Humoral Immunodeficiency - B cell deficiency

Question 1

Clues from the history in primary antibody deficiency

Answer 1

1) Recurrent ear/sinus/chest infections are common (staphylococcal, streptococcal, pneumococcal, Haemophilus influenzae bacteria)
2) A second system is usually involved: skin sepsis, gut infections (enterovirus, Giardia) or meningitis
3) Infections are due to common bacteria (encapsulated bacteria)

• Fungal and viral infections are uncommon

Question 2

Encapsulated bacteria

Answer 2

· Streptococcus pneumoniae
· Haemophilus influenzae type B (B polysaccharide)
· Neisseria meningitidis

Question 3

Humoral immunodeficiencies

Answer 3

1) Transient hypogammaglobulinemia of infancy
2) Bruton’s X-linked agammaglobulinemia (XLA)
3) X-linked hyper IgM syndrome/ CD40L deficiency

Question 4

Children typically do not begin to develop severe signs of most primary humoral deficiencies until they reach the age of 6 months to 2 years. why is that?

Answer 4

because maternally acquired IgG (across the placenta) and IgA (in breast milk) protect the infant for the first year of life

Question 5

Transeint hypogammaglobulinaemia of infancy is caused by?

Answer 5

IgG lower than 97% in infants over 6 months of age (compared to infants of the same age)

* in normal infants synthesis of IgG begins at 3 months

Question 6

Transient hypogammaglobulinaemia of infancy results in?

Answer 6

increased susceptibility to recrrent pyogenic infections for months (esp. upper respiratory system infections)

Question 7

* general info for exam

Tx of Transient hypogammaglobulinaemia of infancy

Answer 7

Prophylactic antibiotics and immunoglobulin replacement can be given

Question 8

* X-linked (Bruton) agammaglobulinaemia

Defect in ———-, a tryosine kinase gene –> No B-cell maturation; X-linked recessive disorders (↑ In Boys)

Answer 8

BTK

Question 9

Defect in BTK, a tryosine kinase gene –> No B-cell maturation; X-linked recessive disorders (↑ In Boys)

immunodeficiency?

Answer 9

X-linked (Bruton) agammaglobulinaemia (XLA)

Question 10

Bruton’s disease is X-linked recessive/ dominant

Answer 10

X-linked recessive (Boys> girls)

Question 11

* Bruton’s disease

Defect in BTK, a tryosine kinase gene –>————-; X-linked recessive disorders (↑ In Boys)

Answer 11

Defect in BTK, a tryosine kinase gene –> No B-cell maturation; X-linked recessive disorders (↑ In Boys)

Question 12

CF of Bruton’s disease (X-linked agammaglobulinaemia)

Answer 12

1) Increased susceptibility to encapsulated bacteria and blood-borne viruses after 6 months (when maternal IgG drops)
2) Abscent or scanty lymph nodes

Question 13

Lab findings that diagnose Bruton’s disease

Answer 13

1) Agammaglobulinemia (Lack of all immunoglobulins)
2) Absent / low levels of circulating mature B cells (CD19)
3) NORMAL T cells
4) identification of Btk mutation

Question 14

what can you observe? what does this patient most likely have?

Answer 14

Obv: absence of B-cells in this patinet
diagnosis: Bruton’s disease

Question 15

CD40L is found where?

Answer 15

T cells
(note: CD40 on B cells bind to CD40L to become activated)

Question 16

CD40 are found where?

Answer 16

on B cells

Question 17

——— is caused by CD40L deficiency

Answer 17

X-linked hyper-IgM Syndrome

Question 18

patho of X-linked hyper-IgM syndrome

Answer 18

defect : failure of the CD40L accessory molecule on activated T cells which interacts with CD40 on B cells and DCs
(this required for APC activation and B cell activation -> immunoglobulins not formed)

Question 19

Absence of activated B cells results in?

Answer 19

1) poor organisation of GCs
2) no antibody class switch
3) lack of memory B cells
4) reduced somatic hypermutation

Question 20

lab findings of X-linked recessive Hyper-IgM syndrome (CD40L deficiency)

Answer 20

1) High to normal IgM antibodies , without or with reduced numbers of the other isotypes (IgG, IgA, IgE) [due to inability of B cells to isotype switching]
2) Normal no. of B and T cells

Question 21

Pateints w/ CD40L deficiency fail to make ——–

Answer 21

Germinal centers in the lymph nodes

Question 22

mode of inheritance of X-linked hyper-IgM syndrome (CD40L deficiency)

Answer 22

X-linked recessive
(defects in T cell function)

Question 23

Clinical presentation of X-linked Hyper-IgM Syndrome (CD40L deficiency)

Answer 23

1) increased Susceptibility to encapsulated bacteria and opportunistic pathogens (Pneumocystis jirovecii infection also associated with T cell defects such as HIV, SCID) that begins early in life
2) Development of lymphoid and other malignancies in older patients

Question 24

CD25 are?

Answer 24

IL-2 receptors
(expressed after T-cell activation)