Immunological unresponsiveness to self is referred to as tolerance or selftolerance Very important to human health How is this achieved cells with receptors for selfantigens are destroyed in the thymus or bone marrow central tolerance ID: 935899
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Slide2Slide3Slide4Tolerance and Regulation of the Immune Response
Immunological unresponsiveness to self is referred to as
tolerance
or
self-tolerance
Very important to human health
How is this achieved?
-cells with receptors for self-antigens are destroyed in the thymus or bone marrow (central tolerance)
-self-reacting lymphocytes are made to become non-responsive (
anergy
) or induced to self destruct (peripheral tolerance)
-if this is not balanced well it leads to
autoimmunity
Slide5Tolerance and Regulation of the Immune Response
The immune system also needs to regulate the length and size of a response
Long term inflammation is destructive to the host
There is a
wealth of data
showing that chronic immune infections such as CMV and HIV result in premature aging of the immune system
Toxic shock syndrome
-high numbers of activated T cells produced
-huge amount of cytokines produced
-leads to shut down of organ systems and sometimes death
Slide6Autoimmunity
Autoimmune diseases:
-Diabetes, Rheumatoid Arthritis, Lupus, Multiple Sclerosis
Thought that regulation of the immune system is involved, not just self-reactive lymphocytes
Some genetic factors involved
-certain MHC alleles
-more women than men affected
May be triggered by infectious organisms with antigens similar to normal host antigens
Slide7Edward Jenner
(1749-1823)
&
The Discovery of
Vaccination (1796)
“
Vaccinia
(cowpox)”
&
“human smallpox”
Slide8Vaccination
A process of induction of immunity to a pathogen by
deliberate injection of a weaken, modified or related form of
the pathogen which is no longer pathogenic.
Slide9Other historic events & important findings:
L. Pasteur (1880s)
Vaccines against cholera, and rabies
R. Kock (late 19
th
century)
Infections caused by microorganisms
P. Ehrlich et al. (1890s)
Serum factors transfer of immunity
Behring & Kitasato (1890s)
Antibodies in serum bound to pathogens
Porter & Edelman (1960s)
Antibody structure
J. Gowans (1960s)
Immunological importance of lymphocytes
Slide10Measles attacks &
immunological memory
Slide11“
Memory” in adaptive immunity
1
st
infection
memory
2
nd
infection
slow response fast response
pathogen proliferate pathogen killed
disease no disease
symptoms no symptom
Slide12Slide13Immunological memory & vaccination
Natural infections:
1
st
infection
memory 2
nd
infection
slow response fast response
pathogens multiply pathogens disposed
Symptoms/
disease
no disease
Vaccination
memory nature infections
no disease fast response
pathogens disposed
no disease
Slide14Vaccination protects us from infection by inducing the adaptive immune response, but
bypassing
the need for a primary infection
Slide15Theoretical basis for immunological specificity and memory
Theory of Clonal Selection
Establishment of lymphocyte memory pool
Slide161
2
4
3
Ehrlich’s “Side-chain Hypothesis”
(1900)
Slide17Burnet’s “Clonal Selection” Theory
Each lymphocyte produces one type of Ag receptors only, antigen selects and stimulates cells carrying receptors specific for the antigen
1
n
2
2
2
2
2
2
2
Slide18s
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