immuno2 cells of the immune system
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Clonal Selection Theory
1. T and B cells exist with almost unlimited specificitiesbefore any contact with foreign Ags
2. Ag-specific receptors that recognize foreign Ags:
1. Abs are the B cell receptors on the surface of B cell &
2. T-cell receptor (TCR) on T cell
3. Each lymphocyte has a single specificity
4. The antigenic determinant (epitope) on the Ag binds
with lymphocyte (B or T) and triggers theirdifferentiation and proliferation
5. Negative selectionby self Ags shut off cells thatrecognize them during maturation
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Clonal Selection
Epitopes
2, 103, 821
No specialized
receptor
Epitopes
2, 103, 821
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Harmful Effects of the Immune System Hypersensitivity or allergic reactions:
Type I, immediate hypersensitivity Type II, cytotoxic Ab-mediated reactions
Type III,immune complex Ab-mediated
Type IV, delayed-type cell-mediated
Autoimmune diseases The immune system attacks bodys own Ags causing diseases
like rheumatoid arthritis, diabetes mellitus and systemic lupuserythematosus
Immunodeficiencies
Occur when one or more components of the immune system failto function properly
This can be result of genetic defect (SCID) or acquired (AIDS)
Graft rejection
Occurs because of immune response against transplants Ags
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Genetic Recombination & Immune
Response Diversity 106-107 of antigenic specificities might exist
If 1 gene = 1 response, are 107 genes needed?
No
Genetic recombination within a gene thatencodes the Ig proteins is the answer
So, the basic Ab is composed of 2 types of
polypeptides: H-chain, L-chain and each chainhas a variable domain
This mechanism generates Ab & T cell receptor(TCR) specificity
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Regulation of the immune system
Why regulation? Immune response proliferation and increased
synthesis of specific molecules that will not be
useful after their job is finished (infection
response cure)
Homeostasis or equilibrium must be establishedby shutting down the system
Deregulation of the immune system has severeconsequences
Immune response to self Ags Autoimmunity
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LECOM-Pharmacy School
Immunology 02
Cells, Tissues & Organs of the Immune
SystemDr. Saber Hussein
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Objectives1. B and T lymphocytes and NK cells
2. T cells Subpopulations:Helper, cytotoxic and suppressor3. Antigen presenting cells
4. Phagocytes: Monocytes (macrophages) & granulocytes(eosinophil, neutrophil, basophil & mast cells)
5. granulocyte and platelet role in inflammatory response
6. Primary tissues of the Immune System:
1. Bone marrow &
2. Thymus
7. Secondary tissues:
1. Lymph nodes,
2. spleen,
3. Payers patches
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Cells of the Immune System
Lymphoid Lineage
T helper cells (TH) Cytotoxic T cells (Tc or CTL)
B cells
Natural Killer [NK cells. A type of white blood cell that containsgranules with enzymes that can kill tumor cells or microbial cells.Also called large granular lymphocytes (LGL)]
Myeloid Lineage
Polymorphonuclear granulocytes
Neutrophil
Basophil & Mast cells Eosinophil
Mononuclear phagocytes
Dendritic cells & Macrophages
Megakaryocytic Lineage
Platelets
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Hematopoiesis
Hematopoiesis is the process of blood cell maturationfrom the stem cell to the active, functional blood cell(red or white)
Red blood cells and white blood cells are formed in thebone marrow
Stem cells are totipotent orpluripotent
Totipotency - The ability of a cell, such as an egg, to giverise to unlike cells [differentiate] and thus to develop into orgenerate a new organism or part.
Pluripotency - The potential of a cell to develop into morethan one type of mature cell, depending on environment
Myeloid cells and lymphoid cells are pluripotent cellswith a common ancestor, a totipotent cell
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Hematopoiesis
Myeloid cell Erythrocyte;
Neutrophil,
Monocyte Macrophage;
Eosinophil;
Basophil & Mast cell;
Megakaryocyte Platelet
Lymphoid cell Lymphocytes:
T cell
B cell Plasma cell
NK cell
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Cells involved in the immune responseCells involved in the immune response
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Polymorphonuclear
neutrophil
Subject to chemotacticstimulation by:
Complement fragments (C5a)
Products of platelets & leukocytes Bacterial products
Other protein products offibrinolysis
Lysosomes containi. Primary granules(Azurophilic) contain
Hydrolases
Peroxidases
Lysozyme
ii. Secondary, specific,granules contain:
Lactoferrin
Lysozyme
Primary
granules
Secondary
granules
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Neutrophils Have multilobed nuclei
Their primary function is Phagocytosis
enhanced by opsonization with complement and Abs
Important secondary function
promote inflammation Neutrophils produce
reactive oxygen metabolites
hydrolytic enzymes
nitric oxide and antibiotic proteins such as
defensins
seprocidins
cathelicidins
bacterial permeability inducing protein
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Polymorphonuclear Granulocytes PMNs include
Mainly neutrophils
Eosinophils
Basophil & mast cells
From bone marrow at 7 million/minute
Short lived (2-3 days)
About 60-70% of WBCs
Diapedesis:
PMNs leave the circulation by adhering to the endothelium& squeezing out
It is promoted by chemokines
IL-1
IL-8 (RANTES [Regulated on activation, normal T expressed andsecreted])
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Functions of PMNs Important part in acute inflammation
No specificity for Ags
Cooperate with Abs & complement
Phagocytosis
Polymorph extravasation deficient
individuals and those with low numbersof PMNs increased susiptibility toinfections
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Basophils &
Mast cells
Basophils are in circulation
Have S-shaped nucleus
Are round Mast cells are stationary:
1. Mucosal mast cells (MMC)
2. Connective tissue mast cells
(CTMC)
Granules contents are
called mediators such as:
Heparin,
Histamine
SRS-A (slow-reacting
substance of anaphylaxis)
ECF-A (eosinophil
chemotactic factor A)
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Basophils and
mast cells
Basophils and mast cells arethe least prevalent of theleukocytes
They possess high affinity Fcreceptors for IgE
They release the chemicalmediators of immediatehypersensitivity, including:
Histamine Prostaglandins
Thromboxanes
Leukotrienes
Heparin
They also produce eosinophilchemotactic factor (ECF)
which causes eosinophils toenter the area of worminfestation or allergenlocalization
MC
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Eosinophils
Bilobed nucleus Granules stain with acid
dyes- eosin
Capable of
phagocytosing & killingmicroorganisms
Degranulation: releaseof contents in
surrounding area Can kill parasites with
basicproteins andcationic proteins
Schistosoma mansoni
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Monocytes/Macrophages
Monocytes enter circulation from
bone marrow then migrate intovarious organs and tissues
There they mature into:
macrophages
Kupffer cells (liver)
histiocytes (M* found in connective
tissue)
dendritic cells (lymph nodes, spleen)
glial cells (brain)
Langerhans' cells (skin) Collectively, these cells form a
network known as the
reticuloendothelial system (RES)
or the mononuclear phagocyte
system
M* in the process
of surrounding
tumor cell
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Differential White Blood Cell Count
CELL TYPE % OF WBC'S CELLS/cmm
Neutrophil
Eosinophil
Basophil
Lymphocyte
T cell
B cell
NK cell
Monocyte
50 60
1 4
0.5 220 40
80 - 85*
5 - 15*
5 - 15*
2 - 9
3000 - 7000
50 400
25 1001000 4000
100 - 600
*% of lymphocytes in peripheral blood
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Reticuloendothelial
System
(mononuclear phagocyteSystem)
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Platelets Anucleate Derived from
megakaryocytes
Contain granules at theultrastructural level
Their major functions are
blood clotting
inflammation
Following injury toendothelial cells, plateletsadhere to the surface of the
damaged tissue, where theyrelease substances that increase vascular
permeability,
activate complement and
attract leukocytes
Platelets aggregating
at the site of a wound
in a blood vessel
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NK
Functions of Lymphocytes
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B and T lymphocytes
T cells develop in the thymus
B cells differentiate
in fetal liver &
in postnatal bone marrow
Ag recognition via specific receptors
NK (natural killer) cells do not express Ag receptor
Lymphocytes have high N:C (nucleus : cytoplasm) ratio
LGL (NK; Large granular lymphocytes) have
lower N:C ratio
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T Cells
Majority of T cellsexpress EF-TCR
T-helper cells (TH)
T-cytotoxic cells (Tc) TCR is an
immunoglobulin
Carry Gall body (Gb) in
the cytoplasm Gb: A cluster of lysosomes
+ Lipid droplet
MHC-I
CD4CD8
THCell
TC Cell
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Subpopulations of T cells
KH T
TH
CD4
EFT
TH2
Tc
CD
TH
1
T0
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NK Cell
H
ave LGL morphology Contain larger number of
azurophilic granules than
granular T cells
Have no specific receptorfor Ag recognition
Derived from lymphoid
cell progenitors in the
bone marrow How can you distinguish NK from T &B?
1. No specific receptor
2. NK can lyse certain tumor cell lines
in vitro without prior sensitization
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APCs are heterogenous leucocytes
They present Ags to TH or Tc cells
Ability to digest protein Ags is important
Present primarily in:
Skin
Spleen
Lymph nodes
Antigen presenting cells
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What cells can serve as APC?
1. Langerhans cells (LC)
2. Dendritic cells
1. Interdigitating dendritic cells (IDC)
2. Follicular dendritic cells (FDC)
3. Germinal center dendritic cells (GCDC)
3. B cells
4. Macrophages
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Lymphoid organs
The lymphoid organs are those organs in which maturation,
differentiation and proliferation of lymphocytes take place
The primary, orcentral, lymphoid organs are those in which T and
B lymphocytes begin expressing their antigen receptors
The secondary lymphoid organs are those in which lymphocytes are
induced to proliferate and differentiateby contact with antigen
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Primary lymphoid organs Bone marrow in which B cells develop
Thymus, where T cells develop. Progenitor cells from the bone
marrow migrate to the thymus gland to develop into T cells The thymus is a bilobed structure, whose size reaches its maximum at birth,
then atrophies with age.
The cortex contains mostly immature thymocytes, some of which
mature & migrate to the medulla, where they learn to discriminatebetween self and nonself during fetal development and for a short timeafter birth.
T cells leave the medulla to enter the peripheral blood circulation, throughwhich they are transported
to the secondary
lymphoid organs
DiGeorge syndrome:congenital absence of thymus
results in an immediate and
drastic reduction in T cells
that produces a potentially
lethal wasting disease
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Secondary lymphoid organs
The secondary lymphoid organs have two majorfunctions:
they trap and concentrate foreign substances, and
they are the main sites of production of antibodies andantigen-specific T cells
The major secondary lymphoid organs include the Spleen, which is responsive to blood-borne antigens
Lymph nodes, which protect the body from antigens thatcome from skin or internal surfaces via the lymphatic
system Mucosa-associated lymphoid tissue (MALT) scattered
along mucosal linings, which protects the body fromantigens entering the body directly through mucosalsurfaces
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Spleen
Schematic representation of the spleen and a cross-section
of the periarteriolar lymphoid sheath (PALS)
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Lymph nodes
Clusters of lymph nodes (ovoid structures usually less than 1 cm indiameter) are strategically placed in the neck, axillae, groin,
mediastinum and abdominal cavity, where they act to filterantigens from the interstitial tissue fluid and the lymph during itspassage from the periphery to the thoracic duct
Somatic nodes: Lymph nodes that protect the skin
Visceral nodes: Deep lymph nodes protecting the respiratory,digestive and genitourinary tracts
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Mucosa-associated lymphoid tissue (MALT) The bulk of the body's lymphoid tissue (>50%) is found associated
with the mucosal system.
MALT is composed of gut-associated lymphoid tissues (GALT) lining the intestinal tract,
bronchus-associated lymphoid tissue (BALT) lining the respiratory tract,
lymphoid tissue lining the genitourinary tract.
The major effector mechanism at these sites is secretory IgA (sIgA)secreted directly onto the mucosal epithelial surfaces. Examples ofMALT include the Peyer's patches lining the small intestine,
the tonsils and
the appendix. "M" cells (because they have numerous microfolds on their luminal surface)
absorb,
transport,
process and
present antigens to subepithelial lymphoid cells