Selective igA deficiency


Published on

Published in: Health & Medicine
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide
  • Explain the pic ( there are 2 types of light chain, they differ in their C region but have same function.And there are 5 types of heavy chain, such as ……..That also differ in there C region. Antibodies that contain different type of heavy chain belong to different type of Isotype or class.antibody heavy chain is changed the main idea
  • Mature B cells that have not encountered antigen, are membrane bound IgM and IgD. After stimulation by antigen and helper T lymphocyte may expand and differentiate into progeny that secret antibodies. ( class switching couldn't occur with out T cell).Heavy chain isotype switching is induced by a combination of Cd40L mediated signal and cytokines. The defect on cytokines could lead to selective IgA deficiency, because cytokines produced by helper T cell determine heavy chain isotype.
  • The primary transcript of the arranged VDJ heavy chain gene is spliced onto the m mio messenger RNA to produce mio heavy chain and IgM antibody.Signal from helper T cells ( CD40 and cytokine ) may induce recombination of switch S region.The enzyme activation-induced deaminase ( AID ) alters nucleotides in the switch regions so that they can cleaved by other enzymes and joined to down stream switch region.The VDJ primary RNA is spliced onto the RNA from the down stream C gene, producing a heavy chian with a new constant region and a new class Ig.
  • increase in the antigen binding strength as a result of repeated stimulation by an antigen.
  • Some of the B cells that are activated by antigen, with help from T cells, migrate into follicles to form germinal center, where the go under rapid proliferation and accumulate mutation in their immunoglobulin V region. The mutation generate B cells with different affinities for the antigen. Follicular dendritic cells display the antigen, and the B cells that recognize the antigen are selected to survive. FDCs display the antigen, B cells also bind the antigen and present it to helper T cells in the germinal center. As more antibody is produced, the amount of available antigen decreases, so the B cells that are selected have to express receptors with higher affinities to bind the antigen. The B cells who recognize the antigen on FDCs or inter act with helper T cells are selected to survive. Other B cells die.
  • The enzyme AID is play an important role in somatic mutation by changing the nucleotides in the Ig genes and making them go to mutationThis mutation in the V region of the immunoglobulin genes.
  • Pentamer with 10 antigen binding site
  • primary immunodeficiency diseasThe disorder is termed "selective" because other serum immunoglobulins, such as IgM and IgG, are present at normal or increased levels. Additionally, IgA deficient persons have normal or near normal T-cell, phagocytic cell and complement system function.
  • The disorder is termed "selective" because other serum immunoglobulins, such as IgM and IgG, are present at normal or increased levels. Additionally, IgA deficient persons have normal or near normal T-cell, phagocytic cell and complement system function.
  • . The failure of B cells to terminally differentiate into IgA-secreting plasma cells may be due to the lack of effects caused by co-stimulatory molecules or cytokines such as IL-4, IL-6, IL-7, or IL-10.
  • asymptomatic, meaning that they do not experience the symptoms of the disorder until later in their life.
  • Lung function testsUrinalysisThyroid function testsKidney function testsAbsorption of nutrients in the GI tract
  • If transfusions are necessary, washed cells may be cautiously given.
  • Anapgylactic : hypersensitive due toearlier exposure to causative agent.
  • Anapgylactic : hypersensitive due toearlier exposure to causative agent.a special case of IgA deficiency which is complete IgA deficiency. Sometimes this deficiency is also associated with IgG subtype deficiency for which IVIG is given but some patients with this deficiency develop antibodies against IgA, therefore IgA is removed from the IVIG before it is given to these patients.
  • Selective igA deficiency

    1. 1. Done by : FATIMAH ALLUWAIM Group NO. : 3 Tutor : DR. DALIA ASHOR
    2. 2. Objectives • • • • • • • • • • • • • • • class switching. affinity maturation. What is immunoglobulin. IgA Definition. IgA types. Definition of Selective IgA deficiency . Types. Causes. Risk factors. Pathophysiology. Symptoms. Diagnosis. Treatment. What is the adverse reaction. The patient can take influenza vaccination and other vaccines.
    3. 3. Immunoglobulin Antibodies are substances made by the body's immune system in response to bacteria, viruses, fungus or cancer cells. Antibodies attach to the foreign substances so the immune system can destroy them.
    4. 4. class switching Isotype class switching is a biological mechanism that changes a B cell's production of antibody from one class to another. for example, from an isotype called IgM to an isotype called IgA.
    5. 5. What is the affinity maturation It is the process by witch the affinity of antibodies produced in response to protein antigen increases with prolonged or repeated exposure to that antigen.
    6. 6. Where do you think Affinity maturation occurs ?
    7. 7. • Affinity maturation occurs in the germinal centers of lymphoid follicles.
    8. 8. • Two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs: 1. somatic hypermutation. 2. clonal selection.
    9. 9. Molecular basis of affinity maturation 1. Activation of B cells and migration into germinal center. 2. B cell proliferation. 3. Somatic hypermutation of Ig genes. 4. B cell recognition of antigen on follicular dendritic cells, selection of high-affinity B cells. 5. Death of B cells that do not bind antigen. 6. Generation of memory and balsama cells.
    10. 10. Immunoglobulin A • Immunoglobulin A (IgA), as the major class of antibody present in the mucosal secretions. • represents a key first line of defense against invasion by inhaled and ingested pathogens at the vulnerable mucosal surfaces.
    11. 11. IgA Subclasses • IgA1, comprises approximately 85% of total IgA concentration in serum. IgA1 shows a good immune response to protein antigens and, to a lesser degree, to polysaccharide and lipopolysaccharides. • IgA2, representing only up to 15% of total IgA in serum, plays an important role in the mucosa of the airways, eyes, and the gastrointestinal tract to fight against polysaccharide and lipopolysaccaride antigens. It also fighting bacterial infections.
    12. 12. Secreting form
    13. 13. Selective deficiency of IgA is the most common (PIDD). Persons with this disorder have low or absent levels of a blood protein called IgA.
    14. 14. Do you know why the disorder termed “selective”
    15. 15. Classification • Severe IgA deficiency refers to serum levels below 0.7 mg/mL, which is the lower limit of detection for most assays. • Partial IgA deficiency refers to serum levels above 0.7 mg/mL, but below the lower limit of normal.
    16. 16. causes • Unknown in many cases • mutation of heavy chain constant regionin some. • IgA deficiency is could be inherited (20% of cases) , which means it is passed down through families. It may be inherited as an autosomal dominant or autosomal recessive trait.
    17. 17. PATHOPHYSIOLOGY “B lymphocytes are unable to produce Ig A”
    18. 18. Risk factor • Caucasians People have a higher risk factor, it is found in approximately 1 in 700 individual. • Family history especially if the patient has First-degree relative in this condition.
    19. 19. Symptoms (1) 85–90% of IgA-deficient individuals are asymptomatic.  The most common symptom of Selective IgA Deficiency is susceptibility to infections including: • • • • • Bronchitis. Chronic diarrhea. Conjunctivitis. Gastrointestinal inflammation. Mouth infection.
    20. 20. Symptoms (2) • • • • • • Otitis media. Pneumonia. Sinusitis. Skin infections. Upper respiratory tract infections. Bronchietasis(a disease in which the small air sacs in the lungs become damaged and enlarge). • Unexplained asthma.
    21. 21. Diagnosis Patient & family history. Quantitative immunoglobulins. Serum Immunoelectrophoresis.
    22. 22. Patient & family history • Family history of selective IgA deficiency. • Either chronic or recurrent infections, allergies, auto-immune diseases, chronic diarrhea, or some combination of these problems.
    23. 23. Quantitative immunoglobulins • rapid and accurate measurement of the amounts of the immunoglobulins M, G, and A. • tests of blood serum demonstrate absence of IgA with normal levels of the other major classes of immunoglobulins (IgG and IgM). NORMAL results of Ig M, G and A IgG 560 to 1800 mg/dL IgM 45 to 250 mg/dL IgA 100 to 400 mg/dL
    24. 24. Serum Immunoelectrophoresis • detect the presence of certain antibody. • It is used to detect if the patient have anti-IgA antibodies.
    25. 25. Complication • An autoimmune disorder such as rheumatoid arthritis. • severe, even life-threatening, reactions to transfusions of blood and blood products because they develop anti-IgA antibody .What if transfusions are necessary? • Some patients develop common variable immunodeficiency.
    26. 26. Management • patients who do not have any symptoms do not need any treatment. • prevent anaphylactic reaction secondary to blood transfusion. • treatment of associated diseases.
    27. 27. Treatment • No specific treatment is available. Some people gradually develop normal levels of IgA without treatment. • Infections should be treated with antibiotics. • Those with selective IgA deficiency who also have IgG subclass deficiencies can benefit from Intravenous immunoglobulin (IVIG).
    28. 28. Intravenous immunoglobulin (IVIG) • It is a sterile solution of concentrated antibodies extracted from healthy donors which is administered into a vein. • IVIG is used to treat disorders of the immune system or to boost immune response to serious illness.
    29. 29. The side effects for IVIG treatment (1) • People with complete IgA deficiency may develop anti-IgA antibodies if given blood products and IVIG. This may lead to allergies or lifethreatening anaphylactic shock. (These individuals can safely be given IgA-depleted IVIG if this deficiency is also associated with IgG subtype deficiency)
    30. 30. The side effects for IVIG treatment (2) • • • • Headache. dermatitis - usually peeling of the skin. infection (such as HIV or viral hepatitis). damage such as hepatitis caused directly by antibodies contained in the pooled IVIG. • acute kidney injury. • venous thrombosis.
    31. 31. Prevention There is no means of prevention of Selective IgA Deficiency. • Because IgA Deficiency does not become detectable until approximately six months of age, prenatal and neonatal detection of this disorder is currently not possible. • But genetic counseling may be of value to prospective parents with a family history of selective IgA deficiency. • Vaccines, including the pneumococcal vaccine, may be administered to prevent infections that are commonly associated with the disorder.
    32. 32. Vaccination and IgA deficiency • Local live virus vaccine, such as intranasal influenza vaccine, yellow fever vaccine and live rotavirus vaccine, should not be given to patients with IgA deficiency until their immune status is fully evaluated. • Other vaccines, such as those against pneumococcus, are specifically recommended.
    33. 33. References • • • • • • • • Basic Immunology, Abbas 3th ed. es/A/immuno-table.pdf