T Cell Defects and Combined Immunodeficiencies

Question 1

T cells are part of the ____ immunity

Answer 1

adaptive immunity (cellular is T cells and humoral is B cell/antibodies)

Question 2

infectious disease susceptibility with someone with a T cell deficiency

Answer 2

bacterial, viral, fungal, mycobacteria, parasitic.

Question 3

T/F Pneumocytsis jivroecii is opportunitic

Answer 3

true. you have to be immunocompromised to get infected with htis.

Question 4

note: every time you have an immuno deficiency case, make sure you test for HIV

Question 5

HIV causes a depletion of _____ type T cells

Answer 5

CD4+ t cells. causes susceptibility to infections and cancers.

Question 6

drugs that cause acquired T cell defects

Answer 6

steroids, chemotherapies, immune suppressants like tacrolimus and cyclosporine.

Question 7

infections that can cause acquired T cell defects

Answer 7

CMV, HIV, EBV?

Question 8

defects in the interferon and IL-12 axis can cause MSMD. What is this?

Answer 8

mendelial susceptibility to mycobacterial diseases. causes them to be susceptibel to intracellular organisms: atypical mycobacteria, slamonella, INTERferon (gamma) fights INTRAcellular pathogens. without it, there will be atypical mycobacterial infections and recurrent bouts of salmonella

Question 9

what is chronic mucocutaneous candidiasis

Answer 9

persistent or recurrent infections of theskin, nails and mucous membranes by candida albicans. responds to antifungals but recurs when stopped.

Question 10

mechanism behind CMC

Answer 10

due to defects in the T helper 17 cells, which usually secrete IL-17.

IL-17 stimulates granulopoiesis, recruits neutrophils to the site of infection adn stimulates the production of antimicrobial peptides. When IL is down because T cells are defective, thrush cannot be fought properly.

Question 11

What is a combined immunodeficiency

Answer 11

when t cells along with other cell lines are not working. usually it is when B cells are also not functioning so there are not many antibodies.

• most severe defects, causes recurrent viral, bacterial, and fungal infections. Often riddled with opportunistic infections, failure to thrive and autoimmune disordes common. more common in kids but we are seeing more adult onset.

Question 12

what marker is an indicative of SCID in peds?

Answer 12

this is an emergency, CD3<300/ml. Very low T cell functioning with PHA <10% normal.

Question 13

investigations for possible SCID

Answer 13

CBC: look at lymphocyte count

lymphocyte subsets: T, B, and NK cell numbers. IgG, igA, igM levels, vaccine titers if appropriate.

• MITOGEN test– tests lymphocyte function.

Rule out HIV

Maternal engradtment studies.

if lymphocyte count is LOW and consistent with SCID, go for genetic testing.

Question 14

in a case of SCID, there may be decreased T and NK cells, and NORMAL B cells, but undetectable IgG, IgA and IgM levels. How is this so?

Answer 14

the body may be presented but the antibodies are not targeted towards anything.

Question 15

NOTE: lymphocyte counts are much higher in infants than adults and decrase with age; a normal ALC of 1.5 is NOT NORMAL in an infant.

ALC= absolute lymphocyte count (normal at 3 months is 2.8-14.4;, normal WBC 6-18)

Question 16

X linked SCID: a Common cause of SCID (you’d see lymphopenia). Explaiin.

Answer 16

due to defect in the common gamma chain (X linked) on the lymphocyte. the common gamma chain is normally a cytokine receptor subunit for many interleukin receptors.

causes Arrest of T and NK cell development and B cell maturation defect

Question 17

how to treat X linked SCID

Answer 17

complete bone marrow transplant for a new immune system.

Question 18

ADA decifiency as a cause for SCID. Treatment?

Answer 18

adenosine deaminase deficient SCID:

◻Defective enzymes in the purine salvage
pathway causes lymphopenia due to metabolic poisoning of the cells
care
◻Neurologic and skeletal abnormalities common

Treatment
⬜PEG–ADA can partially correct (enzyme replacement)
⬜Gene therapy – first disease where it is standard of
⬜BMT

Question 19

SCID management

Answer 19

lots of prophylaxis and supportive care.

Question 20

T/F kids with SCID can have live vaccinations

Answer 20

FALSE. NO LIVE VACCINATIONS. they have no T cells, they’ll get the actual disease.

they can only have CMV safe, irradiated blood products only.

Question 21

why must blood products be irradiated and CMV safe for kids with SCID?

Answer 21

CMV safe because they have no T cells to protect them. Irradiated to prevent graft vs host.

Question 22

how do we test babies for SCID?

Answer 22

TREC: PCR for t cell excission circle.

• heal poked, blood spotted onto filter paper. Looks for a piece of DNA excised when the T cell receptor gene is rearranged in the thymus. IN a healthy newborn, you’d see lots of TREC

Question 23

Combined immune deficiency mechanism

Answer 23

it’s not as severe as SCID and can present at an older age, but it is sometimes caused by mutations in the same genes that cause SCID, but the proteisn still work a bit.

Question 24

Wiskott Aldrich triad

Answer 24

a combined immune deficieny with a triad of eczema, recurrent infection and thrombocytopenia with small platelets

Question 25

DOCK8 deficiency

Answer 25

a type of Hyper igE syndrome. high igE with combined immune defect.

Question 26

DiGeorge CID triad

Answer 26

1. conotruncal cardiac anomalies
2. hypoplastic thymus
3. hypocalcemia

(In addition to low T cells)

caused by a complete or partial absence of the thymus due to a chromosome 22 microdeletion.

Question 28

Ddx?

Answer 28

GATA2 deficiency aka Monomac, embergers syndrome.

GATA2 is normally expressed on hematopoiuetic rogenitors, and can also affect endothelial cells.

characterized by low monocytes, CD4, and B cells.

causes lots of viral infections like herpes and EBC, DIC, bacterial infections and fungal infections, as well as LYMPHEDEMA DUE TO ENDOTHELIAL CELL DYSFUNCTION.

Question 29

what immune defects would you see in a GATA2 deficiency

Answer 29

1. innate problems
   - neutropenia (associatd with MDS and AML)
   - monocytopenia: monos important for intracellular pathogens, bacterial, parasitic, mycobacteria.

NK cells: herpes group infections, warts, WPV

2. Adaptive

CD4T cells: viral, fungal and opportunisitc susceptibility

B cells: bacteria, sinopulmonary infections

OVERALL, LOOK AT ALL THE CELLS ON THE CBC

Question 30

what is GATA2

Answer 30

GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming, lympathic system-forming, and other tissue-forming stem cells. (which is why it causes broad symptoms)

Question 31

GATA2 deficiency treatment

Answer 31

overall its just prophylaxis for all the infections they can get lol. Also hematopoietic stem cell transplant.