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Immunology

Immunobiology:

The Immune System in Health & Disease

8th Edition

Chapter 1

Basic Concepts in Immunology

Kenneth Murphy, Paul Travers, Mark Walport,

What is Immunology?

- body’s defense against infection

Edward Jenner (1749-1823) the father of Immunology

Virus variola

Small pox in 18C

Cowpox

Vaccination vacca: cow

Just a Few Important Historical Names

(1796)

Robert Koch (1843-1910)

Germ theory of disease - infectious diseases are caused by microorganisms

disease causing microorganisms :

Fungi

Viruses

HIV Influenza

Parasites Schistosomiasis

Candida

Bacteria E coli

Mycobacteria

M TB

vaccines against cholera and rabies (late 1800’)

Louis Pasteur (1822-1895)

Emil von Behring (1854-1917) Shibasaburo Kitasato (1853-1931) Nobel prize (1901)

antibody in serum

Elie Mechnikoff (1845-1916)

macrophages and innate immunity

Adaptive immunity - lymphocytes

Innate immunity – granulocytes, macrophages

Functions of the immune response

Immunological recognition

Immune effector functions

Immune regulation

Immunological memory

Principles of innate and adaptive immunity

The cells of the immune system derive from precursors in the bone marrow

• Red blood cells

• Platelets

• White blood cells in blood

derive from

hematopoietic stem cells in bone marrow (BM)

Myeloid progenitor is precursor of

• Granulocytes :

neutrophils, eosinophils, basophils

• Macrophages (MØ )

• Dendritic cells (DC)

• Mast cells

Lymphoid progenitor is precursor of

• Lymphocytes : B & T cells

• Natural killer (NK) cells

• Dendritic cells

The cells of the hematopoietic system and their sites of differentiation in the body

The myeloid lineage comprises most of the cells of the innate immune system

Cell type Relative representation (%)

Neutrophil granulocytes 60 - 70

Eosinophil granulocytes 1 - 3

Basophil granulocytes < 2

Monocytes 5 - 10

Lymphocytes 20 - 40

No antigen specific receptors

Innate immune system

Kill tumor and cells infected with viruses

The lymphoid lineage comprises the lymphocytes of the adaptive immune system and the natural killer cells of innate immunity

B lymphocytes or B cells

plasma cells – secrete antibodies

T lymphocytes or T cells

helper T cells

cytotoxic T cells

Lymphocytes are able to mount a specific

immune response to any foreign antigens

Each individual lymphocyte bears a huge

repertoire of antigen receptors (BCR or TCR)

Prior to antigen activation lymphocytes have little cytoplasm and are transcriptionally relatively inert

Both antigen and co-stimulatory molecule are needed to fully activate lymphocytes

The 4 cardinal properties of the adaptive immune system are embodied by lymphocytes and are attained by the mechanisms by which they develop and differentiate

1. Specificity

2. Diversity

3. Memory

4. Self/nonself recognition

Lymphocytes mature in the bone marrow or the thymus and then congregate in lymphoid tissues throughout the body

Lymphoid organs-tissues containing lymphocytes

Central (primary) lymphoid organ

- produce lymphocytes - BM, thymus

Peripheral (secondary) lymphoid organ

- initiate adaptive immune responses - maintain lymphocytes - lymph node, spleen, mucosal lymphoid tissues

Figure 1-7

The distribution of lymphoid tissues in the body

Most infectious agents activate the innate immune system and induce an inflammatory response

MØ & neutrophil of innate immune system:

- 1st line of defense

- Initiate adaptive immune responses

Lymphocytes of adaptive immune system:

- more versatile defense

- increased protection against subsequent reinfection with same pathogens

Infection triggers an inflammatory response by activating innate immunity

MØ defend against pathogens by means of surface receptors

Activated MØ secrete cytokines and chemokines

These induce local inflammation :

heat, pain, redness and swelling

Infection triggers an inflammatory response by activating innate immunity

Activation of specialized antigen-presenting cells is a necessary first step for induction of adaptive immunity

Immature DC recognizes and engulf pathogens and

presents pathogen Ag to T cells

On activation DC matures into APC and activates

pathogen-specific lymphocytes

The innate immune system provides an initial

discrimination between self and nonself

- Receptors recognizing simple molecules and molecular

patterns expressed by bacterial and fungal pathogens

Lymphocytes activated by antigen give rise to clones of antigen-specific cells that mediate adaptive immunity

Each naïve lymphocyte bears Ag receptors of a single specificity

Specificity of receptors is determined during lymphocyte development in BM and thymus

Lymphocyte receptor repertoire: millions of different variants of genes encoding receptor molecules

proposed “clonal selection theory” postulating pre-existence of many different potential Ab producing cells in the body

On binding Ag, the cells is activated to produce many identical progeny, clone, which secrete clonotypic Abs

Clonal selection of lymphocytes is the central principle of adaptive immunity

Macfarlane Burnet (1899-1985)

Lymphocytes develop and acquire their antigen specificity in the absence of antigenic stimulation

The specificity and diversity of antigen receptors are generated during lymphocyte development

Figure 1-14 part 2 of 2 Antigen stimulation is required for lymphocyte proliferation

It is during antigen stimulation that memory lymphocytes are generated

The structure of the antibody molecule illustrates the central puzzle of adaptive immunity

Each developing lymphocyte generates unique antigen receptor by rearranging its receptor gene segments

Immunoglobulins bind a wide variety of chemical structures, whereas the T-cell receptor is specialized to recognize foreign antigens as peptide fragments bound to proteins of the major histocompatibility complex

Usual antigens encountered in an infection are proteins, glycoproteins, polysaccharides

Antigenic determinant or epitope - a small part of the molecular structure of an antigenic molecules which is recognized by antigen receptor

The development and survival of lymphocytes are determined by signals received through their antigen receptors

T cells – thymic epithelial cells / dendritic cells

B cells – BM stromal cells

Strong signal – apoptosis, clonal deletion

No signal – apoptosis

Survival signal