cells, tissues, & organs of the immune system

Cells, Tissues, & Organs of The Immune System

• Pin Ling ( 凌 斌 ), Ph.D.

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

• 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 antibodies against the toxoid disappear from the circulation within a year?

2. Why is the vaccine against tetanus always effective, whereas the vaccine against influenza protects on some occasions but not others?

=> Memory lymphocytes are still existed and reactivated instantly.

=> Toxoid is more stable but influenza changes frequently.

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• Cells Cells of of the the Immune Immune SystemSystem

• 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.

Figure 1-3Cells 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 furtherdeveloped in Thymus for maturation.

Cells of Adaptive immunity1. 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 A

g-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 & R

egulate 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 re

sponses

3. NK cells

Identification of cell populations

1. Molecules on or in cells

=> Identification & Classification

2. Methods: (1) Immunofluorence (2) Flow cytometry & sorting (3) ELISPOT

Lymphocytes

Plasma Cells-Ab Secretion

Cells of innate immunity

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

Maturation of Macrophages

Activated Macro

Dendritic cells as Ag-presenting cells (APCs)

APCs link the innate & adaptive immune systems.

Dendritic cells as Ag-presenting cells-II

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• Cells of the Immune System

• Anatomy & Functions of Lymphoid TissAnatomy & Functions of Lymphoid Tissues & Organsues & 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 cellsEx. 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-I1. 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

2nd Lymphoid Organ-Lymph Node (LN)LNs => Small nodularorgan => Body => Lymphocyte activatio

n

Lymphocytes => Segregated in the distinct regions of LN

The outer cortex => B cell zone (follicle)=> Germinal Center (2nd follicle)=>B cell activatio

n

The inner region=> T cell zone

Lymph Node (LN)-II

Spleen1. The site of immune responses to blood Ags => A filter of blood

2. White pulp marginal zone Red pulp

3. T cells => periarteriolar lymphoid sheaths B cells => follicle => marginal zone

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• Cells of the Immune System

• Anatomy & Functions of Lymphoid Tissues & Organs

• Mechanisms of Lymphocyte Activation, Mechanisms of Lymphocyte Activation, Recirculation & HomingRecirculation & Homing

• Summary & Question

Overview of Lymphocyte Generation & Activation-I

Overview of Lymphocyte Generation & Activation-II

Activation of LymphocytesIn 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

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• Cells of the Immune System

• Anatomy & Functions of Lymphoid Tissues & Organs

• Mechanisms of Lymphocyte Activation, Recirculation & Homing

• Summary &Summary & Question 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 Ags from tissues or blood for lymphocyte activation.

QuestionQuestion

What effect you expect on the immune system if the thymus was removed?