Manipulations of the Immune System Flashcards
Contrast active and passive immunity.
active = activates immune response; immunological memory passive = direct transfer of antibodies; no memory
Why are boosters needed?
to achieve protective levels of immunity, requires 3 exposures
What are the components of the DTaP vaccine?
- diphtheria
- tetanus
- acellular pertussis
Describe the role of pertussis bacteria in the DTaP vaccine.
- adjuvant
- upregulates B7 on APCs
- increased inflammation and pain at site of injection
Define inactivated vaccine.
- toxins/pathogens are killed by heat or chemicals
- epitopes maintained, but cannot reproduce in the host
- requires boosters
List some requirements for safe vaccines.
- low toxicity
- herd immunity
- long lasting immunity (boosters)
- inexpensive
- induces immune response (antibodies, T cells)
List antigen sources for vaccines.
- killed/inactivated
- toxoid
- viral subunit
- live attenuated
What type of immune response is required for intracellular infections?
TMMI (Cell Mediated)
- think: Th1, IFNg, macrophages, proinflammatory
What type of immune response is required for fungal infections?
IL17
What type of immune response is required of infections that avoid phagocytosis?
B cells
What type of immune response is required for viral infections?
T and B cells
List pros and cons of inactivated vaccines.
Pros:
- safer
- more stable than attenuated
Cons:
- weaker cell mediated response
- boosters required
- contains contaminants
List pros and cons of live attenuated vaccines.
Pros:
- better cell-mediated response
Cons:
- reversion
- causes infection in immunocompromised patients
- measles, encephalitis
- less stable
List pros and cons of vaccines using molecular components.
Pros:
- very stable
- no living pathogen
Cons:
- fewer epitopes
- weaker cell-mediated response
List some tumor antigen sources and examples.
Tumor antigens are usually self-peptides that have been modified or are overexpressed - cell-type specific => GP-100 (melanocytes) => CD33 (AML) => CD20 (B cells)
- shared
=> HER2/neu (breast cancer) - viral
=> HPV
Describe specific antigen vaccines.
- used for tumors with well-defined antigens
- ex: GP100 (widely expressed in tumors)
- delivery with adjuvant, viral vector, or through DCs
Describe whole tumor vaccines.
- must increase immunogenicity b/c tumor cells are poorly immunogenic
- add adjuvant, cytokines, B7
- must prime T cells in vitro
List ways tumors evade the immune system.
- downregulation or loss of antigen variant being attacked by T cell => loss of antigen-specific T cells and B cells
- loss of MHC Class I expression, TAP (for antigen processing)
- inhibitory cytokine release
- downregulation of immune checkpoints CTLA4 and PD1
Describe tumor passive immunotherapy.
- antibodies against tumor cell
=> anti-CD20 for non-hodgkins lymphoma
=> anti-HER2/neu for breast cancer - in vitro activated T cells
Define Rituxan.
- anti-CD20 monoclonal antibody therapy
- high response rate in B cell lymphomas
- works synergistically with chemotherapy and radiation
- recognizes B cell marker to regulate B cell activation
- induces growth arrest and apoptosis
Define Herceptin.
- anti-HER2 monoclonal antibody therapy
- works synergistically with chemotherapy and radiation
- recognizes EGF-like Receptor (ERBB2) to regulate cell proliferation
- induces growth arrest and apoptosis
Define TILs.
Tumor Infiltrating Lymphocytes (TILs)
- passive tumor therapy
- patient’s T cells are isolated, activated, and retransferred
- specific for that tumor
- most effective for highly immunogenic tumors (can be boosted with Tumor specific antigen vaccination)
- cons: cells don’t last forever, specificity
Define CARs.
Chimeric Antigen Receptors
- passive tumor therapy
- infusion with modified T cells expressing genetically engineered CAR
- components = Vh/VL from TAA antibody + TCR intracellular domains + zeta chain
- steps: leukapheresis + transduction with CAR T cells => expansion => infusion + chemotherapy
- activation of CAR leads to release of granzymes and proinflammatory cytokines => apoptosis induction in tumor cell
Describe the use of CTLA4 monoclonal antibodies in tumor therapy.
- Typically, CTLA4 is expressed on T cells after B7:CD28 activation to interact with B7 and inhibit immune response
- using CTLA4 mab blocks CTLA4 from binding to B7 and allows immune response to continue (good for killing tumors)
