Flashcards in Ch8: Immunodeficiency and Transplantation Deck (86):
What is primary immunodeficiency?
Due to genetic mutations and are inherited
Types of primary immunodeficiency?
What is secondary immunodeficiency?
What can cause secondary immunodeficiency?
Classical complement pathway deficiency results in what?
MBL pathway deficiency results in what?
Alternative pathway deficiency results in what?
Infection with pyogenic bacteria and neisseria
Problem with C3b deposition results in what?
Pyogenic bacteria and Neisseria (maybe immune-complex)
Problem with C5 through C9 result in what?
Deficiency with Neisseria species
Problem with DAF or CD59?
Problem with C1INH results in what?
Hereditary angioneurotic edema (HANE)
What is the genetic of C1INH disease?
C1INH is a member of what family of molecules?
Serpin protease inhibitors
How does C1INH work?
Binds to C1r or C1s and is cleaved by it.
HANE results in what?
Swelling of face, larynx and abdomen
HANE is commonly seen when?
Trips to dentist
Leukocyte adhesion deficiency results in what?
No recruitment of phagocytes to infection site resulting in widespread infections
What is cause of chronic granulomatous disease?
Defective NADPH oxidase so that macrophages can't kill bacteria resulting in huge granulomas forming.
What is G6PD deficiency?
Defective respiratory burst so that phagocytosed bacteria can't be killed
What is myeloperoxidase deficiency?
Deficiency in neutrophil granules and macrophage lysosomes resulting in lack of oxygen species so that phagocytosed bacteria can't be killed.
What is Chediak-Higashi syndrome?
Defect in forming phagolysosome so results in persistent bacteria infections
LAD-1 deficiency is caused by what?
Mutations in Beta-2 integrins
LAD-2 deficiency is caused by what?
No sialyl lewis
Herpes simplex I is caused by what?
Defective antiviral immunity in CNS
Recurrent bacteria pneumonia is caused by what?
Defective innate immune response to pyogenic bacteria.
X-linked agammaglobulinemia (XLA) is a defect in what?
Btk that does intracellular signaling in B cell receptor
People with XLA can develop B cells how far?
Defects in ADA or PNP result in what?
No Pro or Pre B or T cells
Defects in RAG1 and RAG2 result in what?
No Pre B or T cells
Defect in Zap70 results in what?
No cytotoxic T cells
Defect in MHC class II results in what?
No CD4 T cells
IL-12 receptor deficiency results in what??
Recurrent intracellular bacteria like myobacterium
Which is worse, absence of a cytokine or a receptor?
Receptor because cytokines can be compensated by other cytokines
No IL-12 would mean what?
Can't activate NK Cells
Can't activate CTL hence Th1 cells
No IFN-gamma receptor would result in what?
Inability to clear intracellular bacteria because macrophages wouldn't respond to IFN-gamma
What cell signaling is interrupted with no IFN-gammareceptor?
Defect in IL-2 receptor gamma signaling chain affects what?
Affect signaling for a ton of cytokines
X-linked SCID is what?
No gamma chain on IL-2 receptor
Autosomal recessive SCID is what?
Jak3, ada, pnp
X-linked hyper IgM syndrome patients lack what?
What happens in x-linked hyper IgM?
No CD40 so B cells are not activated and continue to release IgM at high amounts
STAT3 mutation would result in what?
No Th17 cells
No IL-12R or IFNgamma-R's would result in what?
AID mutations result in what?
Hyper-IGM syndrome (autosomal)
B cell deficiencies have what abnormalities?
What takes advantage?
No germinal centers
Reduced serum Ig levels
Pyogenic bacterial infections
T cell deficiencies have what abnormalities? 3
What takes advantage?
Reduced T cell zones
Reduced DTH reactions
Defective T cell proliferation
Innate immune deficiencies have what consequences? (2)
1. pyogenic bacteria
How long does it take for IgG to be made well enough by child?
HIV has what effect on immune?
No CD4 T helper
Irradiation and chemo have what effect on immune?
No progenitor lymphocytes
Immunosuppression for graft rejection and inflammatory diseases cause what?
Bone marrow cancers have what effect on immune?
Less leukocyte development
Protein-calore malnutrition result in what?
Metabolic derangements that affect lymphocytes
Removal of spleen results in what?
Less phagocytosis of microbes
Two types of rejections?
Host vs graft
Graft vs host
Hyperacute rejection is the result of what?
Acute rejection is the result of what?
Direct allorecognition by pre-formed T cells
Chronic rejection is the result of what?
Indirect allorecognition where a whole immune response is developed.
What is xenograft?
Donor and recipient different species
What is allograft?
Donor and recipient same species
What is syngraft?
Donor and recipient are twins
What is autograph?
Donor is recipient
Which are generally rejected of the types of grafts?
Xeno and ALlo
Rejection of organ is mediated by what? 2
What is the best donor blood?
What happens in hyperacute rejection of fetus?
Mother has antibodies against father's HLA/MHC in fetus
What is hyperacute transplant rejection?
Pre-formed antibodies bind to the transplant are complement cascade is activated which results in cell lysis through MAC formation
What is a microcytotoxicity test?
Ab against an HLA is performed.
Complement is added to punch holes
Trypan blue is added to see if antibody actually bound and let complement punch holes.
What is mixed lymphocyte reaction?
Take peripheral blood from both donor and recipient.
Irradiate one set to stop growing and then mix with the other cells.
If there is a reaction and the non-irradiated cells react to the others, then there is a mismatch.
What is direct allorecognition due to?
Trying to match MHC before between donor and recipient
What happens in direct allorecognition?
DC from donor tissue express MHC that is recognized by host cells but the peptides are not, so there is a response to kill foreign cells shortly after transplantation.
How long til indirect allorecognition occurs?
What is indirect allorecognition?
Breakdown of donor MHC-expressing cells leads to recognition by B cells and T cells and the host establishes effective immune response against the graft.
What specifically happens in both direct and indirect allorecognition?
Direct: Recipient T cells recognize donor MHC with the donor antigen.
Indirect: Recipient T cells do not recognize donor MHC, and must have recipient DC present antigens
Indirect allorecognition can induce what?
How to stop anti T cell antibodies? (2)?
1. Anti-lymphocyte serum
2. Anti- T cell serum
Three main categories of immunosuppressive drugs?
2. Cytotoxic drugs
3. Microbial products
Corticosteroids have what main response?
Change gene expression and shut down inflammation
Cytotoxic drug treatment results in what?
Death of proliferating cells
Microbial products have what effect in immune?
INhibit T cell activation?
Three examples of microbial products?
1. Cyclosporin A
Microbial products inhibit what?
T-cell receptor signaling
When does graft versus host disease occur?
Following allogenic or xenogeneic bone marrow transplant
GVHD leads to what?
Organ damage and death
What are immune privileged sites?
Sites that tolerate graft well without an immune response such as eyes, brain, testis, and bone.