Immunodeficiency

Question 1

When should immune evaluation be considered?

Answer 1

two or more invasive bacterial infections, persistent or recurrent sinopulmonary infections, unusual etiologic agents or unusual severity of common infection

Question 2

What are some physical examination findings that may indicate immunodeficiency?

Answer 2

less growth/development, enlarged/absent tonsils, nodes, liver, spleen, thrush, rash

Question 3

What are the four limbs of the immune system?

Answer 3

cellular immunity, humoral immunity, complement, phagocytes

Question 4

What is the most common immunodeficiency?

Answer 4

selective IgA deficiency, can be asymptomatic

Question 5

What is severe combined immunodeficiency? What is the prognosis? (SCID)

Answer 5

no T cells or B cells, early death without BM transplant

Question 6

What causes SCID?

Answer 6

IL-2 gamma chain defect

Question 7

Why does a IL-2 gamma chain defect cause immunodeficiency?

Answer 7

IL-2 gamma chain is the critical signal transduction component of the IL-2 receptor

Question 8

What signals can no longer be processed if there is an IL-2 gamma chain defect?

Answer 8

B-cell maturation, NK cell development, hematopoises, T-cell development, class-switch, peripheral T cell homeostasis signals

Question 9

How can you diagnose SCID?

Answer 9

lymphopenia, analysis of lymphocyte proliferation in response to mitogens, non-self HLA antigens in mixed lymphocyte culture or specific antigens (would have to know hx of what they should be responsive to), thrush

Question 10

What are mitogens? What are 3 examples?

Answer 10

plant lectins that bind to sugars on cell surfaces, crosslink them, and stimulate T cells and B cells
-PHA, conA, pokeweed

Question 11

What occurs in mixed lymphocyte culture?

Answer 11

Look at proliferation of self lymphocytes in response to irradiated stimulating lymphocytes (that will not proliferate), tests reaction to non-self HLA

Question 12

Why is it important to know the history of patient exposures for lymphocyte proliferation analysis?

Answer 12

for testing specific antigens, need to know if they should be responsive to it

Question 13

What are treatments for SCID?

Answer 13

aggressive Abx and antivirals, BM transplant, replacement Ig (half-life of 2-3 weeks)

Question 14

What is the most common presentation of humoral immunodeficiency?

Answer 14

respiratory infection or unusual enteric infection from lack of IgA or increased severity of a usually not severe infection

Question 15

What causes X-linked agammaglobulinemia?

Answer 15

absence of B-cells due to mutation in Bruton’s tyrosine kinase, cannot mature

Question 16

What does a CD40L deficiency result in for humoral immunity? cell-mediated immunity?

Answer 16

hypo-IgG/IgA with hyper-IgM, can’t class switch because need CD40L-CD40 interaction with T cell for IL-4 stimulation of B cell, no germinal centers in lymph nodes, macrophages will not be activated

Question 17

What type of infections is there an increased risk for with humoral immunodeficiency?

Answer 17

encapsulated pathogens, esp. pneumococci, chronic enterovirus meningoencephalitis

Question 18

What type of immunodeficiency leads to increased risk for lymphoma? Why?

Answer 18

humoral, lack of T cell and B cell interactions leads to tumors

Question 19

What Ab deficiency has a defect in producing Ab to polysaccharide antigens?

Answer 19

selective IgA

Question 20

What would cause increased susceptibility to Neisseria meningitis or gonorrhea?

Answer 20

complement immunodeficiency

Question 21

How can you treat complement deficiency?

Answer 21

vaccinate against meningococcus since B cells are normal and will produce antibodys, treat pts with antibiotic prophylaxis

Question 22

What indicates a phagocyte deficiency?

Answer 22

fungal infection, unusual suppurative infection, chronic granulomatous disease

Question 23

What is the most common qualitative neutrophil defect called? What is it?

Answer 23

chronic granulomatous disease, eats the bacteria but isn’t generating an oxidative burst so it forms a granuloma, need activated macrophage to kill bacteria

Question 24

What is NBT reduction assay?

Answer 24

when put the clear solution on activated neutrophils it turns into blue crystals
if it stays clear the neutrophils aren’t work right

Question 25

Where is the risk for infection higher with phagocyte deficiency, in catalase positive or catalase negative bacteria?

Answer 25

catalase positive- they get rid of the peroxide they generate and rely on phagocyte to give oxidative burst
catalase negative bacteria make peroxide that is not broken down further so it can build up in phagosome and help kill bacteria over time

Question 26

How do you treat phagocyte deficiency?

Answer 26

antibiotic prophylaxis, early identification and treatment of infections, IFNgamma to activate macrophages

Question 27

What is DiGeorge’s syndrome?

Answer 27

abnormal embryonic development of the 3rd and 4th pharyngeal pouches, congenital thymic hypoplasia/aplasia (no maturation of Tcells), and hypoparathyroidism (abnormal calcium levels)

Question 28

What are infection risks for cellular immunodeficient patients?

Answer 28

viral and fungal diseases

Question 29

Why do you use irradiated blood products for cellular immunodeficient patients?

Answer 29

T cells can come in on blood products and attack host tissues, irradiate the blood product to kill those T cells

Question 30

Why is there some improvement in cellular immune function over time?

Answer 30

more extrathymic maturation of T cells as you age

Question 31

What cells do HIV target?

Answer 31

CD4+ T cells, macrophages (but not killed)

Question 32

What malignancies are associated with HIV?

Answer 32

Kaposi’s sarcoma, lymphoma, squamous cell carcinoma