All of them! Flashcards
Proper response to fungi
Neutrophils, Th1 - granuloma
Cyclosporine?
Drug for immunosuppression - inhibits IL-2 and INF-gamma
Nephrotoxic
Treating acute GVHD
Remove mature T cells from bone marrow in vitro
Treat with anti-CD3 Ab
This also reduces chance of engraftment…
Some GVHD good b/c rids pt of remaining cancers
Autologous bone marrow transplantation
Administer G-CSF (granulocyte colony stimulating factor)
Puts bone marrow stem cells to blood, extract it, can use later as bone marrow transplant stuff
How does trophoblast keep NK cells from killing it?
Trophoblast cells lack paternal MHC
HLA-G, an MHC 1-like protein, prevents NK activation where no MHC expression occurs
Secrete TGF-beta
Prevent tryptophan from crossing placenta - starves T-cells
- done by INDOLAMINE 2,3-DIOXYGENASE
Abnormalities predisposing to autoimmune diseases
Abnormalities of lymphocytes and APC’s
Genetic predisposition
Microbial infections (viruses)
What causes rheumatic fever?
Cross-reaction of streptococcal Ab with heart valve tissue
molecular mimicry
Cell types of sarcomas, lymphomas, leukemias
muscle, fat, fibroblasts
lymphoma - solid lympoid tissue
leukemia - lymphocytes and hematopoietic cells
Tumor Specific Antigen
unique to particular tumor, not present in other cell types
due to point mutations/gene rearrangements
not common in human tumors
Tumor Associated Antigens
Antigens shared by different tumors, also found on normal tissues
Oncofetal antigens - on fetal tissues, not adult tissues
Alpha fetal protein - certain liver cancers
Carcinoembryonic antigen - increased in colon cancer and smokers
NOT THERAPEUTIC TARGERS; USEFUL FOR DETECTION AND MONITORING TREATMENT
Differentiation antigens
Aid in diagnosing tumor cell origin of certain tumors
Does immune system respond to spontaneous tumors?
Not really
Rarely cause inflammation, don’t elicit co-stimulatory molecules; many tumors don’t express unique antigenic peptides
What is most effective immunologic response against virus-induced tumors?
CTL!
What do NK cells do with tumors? How are they activated?
Lyse cells of hematopoietic and viral origin
ADCC may be important
Activating signal: downregulation of I MHC
Interferons, TNF-alpha, and IL 2 (turns NK cell into LAK cell)
How do macrophages kill tumor cells?
ADCC
release of TNF-alpha
Tumor evasion strategies
Lack of expression of MHC/mutated MHC
Induce tolerance
“Sneaking through” - the tumor is the one cell the immune system can’t catch
Create their own “immunopriveleged site” by encasing in collagen and fibrin
How can you vaccinate against tumor cells?
Treat tumor cells with specifically increased immunogenicity; effective against melanoma antigens in clinical studies, incudes CTL’s
Hep B vaccine
Ab therapies against tumors
w/B cell lymphoma: Anti-idiotypic Ab to surface immunoglobulin
Ab against growth factor receptors of tumor cells (Herceptin)
Bi-specific antibodies - genetically engineered to recognize 1 tumor Ag and 1 immune cell
Immunoconjugates
What’s an immunoconjugate?
Ab coupled with toxins - specific delivery to tumor cell. (Have to use true tumor-specific Ag, and F(ab’)2 fragments must be used to avoid non-specific binding)
But - the conjugate must be endocytosed
How can you “purge” bone marrow of tumor cells?
In vitro - anti-tumor antibodies and complement
Used with autologous bone marrow transplantation in B cell lymphoma pt’s after chemo and radiation
Adoptive cell immunotherapy - making LAK’s
Culture NK cells in lots of IL-2 –> LAK cell
Reinfuse LAK cell to pt, kills tumors
Most success with renal cell carcinoma, malignant melanoma
Doesn’t work so well when you just dose the pt with IL-2 (or TGF-alpha)
What happens when you’re infected with HIV? (from 1 week to 10 years)
First few weeks - feel sick; acute illness
Seroconversion
Latent phase - up to 10 years