Cells, Tissues, & Organs of The Immune System Pin Ling ( 凌斌 ), Ph.D. ext 5632;...

Cells, Tissues, & Organs of The Immune System

• Pin Ling ( 凌斌 ), Ph.D.

ext 5632; lingpin@mail.ncku.edu.tw

• 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

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?

Downloaded from: StudentConsult (on 29 August 2006 10:33 AM)

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

Cells, Tissues, & Organs of The Immune System Pin Ling ( 凌斌 ), Ph.D. ext 5632;...

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