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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
OutlineOutline
• Cells of the Immune SystemCells 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”.
Figure 1-3
Cells of the Immune System-I
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 furthereducated 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.
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
Classes of innate immune cells
Development of monocytes & granulocytes
1. Myelopoiesis – Development
of myeloid cells.
2. Cytokines from stromal cells, myeloid, &
lymphoid cells are involved in this process.
Bruce A. Beutler Jules A. Hoffmann Ralph M. Steinman
The Nobel Prize in Physiology or Medicine 2011
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 Lymphocytes1. 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
OutlineOutline
• Cells of the Immune System
• Anatomy & Functions of Anatomy & Functions of Lymphoid Tissues & OrgansLymphoid 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 cellsEg. 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 nodularorgan => 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
Spleen1. 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)
OutlineOutline
• Cells of the Immune System
• Anatomy & Functions of Lymphoid Tissues & Organs
• Summary & QuestionSummary & Question
SUMMARY1. 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.
QuestionQuestion
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-I1. 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
