B Cell Defects (Humoral Immunodeficiencies)

Question 1

the adaptive immune system can be broken down into ___ and ___ processes

Answer 1

humoral and cellular lines.

Question 2

combined immunodeficiencies are aka

Answer 2

hyper IgM syndromes

Question 3

3 ways antibodies work

Answer 3

1. opsonization to induce death via phagocytosis
2. attack by complement
3. neutralize microbes (bind receptor on a virus required for cell invasion)

Question 4

agammaglobulinemia

Answer 4

abnomral B cell maturation resulting in low B cell numbers. no B cells = no antibodies

Question 5

CVID, selective antibody deficiency or hyper-igM syndromes:

Answer 5

B cells are present, but can’t make antibodies. There is a defect in the ability for B cells to produce antibodies.

Question 6

Hyper IgM syndromes, CVID has which mechanism of humoral immunodeficiencies?

Answer 6

a defect in the communication of T cells with B cells to rpdouce antibody. B cells are present and can make antibody, but can’t get the signal to do it.

Question 8

clinical presentation of someone with humoral immunodeficiency

Answer 8

clinical presentation

1. recurrent sinopulmonary infections(sinusitis, otitis media, pneumonia)
2. sepsis with diarrhea (giardia, rotavirus), meningoencephalitis
3. neutropenia and other autoimmune cytopenias
4. malignancy

Question 9

when does humoral immunodeficiency usually present?

Answer 9

after 6 months ofa ge when maternal Ab titers wane. can present in late childhood or even in adult hood (CVID)

Question 10

Normal immunoglobulin levels for healthy neonates

Answer 10

low/absent IgM and IgA,

adult level IgG by 3rd trimester.

Question 11

what is transient hypogammaglobulinemia of infancy and what care do you provide?

Answer 11

delayed maturation of the immune system that usually resolves itself by 3-5 years of age. rarely has difficulty with infections (can still produce antibodies of importance), but you still need to treat fevers and the bacterial infections more aggressively.

Question 12

most common primary immunodeficiency

Answer 12

OgA deficient: a great majority are asymptomatic but some cases have increased susceptibility to autoimmunity (celiac disease)

• normal IgG and IgM but low IgA >4 y/o

Question 13

Why should you be hesitant on giving IVIG with someone who is IgA deficient?

Answer 13

because they may have an anaphylactic reaction

Question 14

what is selective polysaccharide antibody deficiency

Answer 14

difficulty responding to polysaccharide antigens. T cell indepednet response. Other Ags recruit T cells to caoch the B cells (needs a t cell dependent response)

Question 15

what infection is someone with selectiev antibody deficiency susceptible to? how to treat?

Answer 15

streptococcus pneumoniae infections. S. pneumoniae is coated with sugars which should normally generate an antibody response. these patients cannot. there is also no response to the pneumovax vaccine.

• patients may end up requiring antibody replacement therapy (IVIG)

Question 16

name encapsulated bacteria

Answer 16

Yes, Some Killer Bacteria have nice capsules

yersinia, streptococcus, klebsiella, bacillus, haemophilus, neisseria meningitidis, cryptococcus neoformans

Question 17

ddx?

Answer 17

no tonsils = immunocompromised because this is a lymphoid tissue. If all antibodies are undetectable, he probably as agammaglobulinemia

Question 18

outline the hereditery and pathophysiology mechanism of agammaglobulinemia

Answer 18

usually X linked.

results in bruton tyrosine kinase resulting in a block in B cell maturation. Agammaglobulinemia results from an absence of mature B cells.

Question 19

this clinical presentation is most likely of:

+ no tonsils

Answer 19

agammaglobulinemia. honestly, most immunocompromised illnesses manifest with similar clinical presentation.

No B cells = barely detectably lymphatic tissue.

Question 20

hypo vs agammagloulinemia.

Answer 20

Question 21

Dx?

Answer 21

CVID: decreased levels of at least 2 Ig isotypes (in this case IgG and IgA), impaired specific antibody productioni (poor vaccine repsonses). diagnosed when all other causes of immune deficiency ruled out

Question 22

clinical presentation of CVID

Answer 22

• often with lymphoproliferation with adenopathy, splenomegaly
• may hav elymphopenia and decreased T cell function
• bacterial and ivral infections.
• most common in white people

Question 23

note;

Question 24

acquired humoral immune deficiencies

Answer 24

Question 25

investigations for humoral deficiencies

Answer 25

1. number
2. function
3. albumin and urine protein to r/o secondary causes
4. lymphocyte immunophenotyping (measures the number of T,B, NK cells by flow cytometry)

Question 26

methods of testing “do the B cells work”

Answer 26

IgGAME

titers to vaccines

Question 27

general management of humoral immunodeficiencies

Answer 27

• IVIG
• prophylactic antibiotics, and then aggressive antibiotic therapy for infections when present.
• monitoring for long term complications like chronic lung disease
• watch for autoimmune complications (CBC, liver enzymes, screening for SLE, thyroid, renal function, glucose)
• high index of suspicion for malignancy.