Immunodeficiencies Flashcards
In B cell deficit/immunodeficiencies, what areas of the lymph organs are affected?
reduced or no follicles
reduced or no germinal centers
In B cell deficit/immunodeficiencies, what following “cell line” will be decreased?
Ig’s !! (antibodies)
In B cell deficit/immunodeficiencies, what type of infections are they more susceptible to?
- pyogenic bacterial infections
- enteric bacterial and viral infections
In T cell deficit/immunodeficiencies, what areas of the lymph organs are affected?
reduced T cell zones (duh :p)
-more specifically reduced deep cortex of LN
In T cell deficit/immunodeficiencies, what type of infections are these patients more susceptible to?
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
In innate immunodeficiencies, what areas of the lymph organs are affected?
Trick question! Depends on the missing component
In innate immunodeficiencies, what type of infections are these patients more susceptible to?
Again, this is variable depending on the component but are more susceptible to pyogenic/viral infections
What is XLA (x-linked something) associated with?
BTK
-so in Xlinked SCID you have a deficit in BTK
RAG 1 & 2 and ARTEMIS are involved in what immunology process?
VDJ recombination
(most definitely related to others as well, but this is th one in notes)
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
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.
WTF is BTK?
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
Compare X linked SCID & XLA
**I am worried teacher may have been using these interchangably, but they are different
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
What are the types of SCID?
What cell lines do all of these affect?
Types
- X-linked SCID
- Autosomal Recessive SCID
- other [autosomal recessive?] SCID
All of these affect both T and B cells
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
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!
Other type of autosomal recessive SCID…
1) what is mechanism
2) what is the functional deficit (cells affected)
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
How do you cure SCID?
Bone marrow transplant!!!
What is the classic/constant CD marker on T cells?
CD 3
What is the classic/constant CD marker on B cells?
CD 19
What are the kinds of disorders that affect both T & B cells?
- all 3 types of SCID
- Hyper IgM syndrome
What disorders affect T cells? (that your teacher taught about…6 of em)
- 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
Let’s talk Hyper IgM syndrome.
1) how is it genetically passed on/inherited
2) what is mechanism
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
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?
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
What is the CATCH-22 mnemonic? What dz does it help you remember? **
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?
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
- STAT3 mutation –> Deficiency of Th17 cells –> impaired recruitment of neutrophils to sites of infection [i.e. decreased cell mediated inflammation]
- 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
Th1 deficit
1) how does this deficit cause problems? or what does this deficit lead to issues with?
1) cell mediated macrophage activation (it becomes decreased)
T Cell R deficit
1) how does this deficit cause problems?
hint: know the mutations that lead to this
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
MHC II defect
1) how does this deficit cause problems?
defect in MHC-II expression –> no MHC-II –> defective CD4 T cell activation
What tests for B cell response? What tests for T cell response? ( both related to T cell proliferation)
??? sorry this one sucks
mitogens test T cell response
LPS tests B cell response
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?
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)
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
IL-12
IFNg (gamma)
Defects in what complement #’s are involved in immune complex disease?
C1,2, & 4
Defects in what complement #’s are involved in being susceptible to CAPsulated bacteria?
hint there is another factor too!
C3!!
remember 3 letters in CAPsulated bacteria
Also Factor 1 deficiency causes the same thing (susceptible to capsulated bacteria)
Defects in what complement #’s are involved in being susceptible to neisseria?
C5-9
reminder: Neisseria = Nine
Defects in what innate immunity [complement] proteins are involved in being susceptible to neisseria AND capsulated bacteria?
Factor D & properdin
If I have defects in DAF & CD59 what disease do I have?
remember our saying
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
1) What is HANE?
2) what deficit causes this?
1) Hereditary angioneurotic edema AKA angioedema
2) C1-inhibitor deficiency
