immunosuppression & immunodeficiency Flashcards
What expressions are impt in the generation of BCR and TCR?
If there is deficiency in these enzymes, are B cells and T cells gg to generate?
RAG and TdT expression
NO!!
What are the keys to T cell proliferation?
IL-2/IL-2R
CD20 is only expressed on
B cells
Corticosteroids (immunosuppressants) MOA
inhibit inflammatory and cytokine production and activities
Methotrexate/ azathioprine (chemo drugs) MOA
inhibit lymphocyte growth
Rituximab (anti-CD-20), Belimumab (anti-BAFF)
(B cell-specific drugs) MOA
- deplete b cells
- inhibit B cell growth
_______ is used to prevent rejection reactions. They reduce T cell response to IL-2
Rapamycin
Cyclosporine A inhibits _____ proliferation. They are used when milder immunosuppressants such as ______ have failed.
T cell;
steroids
Cyclophosphamide (alkylating agents) inhibit cell growth by ___________. It adds an alkyl group to the guanine in DNA to break DNA strands.
interfering with DNA replication
If Btk is deficient, what will happen?
disrupts the AP-1 pathway of BCR signalling;
thus lack of B cells and antibodies
If adenosine deaminase (ADA) / purine nucleotide phosphorylase (PNP) is deficient, what will happen?
can generate toxic adenosine metabolites causing loss of T/B cells and function;
can affect the differentiation of stem cells to T/B cells
____ deficiency: disrupts IL-2R, IL-4R, IL-7R, IL-9R, IL-15R, IL-21R ________.
Yc,
signalling
Loss of IL-7R signalling alone disrupts __________. This causes _______
T/B cell generation from lymphoid precursors;
causes SCID
____ deficiency increases gut infections
IgA
B cell deficiency leads to mutations in _____, increases _____________
CD40L;
increases susceptibility to infection, cancer & autoimmunity
____ deficiency increases infection and cancer
CD4
SCID (Severe combined immunodeficiency) – lack of _____ cells
T & B cells
DiGeorge syndrome:
- no ______
- complete or partial lack of ___ and ___ cells
- loss of ______ & _______ immunity
- no thymus
- complete or partial lack of CD4 and CD8 T cells
- loss of humoral & cellular immunity
DiGeorge syndrome: can it be recurrent?
yes
SCID: loss of what cells?
T cells, B cells or nK cells
Can vaccintation with live attenuated vacines be fatal?
Yes
X-linked hyper Ig-M syndrome:
defects in _____________ and _________
helper T cell-dependent B cell and
macrophage activation
X-linked hyper Ig-M syndrome:
mechanism of defect?
mutation in CD40 ligand
Defective class II MHC exp (the bare lymphocyte syndrome): lack of class II exp and impaired \_\_\_\_ cell development and activation
CD4+ T cell
Defective class II MHC exp (the bare lymphocyte syndrome): mechanism of defect?
mutation in genes encoding transcription factors required for class II MHC gene exp
TAP deficiency: lack of class __ MHC molecule exp, decreased no. of _____ cells; susceptibility to _________
lack of class I MHC molecule exp, decreased no. of CD8+ T cells; susceptibility to bacterial infections
TAP deficiency: mechanism of defect?
mutation in the TAP genes preventing peptide loading of class I MHC molecules
Bare lymphocyte syndrome:
- MHC II deficiency caused by failure to _________
- MHC I deficiency due to failure to ______________
- loss of T cell function
- switch on MHC genes
2. process antigens for MHC I (eg. lack of TAP)
Hyper-IgM syndrome:
- no _____, no germinal centre
- no ____ class switch to ________
- increased susceptibility to infections
- no CD40L
- no IgM class switch to IgA, IgG, & IgE
X-linked hyper Ig-M syndrome impairs _______ functions as well
macrophage
______ is the most common cause of immunodeficiency worldwide.
It is associated with a significant impairment of ____________, _______ function, _______ system, secretory ____ and ______ production.
Malnutrition
It is associated with a significant impairment of cell-mediated immunity, phagocyte function, complement system, secretory IgA and cytokine production.
HIV: retroviruses have an enzyme called ___________ that gives them unique property of __________ into host cell DNA
reverse transcriptase;
transcribing RNA
HIV infects ___ cells
CD4 T cells
AIDS: infects CD4 T cells and also ______, _____ and _____ using CD4 and ______ to enter cells
macrophages, monocytes and dendritic cells using CD4 and chemokine receptor 5 (CCR5)
Treatment for AIDS
anti-retroviral drugs like Abacavir, Gancyclovir that inhibit viral replication
