Immunodeficiency

Question 1

Bruton agammaglobulinemia was the first

Answer 1

primary immunodeficiency disease to be described.

Question 2

In 1952, Colonel Ogden Bruton noted the absence of

Answer 2

immunoglobulins in a boy with a history of pneumonias and other bacterial infections.
Dr Bruton was also the first physician to provide specific immunotherapy for this X-linked disorder by administering intramuscular injections of immunoglobulin G (IgG).

Question 3

Primary or congenital immunodeficiencies: are

Answer 3

genetic defects that result in an increased susceptibility to infection

Question 4

Primary or congenital immunodeficiencies: is frequently manifested in

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infancy and childhood.

Question 5

Primary or congenital immunodeficiencies: such diseases affect about

Answer 5

1 in 500 people in the United States

Question 6

Secondary or acquired immunodeficiencies

develop as a consequence of

Answer 6

malnutrition,
disseminated cancer,
treatment with immunosuppressive drugs, or
infection of cells of the immune system.

Question 7

Integrity of the immune system is essential for defense against

Answer 7

nfectious organisms and their toxic products. Thus, the immune system is important for our survival!!!

Question 8

Toll-Like Receptors are conserved across

Answer 8

widely diverse species!!!

Any loss-of-function mutation affecting a TLR has negative consequences for survival

Question 9

Primary (or genetically determined) immunodeficiency disorders may

Answer 9

affect one or more components of the immune system, including T-, B-lymphocytes, and Natural Killer cells, as well as phagocytic cells and complement proteins.

Question 10

Immunodeficiencies may result from

Answer 10

defects in leukocyte maturation or activation or from defects in effector mechanisms of innate and adaptive immunity.

Question 11

The principal consequence of an immuno-deficiency is an increased susceptibility to

Answer 11

infection:

Question 12

The nature of the infection in a particular patient depends largely on

Answer 12

the component of the immune system that is defective.

Question 13

In other words, the types of recurring infections can predict the

Answer 13

type of immunodeficiency.

Question 14

Deficient humoral immunity usually results in

Answer 14

increased susceptibility to infection by pyogenic bacteria.

Question 15

X-linked Agammaglobulinemia - XLA(also known as Bruton’s Agammaglobulinemia)

All Antibody Isotypes are

Answer 15

very low – not even IgM or IgD

Question 16

X-linked Agammaglobulinemia - XLA(also known as Bruton’s Agammaglobulinemia):

Circulating B cells are usually

Answer 16

absent.

Question 17

X-linked Agammaglobulinemia - XLA(also known as Bruton’s Agammaglobulinemia):

Pre-B cells are present in

Answer 17

reduced numbers in the bone marrow.

Question 18

X-linked Agammaglobulinemia - XLA(also known as Bruton’s Agammaglobulinemia):

Tonsils are usually very

Answer 18

small and lymph nodes are rarely palpable due to absence of germinal centers.

Question 19

X-linked Agammaglobulinemia - XLA(also known as Bruton’s Agammaglobulinemia):

Thymus architecture is

Answer 19

normal, as are the T cell-dependent areas of spleen and lymph nodes.

Question 20

X-linked Agammaglobulinemia - XLA(also known as Bruton’s Agammaglobulinemia): Most boys afflicted with X-linked agammaglobulinemia (XLA) remain

Answer 20

well during the first 6 to 9 months of life by virtue of maternally transmitted IgG antibodies. Thereafter, they repeatedly acquire infections with extracellular pyogenic organisms such as pneumococci, streptococci, and haemophilus

Question 21

X-linked Agammaglobulinemia

Answer 21

1) Circulating B cells are usually absent. 2) Pre-B cells are present in reduced numbers in the bone marrow

Question 22

The defect in this disease is associated with a loss of function of

Answer 22

Bruton Tyrosine Kinase that is important for pre-B cell expansion and maturation into Ig-expressing B cells

Question 23

X-linked immunodeficiency with hyper-IgM is characterized by

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very low serum IgG, IgA, and IgE

a markedly elevated concentration of polyclonal IgM

Question 24

Like boys with XLA, patients with hyper-IgM may become

Answer 24

symptomatic during the first or second year of life with recurrent pyogenic infections

These include otitis media, sinusitis, pneumonia, and tonsillitis.

Question 25

In contrast to patients with XLA, however, hyper-IgM patients have

Answer 25

lymphoid hyperplasia.

Question 26

X-linked immunodeficiency with hyper-IgM: The defect in this disease is associated with a loss of function of

Answer 26

CD40 ligand (aka CD154) that is expressed on helper T cells. The loss of this molecule prevents the T cell from co-stimulating antigen-specific B cells (through CD40). Thus, B cells are not signaled by the T cell to go through isotype switching and only produce IgM.

Question 27

Immunodeficiency Treatment is routine --

Answer 27

prophylactic antibiotics and/or gamma-globulin therapy. | Dr. Ogden Bruton pioneered this therapy.

Question 28

Deficient cell-mediated immunity usually results in

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increased susceptibility to viruses and other intracellular pathogens.

Question 29

Whereas treatment of deficiencies of the humoral immune response may be routine, there are few if any treatments for

Answer 29

defects associated with deficient T cell responses.

Question 30

In fact, it is rare that patients with absolute defects in

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T-cell function survive beyond infancy or childhood.

Question 31

DiGeorge’s syndrome : This is a developmentally-related disease associated with

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tissue morphogenesis -- the thymus does not develop.

Question 32

DiGeorge’s syndrome: Thymic hypoplasia results from defects in

Answer 32

morphogenesis of the third and fourth pharyngeal pouches during early embryogenesis, Other structures forming at the same age are also frequently affected, resulting in anomalies of the great vessels (right-sided aortic arch), esophageal atresia, bifid uvula, upper limb malformations, congenital heart disease (atrial and ventricular septal defects), a short philtrum of the upper lip, hypertelorism, an antimongoloid slant to the eyes, mandibular hypoplasia, and low-set, often notched ears.

Question 33

DiGeorge’s syndrome: Immunologically speaking, the percentage of T cells is variably

Answer 33

decreased; as a result, there is a relative increase in the percentage of B cells. B-cell function is impaired only to the extent of needing helper T cells.

Question 34

DiGeorge’s syndrome: Most infants die from

Answer 34

infections, cardiovascular defects or seizures within the first few months or second year of life. Patients who survive infancy are usually mentally retarded. There are clinical similarities between DiGeorge’s syndrome and fetal alcohol syndrome.

Question 35

X-linked Recessive Severe Combined Immunodeficiency Disease: Severe combined immunodeficiency is a

Answer 35

rare, fatal syndrome characterized by profound deficiencies of T- and B-cell function.

Question 36

X-linked Recessive Severe Combined Immunodeficiency Disease: X-linked SCID (XSCID) is the most

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common form, accounting for approximately 42% of cases.

Question 37

X-linked Recessive Severe Combined Immunodeficiency Disease: Affected infants present within the first few months of life with frequent episodes of

Answer 37

diarrhea, pneumonia, otitis, sepsis, and cutaneous infections.

Question 38

X-linked Recessive Severe Combined Immunodeficiency Disease: Growth may appear normal initially, but extreme wasting usually develops after

Answer 38

infections and diarrhea begin.

Question 39

X-linked Recessive Severe Combined Immunodeficiency Disease : Persistent infections with

Answer 39

opportunistic organisms | Candida albicans, Pneumocystis carinii, varicella, measles, parainfluenzae, cytomegalovirus, and EBV.

Question 40

X-linked Recessive Severe Combined Immunodeficiency Disease : These infants also lack the ability to reject

Answer 40

foreign tissue and are therefore at risk for GVHD. | GVHD can result from maternal T cells that cross into the fetal circulation while the SCID infant is in utero.

Question 41

X-linked Recessive Severe Combined Immunodeficiency Disease: XSCID patients have few or no

Answer 41

T cells, and NK cells

Question 42

X-linked Recessive Severe Combined Immunodeficiency Disease: Patients with XSCID usually have

Answer 42

elevated percentages of B cells. However, these B cells do not produce immunoglobulin normally, even after T-cell reconstitution by bone marrow transplantation.

Question 43

Secondary or acquired immunodeficiencies | develop as a consequence of

Answer 43

malnutrition, disseminated cancer, treatment with immunosuppressive drugs, or infection of cells of the immune system.

Question 44

Treatment of Immunodeficiencies

Answer 44

Current treatments of immunodeficiences have two aims – 1. to minimize and control infections and 2. to replace the defective or absent components of the immune system by adoptive transfer and/or transplantation. Passive immunization with pooled gamma globulin is enormously valuable for agammaglobulinemic parients and has been life saving for many with this disease. Bone marrow transplantation is currently the treatment of choice for various immunodeficiency diseases and has been successful in the treatment of SCID and other similar diseases.