Infections & Cancer Flashcards
First Vaccination
Edward Jenner
Vacca = cow
Immune correlates of protection
Signs that a person is immune
E.g. antibodies, neutralizing antibodies
Primary immunodeficiencies
IFNAR1 mutation
Signaling molecules down/upstream
TLR3 endosomal TLR that detects RNA
=> immune response not fast enough
Short lived antibody responses
IgM & IgA
SARS-CoV-2 vaccine
Target spike protein
mRNA in lipid capsule
replication incompetent adenovirus vector
recombinant protein vaccine => sabilized protein
Elicit T-cell effector and memory responses
Immediate immune responses
Nonspecific, innate, no memory, no specific T-cells
Barriers like skin, mucins, acid
Phagocytes, early innate immune responses (NK), type 1 IFN
Persistent viruses
Target MHC class I restricted antigen presentation
Block TAP
Immunesystem evolution
To be a selection pressure for a species, the pathogen has to be (life) threatening for a large enough amount of a population before reproduction
Cancer
Not a selection criterium for immune system => occurs too late
What do T-cells recognize on tumerous cells?
Oncogenes
=> Mutated gene products
=> overexpression
=> proteins expressed in the wrong stage of development
=> new peptides
2 more??
Tumor escape
No MHC molecules
No stimulation of T-cells: lack co-stimulants and/or cytokines
No antigen
Additional molecules (cytokines, enzymes) that suppress T-cell stimulation
Immune barrier => factors by tumor cell that create privileged-site, no detection by T-cells
No MHC class I
Cells will be targeted by NK cells
Tumor antigens
Mutated oncogene or tumor suppressor gene
=> not in germline, not in thymus
Cancer-testis antigens (at some time in ontogeny expressed, but not anymore, except in testis)
Get rid of tissues => e.g. proteins required for melanocyte development
=> vitilligo is immune response
=> anticancer: target tissues that are not essential
=> oncoviral proteins
Overexpressed/less glycosylated peptides
Immune modulatory treatment
Adjuvents, fusion proteins, vaccines against tumor viruses
Antibody therapy
Antibody variable region binds molecule on tumor cell, constant region interacts with e.g. NK/myloid cells Fc receptors
Antibody-toxin conjugates
Radionucleotides attached to antibody => target tumor cells specifically
Leukemia
T/B-cell lymphoma
Oncoviruses treatment
Target viral proteins
Vaccines
Adoptive T-cell therapy
Collect T-cells, expand, reintroduce
Against EBV caused tumors =>
Chimeric antigen receptors (CARs)
Antibody fragment and adoptive T-cells
=> bring new receptor in T-cell, instead of TCR
=> extracellular domain of receptor replaced by antibody variable region, link signaling domains of T-cell receptor with co stimulating signaling domains = chimeric antigen receptor
Checkpoint blockade
Block receptor for inhibitory signal to T-cells with antibody
Mutational load of tumors
Correlates with therapeutic efficacy
Higher in tumors that are highly mutated => e.g. melanoma (UV), lung cancer bc. smoking
