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73 Cards in this Set
- Front
- Back
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How many billion B cells mature from the bone marrow daily? How many do not?
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30 billion. 55 billion.
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Characteristics of pro B cells
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Assemblage of the heavy chain in two steps: first DJ in early and then VDJ in late
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Characteristics of large pre-B cells
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Expression of the heavy chain for selection, with a surrogate light chain
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Characteristics of small pre-B cells
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Assembly of light chain
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Characteristics of immature B cells
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IgM expressed
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Characteristics of mature, naive B cells
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IgM and IgD expressed.
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What are the two weird genetic facts of X-linked Agammagolbulinemia
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1. No antibodies, but immunoglobulin chains are not coded on the X chromosome
2. No B cells either |
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Review: 3 main activities of antibodies
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1. Neutralization (toxins)
2. Opsonization 3. Complement activation |
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Clinical presentation of Bill Grignard
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Multiple pneumonias, low IgG, no IgA, low IgM. . . rales and no tonsils, but normal growth and development.
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What marker in the flow cytometry did Bill fail to show?
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CD19 = no b cells
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What is required for the clearance of pyogenic bacteria?
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Neutrophils
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What is the effect of chronic pyogenic infection?
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Anatomic damage (to the lungs) due to bacterial proteolytic enzymes.
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Fatal outcome of x-linked agammaglobulinemia?
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Lung disease, bronchioectasis, death.
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The 5 Cohn fractions of ethanol treated plasma
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I = fibrinogen
II = Gamma globulin III = Beta globulins (IgA, IgM) IV = alpha globulins V = albumin |
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Commerical IgG is sold as what? At what percentage can it be administered and why?
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16%. Because it will aggregate and behave like immune complexes at high percentages, the safe dose is 5% IV.
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What is the genetic defect in X-linked agammaglobulinemia?
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Xq22 codes for Btk, which is required for B cell growth, differentiation and maturation.
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Can you live without T cells? What is T cell deficiency called?
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No. SCID.
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Do B cells work in SCID?
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No, because all B cells require activation from T cells.
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Is SCID a phenotype or genotype?
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Phenotype. A number of genetic errors can cause the disease. The most common genetic error is on the X chromosome, which explains why males get the disease 3 times more than females.
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When is the thymus a mature central lymphoid organ?
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By the sixth week of gestation.
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When do mature T cells begin circulation in the fetal bloodstream?
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20 weeks of gestation.
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What is the common anatomical defect in SCID?
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There will be no mature, functioning thymus. Suggesting the defect has nothing to do with T cell formation, but maturation.
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The three categories of SCID
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1. Failure of lymphocyte survival - ADA deficiency causes fatal toxicity
2. Defects in somatic gene rearrangement - RAG genes do not code for recombinase 3. Defects in cytokine receptors necessary for T cell maturation and proliferation - IL 2 receptor |
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What is ADA?
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Adenosine deaminase
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Histological appearance of a SCID thymus
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No corticomedullary distinction
Almost no thymocytes No Hassall's corpuscles |
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General trend of cell-surface receptor expression in maturing thymocytes
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1. Double neg - neither CD4 and CD8
2. Double pos AND a T-cell receptor 3. Single pos AND a T-cell receptor --97% of thymocytes die in the double pos stage |
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What is the specific gene defect in X-Linked SCID
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A mutation in Xq11m the gamma chain of the IL-2 receptor
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Will a SCID patient have B cells?
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Yes, but they don't work.
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Do SCID patient's serum react to anti-CD3 antibodies?
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No, they have no T cells. Remember that CD3 is the complex required to hold the T-cell receptor in place.
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Do SCID patients' serum react to anti-CD16? Anti-CD20?
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CD16 is the indicator for NK cells, so yes, there should be some reaction. CD20 is B cells, and there will be B cells.
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Did baby Martin have normal levels of antibodies?
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No. His IgG was markedly low.
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Did Martin's mononuclear cells react to hemagglutinin? Any of his previously injected toxins?
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Not at all. He failed to develop an immune response to any attenuated vaccine. In fact, he had no learned immune responses to antigens at all.
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How can you test females in a family for X-linked immunodeficient disorders, whether B or T cell, to see if they are carriers?
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Think about it. One X chromosome is randomly inactivated in women's cells. But if a B or T cell inactivates the healthy X chromosome, the defective X chromosome will not permit maturation of the lymphocyte. So in a random test, it will look like ALL of the woman's cells are healthy. If you have a marker to tell the difference between either X chromosome, it will reveal ALL cells as expressing one X over the other = she's a carrier.
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How do you know Bill's T cells are working?
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Phytohemagglutinin and concanavalin A cause T cell division, along with previously inoculated antigens. If a radiolabeled thymidine is added, the relative division and uptake can be measured. His T cells were working.
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What immune defect can mimic X-linked agammaglobulinemia?
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C3 component deficiency. Opsonization will fail, and it will appear as though IgG2 is not present or working. Specifically, IgG2 is helpful against pyogenic bacteria.
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The lower the serum concentration of IgG. . .
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The longer the half-life of injected IgG, which is lucky for Bill.
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How do women present with agammaglobulinemia?
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Autosomal recessive defect in any number of components with the B-cell receptor.
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How is SCID treated?
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A bone marrow transplant depleted of donor T cells that is not rejected.
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First major indicative symptoms
of SCID? |
Oral and rectal thrush. PCP. Intractable diarrhea.
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Autosomal recessive SCID
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ADA deficiency or, rarely, purine nuceloside phosphorylase, PNP. The result are substrates toxic to T cells.
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Uncommon causes of autosomal recessive SCID
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Jak3 signaling deficiency. IL-7 receptor defects. T-cell receptor signaling cascade defects.
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Do mice with IL-2 deficiencies develop SCID?
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No, which is problematic for the assumed cause. The involvement of the gamma chain in a wide variety of other cytokine receptors may be more indicative.
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What receptor defect is most important in the development of SCID?
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IL-7. It has the same gamma chain as a variety of other receptors, including IL-2. While IL-2 deficiency will not cause SCID, IL-7 deficiency will in both humans and mice.
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Why is Martin's mother chosen for a bone marrow transplant?
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The XX karyotype was a marker for the graft, even though her cells carry the defect.
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What is chimerism?
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When a human's cells carry both XY and XX karyotypes, usually due to bone marrow transplantation.
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Why do you need to treat PCP or other infections before inducing chimerism?
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The new T cells will work, and incite a serious inflammatory response against antigens
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Will BCG kill a SCID patient?
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You bet.
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Bottom-line on live vaccines and immunodeficient patients?
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DON'T DO IT, THEY WILL LIKELY DIE.
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Review of complement cascade steps to attack complex formation
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1. C5 binds and splits, C5b stays bound
2. C6 and C7 bind, consecutively, inserting into lipid bilayer. 3. C8 binds and initiates polymer of C9 4. C9 polymer creates a channel in the membrane 5. Fluid rushes in the cell = lysis |
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What cell-surface protein inhibits complement attack in the body?
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CD59
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What bacteria is the most dangerous to complement deficient patients?
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The Neisseria family.
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What does the CH50 assay measure?
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The ability of blood to perform complement mediated hemolysis. Specifically, how much complement is needed to lyse sheep cells in an hour at physio temp.
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Deficiences in C1, C4 or C2
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Immune-complex disease, fatal
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Deficiencies in properdin, or any C5-C9
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Susceptibility to Neisseria infections
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Deficiency in C3
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Susceptibility to pyogenic infection
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HLA types linked to C2 deficiency
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HLA-B18, HLA-DR2
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Caucasian complement deficiency
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Beta chain of C8
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Black complement deficiency
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Alpha chain of C8
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How does complement kill encapsulated bacteria?
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When they divide, encapsulated bacteria are vulnerable to the attack complex
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Why do you need to treat PCP or other infections before inducing chimerism?
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The new T cells will work, and incite a serious inflammatory response against antigens
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Will BCG kill a SCID patient?
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You bet.
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Bottom-line on live vaccines and immunodeficient patients?
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DON'T DO IT, THEY WILL LIKELY DIE.
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Review of complement cascade steps to attack complex formation
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1. C5 binds and splits, C5b stays bound
2. C6 and C7 bind, consecutively, inserting into lipid bilayer. 3. C8 binds and initiates polymer of C9 4. C9 polymer creates a channel in the membrane 5. Fluid rushes in the cell = lysis |
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What cell-surface protein inhibits complement attack in the body?
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CD59
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What bacteria is the most dangerous to complement deficient patients?
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The Neisseria family.
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What does the CH50 assay measure?
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The ability of blood to perform complement mediated hemolysis. Specifically, how much complement is needed to lyse sheep cells in an hour at physio temp.
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Deficiences in C1, C4 or C2
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Immune-complex disease, fatal
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Deficiencies in properdin, or any C5-C9
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Susceptibility to Neisseria infections
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Deficiency in C3
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Susceptibility to pyogenic infection
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HLA types linked to C2 deficiency
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HLA-B18, HLA-DR2
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Caucasian complement deficiency
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Beta chain of C8
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Black complement deficiency
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Alpha chain of C8
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How does complement kill encapsulated bacteria?
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When they divide, encapsulated bacteria are vulnerable to the attack complex
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