MECH 430 Lecture Notes - Lecture 13: Autoimmune Disease, Cytotoxic T Cell, Rheumatoid Arthritis
9 Jun 2018
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Lecture 13
➢ Autoimmune Disease
o Due to phenomenon of autoimmunity whereby the body produces antibodies and cytotoxic T
cells that target normal body cells
o Most autoimmune diseases appear to develop spontaneously and at random
o Some common features of autoimmune disease have been noted
▪ Occur more often in older individuals
▪ More common in women than men
o About 1 in 30 (Graves’ disease, type 1 diabetes, pernicious anemia, rheumatoid arthritis,
Hashimoto’s disease and vitiligo = about 93% of affected individuals
▪ Vitiligo = depigmentation of skin; often Abs against tyrosinase (melanin synthesis)
o Most common ➔ autoimmune thyroid diseases & type I diabetes
➢ Sex Differences in autoimmunity
o There are sexual differences in terms of autoimmunity
o Diabetes is slightly more males than females who have that syndrome
o Whereas for the diseases on the left side, more women are diagnosed with them
➢ Estrogens and autoimmunity
o You immune system needs to be repressed
for implantation to occur
o Estrogen seems to be related and stimulate autoimmunities
o High levels of estrogen causes more issues
o T cell response is suppressed as long as your reproductive
system is active
o B cell issues when there is high levels of estrogen & T cell
related issues when there are low levels of estrogen
o Age-related changes in male and female
hormone and ranges for common
autoimmune diseases
o There is a significant change in the levels of
many hormones in males and females with
increasing age and specific stages of life
o Box inserts in age-range bars indicate
female:male ratios of disease
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➢ Theories to explain the etiology of autoimmunity
o T cells may encounter self-antigens that are normally “hidden” in sites
where T cells rarely go
▪ Sequestered antigens
▪ i.e. the lens, sperm & CNS
▪ sperm themselves are antigens, so if your immune system sees
the testicular tissue, an immune system will be mounted against
them → physical damage that may expose that tissue
▪ lens of eyes is not normally seen by the immune system
▪ we have a mechanism to synthesize the cells all the time to protect our body but to
protect our other cells, therefore there is usually specificity
o infections with a variety of microorganisms may trigger autoimmunity as a result of molecular
mimcry
▪ occurs when an infectious agent has an antigenic determinant that is similar or identical
to a self-antigen
▪ the body produces auto-antibodies that damage body tissues
o failure of the normal control mechanisms of the immune system → diminished suppressor T cell
function)
➢ Autoimmune diseases can be organ-specific or systemic
o There can be either organ specific of systemic autoimmune diseases
➢ Some autoimmune endocrinopathies, antigens and autoantibodies
o Read the table and learn the different diseases
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➢ Immunologically Privileged Sites
o Some parts of the body exclude immune
responses
o These are immunologically privileged sites
▪ Brain, eye, testis, uterus (fetus), hamster
cheek pouch
o Injury to immunologically privileged sites can
lead to autoimmunity
➢ Autoantibodies (IgG) can cross the placenta and
affect the fetus
o Ex: Grave’s Disease is an autoimmune form of hyperthyroidism
o Some of these antibodies can cross the fetal placental circulation and thus born hyperthyroidic
➢ Osteoimmunology
o The bone marrow is the home of the hemapoietic stem cells that give rise to all cells of the blood
o Hematopoiesis is a continuous process
▪ About 3.7x1011 white blood cells are produced per day
o Steady state is regulated by:
▪ Cytokines produced by bone marrow stromal cells & other cell types, such as activated
T-cells (paracrine action)
▪ Expression of receptors to hemapoietically active cytokines in stem cells and progenitor
cells
▪ Removal of some cells by controlled induction of cell death
(apoptosis)
▪ More than 40 cytokines have been identified
o Osteoimmunology deals with the complex interaction between bone
metabolism and the immune system
➢ The Human Lymphod System
o Blood system originate from hematopoietic stem cells in the bone
marrow where they differentiate into specialized cells
▪ Some mature in other organs (shown in red) such as the T-cells in
the thymus
o Some of our cell types mature with regards to our immune system (B
cells -Bone)
o The T cell lineages mature in the Thyroid
o However the origin are all from bone marrow
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