3. 1. INTRODUCTION
‘‘A healthy immune system defends the
body against disease and infection. But if
the immune system malfunctions, it
mistakenly recognizes its own constituent
parts as non-self which allows an immune
(abnormal) response against its own cells,
tissues and organs. This phenomenon is
known as autoimmunity.’’
3
4. 1. INTRODUCTION CONT..
T cells
B cells
Complement
Immune
system
Acquired
Innate
Humoral
Cell-
mediated
4
A defect in any arm of the immune system can trigger autoimmunity.
5. IMMUNE SYSTEM MALFUNCTION
Immune system cells called T lymphocytes (T cells) use special
receptors on their surfaces to identify foreign microbes such as bacteria
and viruses. The 'self-attacking' T cells that escape destruction (by the
thymus) may be activated by a trigger. The exact triggers are unknown,
but viral infections and hormones are among the suspects. The T cells
then instruct B lymphocytes (B cells) to make antibodies against the
particular tissue, organ or system. Such antibodies are called
'autoantibodies’. The mechanisms involve molecular mimicry, abnormal
presentation or overproduction of self antigens, failure to delete auto-
reactive lymphocytes etc. 5
7. 1.A. CAUSES OF AUTOIMMUNITY
The exact causes of autoimmune disorders are not known. The risk
factors seem to include:
• Genetics – a predisposition to autoimmune disorders seems to run in
families. However, family members can be affected by different
disorders; for example, one person may have diabetes, while another
has rheumatoid arthritis.
• Gene-environment interaction – a family's susceptibility to autoimmune
disorders may be linked to common environmental factors, perhaps
working in conjunction with genetic factors e.g., gene-environment 7
8. 1.A. CAUSES CONT..
• Gender – the incidence of autoimmune diseases such as MS, lupus and
RA is higher in women than in men.
• Sex hormones – Androgens, testosterone and progesterone may
protect from autoimmune diseases; estrogen seem to protect from
rheumatoid arthritis but to be deleterious in lupus.
• Childhood poverty – researchers discovered a link between lower
socioeconomic status in childhood and rheumatoid arthritis in
adulthood.
8
9. 1.A. CAUSES CONT..
• Diet – vitamin D may be important for preventing immune dysfunction
in older populations; dietary micronutrients could either improve or
worsen lupus symptoms.
• Sunlight – exposure to UV rays from sunlight may be connected to the
development of juvenile dermatomyositis, an autoimmune disease
associated with muscle weakness and skin rashes.
• Agricultural chemicals – exposure to some pesticides may play a role in
the development of RA in male farm workers.
9
10. 1.A. CAUSES CONT..
• Organic mercury – Methylmercury, even at exposure levels generally
considered safe, may be linked to development of autoantibodies in
women of reproductive age. These antibodies could lead in turn to
autoimmune diseases such as IBD, RA and MS.
• Infection – some disorders seem to be triggered or worsened by
particular infections.
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13. 2.1. TYPE-1 DIABETES MELLITUS (T1DM)
13
The disease is characterized by an absolute deficiency of insulin
caused by an autoimmune attack i.e., infiltration of islets of Langerhans
with T cells (insulitis) which leads to gradual depletion of the β-cell
population and thus, functional β cells are low to absent.
Symptoms involve polyuria (frequent urination), polydipsia (excessive
thirst) and polyphagia (excessive hunger), often triggered by stress or an
illness. These are usually accompanied by fatigue, weight loss, and
weakness.
14. 2.1.A. NATURAL COURSE OF T1DM
I. Initiating event – Exposure to a virus or toxin (environmental factor)
may start the process of β-cell destruction in individuals with a
genetic predisposition that allows the β cells to be recognized as
“nonself’’.
II. Slow β-cell destruction – Over a period of years, this autoimmune
attack on the β cells leads to gradual depletion of the β-cell
population.
III. Clinical disease – When the insulin secretory capacity falls below a
threshold i.e., when 80–90% of the β cells have been destroyed, the 14
15. 2.1.B. DIAGNOSIS OF T1DM
The diagnosis is confirmed by a glycosylated haemoglobin
concentration ≥ 6.5 mg/dl (normal < 5.7). [Note: The rate of formation
of HbA1c is proportional to the average blood glucose concentration
over the previous 3 months.]
The diagnosis can also be confirmed by a Fasting Blood Glucose test
(FBG) ≥ 126 mg/dl (normal is 70–99). [Note: A FBG of 100–125 mg/dl is
categorized as an impaired FBG.] Fasting is defined as no caloric intake
for at least 8 hours. The diagnosis can also be made on the basis of a
non-fasting (random) blood glucose level greater than 200 mg/dl in an
individual with symptoms of hyperglycaemia.
15
16. MAJOR METABOLIC ABNORMALITIES IN T1DM
16
Absolute or relative insulin deficiency
Multiple metabolic effects
CHO metabolism
• Glucose uptake by
certain tissues (adipose
tissue & muscle)
• Glycogenolysis
• Gluconeogenesis
Lipid metabolism
• Lipolysis
• Free fatty acids in
plasma
• Hepatic production of
ketone bodies
Protein metabolism
• Protein synthesis
• Tissue protein
degradation
• Production of amino
acids
Hyperglycaemi
a
Ketoacidosi
s
21. 2.1.C. TREATMENT OF T1DM
21
Insulin therapy
Standard
treatment
Intensive
treatment
Hypoglycaem
ia
unawareness
Individuals with type 1 diabetes must rely on exogenous insulin injected
subcutaneously to control the hyperglycaemia and ketoacidosis.
22. 2.1.C. TREATMENT OF T1DM CONT..
I. Standard insulin therapy:
Standard treatment typically consists of one or two daily injections of
recombinant human insulin.
Mean blood glucose levels obtained are typically in the 225–275 mg/dl
range, with a haemoglobin A1C (HbA1c) level of 8–9% of the total
haemoglobin. [Note: Normal mean blood glucose is approximately 100
mg/dl, and HbA1c is 6% or less.]
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23. 2.1.C. TREATMENT OF T1DM CONT..
II. Intensive insulin therapy:
Intensive treatment seeks to more closely normalize blood glucose
through more frequent monitoring and subsequent injections of insulin,
typically three or more times a day.
Mean blood glucose levels of 150 mg/dl can be achieved, with HbA1c
approximately 7% of the total haemoglobin. [Note: Normal mean blood
glucose is approximately 100 mg/dl, and HbA1c is 6% or less.]
23
24. COMPLICATION OF INSULIN THERAPY
24
Hypoglycaemia
Glucagon and epinephrine
Hepatic production of glucose
as the disease progresses
Glucagon and epinephrine
secretion
Symptom-free condition known as “hypoglycaemia
unawareness”
25. 2.2. RHEUMATOID ARTHRITIS
RA is the most common form of autoimmune
arthritis. About 75% of RA patients are women. The
disease most often begins between the ages of 30
and 50. However, RA can start at any age.
Its symptoms include joint pain, stiffness, swelling
and decreased movement of the joints. Stiffness for
a long time in the morning is a clue that one may
have RA. For instance, osteoarthritis most often does
not cause prolonged morning stiffness.
25
26. 2.2.A DIAGNOSIS OF RHEUMATOID ARTHRITIS
• Examining blood test results:
Blood tests are run to look for antibodies in the blood that can been
seen in RA. If antibodies are found in people without RA, this is called a
false positive result. Blood tests are also run to look for high levels of
inflammation. Abnormal blood tests commonly seen in RA include:
Anemia (a low red blood cell count), Rheumatoid factor (an antibody, or
blood protein, found in about 80% of patients with RA in time, but in as
few as 30% at the start of arthritis)
26
27. 2.2.A DIAGNOSIS OF RA CONT..
• Elevated erythrocyte sedimentation rate (a blood test that, in most
patients with RA, confirms the amount of inflammation in the joints)
• Examining the joints and organs
• Reviewing x-ray or ultrasound images
• X-rays can help in detecting RA, but may be normal in early arthritis.
MRI and ultrasound scanning can be done to help confirm or judge the
severity of RA.
27
28. 2.2.C TREATMENT OF RA
If a person receives a diagnosis of RA, the
doctor may refer them to a specialist known as a
rheumatologist, who will advise on treatment
options. There is currently no cure for RA, but
treatment can help to:
• reduce inflammation to the joints; relieve pain
• minimize any loss of function caused by pain,
joint damage, or deformity
• slow down or prevent damage to the joints 28
29. 2.2.C TREATMENT OF RA CONT..
Treatment options include:
• Medications i.e., Nonsteroidal Anti-Inflammatory Drugs (NSAIDs),
corticosteroids
• physical therapy,
• occupational therapy and counseling,
• surgery
Medications such as NSAIDs and corticosteroids reduce pain and
inflammation and may play a role in slowing down joint damage, but
29
30. 2.2.C TREATMENT OF RA CONT..
• Disease-modifying antirheumatic drugs (DMARDs) can slow the
progression of the RA and prevent permanent damage to the joints and
other tissues by interfering with the overactive immune system. A person
usually takes a DMARD for life. Examples include leflunomide,
methotrexate, sulfasalazine, minocycline and hydroxychloroquine.
• Tumor necrosis factor-alpha inhibitors (TNF-alpha inhibitors) prevent
inflammation. They can reduce pain, morning stiffness, and swollen or
tender joints. Examples include (Enbrel), infliximab (Remicade) and
adalimumab (Humira). 30
31. 2.2.C TREATMENT OF RA CONT..
Occupational therapy
• An occupational therapist can help the individual learn new and
effective ways of carrying out daily tasks. This can minimize stress to
painful joints.
• For example, a person with painful fingers might learn to use a specially
devised gripping and grabbing tool.
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32. 2.2.C TREATMENT OF RA CONT..
If medication and physical therapy do not help, surgeries can be done
to repair damaged joints, correct deformities, reduce pain etc.
The following procedures are possible:
i. Arthroplasty: In a total joint replacement, the damaged parts are
removed and a metal and plastic prosthesis, or artificial joint is
inserted
ii. Tendon repair: loosed or ruptured tendons are restored through
surgery
iii. Arthrodesis: a bone or joint is fuse to decrease pain and realign or 32
33. 2.3 MULTIPLE SCLEROSIS
• Multiple sclerosis (MS) is a potentially disabling
disease of the brain and spinal cord (central
nervous system).
• In MS, the immune system attacks the
protective sheath (myelin) that covers nerve
fibers and causes communication problems
between your brain and the rest of your body. A
combination of genetics and environmental
factors appears to be responsible for its
progression and can cause permanent damage 33
34. 2.3.A SYMPTOMS OF MS
Multiple sclerosis signs and symptoms may differ greatly from person
to person and over the course of the disease depending on the location
of affected nerve fibers.
Symptoms often affect movement, such as Numbness or weakness in
one or more limbs that typically occurs on one side of your body at a
time, or the legs and trunk; Electric-shock sensations that occur with
certain neck movements, especially bending the neck forward; Tremor,
lack of coordination or unsteady gait
34
35. 2.3.A SYMPTOMS OF MS CONT..
• Partial or complete loss of vision, usually in one eye at a time, often with
pain during eye movement, prolonged double vision.
• Fatigue
• Dizziness
• Tingling or pain in parts of your body
• Problems with sexual, bowel and bladder function
35
36. 2.3.B. TREATMENT OF MS
Corticosteroids, such as oral prednisone and intravenous
methylprednisolone, are prescribed to reduce nerve inflammation.
Plasma exchange (plasmapheresis), the liquid portion of part of your
blood (plasma) is removed and separated from your blood cells. The
blood cells are then mixed with a protein solution (albumin) and put
back into your body.
Beta interferons, these medications are among the most commonly
prescribed medications to treat MS. They are injected under the skin or
into muscle and can reduce the frequency and severity of relapses.
36
37. 2.3.B. TREATMENT OF MS CONT..
Glatiramer acetate (Copaxone, Glatopa). This medication may help
block your immune system's attack on myelin and must be injected
beneath the skin
Fingolimod (Gilenya)
Dimethyl fumarate (Tecfidera),
Teriflunomide (Aubagio),
Siponimod (Mayzent) etc.
37
38. 2.4 CELIAC DISEASE
Celiac disease, sometimes called gluten-sensitive
enteropathy, is an immune reaction to eating gluten, a
protein found in wheat, barley and rye. Eating gluten
triggers an immune response in small intestine. Over
time, this reaction damages small intestine's lining and
prevents it from absorbing some nutrients
(malabsorption).
• The intestinal damage often causes diarrhea, fatigue,
weight loss, bloating and anemia, and can lead to
serious complications. 38
39. 2.4 GLUTEN CONTAINING FOODS
A strict, lifelong gluten-free diet is the only way to manage celiac
disease. Besides wheat, foods that contain gluten include:
• Barley
• Durum
• Farina
• Spelt (a form of wheat)
• Graham flour
• Malt
• Rye
• Semolina
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40. 2.4.A SYMPTOMS OF CELIAC DISEASE
Symptoms in Adults
Diarrhea
Fatigue
Weight loss
Bloating and gas
Abdominal pain
Nausea and vomiting
Constipation
Symptoms in Children
Nausea and vomiting
Chronic diarrhea
Swollen belly
Constipation
Gas
Pale, foul-smelling stools
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41. 2.4.A SYMPTOMS OF CELIAC DISEASE
CONT..
Digestive Problems in Adults
Anemia, usually from iron deficiency
Osteoporosis and Osteomalacia
Itchy, blistery skin rash
Mouth ulcers
Headaches and fatigue
Reduced functioning of the spleen
Digestive Problems in
Children
Failure to thrive for infants
Damage to tooth enamel
Weight loss
Anemia
Short stature
Delayed puberty
Neurological disabilities
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42. 2.4.B CAUSES OF CELIAC DISEASE
When the body's immune system overreacts to
gluten in food, the reaction damages the tiny, hair-
like projections (villi) that line the small intestine.
Villi absorb vitamins, minerals and other nutrients
from the food you eat. If your villi are damaged, you
can't get enough nutrients, no matter how much
you eat.
Sometimes celiac disease becomes active after
surgery, pregnancy, childbirth, viral infection or
42
43. 2.4.C COMPLICATIONS OF CELIAC DISEASE
Malnutrition
Bone weakening and infertility
and miscarriage (Malabsorption of
calcium and vitamin D)
Lactose intolerance: Damage to
your small intestine might cause
you abdominal pain and diarrhea
after eating or drinking dairy
products that contain lactose.
Cancer: People with celiac disease
who don't maintain a gluten-free
diet have a greater risk of
developing several forms of
cancer
Nervous system problems: Some
people with celiac disease can
develop problems such as
seizures 43
44. 2.4.D TREATMENT OF CELIAC DISEASE
A dietitian who works with people with celiac disease can help you
plan a healthy gluten-free diet. Even trace amounts of gluten in your diet
can be damaging, even if they don't cause signs or symptoms. Removing
gluten from your diet will gradually reduce inflammation in your small
intestine, causing you to feel better and eventually heal. Children tend to
heal more quickly than adults.
If anemia or nutritional deficiencies are severe, supplements are
recommended i.e. vitamin B complex, zinc etc.
Steroids that control inflammation while the intestine heals.
44
45. 3. DIAGNOSIS OF AUTOIMMUNITY
Complete blood count (CBC), a collection of tests measuring the
size, number and maturity of different blood cells in a specific
amount of blood. Two important tests are: white blood cell count
(WBC), which measures the number of white blood cells present, and
haematocrit, which measures the number of red blood cells present.
Erythrocyte sedimentation rate (ESR or sed. rate), which measures
how quickly red blood cells fall to the bottom of a test tube. If the
cells to clump together and fall more rapidly than normal, it can
signal inflammation in the body.
45
46. 3. DIAGNOSIS CONT..
Antinuclear antibody (ANA), which can detect certain abnormal
proteins called antinuclear antibodies that the immune system makes
when attacking the body's own tissues.
Rheumatoid factor (RF), which, like ANA, can detect an abnormal
protein that the immune system makes when attacking the body.
Complement, which measures the blood's level of complement, a
group of proteins that are part of the immune system. Low levels of
complement may indicate an autoimmune problem.
46
47. 3. DIAGNOSIS CONT..
C-reactive protein (CRP), which measures the amount of a special
protein made in the liver. CRP levels tend to shoot upward when there's
severe inflammation like the kind seen in autoimmune diseases
somewhere in the body.
Immunoglobulins Blood Test, which checks the amount of
certain antibodies called immunoglobulins in your body. If your
immunoglobulin level is high, it might be caused by an autoimmune
disorder that makes your immune system overreact, such as rheumatoid
arthritis, lupus, or celiac disease. 47
48. 4. TREATMENT OPTIONS FOR AUTOIMMUNE
DISEASES
Treatments can’t cure autoimmune diseases, but they can control the
overactive immune response and bring down inflammation or at least
reduce pain and inflammation. Drugs used to treat these conditions
include:
• Nonsteroidal anti-inflammatory drugs (NSAIDs) – to reduce
inflammation and pain such as ibuprofen (Motrin, Advil) and naproxen
(Naprosyn)
• Pain-killing medication – such as paracetamol and codeine
48
49. 4. TREATMENT OPTIONS CONT..
• Corticosteroids – to reduce inflammation, such as prednisone and
cortisone
• Treatment for the deficiency – for example, insulin injections in the
case of diabetes
• Cytotoxic drugs – to reduce disease activity in skin or internal organs
i.e., contain chemicals which are toxic to cells, preventing their
replication or growth
• Surgery – for example, to treat bowel blockage in the case of Crohn's
49