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. Male D., J. Brostoff, D. B Roth, and I. Roitt
Immunology (7th ed., 2006), Chapter 2
2. Abbas, A, K. et.al, Cellular and Molecular
Immunology (6th ed., 2007), Chapter 3
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• 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
educated in Thymus for maturation.
Cells of innate immunity-I
1. Innate immune cells are derived from Bone Marrow.
2. Their primary function is to identify and kill microbes.
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.
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
Development of
monocytes &
granulocytes
1. Myelopoiesis – Development
of myeloid cells.
2. Cytokines from stromal
cells, myeloid, & lymphoid
cells are involved in this
process.
The Nobel Prize in Physiology or Medicine 2011
Bruce A. Beutler
Jules A. Hoffmann
Ralph M. Steinman
The Nobel Prize in Physiology or Medicine 2011 was divided, one half jointly to
Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the
activation of innate immunity" and the other half to Ralph M. Steinman
"for his discovery of the dendritic cell and its role in adaptive immunity".
Identification of
cell populations
1. Molecules on or in cells
=> Identification &
Classification
e.g. CD3, CD4, CD8….
2. Methods:
(1) Immunofluorecence
(2) Flow Cytometry
& Sorting
(3) ELISPOT
Identification & isolation of cell
populations
Maturation of Macrophages
Activated Macro
Key concepts of
Monocytes/Macrophages
1. Relatively long-lived and distributed throughout the
whole body.
2. Engulf and kill pathogens by phagocytosis.
3. Express various receptors to recognize different
pathogens, e.g. PRR, Scavenger receptor,….etc.
4. Trigger inflammation and Antigen presentation
Phagocytosis by innate immunity
Ag-presenting cells (APCs) link the innate
& adaptive immune systems
Polymorphonuclear Granulocytes:
Neutrophils
1. Comprise over 95% of
granulocytes
2. Short-lived (2-3 days)
3. Multi-lobed nucleus
4. Kill pathogens by
phagocytosis & releasing
cytotoxic substances.
Basophils & mast cells: critical
for immunity against parasites
Eosinophils
Dendritic cells (DCs) as Ag-presenting
cells (APCs)
FDC:Follicular DC
Key concepts of Dendritic
Cells (DCs)
1. Most effective Ag-presenting cells linking innate and
adaptive immunity
2. High MHC-II expression on DCs
3. Several types of DCs:
(1) Myeloid DCs (also known as conventional DCs)
(2) Lymphoid DCs => Plasmacytoid DCs
(3) Lymphoid organ-specific DCs:
Follicular DCs in Lymph nodes (lacking MHC-II)
Interdigitating Dcs in Lymph nodes & Thymus
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
=> 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
T cells vs B cells
Lymphocytes
Small Lymphocytes
Large Granular Lymphocytes
Plasma Cells-Ab Secretion
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• 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
Eg. 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
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: thymic epithelial
cells (TECs), DCs, Macrophages
=> Cell-cell interactions and
Cytokines
Thymus-II
Positive selection
Negative selection
T cell
differentiation
in the Thymus
2nd Lymphoid Organ-Lymph Node (LN)
LNs => Small nodular
organ => Body
=> Lymphocyte activation
Lymphocytes =>
Segregated in the
distinct regions of LN
The outer cortex
=> B cell zone (follicle)
=> Germinal Center (2nd
follicle)=>B cell activation
The inner region
=> T cell zone
Lymph Node (LN) Section
Lymph Node (LN) Section-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
Mucosa-Associated Lymphoid Organs
(MALT)
Outline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid
Tissues & Organs
• 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 effect would you expect the
thymus removal (thymectomy) to have
on the ability of host immunity against
infection?
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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
Migration of Lymphocytes-II