Exam 4 Immuno Flashcards
mAb synthesis
B cell + V(D)L KO’d multiple myeloma cell
Nuclei fuse - mAb production
Mice Can Heal Humans
Murine - 1x, HAMA
Chimeric - multi x, HACA (mouse VH/VL human Fc domain)
Humanized - good, HAHA (mouse CDRs)
Fully Human
Natural Killers cells
Large, granular lymphocytes
Innate, recognize DAMPs
Kill by ADCC or NK receptor killing
Antibody dependent cell-mediated cytotoxicity
IgG bind target cell
NK binds Fc and induces apoptosis in target cell
Tumor specific mAb mechanisms
Activate complement
Induce ADCC
Tag with radioisotope (imaging or killing)
BiSpecific T Cell Engager
Binds tumor (ex CD19 in Bcell lymphoma) and Tcell CD3 Ex: Blinatumomab (Philly negative ALL)
Drug used in Solid Organ Transplant
Azathioprine/Mycophenolate Glucocorticoids Cyclosporin Tacrolimus Sirolimus (Rapamycin) ATGAM mAbs
Isohemagglutinins
IgM response to blood types (carbohydrate epitopes) Naturally occurring (or at least close) "Immunized" by 3-6 months IgG is rare, but automatically high risk pregnancy
Rh Factor
Not naturally occurring, need to be exposed
Hemolytic Disease of the Newborn
Erythroblastosis Fetalis
Rh+ fetus
Last trimester/at birth = exposure
Mom exposed -> will attack subsequent fetal RBCs
Fetus born excess bili (jaundice)
RhoGAM
prevention
give to avoid mom become “immunized”
Heterophile Antibody
Cross reactive antibodies
Ex: Mono test using horse ab
Ex: Trep palli and beef heart
HIV-1 virus binding
GP120 high affinity for CD4 (all T helper, also APC and DC)
Conformation change - CCR5 binds
GP120 moved by CCR5, GP41 fuses with membrane
GP41 is on virus and has large hydrophobic sections
HIV-1 virus in cell
Virus brings reverse transcriptase with integrase function
Activation site similar to IL-2 promotor (cross talk)
RT has high error rate - many viral variations
Risk groups
Long term survivors - CCR5 mutation, decreased express
Elite controllers - infected but effective T killers, HLA-B57
Diagnosis of HIV
Virus peaks at 6 weeks
Antibodies peak at 9 weeks
HIV Tests
Quick fast (ELISA w/ antigen): high false positive Check with Western for binding of GP120, GP41 Self test: check IgG in cravicular fluid: high false negative
Evidence for Cancer Immunosurveillance
Immunodeficient (esp Tcell) = higher tumor rates
Activated Tcell against tumor = good prognostic sign
Spontaneous regression of tumors
Paraneoplastic syndromes = autoimmune mech
Immunoediting categories
- Elimination
- Equilibrium
- Escape (upregulation of CTLA-4, PD-1)
2 Types of Tumor antigens
Tumor associated antigens (abnormal or excessive expression)
Tumor rejection antigens (recognized by immune)
2 Types of tumor mutations
Prognosis for mutation #
Driver: oncogenes/TSgene mutations
Passenger: more common, don’t affect growth
More mutations = more immuno targets = better prog
T Cell and APC interaction mech
- Stimulation: CD28 (Tcell) to CD80/86 on APC
- Inhibition: CTLA-4 to CD80/86 (early brake)
- More inhibition: PD-1 to PD-L1 (late brake)
Tumor resistance via CD80/86 and PD-L1
CD80/86 and PD-L1 not expressed on tumor, but on nearby immune cells
If invading cells: good prognosis, protecting self
If within tumor: bad prognosis, can’t attack tumor
Immune mechs to kill tumor
- CTL - target high MHC cells
- NK - target low MHC cells
- Th1 - Activate M1 (tumor often creates M2 response)
- Antibody and complement
5 Methods of Immunotherapy
- Specific immunization (patient DC + TAA protein)
- Innocent bystander killing (BCG vaccine)
- mAb anti-tumor
- Autologus cell therapy
- Chimeric antigen receptors
Chimeric antigen receptors
CTL good killers, but need MHC with protein expression
Mix CTL with tumor target (mAb specificity)
BUT overagressive, hard to stop/control
New: Split CAR joined by small molecule
