Autoimmune disorders occur when the immune system attacks the body's own tissues. Common autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, Graves' disease, Hashimoto's thyroiditis, and myasthenia gravis. Females are affected more often than males. The specific mechanisms that cause each disease vary and can involve autoantibodies, activation of cytotoxic T cells, or other immune responses against self-antigens. There is no cure for many autoimmune diseases, but treatment aims to reduce symptoms, inflammation, and prevent flare-ups.

1. Autoimmune disorders

2. • In an autoimmune disease or autoimmunity, the
immune system fails to display self-tolerance and
attacks the person’s own tissues.
• Autoimmune diseases usually arise in early adulthood
and are common, afflicting an estimated 5% of adults
in North America and Europe.
• Females suffer autoimmune diseases twice as often as
males.
• Recall that self-reactive B cells and T cells normally are
deleted or undergo during negative selection.

3. • A variety of mechanisms produce different autoimmune
diseases.
• Some involve production of autoantibodies, antibodies that
bind to and stimulate or block self-antigens.
• For example, autoantibodies that mimic TSH (thyroid-
stimulating hormone) are present in Graves disease and
stimulate secretion of thyroid hormones (thus producing
hyperthyroidism); autoantibodies that bind to and block
acetylcholine receptors cause the muscle weakness
characteristic of myasthenia gravis.

4. • Other autoimmune diseases involve activation of cytotoxic T
cells that destroy certain body cells.
• Examples include type 1 diabetes mellitus, in which T cells
attack the insulin-producing pancreatic beta cells, and
multiple sclerosis (MS), in which T cells attack myelin sheaths
around axons of neurons.
• Other autoimmune disorders include rheumatoid arthritis
(RA), systemic lupus erythematosus (SLE), rheumatic fever,
hemolytic and pernicious anemias, Addison’s disease,
Hashimoto’s thyroiditis, and ulcerative colitis.

5. Systemic lupus erythematosus
• Systemic lupus erythematosus or SLE, or simply lupus (lupus wolf ) is a
chronic autoimmune, inflammatory disease that affects multiple body
systems.
• Lupus is characterized by periods of active disease and remission;
symptoms range from mild to life-threatening.
• Lupus most often develops between ages 15 and 44 and is 10–15 times
more common in females than males.
• It is also 2–3 times more common in African-Americans, Hispanics, Asian-
Americans, and Native Americans than in European- Americans.
• Although the cause of SLE is not known, both a genetic predisposition to
the disease and environmental factors (infections, antibiotics, ultraviolet
light, stress, and hormones) may trigger it.
• Sex hormones appear to influence the development of SLE.
• The disorder often occurs in females who exhibit extremely low levels of
androgens.

6. Signs and symptoms
• Signs and symptoms of SLE include joint pain, muscle pain,
chest pain with deep breaths, headaches, pale or purple
fingers or toes, kidney dysfunction, low blood cell count,
nerve or brain dysfunction, slight fever, fatigue, oral ulcers,
weight loss, swelling in the legs or around the eyes, enlarged
lymph nodes and spleen, photosensitivity, rapid loss of large
amounts of scalp hair, and sometimes an eruption across the
bridge of the nose and cheeks called a “butterfly rash.”

7. • Two immunological features of SLE are excessive
activation of B cells and inappropriate production of
autoantibodies against DNA (anti-DNA antibodies)
and other components of cellular nuclei such as
histone proteins.

8. Treatment
• There is no cure for lupus, but drug therapy can minimize
symptoms, reduce inflammation, and forestall flare-ups. The
most commonly used lupus medications are pain relievers
(nonsteroidal anti-inflammatory drugs such as aspirin and
ibuprofen), antimalarial drugs (hydroxychloroquine), and
corticosteroids (prednisone and hydrocortisone).

9. Rheumatoid Arthritis
Clinical Signs:
• Symptoms include morning stiffness around the joints lasting
at least 1 hour, swelling of the soft tissue around three or
more joints
• Others include swelling of the proximal interphalangeal,
metacarpophalangeal, or wrist joints, symetric arthritis,
subcutaneous nodules, a positive RF test
• Also included is a radiographic evidence of erosion of the
joints of the hands, the wrist, or both

10. Rheumatoid Arthritis
• Usually begins with nonspecific symptoms such as fever,
malaise, weight loss, and transient joint pain
• Stiffness and joint pain that gradually improves during the day
are characteristics exhibited by most patients
• Joint are involved progressively to larger joints in a symmetric
manner from the knees, hips, elbows, shoulders and cervical
spine
• About 25% of patients have nodules over the bones
• Nodules may also be found in the myocardium, pericardium,
heart valve, pleural, lungs, spleen, and larynx

11. Rheumatoid Arthritis
Immunologic Findings:
• The main immunologic finding is the presence of RF
• RF is a 19S Ab directed against the Fc portion of IgG
• The Ab is not specific for RA as it is found in other diseases
such as scleroderma, Sjogren’s syndrome and B cell
lymphoproliferative disorders
• It has been suggested that RF may be anti-idiotypic antibodies
involved in the regulation of immune response.

12. Rheumatoid Arthritis
• Other auto Abs associated with RA include anticollagen Abs,
Abs against cytoskeleton filamentous proteins etc.
• These Abs may cause immune complex formation with the
activation of complement which contribute to pathogenesis
• Joint damage is due to invasion of inflammatory cells such as
neutrophils, and macrophages
• Proliferation of fibroblast, macrophages, mast cells, and stellar
cells result in the formation of a pannus, an organized mass of
cells that grow into the joint space

13. Rheumatoid Arthritis
Laboratory Diagnosis of Rheumatoid Arthritis:
• Diagnosis is based on a combination of clinical manifestations,
radiographic findings and lab tests
• Laboratory screening test for RF using sheep red cells or latex
particles are available and simple to perform
• Quantitative test are also available which involve
nephelometry and ELISA techniques
• RF is found in other diseases such as syphilis, viral infections,
leprosy, chronic liver disease, neoplasm and other
inflammatory processes

14. Rheumatoid Arthritis
Treatment:
• Treatment include palliatives with rest and nonsteroidal anti-
inflammatory drugs like salicylates and ibuprofen
• Slow-acting antirheumatic drugs (SAARDS) may also be used
to treat the condition
• New therapy include the use of monoclonal Abs that target T
cells

15. Hashimoto’s Thyroiditis
• Hashimoto’s thyroiditis and Graves’ disease are organ specific
autoimmune diseases
• Both diseases interfere with the thyroid gland function
• The thyroid gland located in the anterior region of the neck
consist of units called follicles
• Follicles are lined with cuboidal epithelial cells and filled with
colloid
• The primary constituent of colloid is thyroglobulin which is
made up of triiodothyronine (T3) thyroxine (T4)
• TRH acts on the pituitary gland to induce the release of TSH

16. Hashimoto’s Thyroiditis
• TSH binds to receptors on the cell membrane of the thyroid
gland causing break down of thyroglobulin into T3 and T4
• AutoAbs may interfere with this process and cause under or
overactivity of the thyroid
• Hashimoto’s thyroditis is most often seen in women between
the ages of 30 and 40 years
• Patients develop a combination of goiter or enlarged thyroid,
hypothyroidism and thyroid autoantibodies
• An association with HLA antigens DR4 and DR5 has been
noted. DQA1 and DQB1 genes seem to confer resistance

17. Hashimoto’s Thyroiditis
Immunologic Findings:
• Lymphocytic infiltration is seen with development of germinal
centers that almost replace the normal glandular architecture
of the thyroid
• Cell infiltrates include T and B cells, macrophages and plasma
cells
• Both CD4 and CD8 cells are found thus the disease is
characterized by a cellular and a humoral response
• Autoantibodies are found in up to 80% of cases

18. Hashimoto’s Thyroiditis
• Others are thyroid stimulating immunoglobulin (TSI) and
thyroid growth-stimulating immunoglobulin (TGSI)
• Peroxidase Abs can be measured by particle agglutination
assays, complement fixation, RIA and Indirect IFA
• Abs to thyroglobulin can be measured by precipitaion in agar,
indirect IFA, passive agglutination, RIA, and EIA
• Indirect IFA use human or monkey thyroid tissue fixed to a
slide
• Antithyroglobulin Abs are found in about 80% of patients with
the disease

19. Hashimoto’s Thyroiditis
Laboratory Testing:
• The autoantibodies present include Abs to thyroglobulin and
to thyroid microsomal antigen now known as thyroid
peroxidase
• Some peroxidase Abs inhibit enzyme activity while others may
mediate the cytotoxicity due to natural killer cells
• Abs to thyroglobulin help to produce hypothyroid conditions
• Other Abs include colloid Ab (CA2) thyrotropin-binding
inhibitory immunoglobulin (TBII)

20. Hashimoto’s Thyroiditis
• Others are thyroid stimulating immunoglobulin (TSI) and
thyroid growth-stimulating immunoglobulin (TGSI)
• Peroxidase Abs can be measured by particle agglutination
assays, complement fixation, RIA and Indirect IFA
• Abs to thyroglobulin can be measured by precipitation in agar,
passive agglutination, RIA, and EIA
• Indirect IFA use human or monkey thyroid tissue fixed to a
slide
• Antithyroglobulin Abs are found in about 80% of patients with
the disease

21. Graves’ Disease
• Graves’ disease is another autoimmune disease that affects
the thyroid gland
• Graves’ disease produces hyperthyroidism
• It the most common cause of hyperthyroidism and affects
about 0.5% of the population
• Women are more susceptible than men by a margin of 7:1
and usually present between the ages of 30 and 40.

22. Graves’ Disease
Clinical Signs:
• Disease is presented as thyrotoxicosis with a diffusely
enlarged goiter that is soft instead of rubbery
• Signs include nervousness, insomnia, depression, weight loss,
heat intolerance, sweating, rapid heart beat
• Other signs include fatigue, cardiac dysrhythmias,
restlessness, and exopthalmus

23. Graves’ Disease
Immunologic Findings:
• The thyroid presents with Hyperplasia with a patchy
infiltration of lymphocytes
• Both CD4 and CD8 cells are present and the T cells appear to
play a central role in the pathogenesis of the disease
• The most significant Ab present is thyroid stimulating
hormone receptor antibody (TRab)
• Ag-Ab combination result in the stimulation of the receptor
resulting in the release of the thyroid hormones
• Another group of Abs called thyroid stimulating antibodies or
immunoglobulins (TSab or TSI) may have different specificity

24. Graves’ Disease
Laboratory Diagnosis:
• A key finding in Graves’ disease is elevated levels of total and
free T3 and T4
• In addition, TSH levels are low due to Ab stimulation of the
thyroid
• Measurement of the thyroid Abs may be undertaken if the
above assays are unclear
• Treatment:
• Antithyroid medication may be employed. Radioiodine which
emits beta particles may be used. Surgery is also an option.

25. Insulin-Dependent Diabetes
• This disease is characterized by insufficient production of
insulin due to an autoimmune destruction of the beta cells of
the pancreas
• Peak onset is b/w 10 and 14 years of age
• Disease may be attributed to genetic and environmental
conditions
• About 95% of white diabetics carry the HLA-DR3 or DR4 genes
• It appears that true susceptibility genes for IDDM may occur
in the HLA-DQ region

26. Insulin-Dependent Diabetes
• Viral infections have been linked with diabetes
• Mumps virus, rubella virus, and Coxsakie B4 virus have all
been inconclusively linked to diabetes
• Congenital rubella infection is the only one for which a link
has been definitively identified
• There appears to be similarity between coxsakie viral protein
P2-C and the enzyme glutamic acid decarboxylase.
• Antibodies are formed against glutamic acid decarboxylase in
IDDM
• Molecular mimicry could initiate Ab production against self Ag

27. Insulin-Dependent Diabetes
Immunopathology:
• Inflammation of the islets of Langerhans in the pancreas leads
to fibrosis and destruction of most of the beta cells
• CD4 and CD8 B cells and macrophages are all involved in the
destructive process of the islet cells
• Cellular and humoral immunity are involved in this process
• The subset of T cells that is activated determines whether the
response is cellular or humoral

28. Insulin-Dependent Diabetes
Laboratory Testing:
• IDDM is usually diagnosed by the presence of hyperglycemia
• Abs to islet cells may be screened for by indirect IFA with
human or rat islet cells
• Islet cell may be detected in the sera of newly diagnosed
diabetic cases
• Abs to insulin may be detected by ELISA or RIA methods

29. Insulin-Dependent Diabetes
Treatment:
• Insulin has been the standard form of treatment
• New treatment methods center around the use of
immunosuppressive agents
• Agents that have been tried include azathioprine,
cyclosporine A and prednisone
• All these agents have potentially toxic effects

30. Multiple Sclerosis
• Destruction of the myelin sheath results in the formation of
lesions known as plaques in the white matter of the brain and
spinal cord
• Genetic and environmental factors predispose one to this
disease
• MS is associated with the inheritance of HLA antigen DRw15
and DRw6
• An inflammatory response to bacteria or virus may trigger the
autoimmune process
• Disease is most often seen in those b/w the ages of 20 & 50
and is more common in women

31. Multiple Sclerosis
• 90% of patients alternate between remissions and relapses
for many years
• Within the plaques, CD4 cells, plasma cells and macrophages
are found along with immunoglobulin
• Immunoglobulin is increased in the spinal fluid in 60 to 80% of
patients
• They usually produce oligoclonal bands on protein
electrophoresis
• RIA is used to detect the Abs
• Therapy include use of corticosteroids

32. Myasthenia Gravis
• Symptoms of disease include facial weakness, difficulty in
chewing, and swallowing, difficulty breathing
• Others include inability to maintain support of the trunk, the
neck or the head
• Antibody mediated damage to the acetylcholine receptors in
the skeletal muscle leads to muscle weakness
• May be associated with the presence of other autoimmune
diseases such as SLE
• Appears to be linked with either HLA-B8 or DRw3 antigens

33. Myasthenia Gravis
• 80 to 90% of patients have Abs to acetylcholine receptors
which may be the main contributor to pathogenesis
• Combination of the Abs to the receptors blocks the binding of
acetylcholine which destroy the receptors
• Abs can be detected with RIA methods
• Anticholinesterase agents are employed in therapy

34. Goodpasture’s Syndrome
• Goodpasture’s syndrome is a glomerulonephritis due to Abs
reacting specifically with Ags in the kidney
• Necrosis of the glomerulus is triggered by an Ab that reacts
with glycoprotein present in the basement membrane of the
glomerulus
• Results in immune complex deposit and complement fixation
which causes the damage to the kidney
• This may eventually produce renal failure

35. Severe Combined Immunodefi ciency
(SCID)
• The most extreme forms of CID make up a
family of disorders termed severe combined
immunodefi ciency (SCID).
• The four general categories of events that
have been found to result in SCID include the
following:

36. 1. Defective cytokine signaling in T-cell precursors,
caused by mutations in certain cytokines, cytokine
receptors, or regulatory molecules that control their
expression
2. Premature death of the lymphoid lineage due to
accumulation of toxic metabolites, caused by defects in
the purine metabolism pathways
3. Defective V(D)J rearrangement in developing
lymphocytes, caused by mutations in the genes for RAG1
and RAG2, or other proteins involved in the
rearrangement process
4. Disruptions in pre-TCR or TCR signaling during
development, caused by mutations in tyrosine kinases,
adapter molecules, downstream messengers, or
transcription factors involved in TCR signaling.

37. • Depending on the underlying genetic defect, an
individual with SCID may have a loss of only T cells (TB)
or both T and B cells (TB). In either case, both cellular
and humoral immunity are either severely depressed
or absent.
• Clinically, SCID is characterized by a very low number of
circulating lymphocytes and a failure to mount immune
responses mediated by T cells.
• In many cases, the thymus will not fully develop
without a suffi cient number of T cells, and the few
circulating T cells present in some SCID patientsoft en
do not respond to stimulation by mitogens, indicating
that they cannot proliferate in response to antigens.
• In many cases, myeloid and erythroid cells (red-blood-
cell precursors) appear normal in number and function,
indicating that only lymphoid cells are aff ected.

38. • Infants born with SCID experience severe
recurrent infections that, without early,
aggressive treatment, can quickly prove fatal.
• Infants with SCID oft en suffer from chronic
diarrhea, recurrent respiratory infections, and
a general failure to thrive.
• The life span of these children can be
prolonged by preventing contact with all
potentially harmful microorganisms.

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