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Cells of the
Immune System
Mehrnaz Mesdaghi, MD, PhD
Assistant Professor
Shahid Beheshti University of Medical
Sciences
Cells of the immune system
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Antigen-presenting cells
Lymphocytes
Effector cells
Phases of Adaptive Immune Responses
Fig. 1-6
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Cells
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cells of the innate and adaptive immune
system
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circulating cells in the blood and lymph
anatomically defined collections in lymphoid
organs
scattered cells in virtually all tissues
ability to circulate and exchange among
blood, lymph, and tissues
major cells of the immune
system
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Macrophages:
phagocytes present in tissues with rapid response to
microbes
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Neutrophils: type of phagocyte, abundant in blood
Monocytes: the precursors of tissue macrophages, always present in the
blood
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Dendritic cells
Naive lymphocytes: migrate through body
Effector and memory lymphocytes: circulate in the blood
Phagocytes
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Including
neutrophils
macrophages
identify, ingest, and destroy microbes
 Process of phagocytosis, and destruction of ingested
microbes
 secreting proteins that promote or regulate immune
responses
 important in innate immunity and also in the effector
phase of some adaptive immune responses
Neutrophils
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the most abundant population of circulating WBCs
mediate the earliest phases of inflammatory reactions
Production stimulated by G-CSF
produced in the bone marrow (1011 per day)-half life of 6
hrs
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12-15 μm in diameter with numerous membranous projections
segmented nucleus
cytoplasm contains granules of two types
 specific granules: lysozyme, collagenase, and elastase
 azurophilic granules: lysosomes containing enzymes and
other microbicidal substances, including defensins and
cathelicidins
Morphology of Granular Leukocytes
- multilobed nucleus,
because of which called
polymorphonuclear
- faint cytoplasmic granules
Fig. 2-1
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Mononuclear Phagocytes
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consists of cells whose primary function
is phagocytosis
roles in innate and adaptive immunity
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originate from a common precursor in the
bone marrow
circulate in the blood
mature and become activated in various
tissues
Monocytes
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10-15 μm in diameter
bean-shaped nuclei and finely granular
cytoplasm containing lysosomes, phagocytic
vacuoles, and cytoskeletal filaments
at least two subsets
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inflammatory
source of tissue resident macrophages and some
dendritic cells
Macrophages
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Phagocytosis
recognize and engulf apoptotic cells
Secrete cytokines to instruct cells to respond in ways that
contribute to host defense
serve as APCs that display antigens to and activate T
lymphocytes
promote repair of damaged tissues by stimulating new
blood vessel growth (angiogenesis) and synthesis of
collagen-rich extracellular matrix (fibrosis)
survive much longer at sites of inflammation
Monocytes and Macrophages
Fig. 2-3
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Macrophages in different tissues have special
names:
Microglial cells
Kupffer cells
alveolar macrophages
osteoclasts
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Activation of MQs
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Recognition of microbial molecules as well as host
molecules produced in response to infections
by secreted cytokines and membrane proteins made by T
lymphocytes
binding opsonins on the surface of microbes
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Opsonins are substances that coat particles for phagocytosis;
Examples of these opsonin receptors are complement receptors
and antibody Fc receptors
Rapid response to infections like neutrophils
Longer survival
Basophils
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blood granulocytes with many structural and functional
similarities to mast cells
derived from bone marrow progenitors (a lineage different
from that of mast cells)
mature in the bone marrow, and circulate in the blood
<1% of blood leukocytes
may be recruited to some inflammatory sites
Basophils contain granules that bind basic dyes
express IgG and IgE receptors, bind IgE
their importance in host defense and allergic reactions is
uncertain.
Morphology of Granular Leukocytes
characteristic
blue-staining
cytoplasmic
granules
Fig. 2-1
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Eosinophils
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blood granulocytes that express cytoplasmic granules
Granules contain basic proteins that bind acidic dyes such
as eosin
bone marrow derived
GM-CSF, IL-3, and IL-5 promote eosinophil maturation
from myeloid precursors
Some normally present in peripheral tissues, especially in
mucosal linings of the respiratory, gastrointestinal, and
genitourinary tracts, and their numbers can increase by
recruitment from the blood in the setting of inflammation
Morphology of Granular Leukocytes
- characteristic
segmented nucleus - red staining of the
cytoplasmic granules
Fig. 2-1
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Mast Cells
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Bone marrow-derived cells
present in the skin and mucosal epithelium
abundant cytoplasmic granules filled with cytokines,
histamine, and other mediators
not found in the circulation
round nuclei, and the cytoplasm contains membranebound granules
granules contain acidic proteoglycans that bind basic dyes
plasma membrane receptors for IgE and IgG
defense against helminths but also responsible for
symptoms of allergic diseases
Morphology of Granular Leukocytes
Skin mast cell adjacent to a
small blood vessel
-The purple cytoplasmic
granules are filled with
histamine and other
mediators that act on
adjacent blood vessels
- promote increased blood
flow and delivery of plasma
proteins and leukocytes into
the tissue
-
Fig. 2-1
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Antigen-Presenting Cells
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specialized to capture microbial and other antigens
display them to lymphocytes
provide signals that stimulate the proliferation and
differentiation of the lymphocytes
dendritic cell
 Macrophages
 B cells
 follicular dendritic cell displays antigens to B lymphocytes during
particular phases of humoral immune responses
APCs link responses of the innate immune system to
responses of the adaptive immune system
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Dendritic Cells
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most important APCs for activating naive T cells
long membranous projections and phagocytic capabilities
widely distributed in lymphoid tissues, mucosal epithelium,
and organ parenchyma
part of the myeloid lineage of hematopoietic cells
Maturation depends on a cytokine called Flt3 ligand
Dendritic cell
Fig. 2-4
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
DCs
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express receptors that recognize molecules typically made
by microbes and not mammalian cells
respond to the microbes by secreting cytokines
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conventional dendritic cells: activation by microbes, migration, Ag
presentation
plasmacytoid dendritic cells: early cellular responders to viral
infection
Follicular dendritic cells (FDCs)
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found intermingled in specialized collections of activated B
cells, called germinal centers
in the lymphoid follicles of the lymph nodes, spleen, and
mucosal lymphoid tissues
Not bone marrow derived, of mesenchymal origin
unrelated to the dendritic cells that present antigens to T
lymphocytes
trap antigens complexed to antibodies or complement
products
display these antigens on their surfaces for recognition by
B lymphocytes
Lymphocytes
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unique cells of adaptive immunity
express clonally distributed antigen receptors
fine specificity for a different antigenic determinant
genes encoding the antigen receptors of lymphocytes are
formed by recombination of DNA segments during the
maturation of these cells
total number of lymphocytes in a healthy adult:5×1011
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∼2%: in the blood
∼10% in the bone marrow
∼15% in the mucosal lymphoid tissues of the gastrointestinal and
respiratory tracts
∼65% in lymphoid organs (mainly the lymph nodes and spleen)
Subsets of Lymphocytes
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B lymphocytes, bursa-derived lymphocytes
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follicular B cells
marginal zone B cells
B-1 B cells
T lymphocytes, thymus-derived lymphocytes
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helper CD4+ T lymphocytes C
CD8+ CTLs
CD4+ regulatory T cells
γδ T cells
Natural killer (NK) cells
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similar effector functions as CTLs
distinct receptors from B or T cell antigen receptors
NKT cells: numerically small population of T lymphocytes
with a surface molecule typically found on NK cells and
receptors that are encoded by somatically recombined
genes, that lack diversity
CD Markers
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Membrane proteins are used as
phenotypic markers to distinguish
distinct populations of lymphocytes
Cluster of differentiation (CD)
system
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Widely adopted uniform method for naming cell surface
molecules that are characteristic of a particular cell lineage or
differentiation stage
Recognized by a group ("cluster") of monoclonal antibodies
CD Markers: surface proteins that ("mark") different cell
populations
Also have many functions in the cell types
Class
Functions
αβ T lymphocytes
CD4+helper T
B cell differentiation ,
lymphocytes
MQ activation,
inflammation
CD8+cytotoxic T
lymphocytes
Antigen
Receptor and
Specificity
Selected
Phenotype
Markers
Percentage of Total
Lymphocytes (Human)
Blood
Lymph
Spleen
Node
αβ, peptide-MHC II CD3+, CD4+, 50-60*
complexes
CD8-
Killing of infected cells; αβ, peptide-MHC I CD3+, CD4+, 20-25
rejection of allografts complexes
CD8-
Regulatory T cells regulation of immune
responses,
maintenance of selftolerance)
αβ , Unresolved
CD3+, CD4+, Rare
CD25+
CD3+, CD4+,
& CD8
variable
γδ T lymphocytes
Helper and cytotoxic
functions (innate
immunity)
γδ, Limited
specificities
B lymphocytes
Antibody production
Ab. All molecules Fc R; MHCII; 10-15
CD19, CD21
50-60
50-60
15-20
10-15
10
10
20-25
40-45
The main adaptive immune
system cells are lymphocytes
Lymphocytes (T and B cells) recognize antigens through clonally expressed
antigen receptors
Maturation of Lymphocytes
Fig. 2-5
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Anatomy of Lymphocyte Activation (1)
Fig. 2-6
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Anatomy of Lymphocyte Activation (2)
Fig. 2-6
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Naive Lymphocytes
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Mature T or B cells that reside in the peripheral lymphoid
organs and circulation
typically die after 1 to 3 months if they do not recognize
antigens
Naive and memory lymphocytes, are resting lymphocytes
because they are not actively dividing, nor are they performing
effector functions
Naive (and memory) B and T lymphocytes both often called
small lymphocytes
In response to stimulation, they enter the G1 stage of the cell
cycle before going on to divide
Activation
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Proliferation
Clonal expansion
50,000-fold increase in numbers of T cells & up to
5000-fold in B cells
Differentiation into effector cells
Differentiation into long-lived memory cells
Activated lymphocytes: large lymphocytes or
lymphoblasts
Morphology of Lymphocytes
-8-10 μm
-large nucleus
-dense
heterochromatin
-thin rim of
cytoplasm
-10-12 μm
More cytoplasm –
More organelles
- increased
amounts of
cytoplasmic RNA
Fig. 2-7
Copyright © 2011
Saunders,
an imprint of Elsevier
In
Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright
© by
2012
by Saunders,
an im
Survival of Naive Lymphocytes
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Depends on two types of signals
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by antigen receptors
by cytokines
Antigen receptor of naive B cells generates survival signals
even in the absence of antigen
Naive T lymphocytes recognize various self antigens
"weakly," enough to generate survival signals
Effector Lymphocytes
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Helper T cells
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CTLs
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CD4+, CD40 ligand (CD154+)
secrete cytokines that interact with MQs and B lymphocytes, leading to
their activation
CD8+, Cytoplasmic granules with proteins that kill infected cells
Antibody-secreting plasma cells
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Characteristic nuclei, abundant cytoplasm containing dense, rough
endoplasmic reticulum that is the site where antibodies are synthesized
Distinct perinuclear Golgi complexes where antibody molecules are
converted to their final forms and packaged for secretion
Memory Lymphocytes
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Functionally quiescent or slowly cycling state for months or
years
Without a need for stimulation by antigen
Memory B lymphocytes: IgG, IgE, or IgA, CD27
Memory T cells, like naive but not effector T cells: CD127,
CD45RO