Exam 3: Chapter 13 Flashcards
A history of repeated infections suggests a diagnosis of…..
immunodeficiency
What type of immunodeficiency diseases are caused by inherited gene defects (congenital)?
primary immunodeficiency
What type of immunodeficiency diseases are acquired as a consequence of other diseases, or result from other issues such as starvation or medical intervention?
secondary immunodeficiency
Most gene defects resulting in immunodeficiency are ______________ and many caused by mutations on the ____ chromosome
recessive, x
SCID is caused by mutations in gene __________ on X chromosome. It encodes IL2 receptor
IL2RG
What does SCID stand for?
severe combined immunodeficiency
SCID will have problems with what cells? What immune system does this effect?
B and T cells
will affect the adaptive immune system
If there is a mutation in the IL2RG gene on the X chromosome and causes SCID, what cytokines are affected?
problem w/ signaling of all the IL2 family cytokines (specifically IL7 and IL15)
This can affect the production of cytokines (more common) or the receptor is defective
What interleukins don’t work and will cause T cells and NK cells to not develop properly in SCID patients?
IL7 and IL15
These two are a part of signaling of the IL2 family cytokines
Immunodeficiency diseases can have a genetic defect in B or T cell development. What other issues can arise?
how the cells are called and activated
What happens in immunodeficiency diseases if there is defects in T cell development?
no T cell dependent Ab response nor cell mediated responses
and can result in SCID
Defects in T cell development can result in….
SCID
Defects in signaling from T cell antigen receptors can cause….
SCID
Defects in B cell development result in deficiencies in _________ production that causes an inability to clear extracellular bacteria and some viruses
antibody
If the genetic defect is not a cytokine defect, then it can be a ____ or _____ cell defect
B, T
What do TAP1/2 proteins do?
help to load antigen onto MHC
What does a CD4 T cell help with?
B cell activation
What does a common lymphoid progenitor differentiate into?
B, T, or NK cell
What are the basic steps of B cell differentiation
1) common lymphoid progenitor
2) pro B cell
3) pre B cell
4) immature B cell
5) plasma or memory B cell
What happens if theres a B cell deficiency between the pro B cell and pre-B cell stages?
the appropriate BCR will not show up and will not develop into an appropriate B cell (this can also happen between the pre-B cell and the immature B cell stage)
In this case, the individual is making the B cell, but not enough B cells are capable of actually generating antibodies (incomplete)
B cell development can impact Ab production. How?
may not be able to make multiple types of Abs
B cell decides on class switching when there is a specific antigen here
How does B cell development change from birth to infancy?
hint: 4 bullet points
-born with high level maternal IgG (move across placenta)
-after birth, IgM starts immediately
-IgG starts at 6 months, total IgG falls because maternal IgG is catabolized
-IgG levels are low from 3 months to 1 year of infant
What antibody are we born with high levels?
maternal IgG (moves across placenta)
What antibody starts developing immediately after birth?
IgM
baby IgG starts at ___ months, total IgG falls because maternal IgG is catabolized
6
When are IgG levels low in childhood?
from 3 months to one year
What gene is important for B cell development?
BTK (Bruton’s tyrosine kinase) gene
Stimulation of the pre-B cell receptor recruits cytoplasmic proteins including _______ to transduce a signal that triggers B cell development
BTK (Bruton’s tyrosine kinase)
In X-linked agammaglobulinemia (XLA) the ______ protein gene on the X chromosome is defective.
BTK
in normal situations, BTK allows tyrosine kinase to phosphorylate and produce IgM
BTK is involved in the signaling of receptor
What happens in males with X-linked agammaglobulinemia (XLA)?
no signal is transduced even though the receptor is there
In females w/ X-linked agammaglobulinemia (XLA), half of the pre-B cells will be expressing the defective BTK gene and will not develop further. Why only half?
because this is only 1/2 of the X chromosomes
so 1/2 x chromosomes in each cell is permanently inactivated early in development
Immune deficiencies can be caused by defects in B-cell or T-cell activation and function that lead to abnormal ___________ responses
antibody
Defects in activation and differentiation will have an impact on ______ ____________ and Ab response
cell mediated
Defects specific to activation and differentiation of B cells can impair their ability to do class switching to ___________ and leave cell mediated response intact
IgG, IgA or IgE
Common feature of patients with defects in B-cell class switching is ___________ syndrome. They have normal B & T cell development and normal or high serum IgM, but make limited Ab response that require ____ cell help
hyper-IgM, T
In X-linked hyper-IgM syndrome, the mutation is in the ________. This is on activated T cells allowing them to engage with CD 40 on APCs
CD 40 L
so the defect here would be in B cell development
In X-linked hyper-IgM syndrome, in males w/ this deficiency in CD 40 L the ____ cells are normal but don’t engage w/ ___ cells. B cells do not undergo isotope switching or initiate the formation of germinal centers
B , T
In X-linked hyper-IgM syndrome, patients have severely reduced circulating Ab levels of all except ______ and are highly susceptible to bacterial infections
IgM
Normal pathways for host defense against different infectious agents are pinpointed by genetic deficiencies of cytokine pathways central to type _________ and type __________ responses
1/TH1, 3/TH17
Genetic defects in CD4 T cells are not in antibody production, but in the __________ ___________. Such defects make them susceptible to some bacterial infections.
signaling pathways
Inherited defects in the cytolytic pathway of lymphocytes can cause uncontrolled ______________________ and inflammatory responses to viral infections
lymphoproliferation
While there is impaired release of cytotoxic granules, there is uncontrolled activation and expansion of CD 8 T-cells and macrophages that infiltrate multiple organs, this causes tissue necrosis and organ failure. IFN-gamma is released from CTLs and NK cells and this leads to greater activity of macrophages, and pro-inflammatory cytokines such as….
TNF, IL-6 and CSF
What is the function of CD 8 T cells?
kill infected cell by apoptosis
What defects can happen after cytotoxic T cell activation?
Defects in complement components and complement-regulatory proteins cause defective ________ immune function and tissue damage.
humoral
T/F: bacteria has evolved overtime to mess up our complement system
True!!!!
Extracellular pathogens can subvent all 3 branches of the ____________ cascade (lectin, classical, and alternative pathways) to evade immune destruction
complement
What are the 6 proteins we talked about that S. aureus makes to inhibit complement pathway?
1) SAK (staphylokinase)
2) SSL10
3) Sbi and Spa
4) SCIN
5) Ecb and Efb
6) CHIPS
S.aureus makes several proteins to inhibit the complement system. SAK is one of them. What does SAK (staphylokinase) do?
SAK cleaves IgG and removes it from the bacterial surface
S.aureus makes several proteins to inhibit the complement system. SSL10 is one of them. What does SSL10 (staphylococcal superantigen-like protein 10) do?
SSL10 binds to IgG and blocks initiation of the classical pathway
S.aureus makes several proteins to inhibit the complement system. Sbi and Spa are one of them. What does Sbi (2nd immunoglobulin binding protein) and Spa (staphylococcal protein A) do?
Sbi and Spa block C1q binding to the Fc receptor portion of immunoglobulin, and also blocks the initiation of the classical pathway
S.aureus makes several proteins to inhibit the complement system. SCIN is one of them. What does SCIN (staphylococcal complement inhibitor) do?
SCIN stabilizes C3 convertase in an inactive state (bind to whole entity, so next complement step doesn’t happen, and gets arrested)
S.aureus makes several proteins to inhibit the complement system. Ecb and Efb are one of them. What does Ecb (extracellular complement-binding protein) and Efb (extracellular fibrinogen-binding protein) do?
Ecb and Efb bind to C3d and inactivate both C3 and C5, which prevents C5 convertase activity
S.aureus makes several proteins to inhibit the complement system. CHIPS is one of them. What does CHIPS (chemotaxis inhibitory protein of staphylococcus) do?
CHIPS blocks the C5a receptor on phagocytes (so vasodilation and immune cells will never arrive)
If theres a defect in C1, C2, or C4 protein of the classical pathway, what can happen as a result?
deficiency leads to immune complex disease (immune complex is made, but nothing happens next)
If theres a defect in MBL, MASP1/2, C2, or C4 protein of the MBL pathway, what can happen as a result?
Deficiency of MBL leads to bacterial infections (most commonly in childhood years)
Factor D and Factor P regulate which pathway?
complement, specifically alternative pathway
If theres a defect in Factor D or Factor P of the alternative pathway, then what happens as a result?
deficiency leads to infection w/ pyogenic bacteria and Neisseria spp. but no immune complex disease
In this case, bacteria makes proteins to destroy Factor D and Factor P which means the body will not be able to regulate how much C3 is in the system
If theres low levels of C3, then alternative pathway will not work
What happens if theres a deficiency in the C3b deposition and affects C3 protein?
deficiency leads to infections w/ pyogenic bacteria and Neisseria spp. and sometimes immune complex disease
What happens if there is a deficiency in the membrane attack components, like the C5, C6, C7, C8, or C9 proteins?
deficiency leads to infection w/ Neisseria ssp. only
What are the 2 main treatments to correct genetic defects?
1) hematopoietic stem cell transplantation
2) gene therapy
Extracellular bacterial pathogens have evolved different strategies to avoid detection by ____________ and destruction by antibody, complement, and antimicrobial peptides
pattern recognition receptors