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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