T;B cell co operation Switch defects (hyper IgM sydromes)

Question 1

What does PCP stand for and what test is done for it?

Is it protist or fungi?

Answer 1

pneumocystis jurovicci pneumonia

unsure whether its actually a protest or a fungi.

Question 2

What is used to treat PCP?

Answer 2

The combination of antiboitics called spetrin (cotrimoxazole).

Question 3

What are you looking at when testing responses to tetanus Ab, pneumococcal and Hib vaccine.

Answer 3

toxoid - protein T cell depedent response
pneumococcal: polysaccharide T cell independent response

HIb: conjuage polysacchide diphtheria toxoid vaccine.

Question 4

If low ig levels and hyper IgM seen, what responses to the vaccine would be expected?

Answer 4

Very poor rsponses because they produce vey little IgG and IgG is measured in the response.

Question 5

What is the marker for naive T cells and activated/memory T cells?

Answer 5

CD45RA naive

CD45RO active/ memory

Question 6

What could you suscepct if very high ratio of CD45Ro to CD45RA?

Answer 6

maternal engraftment.

Question 7

Markers for naive
unswitched memory
and switched memory B cells?

Answer 7

IgD+ CD27-
IgD+ CD27+
IgD- CD27+

Question 8

What is low CD21 expression a sign of in B cells?

Answer 8

May be a sign of immune dysregulation.

Question 9

What TF and what chemokine receptor do Tfh cells express?

What costimulatory molecules?

Answer 9

BLIMP1 (like B cells) and CXCR5
OX40 ICOS
CD40L

Question 10

What importnat cytokine do Tfh produce for Ab produciton?

Answer 10

IL-21

Question 11

What chemokine markers are associed with Th1 and Th17 cells?

Answer 11

CXCR3 for Th1 (fh cells)

CCR6 for Th17 (fH cells) (these could stimulate IgA responses)

Question 12

What diseases have a skew for Th17 Tfh cells?

Answer 12

deamatomyositis and other autoimmune disaseas.

Question 13

What PIDs have low Tfh?

Answer 13

BTK (no B cells- recirpocal signals required) CD40L, NEMO and STAT3

Question 14

Why does STAT3 LOF muttions have fewer Tfh cells?

Answer 14

because STAT3 is downstream of IL-21

Question 15

What two roles does AID play?

Answer 15

In SHM, AID will cause deanmiation, leading the mismatch repair errors resulting in base substations.

In CSR, AID targets class switch regions to help excise the constant regions of the heavy chain. UNG is also important in this process.

Question 16

7 causes of CSR defect/ hyper IgM?

Answer 16

CD40L
CD40 
NF-kB pathway deficiency
AID
UNG 
mismatch repair abnormality
NEHJ DNA repair abnormality.

Question 17

what test for CD40L deficiency?

Answer 17

CD40L and CD69 on FACs, using anti CD40L ab or CD40 fusion protein with fluorophore.

Question 18

Management of hyper IgM?

Answer 18

replacement Ig therapy.

Question 19

Is CD40L deficiency X linked? What other condition presents in the same way?

Answer 19

Yes, autosomal recessive CD40 deficiency present in the same way.

Question 20

what indications are there that CD40L deficiency also affects cellular immunity?

Answer 20

Because they are susceptible to PCP and cryptosporidium infections and viral infections.

Question 21

Why is cellular immunity affected in CD40L deficiency?

Answer 21

Becaucse of CD40L: CD40 interactions with APCs, espcially with Th1 responses.
Neutropenia also a feature is some cases.

Question 22

Why might you have autoimmuntiy in CD40L/CD40 deficiency?

Answer 22

Bceause ab reponses that are made may be dyregulated.

Question 23

What are markers of NK cells?

Answer 23

CD16 CD56

Question 24

What stage do neutrophils arrest at in some CD40L/CD40 patients? What might you treat them with as well?

Answer 24

promyelocyte arrest and treat with G-CSF.

Question 25

What ways can they avoid cryptosporidium infections?

Answer 25

boiling water and not going to swimming pools.

Question 26

What disease can cryptosporidium cause in CD40L/CD40 deficiency?

Answer 26

bile duct damage, leading the scherolising cholagitis and hepatocarcinoma.

Question 27

Why can some NEMO (hypomorphic) patients present hyper IgM- low levels of IgG?

Answer 27

NEMO and IkB deficiency required for NFKB activity downstream of CD40/CD40L interactions.

Question 28

Immunologically what kind of impairments do UNG and AID deficiencies cause?

Answer 28

Purely humoural.
AID then lack of SHM and UNG.
But AD only suffers from CSR defects.
UNG definitely impairment of CSR, maybe alsoSH.

Question 29

Which deficiencies present with lymphoid hypertrophy due to giant germinal centres?

Answer 29

UNG and AID deficiency.

Question 30

CSR and SHm involve single and ds breaks which require repair, what diseases can you get with defects in these proteins?

Answer 30

ataxia telangiectasia and nijmegan breakage syndrome.

hyper IgM with T cell immunodeficiency as well (+raiosensitivity and neurological disorders).