Deficiency in Adaptive Immunity (complete)

Question 1

Describe generally primary immunodeficiencies

Answer 1

• Means a disease probably has a genetic cause
• Ask yourself: does it exist at birth or not? (Congenital)
• Ex: if thymus were congenitally dysfunctional

Question 2

Describe generally secondary immunodeficiencies

Answer 2

• Some known process outside the immune system caused the deficiency
• Think: ACQUIRED
• Ex: HIV, measles, malaria, EBV

Question 3

What types of infections would you see with pure B cell deficiency?

Answer 3

• High grade EXTRACELLULAR bacterial pathogens (e.g. Staph, H flu, Stept)
• Just think about the type of immune response that involve B cells

Question 4

What types of infections would you see with pure T cell deficiency?

Answer 4

• Intracellular pathogens (viruses, certain bacteria, yeasts, fungi)
• Just think about the type of immune response that involve T cells :D then you got it!

Question 5

Describe the clinical features which are part of DiGeorge syndrome, excluding immunological features

Answer 5

1) Hypertelorism
2) Down-slanting eyes
3) fishmouth deformity
4) Micrognathia
5) Low-set ears

Question 6

Discuss the incidence of IgA deficiency. What are the associated syndromes?

Answer 6

1 in 500 — most common immunodeficiency disease

10x more frequent in people w/ celiac

1) Diarrhea
2) Sinopulmonary infections
3) Increased frequency/severity of allergies

Question 7

Describe the immunological problem of the Nude mouse. What is the human immunodeficiency condition it resembles?

Answer 7

• Have a genetic mutation and have no thymus, can’t make the stroma —-» no T cells
• Also have no hair
• Very similar to DiGeorge Syndrome, but it’s a different mutation

These mice reject grafts b/c there are no T cells — all around very useful for research

Question 8

What is the enzyme absent in certain cases of SCID?

Answer 8

Adenosine Deaminase

Question 9

Discuss possible approaches to replacing adenosine deaminase

Answer 9

1) Enzyme replacement therapy
2) Blood transfusions of irradiated red cells (RBCs have ADA— radiation gets rid of remaining B/T cells)
3) Purified stem cell transplant (otherwise potential for GvH)

Question 10

Discuss transplantation therapy in immunodeficiency diseases. What are some complications?

Answer 10

Always potential for GvH disease

• BM transplant has 50% success rate in SCID — purified stem cells are preferred to avoid GvH

Question 11

What are the principle tests for determining a B cell deficiency?

Answer 11

1) Serum protein electrophoresis
2) Quantitative IgG, IgA, IgM levels
3) Specific Abs to prior immunizations
4) ABO isohemagglutinins

Question 12

What are the principle tests for determining a T cell deficiency?

Answer 12

1) Skin test w/ recall Ag panel

2) Total lymphocyte count

Question 13

What are the principle tests for determining a phagocyte deficiency?

Answer 13

1) WBC count, differential, morphology

2) NBT test – oxidative burst

Question 14

What are the principle tests for determining a complement deficiency?

Answer 14

1) CH(50)

2) Assay for C1inh (inhibitor)

Question 15

Where in the lymph node are B cells located?

Answer 15

Germinal Centers

Question 16

Where in the lymph node are T cells located?

Answer 16

Paracortex

Question 17

Describe the contents of IVIG

Answer 17

Aka: Human Immunoglobulin

• about 99% IgG
• It’s donated by lots of people

Question 18

Describe the routes of administration for IVIG

Answer 18

• IV use — effective, expensive; often in short supply

- SC use — can be done at home

Question 19

For which conditions would IVIG be useful as replacement therapy?

Answer 19

Those w/ B cell deficiencies

Eg:

• Bruton
• SCID
• HyperIgM
• CVID

Question 20

What are 2 viruses which are immunosuppressive in humans?

Answer 20

1) Measles
2) Mono
3) CMV infection
4) AIDS

Question 21

Describe Severe Combined Immunodeficiency Disease

Answer 21

• T and B cell deficient
• Block in development of lymphoid stem cell
• X linked: defect in gamma chain —» IL-2 receptor problems

Question 22

Describe X-linked (Bruton)n agammaglobulinemia

Answer 22

• Normal T cells
• Low to absent B cells
• Due to developmental block btwn pre-B cells and B cells — most pts have pre-B cells in BM, but deficient in mature B cells
• IgG has less than 10% of normal, no IgA or IgM
• This is why OPV isn’t used in the US

Question 23

Describe X-linked hyperIgM syndrome

Answer 23

• It is how it sounds
• Too much IgM w/ low IgG and IgA
• Defect in IgM-to-IgG switch mechanism

Question 24

Describe Common Variable Immunodeficiency (CVID)

Answer 24

• Normal #s of pre-B and mature B cells
• Difficult to trigger to make a specific Ab — IgG is low
• Can be diagnosed for the first time in pts up to 50yo
• Main phenotype: recurrent bacterial infections
• Tx: IVIG, SCIG
• Causes: unknown