph node
capsule and drain into peripheral sinus, from which further sinuses branch
to enter the lymph node. Passing through the cortex to the medulla and
hence to the efferent lymphatic vessel .This sinus network provides an
excellent filtration system for antigens entering the lymph node from
peripheral tissues.
The cortexes contain primary follicles of B lymphocytes, surrounded by Tcells in the paracortex. In contrast to primary follicles, secondary follicles. In
congerminal centers. These comprise mainly B cells with a few helper T
cells and a mantle zone of the original primary follicle B cells. B cells in a
secondary follicle are antigen-activated and more mature; most have IgG
on their surfaces, whereas those in the primary follicle and mantle zone
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bear both IgD and IgM. Activated B cells migrate from the follicle to the
medulla, where they develop into plasma cells in the medullary cords
before releasing antibody into the efferent lymph.
The architecture of the spleen is similar. The white pulp around arterioles is
arranged into T and B cell areas with primary and secondary follicles.
Antigen challenge results in expansion of the white pulp with B-cell a
activation and the development of secondary follicles plasma cells migrate
to the red pulp.
Major immune cell types: A summary
• Neutrophils
• Monocytes/ Macrophages
• Dendritic cells
• Basophils
• Mast cells
• Eosinophils
• Lymphocytes
Macrophages:
Macrophages are the tissue equivalent of Monocytes and , with
Monocytes, and macrophages are derived from closely related stem cells in
the bone marrow. Each cell lineage has a different colony-stimulating factor
and, once differentiated, there are obvious differences between polymorph
nuclear leukocytes, mononuclear phagocytes and lymphocytes. Whilst most
polymorphonuclear leukocytes develop in the bone marrow and only
emerge when mature macrophages differentiate principally in the tissues.
Monocytes circulate for only a few hours before entering the tissues where
they
are live for weeks or months as mature macrophages. Tissue
macrophages are heterogeneous in appearance, in metabolism and
probably also in function. They include freely mobile alveolar and
peritoneal macrophages, fixed Kupffer cells in the liver and those lining the
sinusoids of the spleen. When found in other tissues, they are called
histiocytes.
A major function of the mononuclear phagocyte system is to phagocytize
invading organisms and other antigens. Macrophages have prominent
lysosomal granules containing acid hydrolases and other degradative
enzymes with which to destroy phagocytosed material. The material may
be an engulfed viable organism, dead cells, debris, antigen or an immune
complex. In order to carry out their functions effectively, macrophages
must be activated by stimuli include cytokines substances which bind to
other surface receptors for polysaccharides/ endotoxin or soluble
inflammatory mediators such as C5a.Activation may result in release of
monokines(cytokines from Monocytes) such as TNF or IL-1 which may cause
further damage in already inflamed tissues. Macrophages are also
important for the presentation of antigen to other cells of the immune
system, as described earlier.
Monocyte (Macrophage):
• First phagocytic cell discovered, 1800’s. Common in blood.
• BM derived, circulate 2d, then reside in tissue, organs, long term
• Phagocytosis (via innate and opsonization), digestion, Ag
presentation for T cell activation—found in every organ in the body
(often with specific historic names: ie Kupfer cells…)
• Phagocytose but also release (i) regulatory and (ii) toxic effector
molecules
• All these phagocytic cells know where to go by being directed by
chemokines.
• Monocytes
• Originate in bone marrow
• Enter circulation
Migrate into tissues - change shape“macrophage”
• Phagocytic cell
Present antigen to T cells-
Neutrophils polymorphonuclear leukocytes:
Neutrophils play a major role in the body defense against acute infection.
They synthesize and express adhesion receptors so they can adhere to and
migrate out of, blood vessels into the tissues. They do this in response to
Chemotactic agents produced at the site of inflammation; such substances
include IL-8, complement-derived factors (such as C3a and C5a),kallikrein,
cytokines released by TH1 cells and Chemotactic factors produced by mast
cells.
Neutrophils are phagocytic cells. They are their most efficient when
entering the tissues. Morphologically, the process of Phagocytosis is similar
in both neutrophils and mononuclear phagocytes. Neutrophils are also able
to kill and degrade the substances which they eat.
Neutrophils
Most common WBC in circulation.
They and monocytes are the two circulating phagocytic cells.
Named for staining properties (granules), hence a type of “granulocyte”.
Also called “polymorphs” or “PMN” (Polymorphonuclear leukocyte)
Increases (from bone marrow) are a hallmark of inflammation.
How do they work
• First line of cellular defense: rapidly released from Bone Marrow and
recruited, via blood, to sites of infection/inflammation. Acts on
bacterial, fungal infection.
• Neutrophils squeeze through capillary walls and into infected tissue
where they kill the invaders (e.g., bacteria) and then engulf the
remnants by phagocytosis.
• Very rapid release , BUT short lived—few hours after extravasation.
How do they know where to go?
• Highly phagocytic, digestion. Produces toxic mediators.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is
Antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism by
which antibody-coated target cells are destroyed by cells bearing Fc
receptors(NK cells, Monocytes, neutrophils)with no involvement of the
MHC. The mechanism of target-cell destruction is not fully elucidated but
includes the release of cytoplasmic components such as peroforin and
granzymes (as with cytotoxic T-cells).
Natural killer cells:
NK cells look large granular lymphocytes. They can kill target cells, even in
the absence of any antibody or antigenic-stimulation. They are non-specific
activated by agents such as mitogens, interferon and IL-12. NK cells form an
integral part of the early host response to viral infection. NK cells are not
immune cells in the strictest sense because , like macrophages, they are not
clonally restricted ,they show minimal specificity and they have no
memory. The range of their potential targets is broad. Animals and rare
patients with deficient NK cell function are said to have an increased
incidence of certain tumours and viral infection. NK cells are therefore
thought to be important in immune surveillance against tumours.
Dendritic Cell:
• Low frequency cells. Found in 1860’s—ignored since so few of them.
• 1980’s-present : Realization of their key role in controlling
initiation of adaptive immunity—or tolerization (making
unresponsive).
• DC are phagocytic/pinocytic
Excellent for Ag uptake
prior to maturation/activation.
and present Ag to begin specific immune
responses.
Dendritic cells
Antigen presenting cells - key role in initiating T cell response to antigen .
Basophil, Mast Cell, Eosinophil
Immune system
Non-specific
• Neutrophils
• Macrophages
• Complement
• Mechanical
• “INNATE”
Specific
• Lymphocytes
• “ADAPTIVE”
Antigen :
Definition
Any substance which • causes a lymphocyte reaction
• reaction is specific to that lymphocyte
• clone - single type of lymphocyte which reacts to an individual
antigen
Example -
In the case of a B lymphocyte • Antibody is produced
Examples • infectious agent - bacteria, virus
• tissue - from another person - transplant
• food !!
Immunogen:
Substance that is capable of inducing an immune response(antibody
response , cell-mediate immunity ) .Some times it is used as a synonym for
antigen, but emphasis is on the ability to elicite a response , rather than on
reactivity with antibodies. The most potent immunogen are proteins and
polysaccharides, but lipids , nucleic acids ,and synthetic polypeptides can
also be immunogenic.
Immunology:
Science deal with the immunity.
Immunity :
State of being immune .
Means the resistance of the individual against the bacteria or
microorganism and their productions.
Classification of immunity: it is classified into two groups
1. Innate immunity or inherited immunity
It means a natural immunity
2. Acquired immunity
It means the taking immunity
The innate immunity divides into
1. Species immunity
2. Races immunity
3. Organ immunity
4. Individual immunity
The acquired immunity divides into
1. Active immunity.
2. Passive immunity.
The active immunity either
a. Natural immunity
b. Artificial immunity
c. Immune response :
Specific response of an human or animal to antigenic stimulation. The
immune response may take the form of antibody production, cell-mediated
immunity, or tolerance.
Immunoincompetent :
Incapable of mounting a normal immune response. For example ,neonatal
mice or thymectomized mice are Immunoincompetent; individuals with
immunodeficiency disease are immunoincompetnce . The lack of
immunological competence may result from failure of B and / or T or B
lymphocyte.
Immunologic competent cell :
Cell capable of specific recognition or specific response to an antigen. The
term is usually used to refer to an antigen. The term is usually used to T or
B lymphocyte.
Specific immunity
• T and B lymphocytes
• Specific response to a single antigen
• Memory for that response
Question
Q1-Enumerate lymphoid precursors cells.
Q2- T-lymphocytes maturation steps.
Q3- Enumerate secondary lymphoid organs and their biological function.
Q4Enumerate primary lymphoid organs and their biological function.
Q5 B-lymphocytes maturation steps.
Q6 B-lymphocytes biological function.
Q7 B-lymphocytes biological function.
Q8 Macrophages maturation steps.
Q9 Macrophages biological function.
Q10 How do neutrophils work.
Q11 Enumerate natural killer cells criteria.
Q12 Dendritic Cell
biological function.
Q13 The most potent immunogenic and low immunogenic component.
Q14 The innate immunity divides into.