固有免疫和适应免疫
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selection)
There is rapid amplification of a response There is memory
Components
Principle Functions
Barriers
Epithelial layers
Prevent entry
Components of Innate
NK cells
Lysis of infected cells, activation of macrophages
Circulating Proteins
Complement (C’)
Killing of microbes, opsonization of microbes, actvn leukocytes
Dance of the Eons
Virtually every organism faces pressure from viral or microbial colonization and so has evolved strategies to control colonization
Likewise, every parasitic organism or piece of selfish DNA has evolved a strategy to mitigate the effects of immunity
Biological Invention of Acquired Immunity
Innate vs. Adaptive Immunity
Memory
Innate Immunity
All animals have an “innate” immune system Innate immunity is manifest in many cells of the body. The basis is the
Defensins (epithelium)
Salmonella infection with and without adaptive immunity
Mice deficient for innate immunity (macrophage)
WT T lymphocyte deficient
Cytokines TNF, IL-1, 6, 18 IFN a, b IFN g IL-12 IL-15 IL-10, TGF b
Inflammation Resistence to viral infection Macrophage activation IFNg production by NK cells Proliferation of NK cells, memory T cells Control of Inflammation Adapted from: Abbas (Saunders)
Colonization of large organisms by smaller organisms or viruses is the “inverse food chain”
Large complex organisms present a source of energy and a habitat for smaller organisms and viruses via colonization
This eternal waltz of parasites and their hosts surely began with the origin of life
Corollaries • Just as predator species improve the fitness of their prey, colonial agents
A third limitation is that there is no memory
Adaptive Immunity
▪ Recognizes any biochemical determinant
Provides a mechanism for immune recognition that can evolve as rapidly as the parasite (clonal
Colonization and defense against colonization is a fundamental principle in biology
The immune system is principally and most importantly evolved to sculpt colonization to benefit the host
select for fitness in their hosts • Just as a host cannot be too permissive for a parasitic agent, the
parasitic agent cannot be too effective in killing a host • The more effective the immune system, the more complicated and
recognition of molecular patterns, that occur in microbes but not animals (e. g., unmethylated DNA sequences, dsRNA, cell wall components, etc) This is the bedrock of immunity in all organisms--even bacteria have defense mechanisms against bacterial viruses
Defensins and Cryptidins Microbial killing
Immunity
Circulating and Tissue Effector Cells
Neutrophils
Early phagocytosis and killing of源自文库microbes
Mast Cells
Immunity in Drosophila (Innate) Toll mutant lacks defense against fungal infections 18 Wheeler lacks defense against bacteria This led to the discovery of a family of receptors known as the Toll-related receptors (TLR) present in vertebrates
Release of inflammatory granules
Macrophages
Efficient phagocytosis and killing of microbes: cytokines
Eosinophils
Nasty toxic cells designed to kill helminths (worms)
Cancer: Evidence in the past year indicates that the immune system does indeed function in tumor surveillance
Hypersensitivity Diseases: Allergy-Incidence rise from 6%-20% in the past two decades Asthma-Incidence rise from 3%-8% of the total population in the past two decades -The hygiene hypothesisHeart Disease-The blood vascular system is an integral part of the immune system. It instructs leukocytes to migrate from the blood to a site of infection. New evidence supports that idea that coronary heart disease results from chronic arterial inflammation
What is the basis for innate immunity, and how does is relate to vertebrates? Drosophila melanogaster mutants were found that were susceptible to fungal and bacterial infections.
Innate Immunity, con’t
An apparent limitation is that parasitic agents have a generation time orders of magnitude less than that of their hosts
A second limitation is that there is only limited amplification of the response
evolved the parasite • Perhaps we should view the host-parasite interaction as a constantly
escalating war or an uneasy (metastable) truce
One view of animal phylogeny
固有免疫和适应免疫
The Triumph of Death - Pieter Brueghel the Elder ca. 1562
Why the immune system?
What is its function? How widely is it present in nature? Why does it affect so many aspects of life? How can we alter it for improved quality of life?
Mannose-binding protein Opsonization of microbes and activation of C’
C-reactive protein
Opsonization of microbes and activation of C’
Lysozyme
Bacterial cell wall lysis
Infectious Diseases: Almost any deficiency in immunity--you die
Immune Evolution
Big bugs have little bugs Upon their backs to bite ‘em Little bugs have littler bugs And so on ad infinitum -Ogden Nash, I think
How does the Immune System (IS) affect your life?
Autoimmune diseases: Graves'/hyperthyroidism, Type I diabetes, pernicious anemia, rheumatoid arthritis, thyroiditis, and vitiligo The incidence of 24 autoimmune diseases is 1/31 Americans. Women are at 2.7x greater risk Clin Immunol Immunopathol 1997 Sep;84(3):223-43
There is rapid amplification of a response There is memory
Components
Principle Functions
Barriers
Epithelial layers
Prevent entry
Components of Innate
NK cells
Lysis of infected cells, activation of macrophages
Circulating Proteins
Complement (C’)
Killing of microbes, opsonization of microbes, actvn leukocytes
Dance of the Eons
Virtually every organism faces pressure from viral or microbial colonization and so has evolved strategies to control colonization
Likewise, every parasitic organism or piece of selfish DNA has evolved a strategy to mitigate the effects of immunity
Biological Invention of Acquired Immunity
Innate vs. Adaptive Immunity
Memory
Innate Immunity
All animals have an “innate” immune system Innate immunity is manifest in many cells of the body. The basis is the
Defensins (epithelium)
Salmonella infection with and without adaptive immunity
Mice deficient for innate immunity (macrophage)
WT T lymphocyte deficient
Cytokines TNF, IL-1, 6, 18 IFN a, b IFN g IL-12 IL-15 IL-10, TGF b
Inflammation Resistence to viral infection Macrophage activation IFNg production by NK cells Proliferation of NK cells, memory T cells Control of Inflammation Adapted from: Abbas (Saunders)
Colonization of large organisms by smaller organisms or viruses is the “inverse food chain”
Large complex organisms present a source of energy and a habitat for smaller organisms and viruses via colonization
This eternal waltz of parasites and their hosts surely began with the origin of life
Corollaries • Just as predator species improve the fitness of their prey, colonial agents
A third limitation is that there is no memory
Adaptive Immunity
▪ Recognizes any biochemical determinant
Provides a mechanism for immune recognition that can evolve as rapidly as the parasite (clonal
Colonization and defense against colonization is a fundamental principle in biology
The immune system is principally and most importantly evolved to sculpt colonization to benefit the host
select for fitness in their hosts • Just as a host cannot be too permissive for a parasitic agent, the
parasitic agent cannot be too effective in killing a host • The more effective the immune system, the more complicated and
recognition of molecular patterns, that occur in microbes but not animals (e. g., unmethylated DNA sequences, dsRNA, cell wall components, etc) This is the bedrock of immunity in all organisms--even bacteria have defense mechanisms against bacterial viruses
Defensins and Cryptidins Microbial killing
Immunity
Circulating and Tissue Effector Cells
Neutrophils
Early phagocytosis and killing of源自文库microbes
Mast Cells
Immunity in Drosophila (Innate) Toll mutant lacks defense against fungal infections 18 Wheeler lacks defense against bacteria This led to the discovery of a family of receptors known as the Toll-related receptors (TLR) present in vertebrates
Release of inflammatory granules
Macrophages
Efficient phagocytosis and killing of microbes: cytokines
Eosinophils
Nasty toxic cells designed to kill helminths (worms)
Cancer: Evidence in the past year indicates that the immune system does indeed function in tumor surveillance
Hypersensitivity Diseases: Allergy-Incidence rise from 6%-20% in the past two decades Asthma-Incidence rise from 3%-8% of the total population in the past two decades -The hygiene hypothesisHeart Disease-The blood vascular system is an integral part of the immune system. It instructs leukocytes to migrate from the blood to a site of infection. New evidence supports that idea that coronary heart disease results from chronic arterial inflammation
What is the basis for innate immunity, and how does is relate to vertebrates? Drosophila melanogaster mutants were found that were susceptible to fungal and bacterial infections.
Innate Immunity, con’t
An apparent limitation is that parasitic agents have a generation time orders of magnitude less than that of their hosts
A second limitation is that there is only limited amplification of the response
evolved the parasite • Perhaps we should view the host-parasite interaction as a constantly
escalating war or an uneasy (metastable) truce
One view of animal phylogeny
固有免疫和适应免疫
The Triumph of Death - Pieter Brueghel the Elder ca. 1562
Why the immune system?
What is its function? How widely is it present in nature? Why does it affect so many aspects of life? How can we alter it for improved quality of life?
Mannose-binding protein Opsonization of microbes and activation of C’
C-reactive protein
Opsonization of microbes and activation of C’
Lysozyme
Bacterial cell wall lysis
Infectious Diseases: Almost any deficiency in immunity--you die
Immune Evolution
Big bugs have little bugs Upon their backs to bite ‘em Little bugs have littler bugs And so on ad infinitum -Ogden Nash, I think
How does the Immune System (IS) affect your life?
Autoimmune diseases: Graves'/hyperthyroidism, Type I diabetes, pernicious anemia, rheumatoid arthritis, thyroiditis, and vitiligo The incidence of 24 autoimmune diseases is 1/31 Americans. Women are at 2.7x greater risk Clin Immunol Immunopathol 1997 Sep;84(3):223-43