1. Clinical Immunology Jasmina Makarevic
ATTA-UR-RAHMAN SCHOOL OF
APPLIED BIOSCIENCES (ASAB)
Clinical Immunology Jasmina Makarevic
Fall Semester 2016

2. Adaptive immunity Adaptive Immunity:
divided into humoral and cellular responses
Humoral responses result in generation of Antibodies (Immunoglobulins-Ig),
reactive with a particular antigen. Igs can be transfered passevly to another
individiual by injection of serum.
Antibody producing lymphocytes, which are dependent on the bone marrow
are known as B-cells. In response to antigene stimulation , B cells will mature
to antibody secreting plasma cells.
Cellular immunity can only be transfered by cells (Lymphoid cells).
T-cells: Thymus-dependent cells
Jasmina Makarevic

3. Humoral response Humoral and Cell-Mediated Immune Responses
The immune system distinguishes two groups of foreign substances. One group consists of antigens that are freely circulating in the body. These include molecules, viruses, and foreign cells. A second group consists of self cells that display aberrant MHC proteins. Aberrant MHC proteins can originate from antigens that have been engulfed and broken down (exogenous antigens) or from virus‐infected and tumor cells that are actively synthesizing foreign proteins (endogenous antigens). Depending on the kind of foreign invasion, two different immune responses occur:
The humoral response (or antibody‐mediated response) involves B cells that recognize antigens or pathogens that are circulating in the lymph or blood (“humor” is a medieval term for body fluid).
The response follows this chain of events:
1. Antigens bind to B cells.
2. Interleukins or helper T cells costimulate B cells. In most cases, both an antigen and a costimulator are required to activate a B cell and initiate B cell proliferation.
3. B cells proliferate and produce plasma cells. The plasma cells bear antibodies with the identical antigen specificity as the antigen receptors of the activated B cells. The antibodies are released and circulate through the body, binding to antigens.
4. B cells produce memory cells. Memory cells provide future immunity.
Jasmina Makarevic

4. Cellular-mediated response
The cell‐mediated response involves mostly T cells and responds to any cell that displays aberrant MHC markers, including cells invaded by pathogens, tumor cells, or transplanted cells. The following chain of events describes this immune response:
Self cells or APCs displaying foreign antigens bind to T cells.
2. Interleukins (secreted by APCs or helper T cells) costimulate activation of T cells.
3. If MHC‐I and endogenous antigens are displayed on the plasma membrane, T cells proliferate, producing cytotoxic T cells. Cytotoxic T cells destroy cells displaying the antigens.
4. If MHC‐II and exogenous antigens are displayed on the plasma membrane, T cells proliferate, producing helper T cells. Helper T cells release interleukins (and other cytokines), which stimulate B cells to produce antibodies that bind to the antigens and stimulate nonspecific agents (NK and macrophages) to destroy the antigens.
Jasmina Makarevic

5. Cellular-mediated response
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6. Summary
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7. Autoimmunity
Def.: is an immune response agains self-antigen or antigens
Autoimmune disease is a tissue damage or disturbed physiological
Function due to an auto-immune response.
Autoimmune disease can occure in any organ of the body.
They have been classified inter A) organ-specific and
B) non-organ specific
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8. Autoimmune diseases
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9. Mechanisms of destruction in cytopenias
Def.: Cytopenis: Reduction in the number of blood cells.
Antibodies attach to antigene on cell surface prior to phagocytosis in spleen- most common
Complement-mediated lysis following antibody binding- less common
Direct complement lysis without antibody involvement-rare
Soluble immune complexes binding via CR1 (C3b) receptors (immune adherence)
Soluble immune complexes binding via Fc receptors (innocent bystander destruction
Jasmina Makarevic

10. Common Anaemia Common Causes of Anaemia Often nutritional deficiences
are the cause for it!
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11. Hemalytic anemia Jasmina Makarevic Hemolytic anemia
Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to
body tissues.
Normally, red blood cells last for about 120 days in the body. In hemolytic anemia, red blood cells in the blood are
destroyed earlier than normal.
Causes
Hemolytic anemia occurs when the bone marrow is unable to replace the red blood cells that are being destroyed.
Immune hemolytic anemia occurs when the immune system mistakenly sees your own red blood cells as foreign substances.
Antibodies then develop against the red blood cells. These antibodies attack the red blood cells and cause them to break
down too early.
Red blood cells may be destroyed due to:
Genetic defects within the red cells (such as sickle cell anemia, thalassemia, and G6PD deficiency)
Exposure to certain chemicals, drugs, and toxins
Infections
Other causes are:
Blood clots in small blood vessels
Transfusion of blood from a donor with a blood type that does not match yours
Symptoms
You may not have symptoms if the anemia is mild. If the problem develops slowly, the first symptoms may be:
Feeling grumpy
Feeling weak or tired more often than usual, or with exercise
Headaches
Problems concentrating or thinking
If the anemia gets worse, symptoms may include:
Blue color to the whites of the eyes
Brittle nails
Light-headedness when you stand up
Pale skin color
Shortness of breath
Sore tongue
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12. At a glance: Symptoms of Hemalytic Anemia
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13. Haematological Diseases/ Mechanisme of Immune distruction
Diseases developed due to antibodies directed against components of blood!
Primary idiopatic, with no known causes
or secondary to preexisting deseases!
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14. How to diagnosis it? The screening test: Coombs‘ test, used in
Immunohematology and immunology.
The direct antiglobulin test is used to detect
These antibodies or complement proteins
That are bound to the surface of red blood cells.
A blood sample is taken and the red blood cells
Are washed and than incubated with anti-human
Globulin. If this produces agglutination of the red
blood cells the direct Commbs‘ test is positiv.
The indirect blood test is used in prenatal testing
Of pregnant women and in testing blood prior to blood
Transfusion. It detects antibodies against
red blood cells that are present unbound in the
patients serum.
Jasmina Makarevic

15. Causes of different types of anaemias
Antibodies in autoimmune haemolytic
Anaemia
Warm reactive IgG autoantibodies,
which are best detected at 37°C
Cold reactive IgM autoantibodies,
which are detected at temperatures
below 37°C
Drug provoked immune haemolytic
anaemias
Complement-activating IgG paroxysmal
cold haemoglobulinuria (a rare disorder
Of stem cells in which a muation in PIG-A
Gene results in the production of
abnormal anchor protein (GIP) in red cells,
Granylocytes and platelets.
Jasmina Makarevic

16. Mechanisms of endocrine autoimmunology
Target
Can just be detected
By specific antigen from the
Specific endocrine gland
Involved!
Evidence suggest that T-cells
And antibodies work in parallel
To produce autoimmune
Endocrine diseases.
Jasmina Makarevic

17. Thyroid disease Thyrotoxicosis is most commonly due to
Graves‘ diseases!
The presence of autoantibodies towards
Thyroid microsomal antigens confirm
an autoimmune process!
In Graveas‘ diseases almost all patients
have TSH receptor antibodies which
stimulate the thyroid cell!
Jasmina Makarevic

18. Pituitary-thyroid axis in Graves‘ disease
The autoimmune thyroid is characteristically
Infiltrated by T-Lymphocytes: both CD8+ and
CD4+ cells are present.
Jasmina Makarevic

19. Symptoms of Graves‘ disease
Exophtalmos (eye disease with
an optic nerv compression)
Pretiial myxodema: subcutaneous
thickening of the legs
Genetic factors are important
Treatment of Multiple sclerosis can
induce Graves‘ disease
Graves‘ disease can be treated
successfully y antithyroid drugs,
radioactive iodine or surgery
Jasmina Makarevic

20. Immunological mechanisms in the pathogenesis of Graves‘ Disease
Thyroid infiltration by T lymphocytes (CD4+ and CD8+) and plasma cells
The presence of circulating autoantibodies to thyroid antigens, especially the TSH receptor.
An increased risk of thyroid diease in first-degree relatives aof patients with Graves‘ disease
Association with other autoimmune diseases, including myastenia gravis, pernicious anaemia and
rheumatoid arthritis
Jasmina Makarevic

21. Hashimoto‘s thyroidis
Much more common in women than in men
Probably the most commonest cause of goitre in UK
Thyroid infiltration by T lymphocytes (both CD4+ and CD8+)
Destruction of Thyroid cells probably occurs by FAS-mediated apoptosis
Symptoms: tender enlargement of the thyroid gland, low-grad fever and general malais.
Jasmina Makarevic

22. Causes of hypothyroidism
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23. Autoimmune thyroid disease.
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24. Diabetes mellitus Diabetes is divided into:
Diabetes mellitus typ1-insulin dependent
Diabetes mellitus typ2-insulin independent
Typ I; divided into 1A: immunologically-mediated
Destruction of the ß-cells of pancreatic islets
IB: several ß-cells destruction without an
immune response
Insulin production fails in autoimmune diabetes
Because the insulin producing ß-cells are
destroid.
Stopping ß-cell destruction by
Immunsuppressive therapies:
cyclosporin or monoclonal antibodies
Jasmina Makarevic

25. Antiodies in first degree relatives
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26. Joints and muscles; Rheumatoid arthritis
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27. Features of rheumatoid arthritis
Rheumatoid nodules
Anaemia
Wight loss and fever
Entrapment neuropathology
Acelerated artherosclerosis
Infection
Osteoporosis
Jasmina Makarevic

28. Immunopathogenesis Joint destruction is driven by Macrophages!
TNF-α plays a major role!
Inhibiting this cytokine leads to
Relief in the inflammation
Process!
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29. The role of TNF-α
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30. Juvenile arthritis
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31. Featerus of rheumatic arthritis and lupus erthematosus
Def: Systematic lupus
Erythematosus is a multi-
System disorder which
Typically affects young women.
Autoantibodies to nuclear antigens.
Most comen feature: arthritis, arthralgia
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32. Nuclear Antigenes
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33. Systematic lupus erythematosous
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34. Thank You for Your Attention!
Jasmina Makarevic