3.

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)
Lymphoid organs
Bone Marrow
Thymus

Secondary (Peripheral)
Lymphoid organs
Spleen
Lymph nodes
MALT
GALT

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 (SC): undifferentiated

pluripotential cells differentiate
into all 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
PHSC : pluripotential hemopoietic 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

Cells of the Immune System

Figure 1-3
1. Originated from
Bone Marrow (BM)
2. Two major
lineages:
- Lymphoid
- Myeloid

Thymus

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
=> Cell-cell interactions and
Cytokines

Lymphoid Tissues
Primary (Central)
Lymphoid organs
Bone Marrow
Thymus

Secondary (Peripheral)
Lymphoid organs
Lymph nodes
Spleen
SALT
MALT

Peripheral lymphoid
organ
The site where lymphocytes
locate,response to foreign antigens,
produce specific antibody and
sensitized T lymphocytes.
- 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)
- peyers patches
- solitary lymphoid follicles of the
intestine
- appendix
- tonsils
- adenoids
- mesentric lymph nodes
Peyers patches have a distinctive
appearance, forming dome-like
aggregates of lymphoid cells
Microfold cells (M cells) : the route by
which Ag enter the Peyers patch from
lumen

The tonsils and adenoids form a ring

of lymphoid tissue
Waldeyers ring around the entrance of
the gut and airway

Similar isolated follicles are

found in other sites
bronchus-associated
lymphoid issues (BALT)
nasal-associated lymphoid
tissues (NALT)
urogenital lymphoid tissue

Homing of Lymphocyte
Homing of lymphocytes: the process by which particular
subsets of lymphocytes selectively enter some tissues, but
not others

Lymphocyte
Recirculation

Lymphocyte recirculation : the process

lymphocytes circulate repeatedly among
blood,lymph,lymphoid organs and tissues.

Overview of immune responses

NK => LGL =Large Granular Lymphocytes

Classes of innate
immune cells
Innate immune cells are
classified as following:
- Monocyte/Macrophage
- Dendritic cell (DC)
- Polymorphonuclear
granulocyte (PMN;
Neutrophil, Eosinophil,
Basophil)
- Mast cell
- NK cells (lymphocyte)
=> Killing virus-infected
cells & tumors

Leucocytes
Leucocytes
- Phagocytes
Granulocytes : basophils, neutrophils and eosinophils
Agranulocytes : monocytes
- Agranulocytes : lymphocytes

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 IgEmediated immediate hypersensitivity responses
Inflammation and allergic reactions
IgE
Allergen

Histamine
3

2
Granule
Mast cell
Degranulation of the cell,
1IgE antibodies produced inOn subsequent exposure to the3

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,
releases histamine and other
receptors or mast cells. nize and bind the allergen.
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 leukocyte 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
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

Effector cells

APCs

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
Which bind to antigen
fragments and then
are transported to the
cell surface in a
process called antigen
presentation
A nearby T cell
Can then detect the
antigen fragment
displayed on the cells
surface

Infected cell
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.

Antigen
fragment

Class I MHC
molecule
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.

T cell
receptor

(a) Cytotoxic T cell

Class I MHC Proteins

Figure 21.15a

The activated
cytotoxic
T cell
2 The activated T cell releases perforin
1 A specific cytotoxic T cell binds to a
molecules, which form pores in the
class I MHCantigen complex on a
target cell membrane, and proteolytic
target cell via its TCR with the aid of
enzymes (granzymes), which enter the
CD8. This interaction, along with
target cell by endocytosis.
cytokines from helper T cells, leads to
the activation of the cytotoxic cell.
Cytotoxic T cell

3 The granzymes initiate apoptosis within the

target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.

Released
cytotoxic
T cell

Perforin

Cancer
cell
Granzymes
1 TCR
Class I MHC
molecule

Target
cell

CD8
2

Peptide
antigen

Apoptotic
target cell

Pore

Cytotoxic
T cell

Class II MHC molecules

Located mainly on dendritic cells,
macrophages, and B cells
Display antigens
1 A fragment of
to helper T cells foreign protein

Antigenpresenting
cell

Microbe

Antigen
fragment

(antigen) inside the

cell associates with
an MHC molecule
and is transported
to the cell surface.

1
2

2 The combination of
MHC molecule and
antigen is recognized
by a helper T cell, alerting it
to the infection.

Class II MHC
molecule
T cell
receptor

(b)

Helper T cell

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.
Dendritic
cell
Bacterium

Cytotoxic T cell
Peptide antigen
Class II MHC
molecule

Helper T cell

Cell-mediated
immunity
(attack on
infected cells)

TCR
2

1 CD4
Dendritic
cell

Cytokines
2 Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHCantigen complex.

B cell
3 The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.

Humoral
immunity
(secretion of
antibodies by
plasma 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

B Cells: A Response to Extracellular

Pathogens
1 After a macrophage engulfs and degrades 2

a bacterium, it displays a peptide antigen

complexed with a class II MHC molecule.
A helper T cell that recognizes the displayed
complex is activated with the aid of cytokines
secreted from the macrophage, forming a
clone of activated helper T cells (not shown).

3 The activated B cell proliferates

A B cell that has taken up and degraded the
same bacterium displays class II MHCpeptide
and differentiates into memory
antigen complexes. An activated helper T cell
B cells and antibody-secreting
bearing receptors specific for the displayed
plasma cells. The secreted
antigen binds to the B cell. This interaction,
antibodies are specific for the
with the aid of cytokines from the T cell,
same bacterial antigen that
activates the B cell.
initiated the response.

Bacterium
Macrophage
Peptide
antigen
Class II
MHC
molecule

B cell
2
1

TCR

CD4
Cytokines

Helper T cell

Activated
helper T cell

Secreted antibody
molecules
Endoplasmic
reticulum of
plasma cell

Clone of plasma cells

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

B cells that
differ in
antigen
specificity

Antigen
receptor

Antigen molecules
bind to the antigen
receptors of only one
of the three B cells
shown.

The selected B cell

proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating cells
develop into long-lived
memory cells that can
respond rapidly upon
subsequent exposure
to the same antigen.

Antibody
molecules
Clone of memory cells

Figure 43.12

Clone of plasma cells

Some proliferating
cells develop into
short-lived plasma
cells that secrete
antibodies specific
for the antigen.

Antibody/Immunoglobulin (Ig)
Isotypes
Classes

IgM
(pentamer)

Immunoglobulin M (IgM)
Immunoglobulin G (IgG)

First Ig class produced after initial exposure to

antigen; then its concentration in the blood declines

J chain

IgG
(monomer)

Immunoglobulin E (IgE)

Most abundant Ig class in blood; also present in

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

Immunoglobulin A (IgA)
Immunoglobulin D (IgD)

Promotes neutralization and agglutination of

antigens; very effective in complement activation
(see Figure 43.19)

Promotes opsonization, neutralization, and agglutination

of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk

IgA
(dimer)
Secretory
component

J chain

Provides localized defense of mucous membranes by

agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant

IgE
(monomer)

IgD
(monomer)

Transmembrane
region

Triggers release from mast cells and basophils of

histamine and other chemicals that cause allergic
reactions (see Figure 43.20)

Present primarily on surface of naive B cells that have

not been exposed to antigens
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)

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

Summary :
Cell-mediated immune response

Humoral immune response

First exposure to antigen

Intact antigens

Antigens engulfed and

displayed by dendritic cells

Antigens displayed
by infected cells

Activate

Activate

Activate

B cell

Gives rise to

Plasma
cells

Memory
B cells

Secrete antibodies that defend against

pathogens and toxins in extracellular fluid

Helper
T cell

Secreted
cytokines
activate
Cytotoxic
T cell

Gives rise to

Gives rise to

Active and
memory
helper
T cells

Memory
cytotoxic
T cells

Active
cytotoxic
T cells

Defend against infected cells, cancer

cells, and transplanted tissues

Results of
antigen
binding

Neutralize
Opsonization
Agglutination
Fixing complement
Precipitation