Infections & Cancer

Question 1

First Vaccination

Answer 1

Edward Jenner
Vacca = cow

Question 2

Immune correlates of protection

Answer 2

Signs that a person is immune
E.g. antibodies, neutralizing antibodies

Question 3

Primary immunodeficiencies

Answer 3

IFNAR1 mutation
Signaling molecules down/upstream
TLR3 endosomal TLR that detects RNA

=> immune response not fast enough

Question 4

Short lived antibody responses

Answer 4

IgM & IgA

Question 5

SARS-CoV-2 vaccine

Answer 5

Target spike protein

mRNA in lipid capsule
replication incompetent adenovirus vector
recombinant protein vaccine => sabilized protein

Elicit T-cell effector and memory responses

Question 6

Immediate immune responses

Answer 6

Nonspecific, innate, no memory, no specific T-cells

Barriers like skin, mucins, acid
Phagocytes, early innate immune responses (NK), type 1 IFN

Question 7

Persistent viruses

Answer 7

Target MHC class I restricted antigen presentation
Block TAP

Question 8

Immunesystem evolution

Answer 8

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

Question 9

Cancer

Answer 9

Not a selection criterium for immune system => occurs too late

Question 10

What do T-cells recognize on tumerous cells?

Answer 10

Oncogenes
=> Mutated gene products
=> overexpression
=> proteins expressed in the wrong stage of development

=> new peptides

2 more??

Question 11

Tumor escape

Answer 11

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

Question 12

No MHC class I

Answer 12

Cells will be targeted by NK cells

Question 13

Tumor antigens

Answer 13

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

Question 14

Immune modulatory treatment

Answer 14

Adjuvents, fusion proteins, vaccines against tumor viruses

Question 15

Antibody therapy

Answer 15

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

Question 16

Leukemia

Answer 16

T/B-cell lymphoma

Question 17

Oncoviruses treatment

Answer 17

Target viral proteins
Vaccines

Question 18

Adoptive T-cell therapy

Answer 18

Collect T-cells, expand, reintroduce

Against EBV caused tumors =>

Question 19

Chimeric antigen receptors (CARs)

Answer 19

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

Question 20

Checkpoint blockade

Answer 20

Block receptor for inhibitory signal to T-cells with antibody

Question 21

Mutational load of tumors

Answer 21

Correlates with therapeutic efficacy

Higher in tumors that are highly mutated => e.g. melanoma (UV), lung cancer bc. smoking