Immunodeficiencies

Question 1

In B cell deficit/immunodeficiencies, what areas of the lymph organs are affected?

Answer 1

reduced or no follicles
reduced or no germinal centers

Question 2

In B cell deficit/immunodeficiencies, what following “cell line” will be decreased?

Answer 2

Ig’s !! (antibodies)

Question 3

In B cell deficit/immunodeficiencies, what type of infections are they more susceptible to?

Answer 3

• pyogenic bacterial infections
• enteric bacterial and viral infections

Question 4

In T cell deficit/immunodeficiencies, what areas of the lymph organs are affected?

Answer 4

reduced T cell zones (duh :p)
-more specifically reduced deep cortex of LN

Question 5

In T cell deficit/immunodeficiencies, what type of infections are these patients more susceptible to?

Answer 5

Defective T cell proliferation to invitro mitogens = infection with intracellular viruses & bacteria

**bonus point if you mention that the bacterial infections are non-tuberculous or i.e. defect in T cells does not mean more susceptible to tuberculosis

Question 6

In innate immunodeficiencies, what areas of the lymph organs are affected?

Answer 6

Trick question! Depends on the missing component

Question 7

In innate immunodeficiencies, what type of infections are these patients more susceptible to?

Answer 7

Again, this is variable depending on the component but are more susceptible to pyogenic/viral infections

Question 8

What is XLA (x-linked something) associated with?

Answer 8

BTK
-so in Xlinked SCID you have a deficit in BTK

Question 9

RAG 1 & 2 and ARTEMIS are involved in what immunology process?

Answer 9

VDJ recombination

(most definitely related to others as well, but this is th one in notes)

Question 10

In Xlinked SCID, tell me:
1) functional deficit (amount of B & T cells)
Bonus: name the mediator signal that is defective

2) mechanism of this defect
Bonus: name the IL signal that is missing in this mechanism

3) what is very similar immunodeficiency to this one? but slightly different

Answer 10

1) BIG decrease in T cells
- Normal or increased B cells
- —-> this leads to decreased Ig’s

?BTK deficit

2) gene mutation in gamma chain cytokine R –> no IL7 signal? –> defective T cell maturation
3) okay, confused on this. I don’t think Xlinked (Brutons) agammaglobulinemia is exactly the same but very similar (or at least both are x linked and both involve BTK.

Question 11

WTF is BTK?

Answer 11

Bruton’s tyrosine kinase

Apparently it is critical mediator of BCR signaling

YOU DO NOT NEED TO KNOW THIS PICTURE BUT THOUGHT IT MIGHT HELP SHOW HOW MUCH BTK HELPS IN THIS PROCESS

Question 12

Compare X linked SCID & XLA

**I am worried teacher may have been using these interchangably, but they are different

Answer 12

Similarities:

• both X linked
• both more common in Males (due to X linked)

Differences

• XlinkedScid causes decrease in T cells, XLA affects B cells
• XlinkedSCID is due to IL-2R gamma chain defect, XLA is defect in BTK

Question 13

What are the types of SCID?

What cell lines do all of these affect?

Answer 13

Types

1. X-linked SCID
2. Autosomal Recessive SCID
3. other [autosomal recessive?] SCID

All of these affect both T and B cells

Question 14

In Autosomal recessive SCID, tell me:
1) mechanism of this defect

2) functional deficit (what does it do to B & T cells)
3) Key word/difference to this vs XlinkedSCID

Answer 14

1) ADA (adenosine deaminase) is deficient + deficient/decreased PNP –> build-up of cytotoxic metabolites in lymphocytes –> cell death
2) above leads to Progressive decrease in T & B cells (mostly T cells tho? per notes)
3) PROGRESSIVE!

Question 15

Other type of autosomal recessive SCID…

1) what is mechanism
2) what is the functional deficit (cells affected)

Answer 15

Only real difference between autosomal recessive SCID and other SCID appears to be the mechanism leading to this/same functional defect!

1) mutation in RAG –> defect in VDJ recombination –> B & T cells can’t mature then

** VDJ recombination is how you make diverse/specific antibodies

2) decrease in both T & B cells and thus antibodies

Question 16

How do you cure SCID?

Answer 16

Bone marrow transplant!!!

Question 17

What is the classic/constant CD marker on T cells?

Answer 17

CD 3

Question 18

What is the classic/constant CD marker on B cells?

Answer 18

CD 19

Question 19

What are the kinds of disorders that affect both T & B cells?

Answer 19

• all 3 types of SCID
• Hyper IgM syndrome

Question 20

What disorders affect T cells? (that your teacher taught about…6 of em)

Answer 20

• DiGeorges syndrome
• MHCII defect
• T cell R complex defect
• Th1 defect
• Th17 defect (aka Autsomal dominant Hyper-IgE syndrome aka Job syndrome)
• IFN-gamma deficit

Question 21

Let’s talk Hyper IgM syndrome.

1) how is it genetically passed on/inherited
2) what is mechanism

Answer 21

Remember our saying: affects 40 yo Males **

CD40 ligand Mutations–>means B cells dont go to germinal centers and you can’t class switch antibodies –> you can only get IgM (normal or slight increase)

1) X-linked
2) above mechanism

**remember actually affects kiddos etc. Just helps remember

Question 22

DiGeorge’s syndrome!

1) tell me the defect that leads to this
2) what cell type does it affect
3) how can we treat this? why won’t a BMT work?

Bonus: what is a tiny loop hole/anatomy to temporarily help get around this immunodeficiency?

Answer 22

1) 3rd & 4th pharyngeal pouches don’t develop –> Thymus can’t develop –> T-cell deficiency (recurrentviral/fungal infections)
2) affects T cells
3) thymic transplant – BMT won’t work because there is no thymus, so nowhere for T cells to mature

Bonus: thymic pouches in groin and armpit!!! temporaarily help mature T cells? but not enough

Question 23

What is the CATCH-22 mnemonic? What dz does it help you remember? **

Answer 23

DiGeorge syndrome

CATCH-22

22q11microdeletion –> 3rd & 4th pharyngeal pouches don’t develop –> Thymus & paraThyroids can’t develop

Cardiac defects, Abnormal facies,Thymic hypoplasia –> T-cell deficiency (recurrentviral/fungal infections), Cleft palate, Hypocalcemia 2° to parathyroid aplasia & you get tetany

**I know you don’t have to know this exactly but sometimes context helps?

Question 24

Th17 deficit

(aka Autosomal dominant hyper-IgE syndrome aka Job syndrome)

1) how does this deficit cause problems?
2) what type of infections does this lead to?

Here’s a mnemonic to help remember: know your ABCDEF’s STAT to get your first Job at age 17

Answer 24

1. STAT3 mutation –> Deficiency of Th17 cells –> impaired recruitment of neutrophils to sites of infection [i.e. decreased cell mediated inflammation]
2. leads to bacterial abscess

**you basically only need to know “Abc’s STAT to get your first Job at age 17” but here is the rest/full ABCDEF’s

Cold (noninflamed) staphylococcal Abscesses, retained Babyteeth, Coarse facies, Dermatologic problems(eczema), IgE, bone Fractures from minor trauma

Question 25

Th1 deficit

1) how does this deficit cause problems? or what does this deficit lead to issues with?

Answer 25

1) cell mediated macrophage activation (it becomes decreased)

Question 26

T Cell R deficit

1) how does this deficit cause problems?
hint: know the mutations that lead to this

Answer 26

1) mutation in CD3 or ZAP-70 –> decrease in TCR expression/signalling –> decreased T cells

our Mnemonic = there are 3 (CD3) letters in TCR and in ZAP

Question 27

MHC II defect

1) how does this deficit cause problems?

Answer 27

defect in MHC-II expression –> no MHC-II –> defective CD4 T cell activation

Question 28

What tests for B cell response? What tests for T cell response? ( both related to T cell proliferation)

??? sorry this one sucks

Answer 28

mitogens test T cell response

LPS tests B cell response

Question 29

IFN gamma deficit

1) 2) what are the 2 types?
2) how does this deficit cause problems?
3) what type of infections does this lead to?

Answer 29

1) No dominant alleles OR
- Heterotype
2) no dominant alleles –> no IFNg or R1 signaling
- heterotype –> some signaling but it still can’t bind JAK/STAT
3) mycobacterium (can’t be destroyed after macrophages eat them)

Question 30

What IL and IFN are part of a positive feedback loop to activate Th1 & NK cells?

**also sorry this sucks, don’t know how else to ask

Answer 30

IL-12

IFNg (gamma)

Question 31

Defects in what complement #’s are involved in immune complex disease?

Answer 31

C1,2, & 4

Question 32

Defects in what complement #’s are involved in being susceptible to CAPsulated bacteria?

hint there is another factor too!

Answer 32

C3!!

remember 3 letters in CAPsulated bacteria

Also Factor 1 deficiency causes the same thing (susceptible to capsulated bacteria)

Question 33

Defects in what complement #’s are involved in being susceptible to neisseria?

Answer 33

C5-9

reminder: Neisseria = Nine

Question 34

Defects in what innate immunity [complement] proteins are involved in being susceptible to neisseria AND capsulated bacteria?

Answer 34

Factor D & properdin

Question 35

If I have defects in DAF & CD59 what disease do I have?

remember our saying

Answer 35

autoimmune paroxysmal nocturnal hemoglobinuria

our saying: when you are a DAD (looks like DAF) and you are 59 (CD-59) yo, then you have to get up in the middle of the night to pee blood sometimes

Question 36

1) What is HANE?
2) what deficit causes this?

Answer 36

1) Hereditary angioneurotic edema AKA angioedema
2) C1-inhibitor deficiency