Transcript Cells of the Immune System-I

Cells, Tissues, & Organs of
The Immune System
• Pin Ling (凌 斌), Ph.D.
ext 5632; [email protected]
• References:
1. Abbas, A, K. et.al, Cellular and Molecular
Immunology (6th ed., 2007), Chapter 3
2. Male D., J. Brostoff, D. B Roth, and I. Roitt
Immunology (7th ed., 2006), Chapter 2
Questions
1. Why is it necessary to vaccinate against tetanus only every 10
years, though
antibodiesare
against
toxoid and
disappear
from theinstantly.
=> Memory
lymphocytes
stillthe
existed
reactivated
circulation within a year?
2.
Why is the
always effective,
whereas
=> Toxoid
isvaccine
more against
stabletetanus
but influenza
changes
frequently.
the vaccine against influenza protects on some epidemics but not
others?
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• Pathways of Lymphocyte Activation,
Recirculation & Homing
• Summary & Question
Key concepts about immune cells
1. The principle cells of the immune system:
Antigen-presenting cells  Lymphocytes => Effector cells
2. All immune cells are derived from “Hematopoietic stem cells”
in Bone Marrow (BM) (& Fetal liver during fetus).
3. Immune cells are divided into two major lineages:
=> Lymphoid & Myeloid
=> Multiple cell types => express distinct “Surface molecules
(markers)” => Classification
4. Development and differentiation of different cell types
depend on “Cell Interactions and Cytokines”.
Cells of the Immune System-I
Figure 1-3
1. Originated from
Bone Marrow (BM)
2. Two major lineages:
- Lymphoid
- Myeloid
3. NK cells
- Large Granular
Lymphocytes (LGL)
NK => LGL
Cells of the Immune System-II
T lymphocytes are first derived from BM and further
developed in Thymus for maturation.
Cells of Adaptive immunity
1. Lymphocytes are the key players of the adaptive
immunity.
2. Lymphocytes are able to specifically recognize and
respond to diverse antigens.
=> Antigen (Ag) receptors on lymphocytes (T & B cells)
=> Specificity (Clone), Diversity (Repertoire: total number
of Ag-specific lymphocytes in an individual; 107-9), &
Memory
3. Lymphocytes are classified into three major groups:
- B cells => Antibodies => Humoral immunity
- T cells => Multiple subtypes => Cell-mediated immunity &
Regulate other immune cells
- NK cells => Innate immunity
Classes of
Lymphocytes
1. B cells => Plasma cells
=> Abs
2. T cells:
- T helper cells
- T cytotoxic cells
- T regulatory cells
=> suppress immune
responses
3. NK cells
4. Subtypes in each class
Identification of
cell populations
1. Molecules on or in cells
=> Identification &
Classification
=> CD (cell differentiation)
molecules
2. Methods:
(1) Immunofluorecence
(2) Flow Cytometry &
Sorting
(3) ELISPOT
Lymphocytes
1. Small lymphocytes (T & B) are at the resting state (No Ag stimulation)
- Large nucleus w/o active organelles
- Die after 1-3 months w/o Ag recognition
2. Large lymphocytes are activated by specific Ags
- More cytoplasm & active organelles
- Become “Effector Lymphocytes” to secret Abs (Plasma cells), Cytokines,
Enzymes => Most of them die shortly
- Some become long-lasting “Memory Lymphocytes” w/ different surface proteins
Small lymphocyte
Large lymphocyte
Plasma Cells-Ab Secretion
NK cells
- Appear as Large lymphocytes
- Contain many cytoplasmic granules
Cells of innate immunity
1. Innate immune cells are derived from Bone Marrow.
2. Their primary functions are (1) to identify and kill
microbes, and (2) Antigen-presenting cells (APCs)
additionally function to present Ag to and activate
lymphocytes.
3. Innate immune cells recognize the common microbial
structures PAMPs through Pattern-Recognition
Receptors (PRRs) -limited diversity.
Interaction between innate and
& adaptive immunity
1. Innate immunity => Ag presentation (by Dendritic cells)
2. Adaptive immunity => Ag recognition (by T & B 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
(most abundant)
Maturation of Macrophages
Monocyte
Activated Macro
Dendritic cells (DCs) as Ag-presenting
cells (APCs)
DCs link the innate & adaptive immune systems.
FDC:Follicular DC
Dendritic cells as
Ag-presenting cells-II
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• Pathways of Lymphocyte Activation,
Recirculation & Homing
• Summary & Question
Primary lymphoid organs:
BM & Thymus
=> Lymphocyte
development, selection,
& maturation.
2nd lymphoid organs:
Lymphoid nodes & Spleen
=> Lymphocyte
activation & effector
functions
BM
 Other immune cells
e.g., DCs, Macrophages,
PMNs
The Lymphatic
System
Link to the blood
circulation system
Bone Marrow
1. The site of generation of
all immune and blood cells
<= Hematopoietic Stem Cell
2. Provides Cell-cell
interactions and Cytokines
for the development of
all immune cells.
<= Stromal reticular cells
& other cells
Bony trabeculae
adipocytes
B cell development in the
Bone Marrow
Thymus-I
1. The site of T cell maturation =>
Thymus-dependent (T) lymphocytes
or T cells => Thymocytes: developing
T cells in thymus
2. Upper anterior thorax (above
the heart).
3. 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
Thymus-II
Positive selection:
 Self MHC
Negative selection:
 Self-Ag
(Autoantigen)
2nd Lymphoid Organ-Lymph Node (LN)
LNs => Small nodular
organ => Body
=> Lymphocyte activation
Lymphocytes => Segregated
in the distinct regions of LN
=> Chemokines
The outer cortex
=> B cell zone (follicle)
=> Germinal Center (2nd
follicle)=>B cell activation
The inner region
=> T cell zone + DCs
Lymph Node (LN)-II
C => Cortex => B
cell zone
P => Paracortex
=> T cell zone
M => Medulla
Spleen
1. The site of immune
responses to blood Ags
=> A filter of blood
2. White pulp => T cell & B
cell zones
Marginal zone (MZ)
Red pulp (RP)
3. T cells => periarteriolar
lymphoid sheaths
B cells => follicle
=> marginal zone
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• Mechanisms of Lymphocyte Activation,
Recirculation & Homing
• Summary & Question
Overview of
Lymphocyte
Generation &
Activation-I
Overview of
Lymphocyte
Generation &
Activation-II
Activation of Lymphocytes
In general, lymphocyte
activation requires “Two
Signals” (from Antigen
presenting cells (APCs))
Signal 1:
Ag  Ag receptor on
lymphocytes (T & B)
Signal 2:
Molecules (innate
response)
Costimulatory receptors
on lymphocytes
Migration of
Lymphocytes-I
1. In LN, naïve lymphocytes
 HEVs
Rolling => Adhesion
=> Transmigration
Adhesion molecules for
cell-cell interactions
2. In peripheral infection
sites, effector
lymphocytes  blood
vessels
High Endothelial
Venules (HEVs)
Migration of Lymphocytes II
- Recruitment of Lymphocytes to the
infection site
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• Mechanisms of Lymphocyte Activation,
Recirculation & Homing
• Summary & Question
SUMMARY
1. Immune cells are derived from “Bone Marrow (BM)”.
T-lineage progenitor cells are first derived from BM and move to
“Thymus” for maturation.
2. Key cells in innate immune responses include
- Macrophage & DCs => Ag presentation
- Granulocytes (PMNs)
- NK cells
3. Key cells in Adaptive immune responses include
- B lymphocytes => Ab => Extracellular bacteria
- Several T cell types => Fight intracellular microbes &
Regulate the program of an immune response
4. Primary lymphoid organs (BM & Thymus)=> Immune cell development
2nd lyphoid organs (LN & Spleen)=> Concentrate Ag from tissues
or blood for lymphocyte activation.
Question
What happened to the host immunity against
infection when the thymus is removed
(thymectomy)?
Questions
1. Why is it necessary to vaccinate against tetanus only every 10
years, though antibodies against the toxoid disappear from the
=> circulation
Memory lymphocytes
within a year?are still existed and reactivated instantly.
2. Why is the vaccine against tetanus always effective, whereas
the vaccine against influenza protects on some occasions but not
others?
=> Toxoid is more stable but influenza changes frequently.