Clinical Immunology

4’th Year

Lecture (1)
Introduction to Autoimmunity &
Autoimmune diseases
By
Dr. Nawfal Yassin Al-Dabbagh
M.Sc (Liverpool), Ph.D. (Glasgow),UK
Asst. Professor

2019-2020
Q) What is the difference between Immunodeficiency and
autoimmunity?
The diseases caused by disorders of the immune system fall
into two broad categories:
• Immunodeficiency, in which parts of the immune system fail to
provide an adequate response. The immunodeficiency could be
inborn or acquired defects in lymphocytes (B or T cells). The
immunodeficiency disease is a disease of impaired immunity
caused by the lack of lymphocytes, defective lymphocytes, or
destructive lymphocytes.
• autoimmunity, in which the immune system attacks its own
host's body ex. rheumatoid arthritis. 4
Autoimmune diseases:
• The cause is generally unknown.
• Some autoimmune diseases such as lupus run in families, and
certain cases may be triggered by infections or other
environmental factors.
• Some common diseases that are generally considered
autoimmune include celiac disease, diabetes mellitus type 1,
Graves' disease, inflammatory bowel disease, multiple
sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus
erythematosus.
• The diagnosis can be difficult to determine.
• Autoimmune disease may be either systemic or organ-specific.5
Signs and symptoms

• Autoimmune diseases have a wide variety of different effects.

• They do tend to have one of three characteristic pathological
effects which characterize them as autoimmune diseases:
• Damage to or destruction of tissues
• Altered organ growth
• Altered organ function

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• It has been estimated that autoimmune diseases are among the
leading causes of death among women in the United States in
all age groups up to 65 years.
• A substantial minority of the population suffers from these
diseases, which are often chronic, debilitating, and life-
threatening.
• Females are more susceptible than males especially during
child-bearing age (14-45) suggesting a possible hormonal
relationship.

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Mechanisms of Tissue Damage in Autoimmune Diseases
The tissue damage that occurs in autoimmune disease can be due to any of
the hypersensitivity reactions except type 1: as occurs in autoimmune
1- cytotoxic reactions(type II) haemolytic anaemias, Hashimoto's
thyroiditis, and Graves disease (hyperthyroidism - thyrtoxicosis)
2- immune complex deposition (typeIII) as SLE and rheumatoid arthritis
3- DHS (typeIV) by T cells as in ulcerative colitis, celiac disease, Gillian-
Barre syndrome (occurs with influenza virus and Campylobactor infection).
These diseases may be organ specific or systemic.

DHS = delayed (cell-mediated) hypersensitivity

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 Classification of Autoimmune
diseases
Organ-specific autoimmune
diseases are characterized by
immune-mediated injury
localized to a single organ or
tissue, e.g., the pancreas in type 1
diabetes and the central nervous
system in multiple sclerosis
(MS). In contrast, non-organ-
specific diseases, such as systemic
lupus erythematosus (SLE), are
characterized by immune
reactions against many different
organs and tissues, resulting in
widespread injury.
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Symptoms of Autoimmune disease

• Anxiety or depression
• Blood sugar changes
• Digestive or gastrointestinal problems
• Dizziness, Fatigue
• Elevated fever and high body temperature
• Extreme sensitivity to cold in the hands and feet
• Infertility
• Inflammation
• Irritability
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diagnostic of autoimmune diseases

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Laboratory Diagnosis of Autoimmune Diseases
1. There is elevated immunoglobulins.
2. Autoantibodies can be detected in the serum , e.g., anti- nuclear
antibody (ANA previously called ANF), anti- smooth muscles,
anti-mitochondrial antibodies, and rheumatoid factor(mainly IgM
against IgG).
3. Testing for antibodies specific to the particular antigen involved in
organ specific disease, e.g., anti-thyroid antibodies.
4. ELISA is used for identification of specific autoantibodies to
nuclear or cytoplasmic antigens of different organs specific
autoimmune diseases such as: Graves disease, insulin dependent
diabetes mellitus.
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5- Complement levels may be decreased.
6- Immunecomplexes may be detected in serum.
7- Biopsy from organs may show immune complex deposition or
lymphocyte infiltrations.
8- the indirect immunofluresence technique which uses various
tissue sections as an antigenic source is a major diagnostic test.
These antigens are recognized by autoantibodies from the patient
serum.
9- microarray based assay allows the analysis of different
autoantibodies. These autoantibodies are immobilized on a
microarray and incubated with a patient serum, the bound
antibodies are detected by a labeled secondary antibody.
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Immune complex diseases

Many diseases are associated with immune complexes deposited in

different tissues. These diseases collectively known as immune complex
diseases:
1. Auto-immune diseases as SLE, rheumatoid arthritis or myasthenia
gravis.
2. Bacterial diseases as post-streptococcal rheumatic fever,
glomerulonephritis, or subacute bacterial endocarditis.
3. Parasitic diseases as schistosomiasis, or leishmaniasis.
4. Malignancy as breast cancers or some leukaemias.
5. Other diseases as celiac disease, or crohn's disease (intestinal diseases).
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• The ANA test detects the autoantibodies present in an
individual's blood serum.
• The common tests used for detecting and quantifying ANAs are
indirect immunofluorescence and enzyme-linked immunosorbent
assay (ELISA).
• In immunofluorescence, the level of autoantibodies is reported
as a titre. This is the highest dilution of the serum at which
autoantibodies are still detectable.
• Positive autoantibody titres at a dilution equal to or greater than
1:160 are usually considered as clinically significant. Positive
titres of less than 1:160 are present in up to 20% of the healthy
population, especially the elderly. 30
 Lecture (2 )
Rheumatoid Arthritis (RA)
By

Dr. Nawfal Yassin Al-Dabbagh

M.Sc (Liverpool), Ph.D. (Glasgow),UK

Asst. Professor

2019-2020
Rheumatoid Arthritis (RA)

* Rheumatoid arthritis (RA) is autoimmune disorder in which

Immune system identifies the synovial membrane as "foreign
and begins attacking it.

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Definition

* Rheumatoid Arthritis(RA) 1s a chronic

inflammatory disorder that may affect many tissues
and organs, but mainly attacks the joints producing
an inflammatory synovitis.

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INCIDENCE of RA

• RA affects 0.5-1.0% of population in USA.

• In 2010, it is resulted in about 49000 deaths globally.

• but people of any age can be affected.

• Peak age 45-65 but onset early from age 20-45 years.

• About 75% of these are women. The disease strikes

women three times more often than men (Females >
males 3:1) 6
Rheumatoid Arthritis

• Rheumatoid arthritis is a chronic inflammatory autoimmune disease

of the joints seen commonly in young women.

• Serum and synovial fluid of patients contain "rheumatoid factor,"

ie, IgM and IgG antibodies that bind fragment of normal human IgG
Deposits of immune complexes (containing the normal IgG
and rheumatoid factor) on synovial membranes blood vessels activate
complement and _ attract polymorphonuclear cells, causing
inflammation.

• Patients have high titers of rheumatoid factor and low titers of

complement in serum during active rheumatoid disease.
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• Criteria for the diagnosis of rheumatoid arthritis
(American College of Rheumatology, 1987 revision)

• For 6 weeks or more

 Morning stiffness > 1 hour
 Arthritis of three or more joints
 Arthritis of hand joints and wrists

• Symmetrical arthritis
• Subcutaneous nodules
• A positive serum rheumatoid factor
• Typical radiological changes (erosions and/or
periarticular osteopenia)
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Diagnosis

• X Rays
• X rays of hands and feet are generally performed in people with RA.
• Magnetic Resonance Imaging (MRI)
• Ultrasounds

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Blood Tests

Rheumatoid Factor (RF)

• RF is a specific antibody in the blood.

• A negative RF does not rule out RA. The arthritis 1s then called seronegative,
most common during the first year of illness and converting to seropositive
status over time.

Anti-citrullinated Protein Antibodies (ACPAs)

• Measured as anti-ccp antibodies

• Like RF, this testing is only positive in a proportion of all RA cases.
• Unlike RF, this test is rarely found positive if RA is NOT present, giving it a
specificity of about 95%.
• It is positive in 75-85 %
• High specificity 90 % 24
Other blood tests performed when RA is suspected

 Erythrocyte Sedimentation Rate (ESR)

• The rate at which red blood cells precipitate in a | hour period.
 C-Reactive Protein
• A protein found in the blood in response to inflammation.
 Full Blood Count
• Gives information about all blood cells.
 Renal Function
• Kidney Function
 Liver Enzymes
• Gives information on the state of a patient’s liver

 Other immunological test include antinuclear antibody (ANA)

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 Lec 3
Systemic Lupus Erythematosus
Immunology
4th stage
Systemic Lupus Erythematosus

• Systemic lupus erythematosus (SLE), is the most common type of lupus.

• SLE is an autoimmune disease in which the immune system attacks its own
tissues, causing widespread inflammation and tissue damage in the
affected organs.

• It can affect the joints, skin, brain, lungs, kidneys, and blood vessels.

• There is no cure for lupus, but medical interventions and lifestyle changes
can help control it.

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How serious is SLE?

The seriousness of SLE can range from mild to life-

threatening. The disease should be treated by a doctor or a team
of doctors who specialize in care of SLE patients. People with
lupus that get proper medical care, preventive care, and
education can significantly improve function and quality of life.

What causes SLE?

The causes of SLE are unknown, but are believed to be linked

to environmental, genetic, and hormonal factors.
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Blood
Anemia is common in children with SLE and develops in about
50% of cases. Low platelet and white blood cell counts may be
due to the disease or a side effect of pharmacological treatment.
People with SLE may have an association with antiphospholipid
antibody syndrome (a_ thrombotic disorder), wherein
autoantibodies to phospholipids are present in their serum.

Another autoantibody finding in SLE is the anti-cardiolipin

antibody, which can cause a false positive test for syphilis 8
 Laboratory tests Diagnosis
• Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-
ENA) form the mainstay of serologic testing for SLE. Several techniques are used
to detect ANAS. Clinically the most widely used method is indirect
immunofluorescence (IF).

• The pattern of fluorescence suggests the type of antibody present in

the people's serum.

• Direct immunofluorescence can detect deposits of immunoglobulins

and complement proteins in the people's skin. When skin not exposed to
the sun is tested, a positive direct IF (the so-called lupus band test) is
an evidence of systemic lupus erythematosus.
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• ANA screening yields positive results in many connective tissue disorders
and other autoimmune diseases, and may occur in normal individuals.

• Subtypes of antinuclear antibodies include anti-Smith and anti- double

stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-
histone antibodies (which are linked to drug- induced lupus).

• Anti-dsDNA antibodies are highly specific for SLE; they are present in 70%
of cases, whereas they appear in only 0.5% of people without SLE.

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Summary
• A chronic disease,
• Affects 8x as many women
• Auto-immune

• Cause is unclear — potential

hormonal or genetic link

• When properly treated,

most individuals can survive
for a normal lifespan
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Most common symptoms of systemic lupus erythematosus

Systemic ---> Low-grade fever - Photosensitivity

Psychological -----> Fatigue - Loss of appetite
Mouth and nose --------> Ulcers
Face ---------> Butterfly rash
Muscles ----------> Aches
Pleura ------> Inflammation
Joints ---------- > Arthritis
Pericardium --------> Inflammation
Fingers and toes ---------> Poor circulation

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Summary (Cont..)
• Types of Lupus

• Systemic Lupus Erythematosus (SLE) : The most common type of lupus.

Any tissue in the body may be affected including the kidneys, heart, lungs,
and brain.

• Discoid Lupus Erythematosus (DLE): Affects the skin; skin develops lesions
and scales.

• Cutaneous Lupus Erythematosus : May be chronic or acute. This type may

only involve the skin or progress to involve other body systems.

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Manifestations of SLE

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