2. Group 13 has created this presentation with the aim of
sensitising others about autoimmune diseases. Autoimmune diseases
are not as rare as the name suggests, so it its important that we
know about the signs/symptoms, causes, diagnoses, and treatment
methods. Do Learn and Enjoy!
3. Autoimmunity is an immune reaction against self- antigens
which evokes the production of humoral mediated (autoantibodies),
cell mediated (self reactive T cells) or complement mediated
immunity. Autoimmunity can cause serious damage and loss of
function to self organs and tissues leading to autoimmune diseases.
Organ specific autoimmune diseases affect tissues of
4. 5 % to 7% adult affected. Two third women. More than 40
human diseases autoimmune in origin.
5. Hashimotos Thyroiditis- The body produces autoantibodies and
TDTH cells against thyroid antigens leading to enlarged thyroid
gland, goitre and hyperthyroidism. Pernicious Anaemia Results from
defective red blood cell maturation due to inept B12 uptake. The
body produces autoantibodies against intrinsic factor which is
needed for B12 transport and uptake. Symptoms: loss of
appetite,
6. Pictures of Diseases
7. Autoimmune Haemolytic anaemia AHA. The body makes antibodies
(IgG/IgM) against a variety of RBC antigens which results in the
destruction or removal of blood cells. Drug Induced Haemolytic
Anaemia. Occurs when a drug causes the bodys immune system to react
against its own red blood cells. Thrombocytopenic Purpura. It is a
life-threatening disorder that results from the destruction of
platelets by autoantibodies. Phagocytes in the liver and spleen
endocytised antibody coated platelets.
8. Goodpasture Syndrome. A rare autoimmune disease of the lungs
and kidneys which involve the production of autoantibodies against
basal membrane of the alveoli and glomeruli. Symptoms include
kidney and pulmonary damage, glomerulonephritis, pulmonary
haemorrhage. Insulin Dependent Diabetes Mellitus Type I Diabetes.
This disease is caused by a directed attack on the insulinproducing
cell -cells in the pancreas by antibody dependent cytotoxicity,
resulting in decreased production of insulin.
9. Graves Disease. This disease arises from the binding of
autoantibodies to the TSH (thyroid stimulating hormone) receptors
resulting in an overproduction of thyroxine. Symptoms include
bulging eyes, hyperthyroidism, increased sweating, palpitation,
heat intolerance. Myasthenia Gravis. A chronic autoimmune disease
resulting from faulty neuromuscular transmission. The body produces
autoantibodies (IgG isotype) which bind to acetylcholine receptors
in the neuromuscular junction thereby blocking Ach which is needed
to stimulate muscle contraction.
10. Systemic Lupus Erythematosus- Lupus is a conditioned
characterised by chronic inflammation of body tissues that affects
mainly women. The body produces autoantibodies against a variety of
antigens like RBC, mitochondrion, lysosomes, and other common cell
organelles. The ratio of female to male patients is 10:1. It occurs
more frequently in Black and Hispanic women than Caucasian women.
Symptoms: erythrematosus skin rashes, glomerulinephritis,
11. Characteristic butterfly rash over the cheeks of a young
girl with lupus[From L. Steinman, 1993, Sci. Am. 269(3):80.]
12. Rheumatoid Arthritis RA. RA is a chronic inflammatory
disease affecting the synovial joints; mainly in middle aged women.
The inflamed synovial membrane is surrounded by inflammatory cells
which destroy the cartilage and bone of the joints. Symptoms are:
weight loss, fever, fatigue. Multiple Sclerosis MS. This disease
affects the central nervous system. It characterised by the
presence of scleroses (scar tissue) in the white matter of neurons,
as a result of the response autoreactive T lymphocytes. Symptoms
include: motor weakness, paralysis in limbs, ataxia, urinary
dysfunction, mental aberration.
13. Sceleroderma- characterised by the deposition of excess
collagen in the connecting tissues which results in the thickening
of the skin and gradual skin lightening. The patient develops CREST
syndrome - calcinosis (excess calcium deposition), Reynaulds
phenomenon (abnormal blood flow in response to stress or cold),
eosophageal dysfunction (difficulty swallowing), scelerodactyl
(tightening scaly skin) and telangiectasia (red spots on skin).
Organs affected includes the skin, kidney, heart, lungs, GI tract,
and joints. Guillian Barre Syndrome. This disease commonly occurs
after an infectious disease or after vaccination. The disease
arises from the antibody-mediated and T-cell mediated damage
against nerve tissues
14. Autoimmunity can be induced in animals in order to carry
out experiments and treatment trials with the autoimmune disease.
Animal models are used to clarify possible causes, mechanisms and
treatment of autoimmune diseases, as some animals develop
autoimmune diseases which share significant features with that of
their human counterparts.
15. pics
16. Obese strain chicken. The OS chicken has a thyroid
condition in which thyroid autoantibodies spontaneously occur which
results in gradual destruction of the thyroid which resembles that
of Hashimotos thyroiditis in human. Experiments on OS chicken have
helped to elucidate the roles of B lymphocytes and T lymphocytes in
this autoimmune disease; these were found to play significant roles
in the development of the disease. Non obese diabetic (NOD) mouse.
NOD mouse shares key features with human insulin-dependent diabetes
mellitus (IDDM). In both cases, the pancreatic -islet of the
Langerhans are destroyed by lymphocytes. Experiments on NOD mouse
found that T cells play the decisive role in IDDM. The experimental
autoimmune encephalomyelitis rat/mouse is the model animal for
multiple sclerosis. When injected with myelin basic protiens or
proteolipids, the rodent
17. In essence, autoimmunity arises from defects in self-
tolerance mechanisms and abnormalities in cellmediated and
antibody-mediated immunity. Self-tolerance mechanism failure to
produce autoantibodies against self-antigens because: 1) clonal
deletion of self-reactive cells, 2) tolerance of TH and B cells to
self-antigens, 3) clonal ignorance whereby selfreactive lymphocytes
remain dormant.
18. Some viruses and bacterial antigens can act as poly-clonal
activators that activate self-reactive B cells which leads to
tissue damages and diseases. Molecular mimicry by cross-reactive
microbial antigens. This describes a condition where surface
antigens on microbes resemble self-antigens of the body. This
results in an immune assault against the microbial antigens and the
self-antigens which they resemble. Availability of sequestered
(isolated) self-antigens. Antigens which have been isolated from
the immune system during embryonic stages become exposed during
injury or trauma. These sequestered antigens may be released and
exposed to immune cells which lack self-tolerance leading to the
development of an autoimmune response. Aberrant (Unusual)
Expression of MHC Class II Molecules. This occurs when MHC class II
proteins are expressed on non-immune cells, self-antigens presented
by them will activate TH cells which in turn activate cell-mediated
immunity and humoral immunity against the selfantigens
19. Currently, autoimmune responses and diseases are treated
via chemotherapeutic methods and organ ablation. Organ ablation is
the removal of the affected organ, in some cases followed by organ
transplant. Treatments are mainly aimed at suppressing an
autoimmune response with the use immunosuppressive drugs, cytotoxic
drugs, plasmapheresis, and organ ablation (removal of a target
organ is indispensable.)
20. Non-steroidal anti-inflammatory drugs mitigate
inflammations by slowing migration of lymphocytes; Cytotoxic drugs
inhibit the antigen-activated T- cells; Plasmapheresis is the
exchange of the affected persons plasma containing autoantibodies
with plasma containing normal antibodies.
21. Immunosuppression (e.g., prednisone, cyclosporin A) Removal
of thymus (some MG patients) Plasmapheresis (remove Ab-Ag
complexes) T-cell vaccination (activate suppressing T cells??)
Block MHC with similar peptide anti-CD4 monoclonal Ab anti-IL2R
monoclonal Ab
22. Main Thesis: Research is being done on model animals in
order to develop alternative ways aimed at inducing tolerance to
the specific selfantigens, or removing self-reactive B and T
lymphocytes. Tolerance Induction. This is achieved by the oral
administration of the self-antigen, which elicits the autoimmune
response, into the body. This method attempts to reintroduce
specific immunity toward self-antigens
23. Monoclonal Antibody Against Autoantigens. Monoclonal
antibodies bind to cells bearing the specific antigens which leads
to the blocking or destruction of the cell. However, the removal of
the irritating antigen does not activate the production of
autoantibodies. Blockage of MHC Molecules. Blocking peptides, which
have a different amino acid sequence from the antigen, are made to
bind to the antigen-binding cleft on the MHC class II molecules.
This prevents MHC class II from binding to the antigens and thereby
autoimmune response. Induction of T-cell suppression. In the case
of the EAE mouse, the administration of low doses of MBP-specific T
cells immunized the mice so that when low doses of MBP is
introduced the mice did not develop encephalitis.
24. Role of MHC. MHC class II molecules are more associated
with autoimmunity because MHC class II are involved in the
selection and activation of TH. TH cells in turn mediate the
activation humoral and cell-mediated immune responses for both
normal immunity and autoimmunity. Role of TH cells in autoimmunity.
Abnormalities in TH cells may lead to the production autoantibodies
because TH are necessary for the production of antibodies. Role of
T-cell receptors autoimmunity. T-cells obtained from patients with
MS and myasthenia gravis show a preferential expression of the TCR
variable gene in the self-reactive T-cells. The absence of the
CTLA-4 gene which codes for CTLA-4 receptor that inhibits
autoimmune response can result in fatal autoimmune response and
massive tissue damage
25. The important genes that regulate the development of
autoimmunity are located within MHC. MHC have got critical role in
maturation of T cell & induction of IR . MHC II genes are
directly responsible for auto antigen processing and presentation.
The structure of Ag binding groove will determine , if specific Ag
will trigger an AU response.
26. REFERENCES Kindt, Thomas. Barbara Osbourne. Richard
Goldsby.Kuby Immunology. (2006).6th Edition. Pearson Education, New
York. Tortora, Gerard. Berdell Funke. Christine Chase.
Microbiology: An introduction. (2010). 10th Edition. Benjamin
Cummings, New York. Kahn, Fahim. Elements of Immunology. (2009).
First Edition. Pearson, New York.