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الرحيم الرحمن هللا بسم
Points described in this research:
A. An overview of the immune system.
B. Components of the immune system.
C. Origin of immune cells.
F. Phagocytic cells.
is the science that studies immune system.
The main function of the immune system is to
prevent or limit infections by microorganisms such as bacteria, viruses,
fungi, and parasites.
intact skin and mucus membrane.
innate immunity :it can function immediately upon
entry of the microorganisms and it is not specific.
it takes several days to become fully functional
and it is highly specific.
CELLS OF IMMUNE RESPONSE
Origin of the immune cells:
- During embryonic development, blood cell
precursors originate mainly in the fetal liver and yolk
-in postnatal life, the stem cells reside in the bone
Then stem cells differentiate as the next figure:
The lymphocytes occupy a very special place among
the leukocytes that participate in one way or another in
immune reactions due to their ability to interact
specifically with antigenic substances and to react to
nonself antigenic determinants.
Lymphocytes differentiate from stem cells in the fetal
liver, bone marrow, and thymus into two main functional
classes T and B.
Their classification based on site of differentiation and
-T cells and naturall killers T - in thymus -
-B cells – bone marrow - (BCR)
(no cell surface specific receptors – NK cells)
They are found in the peripheral blood and in all
most important players of specific immunity.
T lymphocytes have a longer lifespan than B
lymphocytes. Long-lasting lymphocytes are particularly
important because of their involvement on
Contain surface receptors :
1)CD (cluster of differentiation) proteins-
molecules on the cells membrane, allow the
identification of cells.
2)TCR- receptor for antigen.
3)MHC gp I or II class.
allow an identification of T-cell subsets
CD 3 = important in intracellular signaling to initiate
an immune response; closely associated with TCR.
CD 4,8 = are expresed on subclasses of mature T
cells; CD4 reacts with MHC gp II.class),CD8 reacts
with MHC gp I. class on macrophages.
CD 28- receptor for costimulator molecules CD80
Antigen receptors are encoded by several gene
segments that recombine during lymphocyte
Heterodimer consisting of 2 nonidentical
polypeptide chains linked together by disulfide
TCR heterodimer is noncovalently associated with
the γ,δ,ε chains of the CD3 molecule.
COMPLEX TCR- CD3 makes contact with both the
Ag and MHC gp.
FUNCTION OF T LYMPHOCYTE:
1) regulation of immune responses and various
effector functions (cytotoxicity and lymphokine
production being the main ones) that are the
basis of cell-mediated immunity (CMI).
2) carry an antigen-recognition unit on their
membranes, known as T-cell receptors.
3) Several subpopulations of T lymphocytes with
separate functions will be dicussed later.
SURFACE RECEPTORS OF T LYMPHOCYTE:
All T cells contain CD3 and TCR.
T cells are subdivided into two major categories on
the basis of whether they have CD4 or CD8
proteins on their surface. Mature T cells have either
CD4 or CD8 proteins but not both.
CD4 T cells: CD8 T cells:
1) 2/3 of all T cells containging CD3
2) CD4 cell surface molecule
– recognise part of MHC II
molecule that is not part
of peptid binding site
3) Functionally – helper
1) 1/3 of all T cells containing CD3
2) CD8 cell surface molecule
– recognise part of MHC I
molecule that is not designated
to bind peptids
3) Functionally :
Tc cytotoxic – eliminate virus
or i.c.bacteria infected cells
Ts supreesor – increase and
control reactions of specific
T CELL SUBPOPULATIONS:
Subpopulations of T cells have been defined
according to their particular function and their CD
1) Helper:CD4 (T helper 1 and T helper 2).
1) T HELPER(CD4):
recognize the epitopes in association with class II
help B cells to produce antibodies and help
phagocytes to destroy ingested microbes
subsets of Th cells: Th1, Th2 cells in the next table:
a) T helper 1 b) T helper 2
1)INF-γ (gamma interferon) : activates
macrophages to become more effective at
killing phagocytosed microbes, supresses
the development of Th2 cells.
2)IL- 2 : stimulates survival and
proliferation of T cells, called T-cell growth
3)TNF (tumor necrosis factor)- stimulates
the recruitment of neutrophils and
monocytes to sites of infection, activates
these cells to eradicate microbes.
4)IL-3 : promotes expansion of immature
marrow progenitors of all blood cells.
5)GM-CSF : acts on progenitors in the
bone marrow to increase production of
neutrophils and monocytes.
Th1 based immune reaction:
1)Th1 cells stimulate phagocytes to
eliminate ingested microbes.
2)Interferon gamma is the main Th1
1)IL-4 : induces differentiation of Th2
cells from naive CD4+ precursors,
stimulation of IgE production by B cells.
2)IL-5 : activates mast cells.
3)IL-6 : stimulates the synthesis of
acute phase proteins by hepatocytes.
4)IL-10 : inhibits activated
macrophages, supresses Th1
Th2 based immune reaction:
1)Th 2 response provide help for B
cells and are essential for antibody-
2)Antibodies are needed to control
3)The Th2 - type cytokines include IL
4, 5, and 13.
2)T CYTOTOXIC (CD8):
cause lysis of target cells; are active against
tumors, virus-infected cells, transplanted allogenetic
release TNF- depresses proteosynthesis
recognize the foreign epitope in association with
class I MHC molecules
destroy their target cells by releasing perforin
(create poresin the cell membrane and cytoplasm
escapes) and granzymes (degrading essential
Express CD4, CD25, FoxP3.
Regulate the activation or effector function of other
Are necessary to maintain tolerance to self
Memory T cells, as the name implies, endow our host
defenses with the ability to respond rapidly and vigorously for
many years after the initial exposure to a microbe or other
This memory response to a specific antigen is due to several
(1) many memory cells are produced, so that the secondary
response is greater than the primary response, in which very few
(2) memory cells live for many years or have the capacity to
(3) memory cells are activated by smaller amounts of antigen
and require less costimulation than do naïve, unactivated T cells.
(4) activated memory cells produce greater amounts of
interleukins than do naïve T cells when they are first activated.
1) During embryogenesis, B-cell precursors are
recognized first in the fetal liver.
2) 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.
3) Pre-B cells lack surface immunoglobulins and light
chains but do have heavy chains in the cytoplasm.
4) The maturation of B cells has two phases:
a) the antigen-independent phase consists of stem
cells, pre-B cells, and B cells.
b) the antigen-dependent phase consists of the cells
that arise subsequent to the interaction of antigen with the
FUNCTION OF B LYMPHOCYTES:
1) interact with antigenic epitopes, using their
2) subsequently develop into plasma cells, secreting
large amounts of specific antibody.
3) circulate as memory cells.
4) present antigenic peptides to T cells, consequent
upon interiorization and processing of the original
CLONAL SELECTION OF B LYMPHOCYTES:
clonal selection, accounts for antibody formation.
Each individual has a large pool of B lymphocytes (about 107).
Each immunologically responsive B cell bears a surface
receptor (either IgM or IgD) that can react with one antigen (or
closely related group of antigens); i.e., there are about 107
An antigen interacts with the B lymphocyte that shows the best
"fit" with its immunoglobulin surface receptor. After the antigen
binds, the B cell is stimulated to proliferate and form a clone of
cells. These selected B cells soon become plasma cells and
secrete antibody specific for the antigen.
Plasma cells synthesize the immunoglobulins with the same antigenic
specificity (i.e., they have the same heavy chain and the same light chain) as
those carried by the selected B cell.
* Immature B cells express IgM receptors on the surface
* Mature B cells express IgM, IgD molecules on surfaces
* IgM and IgD molecules serve as receptors for antigens
* Memory B-cells express IgG or IgA or IgE on the surface
* B-cells bear receptors for Fc portion of IgG and a receptor for C3 component
of the complement
* They express an array of molecules on their surfaces that are important in
B-cells interactions with other cells such as MHC II, B7 and CD40
• THE END RESULT OF ACTIVATION OF B LYMPHOCYTE IS:
1)Plasma cells 2)Memory cells
Most activated B cells form plasma
produce large amounts of
immunoglobulins specific for the
secrete thousands of antibody
molecules per second for a few days
and then die.
Some activated B cells form memory
can remain quiescent for long periods
but are capable of being activated
rapidly upon reexposure to antigen.
Most memory B cells have surface IgG
that serves as the antigen receptor, but
some have IgM.
The presence of these cells explains
the rapid appearance of antibody in the
Memory T cells secrete interleukins
that enhance antibody production by
the memory B cells.
3.NATURAL KILLER CELL:
Large granular lymphocytes which lack most surface markers of B
* They comprise 5-10% of the peripheral lymphocytes
They are called "natural" killer cells because they are active
without prior exposure to the virus, are not enhanced by exposure,
and are not specific for any virus.
* They function mainly in innate immunity
* They have spontaneous non-specific cytotoxic activity on virus
infected cells, tumour cells and graft cells by secreting cytotoxins
(perforins and granzymes) similar to those of cytotoxic T
lymphocytes and by participating in Fas-Fas ligand-mediated
* They are not MHC restricted and MHC I inhibits their killing
NATURAL KILLER CELL:
They can kill without antibody, but antibody (IgG) enhances
their effectiveness, a process called antibody-dependent
cellular cytotoxicity (ADCC). IL-12 and gamma interferon are
potent activators of NK cells.
• Lack T-cell receptor, CD3 proteins, and surface IgM
Thymus not required for development
• Normal numbers in Severe Combined
Immunodeficiency Disease (SCID) patients
• Activity not enhanced by prior exposure
Granulocytes are a collection of white blood cells
with segmented or lobulated nuclei and granules in
their cytoplasm, which are visible with special
Because of their segmented nuclei, which assume
variable sizes and shapes, these cells are
generically designated as polymorphonuclear
neutrophil leukocytes (PMN).
•Classified according to cell morphology and cytoplasmic
•Neutrophils: stains with BOTH acid and basic dyes
called ‘PMN’ for lobed nucleus; 50% of circ
•Eosinophils: stain with ACID dye (Eosin-red);
bilobed nucleus;1-3% of leuko’s
•Basophils: stain with BASIC dye (Methylene blue);
<1% of leuko’s
• Circulate in peripheral blood 7-10 hr before migrating into tissue;
live only a few days.
• very important component of our innate host defenses, and
severe bacterial infections occur if they are too few in number
(neutropenia) or are deficient in function, as in chronic
• increased # (leukocytosis) used as an indicator of infection
• extravasate in inflam rxn
• attracted by chemotactic factors
• Use both O2-dep and O2-indep digestive mech’s
• Produce high levels of defensins
granules are lysosomes, which contain a variety of
degradative enzymes that are important in the
bactericidal action of these cells.
Neutrophils have receptors for IgG on their surface so
IgG is the only immunoglobulin that opsonizes, i.e.,
makes bacteria more easily phagocytosed. Note that
neutrophils do not display class II MHC proteins on their
surface and therefore do not present antigen to helper T
cells. This is in contrast to macrophages that are also
phagocytes but do present antigen to helper T cells.
Neutrophils can be thought of as a "two-edged" sword.
The positive edge of the sword is their powerful
microbicidal activity, but the negative edge is the tissue
damage caused by the release of degradative enzymes.
An excellent example of the latter is the damage to the
glomeruli in acute post-streptococcal glomerulonephritis.
The damage is caused by enzymes released by
neutrophils attracted to the glomeruli by C5a activated by
the antigen–antibody complexes deposited on the
are white blood cells with cytoplasmic granules that
appear red when stained with Wright stain. The red
color is caused by the negatively charged eosin dye
binding to the positively charged major basic
protein in the granules.
The eosinophil count is elevated in two medically
important types of diseases: parasitic diseases,
especially those caused by nematodes and
hypersensitivity diseases, such as asthma and
serum sickness. Diseases caused by protozoa are
typically not characterized by eosinophilia.
• The function of eosinophils has not been clearly established. It seems
likely that their main function is to defend against the migratory larvae of
nematodes, such as Strongyloides and Trichinella. They attach to the
surface of the larvae and discharge the contents of their granules, which
in turn damages the cuticle of the larvae. Attachment to the larvae is
mediated by receptors on the eosinophil surface for the Fc portion of the
heavy chain of IgG and IgE.
• Another function of eosinophils may be to mitigate the effects of
immediate hypersensitivity reactions because the granules of eosinophils
contain histaminase, an enzyme that degrades histamine, which is an
important mediator of immediate reactions. However, the granules of the
eosinophils also contain leukotrienes and peroxidases, which can
damage tissue and cause inflammation. The granules also contain major
basic protein that damages respiratory epithelium and contributes to the
pathogenesis of asthma.
• Eosinophils can phagocytose bacteria but they do so weakly and are not
sufficient to protect against pyogenic bacterial infections in neutropenic
patients. Although they can phagocytose, they do not present antigen to
helper T cells. The growth and differentiation of eosinophils is stimulated
3.BASOPHILS AND MAST CELLS:
Basophils are white blood cells with cytoplasmic
granules that appear blue when stained with Wright
stain. The blue color is caused by the positively charged
methylene blue dye binding to several negatively
charged molecules in the granules. Basophils circulate
in the bloodstream, whereas mast cells, which are
similar to basophils in many ways, are fixed in tissue,
especially under the skin and in the mucosa of the
respiratory and gastrointestinal tracts.
Basophils and mast cells have receptors on their
surface for the Fc portion of the heavy chain of IgE.
When adjacent IgE molecules are cross-linked by
antigen, immunologically active mediators, such as
histamine, and enzymes, such as peroxidases and
hydrolases, are released. These cause inflammation
and, when produced in large amounts, cause severe
immediate hypersensitivity reactions such as
Mast cells also play an important role in the innate
response to bacteria and viruses. The surface of mast
cells contain Toll-like receptors that recognize bacteria
and viruses. The mast cells respond by releasing
cytokines and enzymes from their granules that mediate
inflammation and attract neutrophils and dendritic cells
to the site of infection. Dendritic cells are important
antigen-presenting cells that initiate the adaptive
response. The role of mast cells in inflammation has
been demonstrated in rheumatoid arthritis. These cells
produce both inflammatory cytokines and the enzymes
that degrade the cartilage in the joints.
Monocytes and macrophages are believed to be
The monocyte is considered a leukocyte in transit
through the blood, which when fixed in a tissue will
become a macrophage.
Monocytes and macrophages, as well as
granulocytes are able to ingest particulate matter
(microorganisms, cells, inert particles) and for this
reason are said to have phagocytic functions.
The phagocytic activity is greater in macrophages
(particularly after activation by soluble mediators
released during immune responses) than in
• Macrophages, monocytes, and related cells play an important role in the
inductive stages of the immune response by processing complex antigens
and concentrating antigen fragments on the cell membrane. In this form,
the antigen is recognized by helper T lymphocytes For this reason, these
cells are known
as antigen-presenting cells (APC).
• APC include other cells sharing certain functional properties with
monocytes and macrophages present in skin (langerhans cells), kidney,
(microglia), capillary walls, and lymphoid tissues.
• Langerhans cells can migrate to the lymph nodes, where they interact with
T lymphocytes and assume the morphological characteristics
of dendritic cells(will discussed later).
• All antigen-presenting cells express one special class of histocompatibility
antigens,designated as class II MHC or la (I region–associated) antigens.
• The expression of MHC-II molecules is essential for the interaction with
helper T lymphocytes.
• Antigen-presenting cells also release cytokines, which assist the
proliferation of antigenstimulated lymphocytes, including interleukins (IL)-1,
-6, and -12.
MECHANISMS OF MACROPHAGE FUNCTION:
Ingestion and killing of microbes in phagolysosomes. Killing caused
by reactive oxygen intermediates such as superoxides, reactive
nitrogen intermediates such as nitric oxide, and lysosomal enzymes
such as proteases, nucleases, and lysozyme.
Presentation of antigen in association with class II MHC proteins to
CD4-positive helper T cells. Also displays B7 protein, which acts as a
costimulator of helper T cells.
Synthesis and release of cytokines such as IL-1 and TNF, and
chemokines such as IL-8.
are a third type of cell that function as "professional" antigen-
presenting cells (macrophages and B cells are the other two); i.e.,
they express class II MHC proteins and present antigen to CD4-
positive T cells.
They are particularly important because they are the main inducers
of the primary antibody response.
The name "dendritic" describes their many long, narrow processes
(that resemble neuronal dendrites), which make them very efficient at
making contact with foreign material.
Dendritic cells are primarily located under the skin and the mucosa,
e.g., Langerhans' cells in the skin.
Dendritic cells migrate from their peripheral location under the skin
and mucosa to local lymph nodes, where they present antigen to
helper T cells.
4 types: Langerhans, Interstitial DC’s, Myeloid DC’s, Lymphoid DC’s.
major role as APC to TH.
MATURATION OF DENDERTIC CELLS:
Loss of endocytic and phagocytic receptors
Increased expression of MHC
Up -regulation of co-stimulatory molecules (CD80
and CD86) required for T-cell stimulation
Up-regulation of CD40 and adhesion molecules
ICAM-1 and LFA-3
Fc receptors (endocytosis) decrease.
FOLLICULAR DENDERITIC CELLS:
have a similar appearance to the dendritic cells but are quite
different from them in their location and function.
Follicular dendritic cells (FDCs) are located in the B-cell-containing
germinal centers of the follicles in the spleen and lymph nodes.
They do not present antigen to helper T cells because they do not
produce class II MHC proteins. Rather, they capture antigen–
antibody complexes via Fc receptors located on their surface.
The antigen–antibody complexes are then detected by activated B
The antibody produced by these B cells undergoes affinity
maturation. (Affinity maturation is the improvement in the affinity of
an antibody for the antigen that occurs upon repeated exposure to
In addition, FDCs produce chemokines that attract B cells to the
follicles in the spleen and lymph nodes.
A) Medical Immunology Fifth Edition,
edited by: Gabriel Virella ,Medical University of South
Carolina .Charleston, South Carolina.
B) Cellular and molecular immunology by:Abul K.
Abbas and Andrew H. Lichtman.
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