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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

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Outline

  • Cells of the Immune System

  • Anatomy & Functions of Lymphoid Tissues & Organs

  • Summary & Question

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Key concepts about immune cells

1. The principle cells of the immune system:

Antigen-presenting cellsLymphocytes => 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”.

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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

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Cells of the Immune System-II

T lymphocytes are first derived from BM and further

educated in Thymus for maturation.

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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.

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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

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Development of monocytes & granulocytes

1. Myelopoiesis – Development

of myeloid cells.

2. Cytokines from stromal

cells, myeloid, & lymphoid

cells are involved in this

process.

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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

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Identification & isolation of cell populations

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Maturation of Macrophages

Activated Macro

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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

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Phagocytosis by innate immunity

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Ag-presenting cells (APCs) link the innate

& adaptive immune systems

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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.

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Basophils & mast cells: critical for immunity against parasites

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Eosinophils

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Dendritic cells (DCs) as Ag-presenting cells (APCs)

FDC:Follicular DC

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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

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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

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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

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T cells vs B cells

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Lymphocytes

Small Lymphocytes

Large Granular Lymphocytes

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Plasma Cells-Ab Secretion

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Outline

  • Cells of the Immune System

  • Anatomy & Functions of Lymphoid Tissues & Organs

  • Summary & Question

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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

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The Lymphatic System

Link to the blood

circulation system

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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

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B cell development in the �Bone Marrow

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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

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Thymus-II

Positive selection

Negative selection

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T cell differentiation in the Thymus

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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

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Lymph Node (LN) Section

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Lymph Node (LN) Section-II

C => Cortex => B cell zone

P => Paracortex => T cell zone

M => Medulla

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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

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Mucosa-Associated Lymphoid Organs (MALT)

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Outline

  • Cells of the Immune System

  • Anatomy & Functions of Lymphoid Tissues & Organs

  • Summary & Question

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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.

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Question

What effect would you expect the

thymus removal (thymectomy) to have

on the ability of host immunity against

infection?