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2.

Organ and cells of immune system

Tiana Milanda
Outline
• Anatomy & Functions of Lymphoid
Tissues & Organs

• Mechanisms of Lymphocyte Activation,


Recirculation & Homing

• Cells of the Immune System


Lymphoid Tissues

Primary (Central) Secondary (Peripheral)


Lymphoid organs Lymphoid organs
Bone Marrow Spleen
Thymus Lymph nodes
SALT
MALT
Bone marrow
• The bone marrow constitutes almost 5% of total body and is
responsible for formation of all blood cells (hemopoiesis) in
the adults from stem cells.
Stem Cells
• Following fertilization of a sperm and an
egg cell, the fertilized egg is called a
zygote.
• The zygote  3-5 days : 12 cells called
a morula
• 5-7 days : 100 cells called a blastocyst,
contains an outer rows of single cells
called trophoblast  develops to form
part of placenta.
• Around 30 cells tucked inside the
blastocyst  inner cell mass  source
of human embryonic stem cells (ES
cells)
• Stem cells (SC): undifferentiated
pluripotential cells  differentiate into all
cells
Stem cells
• First in the mammalian embryo within the liver, then
spleen  represent less than 0.1% of all cells in adult
marrow  human adult-derived stem cells, ASCs 
PHSC : pluripotential hemopoietic stem cells
Cells of the Immune System

Figure 1-3
1. Originated from
Bone Marrow (BM)

2. Two major
lineages: Thymus

- Lymphoid
- Myeloid
Effector cells APCs
B cell development in the
Bone Marrow

The bone marrow also provide a microenviroment necessary for B


lymphocytes maturation and formation of pre-T cells (lymphopoiesis)

Cell-cell interactions and Cytokines


Thymus

1. The site of T cell maturation =>


Thymus-dependent (T)
lymphocytes or T cells =>
Thymocytes: developing T cells in
thymus

2. Multiple lobules => Each has


-Outer Cortex => Dense T cells
-Inner Medulla => Sparse T cells
Other cells: epithelial cells,
DCs, Macrophages
Lymphoid Tissues

Primary (Central) Secondary (Peripheral)


Lymphoid organs Lymphoid organs
Bone Marrow Lymph nodes
Thymus Spleen
SALT
MALT
Peripheral lymphoid
organ
The site where lymphocytes
locate,response to foreign antigens,
sensitized T lymphocytes and
produce specific antibody.
- Lymph node
- Spleen
- Skin associated lymphoid
tissue (SALT)
- Mucosal associated lymphoid tissue
(MALT)
Lymph Node

• The lymph node is the meeting


point of recirculating T cells,
B cells and APC with foreign
antigen
• B cell development continues in
the LN through the process of
CLONAL SELECTION
Spleen
1. The site of immune
responses to blood Ags
=> A filter of blood
Function :
-The site of immunocytes
residence.
-Produce some active
substances,such as
complement
2. White pulp
marginal zone
Red pulp
3. T cells => periarteriolar
lymphoid sheaths
B cells => follicle
=> marginal zone
SALT

The skin contains a specialized


cutaneous immune system
consisting of lymphocytes and
APCs (such as Langerhans cell)
MALT
The mucosal surfaces of the gastrointestinal,
respiratory tracts, urogenital tract and exocrine glands
associated with these organs are colonized by
lymphocytes and APCs that initiate immune responses
to injested and inhaled antigens.
• The mucosal surfaces are thin and permeable barriers to
the interior of the body
- effective defense mechanism
- vulnerability to infection
• The vast majority of infectious agents invade the human
body by these routes
• The mucosal surface are also portals of entry for a vast
array of foreign antigens, that are not pathogenic such as
food antigens
• The healthy large intestine is colonized by at least 1000
species of microorganisms : commensal microorganisms
⇒ contain many foreign antigens

• Mucosa-associated lymphoid tissue is located in


anatomically defined compartments in the gut
Gut-associated lymphoid tissues
(GALT)
- tonsils
- adenoids
- mesentric lymph nodes
- peyer’s patches
- solitary lymphoid
follicles of the
intestine
- appendix
The tonsils and adenoids form a ring of
lymphoid tissue

Waldeyer’s ring around the entrance of


the gut and airway
Peyer’s patches have a distinctive
appearance, forming dome-like
aggregates of lymphoid cells
Microfold cells (M cells) : the route by
which Ag enter the Peyer’s patch from
lumen
Similar isolated follicles are
found in other sites
• bronchus-associated
lymphoid issues (BALT)
• nasal-associated lymphoid
tissues (NALT)
• urogenital lymphoid tissue
Lymphocyte
Recirculation
• Lymphocyte recirculation : the process
lymphocytes circulate repeatedly among
blood,lymph,lymphoid organs and tissues.
Homing of Lymphocyte
Homing of lymphocytes: the process by which particular
subsets of lymphocytes selectively enter some tissues, but
not others
• .
Effector cells APCs
NK => LGL =Large Granular Lymphocytes
Overview of immune responses
Leucocytes
• Leucocytes
- Phagocytes
• Granulocytes : basophils, neutrophils and eosinophils
• Agranulocytes : monocytes
- Lymphocytes (agranulocytes)
Granulocytes
• Granulocytes (from granulocytopoiesis)
– Contain granules in cytoplasm
– 3 granulocytes
• Basophils – dark blue staining
• Neutrophils (PMN – polymorphonuclear leukocytes) – light lilac staining
• Eosinophils – red or orange staining
Granulocytes
• Basophils
– Contain histamines, heparin and chemotactic factors for
eosinophils and neutrophils
– They are similar to mast cells in that they participated in IgE-
mediated immediate hypersensitivity responses
– Inflammation and allergic reactions
IgE
Allergen Histamine
1
3
2

Granule
Mast cell
1 IgE antibodies produced in On subsequent exposure to the 3 Degranulation of the cell,
response to initial exposure same allergen, IgE molecules triggered by cross-linking of
to an allergen bind to attached to a mast cell recog- adjacent IgE molecules,
receptors or mast cells. nize and bind the allergen. releases histamine and other
chemicals, leading to allergy
symptoms.
Granulocytes
• Neutrophils
– Contain alkaline phosphatase, lysozyme, lactoferrin,
phagocytin and type IV collagenase
– Highly phagocytic and motile
– Leave blood and enter infected tissue
– The earliest phagocytic cells to appear in a bacterial
(extracellular pathogens) infection and are
prominent constituent of pus
Granulocytes
• Eosinophils
– Contain histaminase, acid phosphatase and major
basic protein
– Somewhat phagocytic
– Ability to leave blood
– Destroying large parasites (helminths),
phagocytosing antigen-antibody complexes and
combating histamine levels during allergic reactions
Agranulocytes
• Agranulocytes
– Granules not visible after staining
– 2 types
• Monocytes – phagocytic leukocytes in blood
Macrophage – monocyte that has entered tissue and
has matured
• Lymphocytes (T and B) and NK cells
Monocytes
Monocytes :
– Leave circulation to give rise to macrophages within
almost every organ
Macrophages :
– Contain azurophilic granules (lysozomes)
– More phagocytic than neutrophils or esinophils 
degrade larger bacteria within phagosomes via
formation of hydrogen peroxide,hypochlorus acid and
superoxide
– Macrophages and dendritic cells express Class II
MHC (major histocompatibility complex) and can
function as APC (antigen presenting cells) . They
secrete cytokines and tumor necrosis factor
Maturation of Macrophages

Activated Macro
Dendritic cells as
Ag-presenting cells
Classes of
Lymphocytes

1. NK cells

2. T cells:
- T helper cells
- T cytotoxic cells
- T regulatory cells
=> suppress immune
responses

3. B cells => Plasma cells


=> Abs
Lymphocytes
• Natural killer (NK) cells 
innate immunity
– Patrol the body  NK cells
appear early in bacterial
infections, can secrete
interferon and spontaneously
kill some viral infected cells
and tumor cells
– Trigger apoptosis in the cells
they attack
Classes of
Lymphocytes

1. NK cells

2. T cells:
- T helper cells
- T cytotoxic cells
- T regulatory cells
=> suppress immune
responses

3. B cells => Plasma cells


=> Abs
Class I MHC molecules
• Infected cells produce
MHC molecules Infected cell
– Which bind to antigen 1 A fragment of
foreign protein
fragments and then Antigen (antigen) inside the
fragment cell associates with
are transported to the an MHC molecule
cell surface in a and is transported
to the cell surface.
process called antigen
Class I MHC
presentation molecule

• A nearby T cell T cell


The combination of
MHC molecule and
receptor
– Can then detect the antigen is recognized
by a T cell, alerting it
antigen fragment to the infection.
displayed on the cell’s
surface
(a) Cytotoxic T cell
Class I MHC Proteins

Figure 21.15a
The activated
cytotoxic
T cell
1 A specific cytotoxic T cell binds to a 2 The activated T cell releases perforin 3 The granzymes initiate apoptosis within the
class I MHC–antigen complex on a molecules, which form pores in the target cells, leading to fragmentation of the
target cell via its TCR with the aid of target cell membrane, and proteolytic nucleus, release of small apoptotic bodies,
CD8. This interaction, along with enzymes (granzymes), which enter the and eventual cell death. The released
cytokines from helper T cells, leads to target cell by endocytosis. cytotoxic T cell can attack other target cells.
the activation of the cytotoxic cell.

Cytotoxic T cell Released


cytotoxic
Perforin T cell
Cancer
cell
Granzymes
Apoptotic
1 TCR CD8 3
target cell
Class I MHC 2
Pore
molecule

Target
cell Peptide
antigen Cytotoxic
T cell
Class II MHC molecules
• Located mainly on dendritic cells,
macrophages, and B cells
– Display antigens Microbe Antigen-
presenting
1 A fragment of
to helper T cells foreign protein cell
Antigen
(antigen) inside the
cell associates with fragment
an MHC molecule
and is transported 1
to the cell surface.
Class II MHC
2 molecule
2 The combination of T cell
MHC molecule and receptor
antigen is recognized
by a helper T cell, alerting it
to the infection.

Helper T cell
(b)
Class II MHC Proteins

Figure 21.15b
The role of helper T cells
in acquired immunity
1 After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR with the aid of CD4. This
interaction promotes secretion of cytokines by the dendritic cell.
Cytotoxic T cell
Dendritic Peptide antigen
cell Helper T cell Cell-mediated
Class II MHC
Bacterium molecule immunity
(attack on
TCR infected cells)

2 3
Humoral
1 CD4 immunity
(secretion of
Dendritic Cytokines B cell antibodies by
cell plasma cells)
2 Proliferation of the T cell, stimulated 3 The cells in this clone
by cytokines from both the dendritic secrete other cytokines
cell and the T cell itself, gives rise to that help activate B cells
a clone of activated helper T cells and cytotoxic T cells.
(not shown), all with receptors for the
same MHC–antigen complex.
Classes of
Lymphocytes

1. NK cells

2. T cells:
- T helper cells
- T cytotoxic cells
- T regulatory cells
=> suppress immune
responses

3. B cells => Plasma cells


=> Abs
B Cells: A Response to Extracellular
Pathogens
1 After a macrophage engulfs and degrades 2 A B cell that has taken up and degraded the 3 The activated B cell proliferates
a bacterium, it displays a peptide antigen same bacterium displays class II MHC–peptide and differentiates into memory
complexed with a class II MHC molecule. antigen complexes. An activated helper T cell B cells and antibody-secreting
A helper T cell that recognizes the displayed bearing receptors specific for the displayed plasma cells. The secreted
complex is activated with the aid of cytokines antigen binds to the B cell. This interaction, antibodies are specific for the
secreted from the macrophage, forming a with the aid of cytokines from the T cell, same bacterial antigen that
clone of activated helper T cells (not shown). activates the B cell. initiated the response.
Bacterium
Macrophage

Peptide
antigen

Class II B cell
MHC
molecule 2 Secreted antibody
3 Clone of plasma cells
1 molecules
TCR CD4 Endoplasmic
reticulum of
plasma cell
Cytokines

Helper T cell Activated


helper T cell Clone of memory
B cells
B- Lymphocytes
• Generates a clone of short-lived activated effector
cells and a clone of long-lived memory cells
Antigen molecules
Antigen molecules bind to the antigen
B cells that
receptors of only one
differ in
of the three B cells
antigen
shown.
specificity Antigen
receptor

The selected B cell


proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.

Some proliferating cells Some proliferating


develop into long-lived cells develop into
memory cells that can Antibody short-lived plasma
respond rapidly upon molecules cells that secrete
subsequent exposure antibodies specific
to the same antigen. Clone of memory cells for the antigen.
Clone of plasma cells
Figure 43.12
Antibody/Immunoglobulin (Ig)
Isotypes
IgM First Ig class produced after initial exposure to
Classes (pentamer) antigen; then its concentration in the blood declines

Promotes neutralization and agglutination of

• Immunoglobulin M (IgM) J chain antigens; very effective in complement activation


(see Figure 43.19)

IgG Most abundant Ig class in blood; also present in

• Immunoglobulin G (IgG) (monomer) tissue fluids


Only Ig class that crosses placenta, thus conferring
passive immunity on fetus

• Immunoglobulin A (IgA)
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)

IgA Present in secretions such as tears, saliva, mucus,

• Immunoglobulin D (IgD) (dimer) and breast milk

Secretory J chain Provides localized defense of mucous membranes by


component agglutination and neutralization of antigens (see

• Immunoglobulin E (IgE)
Figure 43.19)

Presence in breast milk confers passive immunity on


nursing infant

IgE
(monomer) Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)

IgD Present primarily on surface of naive B cells that have


(monomer) not been exposed to antigens

Acts as antigen receptor in antigen-stimulated


proliferation and differentiation of B cells (clonal
Transmembrane
selection)
region
Results of
antigen
binding
• Neutralize
• Opsonization
• Agglutination
• Fixing complement
• Precipitation
Antibody/Immunoglobulin (Ig)
Isotypes
IgM First Ig class produced after initial exposure to
Classes (pentamer) antigen; then its concentration in the blood declines

Promotes neutralization and agglutination of

• Immunoglobulin M (IgM) J chain antigens; very effective in complement activation


(see Figure 43.19)

IgG Most abundant Ig class in blood; also present in

• Immunoglobulin G (IgG) (monomer) tissue fluids


Only Ig class that crosses placenta, thus conferring
passive immunity on fetus

• Immunoglobulin A (IgA)
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)

IgA Present in secretions such as tears, saliva, mucus,

• Immunoglobulin D (IgD) (dimer) and breast milk

Secretory J chain Provides localized defense of mucous membranes by


component agglutination and neutralization of antigens (see

• Immunoglobulin E (IgE)
Figure 43.19)

Presence in breast milk confers passive immunity on


nursing infant

IgE
(monomer) Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)

IgD Present primarily on surface of naive B cells that have


(monomer) not been exposed to antigens

Acts as antigen receptor in antigen-stimulated


proliferation and differentiation of B cells (clonal
Transmembrane
selection)
region
Classes of innate
immune cells
Innate immune cells are
classified as following:
- Monocyte/Macrophage
- Dendritic cell (DC)
- Neutrophil, Eosinophil,
Basophil)
- Mast cell
- NK cells (lymphocyte)
=> Killing virus-infected
cells & tumors
Types of adaptive
immunity
1. Humoral immunity
=> Molecules in body fluid,
e.g. Antibody (Ab)
=> Key player => B cells
=> Target extracellular
microbes & toxins

2. Cell-mediated immunity
=> Key player => T cells =>
regulate other immune
cells
=> Target intracellular
microbes, e.g. viruses,
bacteria