PSIO 431 FINAL
What is SCID-X1? Where is the defect located? - CORRECT ANSWER-More than half
the cases are X-linked. In the commonest of these (SCID-X1), the defect is in the gene
for the gamma chain that forms part of the receptors for IL-2 (Th1 secretes IL-2, which
helps CTL (killer T cells) get fully activated after they recognize antigen.) and other
growth factors necessary for lymphoid development, or their signaling pathways.
What is the other mode of inheritance (not X linked) for people with SCID? What is it
caused by? - CORRECT ANSWER-SCID cases are autosomal recessive. Most of these
patients lack the enzyme adenosine deaminase (ADA); adenosine accumulates in all
cells but apparently impairs lymphocyte development most severely
Where would the block be if there are normal T cells but low to absent B cells? -
CORRECT ANSWER-Bruton's agammaglobulinemia
If there are normal T cells but low to absent B cells, it may be that there is a
developmental block between the pre-B cell and the B cell. Most patients have pre-B
cells in their bone marrow but are deficient in B cells and antibody.
Where is the block if a patient has high IgM and low IgG and IgA? - CORRECT
ANSWER-X-linked hyperIgM syndrome
A rare patient will have high IgM with low IgG and IgA; in such patients there is a defect
in the IgM-to-IgG switch mechanism. The Tfh cell has an accessory molecule (CD40-
ligand) that interacts with CD40 on B cells, signaling them to switch classes ►If either
molecule is defective, the B cell is driven hard but can't be instructed to switch past
making IgM.
If B cells are not differentiating into plasma cells then what will happen? - CORRECT
ANSWER-there are normal numbers of pre-B cells and B cells, but the B cells are
difficult to trigger to make specific antibody. Serum IgG is low, at 0.5 g/dL or less.
The thymus is a two component organ. What are the two components and where do
they come from? What happens if they develop abnormally? - CORRECT ANSWER-
DiGeorge Syndrome
The lymphoid part comes from precursors in the bone marrow, as we already know; the
stroma is derived in the embryo from the endoderm and ectoderm of the 3rd and 4th
pharyngeal pouches. If these develop abnormally the stroma will not support thymic
lymphoid development, and the patient will have absent T cells with normal B cells.
What is Ataxia Telangiectasia? - CORRECT ANSWER-an autosomal recessive disease
characterized by sinus infections and pneumonia, ataxia (staggering) and telangiectasia
(dilated abnormal blood vessels). There is both T and B cell deficiency, not absolute;
IgA is especially depressed. There is also an interesting defect in DNA repair which may
partially explain the extraordinary incidence of tumors in these patients. The Wiskott-
,Aldrich syndrome is comprised of platelet and B cell deficiency, eczema, and many
bacterial infections. It is X-linked.
What are some treatments for immunodeficiency? - CORRECT ANSWER-1. Isolation =
bubbles.
2. Prophylactic antibiotics. Use these in combinations, which you change monthly
3. Human immunoglobulin, where B cell function is deficient.
4. Transplantation.
5. thymus peptides
What is SCID? - CORRECT ANSWER-If there are low numbers of T and B cells, it is as
if there is a block in the development of the lymphoid stem cell, or its further maturation.
This condition is the worst of the immunodeficiency states and is called Severe
Combined Immunodeficiency Disease, or SCID. Children with the most profound
deficiencies rarely survive beyond a year (they are to some extent protected in the
neonatal period by maternal IgG). There is lymphopenia of both T and B cells, absent
thymic shadow on X-ray, and small tonsils; serum immunoglobulins are low
What is the difference between primary and secondary immunodeficiency? - CORRECT
ANSWER-Primary immunodeficiency (congenital) means a disease with a genetic
cause, while secondary (acquired) implies that some known process outside the
immune system has caused the immunodeficiency.
What kind of cells do primary immunodeficiencies affect? - CORRECT ANSWER-These
can affect T cells or B cells selectively, or both kinds of cells. It is largely by studying the
clinical syndromes associated with immunodeficiency diseases that we know what T
and B cells are really important for in humans.
What does a a skin test with an antigen that produces good Th1-mediated immunity is
positive tell you? - CORRECT ANSWER-the patient can: process antigen in APCs,
recognize antigen, expand a T cell clone, activate T cells, secrete lymphokines, and
respond to lymphokines; which is a lot more information than can be had by measuring
CD4+ cells.
What are initial and advanced tests for people with Bcell defective immunity? -
CORRECT ANSWER-Initial
Serum protein electrophoresis
Quantitative IgG, IgA, IgM levels
Specific Abs to prior immunizations
ABO isohemagglutinins
Advanced
Ab responses to novel Ags
Sequencing of suspect genes
, What are initial and advanced tests for people with Tcell defective immunity? -
CORRECT ANSWER-Initial
Skin test with recall Ag panel
Total lymphocyte count
Advanced
CD3, CD4, CD8 counts
Mitogen responses, MLR, cytokine measurements
What are initial and advanced tests for people with phagocyte defective immunity? -
CORRECT ANSWER-Initial
WBC count, differential, morphology
NBT test, oxidative burst
Advanced
Assays for phagocytosis, chemotaxis
Genetics
What are initial and advanced tests for people with complement defective immunity? -
CORRECT ANSWER-Initial
CH50
Assay for C1inh (inhibitor)
Advanced
Individual complement component levels
What are blood group antigens? - CORRECT ANSWER-Blood group antigens are
glycolipids found on the surface of ►all body cells, including of course red cells. The
lipid backbone spans the plasma membrane, and the terminal sugars confer the
antigenic specificity, A, B or O.
What are blood group substances? - CORRECT ANSWER-Blood group substances are
glycoproteins with the same sugars, found in the body fluids of people who have the
Secretor (Se) phenotype. About 80% of people are secretors; their blood type can be
determined from sweat stains, cigarette butts, etc. There are no particular advantages
to being a secretor.
What types of disorders are people that are type O protected from? - CORRECT
ANSWER-People who are O are somewhat protected from pancreatic cancer and much
less likely to develop venous thromboembolic disorders.
What is H antigen? - CORRECT ANSWER-glycosyl transferases assemble the basic
"core" sugar chain which almost everybody hasit is called the "H" antigen
-group O people have only the basic core, the H antigen
How is the H antigen different in A, B, and AB individuals? - CORRECT ANSWER-
People who are group A have a glycosyl transferase allele which puts an
additional sugar on the H antigen, and people who are B have a different allelic form of
this enzyme which adds a different sugar. Group AB individuals have both the A and B
What is SCID-X1? Where is the defect located? - CORRECT ANSWER-More than half
the cases are X-linked. In the commonest of these (SCID-X1), the defect is in the gene
for the gamma chain that forms part of the receptors for IL-2 (Th1 secretes IL-2, which
helps CTL (killer T cells) get fully activated after they recognize antigen.) and other
growth factors necessary for lymphoid development, or their signaling pathways.
What is the other mode of inheritance (not X linked) for people with SCID? What is it
caused by? - CORRECT ANSWER-SCID cases are autosomal recessive. Most of these
patients lack the enzyme adenosine deaminase (ADA); adenosine accumulates in all
cells but apparently impairs lymphocyte development most severely
Where would the block be if there are normal T cells but low to absent B cells? -
CORRECT ANSWER-Bruton's agammaglobulinemia
If there are normal T cells but low to absent B cells, it may be that there is a
developmental block between the pre-B cell and the B cell. Most patients have pre-B
cells in their bone marrow but are deficient in B cells and antibody.
Where is the block if a patient has high IgM and low IgG and IgA? - CORRECT
ANSWER-X-linked hyperIgM syndrome
A rare patient will have high IgM with low IgG and IgA; in such patients there is a defect
in the IgM-to-IgG switch mechanism. The Tfh cell has an accessory molecule (CD40-
ligand) that interacts with CD40 on B cells, signaling them to switch classes ►If either
molecule is defective, the B cell is driven hard but can't be instructed to switch past
making IgM.
If B cells are not differentiating into plasma cells then what will happen? - CORRECT
ANSWER-there are normal numbers of pre-B cells and B cells, but the B cells are
difficult to trigger to make specific antibody. Serum IgG is low, at 0.5 g/dL or less.
The thymus is a two component organ. What are the two components and where do
they come from? What happens if they develop abnormally? - CORRECT ANSWER-
DiGeorge Syndrome
The lymphoid part comes from precursors in the bone marrow, as we already know; the
stroma is derived in the embryo from the endoderm and ectoderm of the 3rd and 4th
pharyngeal pouches. If these develop abnormally the stroma will not support thymic
lymphoid development, and the patient will have absent T cells with normal B cells.
What is Ataxia Telangiectasia? - CORRECT ANSWER-an autosomal recessive disease
characterized by sinus infections and pneumonia, ataxia (staggering) and telangiectasia
(dilated abnormal blood vessels). There is both T and B cell deficiency, not absolute;
IgA is especially depressed. There is also an interesting defect in DNA repair which may
partially explain the extraordinary incidence of tumors in these patients. The Wiskott-
,Aldrich syndrome is comprised of platelet and B cell deficiency, eczema, and many
bacterial infections. It is X-linked.
What are some treatments for immunodeficiency? - CORRECT ANSWER-1. Isolation =
bubbles.
2. Prophylactic antibiotics. Use these in combinations, which you change monthly
3. Human immunoglobulin, where B cell function is deficient.
4. Transplantation.
5. thymus peptides
What is SCID? - CORRECT ANSWER-If there are low numbers of T and B cells, it is as
if there is a block in the development of the lymphoid stem cell, or its further maturation.
This condition is the worst of the immunodeficiency states and is called Severe
Combined Immunodeficiency Disease, or SCID. Children with the most profound
deficiencies rarely survive beyond a year (they are to some extent protected in the
neonatal period by maternal IgG). There is lymphopenia of both T and B cells, absent
thymic shadow on X-ray, and small tonsils; serum immunoglobulins are low
What is the difference between primary and secondary immunodeficiency? - CORRECT
ANSWER-Primary immunodeficiency (congenital) means a disease with a genetic
cause, while secondary (acquired) implies that some known process outside the
immune system has caused the immunodeficiency.
What kind of cells do primary immunodeficiencies affect? - CORRECT ANSWER-These
can affect T cells or B cells selectively, or both kinds of cells. It is largely by studying the
clinical syndromes associated with immunodeficiency diseases that we know what T
and B cells are really important for in humans.
What does a a skin test with an antigen that produces good Th1-mediated immunity is
positive tell you? - CORRECT ANSWER-the patient can: process antigen in APCs,
recognize antigen, expand a T cell clone, activate T cells, secrete lymphokines, and
respond to lymphokines; which is a lot more information than can be had by measuring
CD4+ cells.
What are initial and advanced tests for people with Bcell defective immunity? -
CORRECT ANSWER-Initial
Serum protein electrophoresis
Quantitative IgG, IgA, IgM levels
Specific Abs to prior immunizations
ABO isohemagglutinins
Advanced
Ab responses to novel Ags
Sequencing of suspect genes
, What are initial and advanced tests for people with Tcell defective immunity? -
CORRECT ANSWER-Initial
Skin test with recall Ag panel
Total lymphocyte count
Advanced
CD3, CD4, CD8 counts
Mitogen responses, MLR, cytokine measurements
What are initial and advanced tests for people with phagocyte defective immunity? -
CORRECT ANSWER-Initial
WBC count, differential, morphology
NBT test, oxidative burst
Advanced
Assays for phagocytosis, chemotaxis
Genetics
What are initial and advanced tests for people with complement defective immunity? -
CORRECT ANSWER-Initial
CH50
Assay for C1inh (inhibitor)
Advanced
Individual complement component levels
What are blood group antigens? - CORRECT ANSWER-Blood group antigens are
glycolipids found on the surface of ►all body cells, including of course red cells. The
lipid backbone spans the plasma membrane, and the terminal sugars confer the
antigenic specificity, A, B or O.
What are blood group substances? - CORRECT ANSWER-Blood group substances are
glycoproteins with the same sugars, found in the body fluids of people who have the
Secretor (Se) phenotype. About 80% of people are secretors; their blood type can be
determined from sweat stains, cigarette butts, etc. There are no particular advantages
to being a secretor.
What types of disorders are people that are type O protected from? - CORRECT
ANSWER-People who are O are somewhat protected from pancreatic cancer and much
less likely to develop venous thromboembolic disorders.
What is H antigen? - CORRECT ANSWER-glycosyl transferases assemble the basic
"core" sugar chain which almost everybody hasit is called the "H" antigen
-group O people have only the basic core, the H antigen
How is the H antigen different in A, B, and AB individuals? - CORRECT ANSWER-
People who are group A have a glycosyl transferase allele which puts an
additional sugar on the H antigen, and people who are B have a different allelic form of
this enzyme which adds a different sugar. Group AB individuals have both the A and B
