13: Antibodies in vaccination and immunotherapy 🏁

Question 1

History of vaccination

Answer 1

1796 - Jenner: Inoculation with coxpox
Roberet Koch: diseases caused by microorganisms
Padsteur: developed virst vaccines against cholera / rabies
van Behring /Kitasato: antibodies
Bordet: heat labile complementary factpr

Question 2

Differerence between primary response and secondary antibody response

Answer 2

Secondary response has a higher frequency of antigen specific B cells, more IgG and IgA, higher affinity antibodies due to somatic hypermutation and affinity maturation

Question 3

Why reperated immunization ?

Answer 3

It increases the amount of antibody (IgG) + the affinity compared to just 1 immunization

Question 4

Antiviral immunity after smallpox vaccination + time (3)

Answer 4

antibody levels stay high for decades
CD4 and CD8 memory T cells have a halflife of 8-15 years

Question 5

Diptheria produces bacterial toxins. Name a main effector mechanism that protects cells from damage

Answer 5

IgG antibodies bind to toxins for neutralization to inhibit cell receptor binding of toxin

Question 6

Name 4 different type of vaccine + 2 examples for each

Answer 6

Live attenauted
Oral Polio vaccine
BCG

Inactivated
Inactivated Polio virus vaccine
Pertussis

Subunit
HepB
HPV

Toxoid
Tetanus / diphteria toxoids

Question 7

What’s the problem with Streptococcus pneumonuae vaccination?

Answer 7

Host defense is type-specific, so antibodies against one type doesn’t really help to prevent infection of other type

Question 8

How do conjugate vaccine work?
Give an example

Answer 8

e.g. Polysacchride epitope linked to tetanus toxoid

B cells bind bact. polysacchride epitope linked to toxoid, internlization and processing for Ag presentation takes place

Peptides from toxoid are presented to T cell, activated B cells produces antibody against polysacchride antigen on surface of bacterium

Question 9

Influenza
main surface proteins
vaccination efficiency is dependent on
how is attenuation achieved ?

Answer 9

Hemagglutinin, neuraminidase

Vaccination efficiency is dependent on subtypes, antigenic shift and antigenic drift would result in altered NA and HA so antibodies / memory against other subtypes have decreased affinity

Normal via growth selection (non human cells) but for Influenza recombinant DNA techniques are used

Question 10

mRNA vaccination - 2 types and difference in one sentence

Answer 10

non replicating and self-amplifying mRNA

self amplifying mRNA with replicase system that makes it possible to replicate mRNA

Question 11

5 functions of antibodies in host defense

Answer 11

bind to bacterial toxins to neutralize them, neutralized toxins can be taken up by macrophages

bind to bacteria in extracellular space for opsonization, opsonized bacteria can be phagocytosed by macrophages, aggregation of IgG on bact. surface allows cross linkinf of Fc receptors on macrophages + complement factors like C3b bind to CR1 that also activates macrophages for phagocytosis, also Fc receptors of NK cells can bind the same way to kill target cell

bind to bacteria in plasma for complement activation, lysis (MAC) and iopsonization by (C3b)

bind to viruses to block receptor binding and fusion (igG/IgA to HA of Influenza)

bind to adhesion molecules of bacteria to block colonization (IgG/IgA against Salmonella)

Question 12

Diseases that still need effective vaccines: 3 examples

Answer 12

Malaria, respiratory infection, HIV

Question 13

Criteria for an effective vaccine

Answer 13

Safety
Protective
long-life
induces neutralizing antibodies
induces protective T cells
Practical considerations like low costs

Question 14

3 New therapeutic targets for human autoimmune disease treatment

Answer 14

Integrin target
- alpha4:beta1 monoclonal antibodies that target Integrins
- Rheomatoid athritis and multiple sclerosis

B cell target
- CD20 specififc monoclonal AB
- Rheomatoid athritis and multiple sclerosis

Cytokine targets
- several option like TNF specific mAB
- Rheomatoid athritis

T cells
- CD3 specific mAb
- type 1 diabetes

Risk
Increased risk of infections

Question 15

4 different kinds of mAB

Answer 15

• omab: fully mouse
• ximab: chimeric
• zumab: humanized
• umab: fully human

Question 16

Using humoral immune response to target tumors (3)

Answer 16

• tumor specific antibodies that bind to tumor cell, NK cells can cell opsonized cells
• tumor specific antibody conjugated to toxin, conjugates internalized, kills cell
• tumor specific antibidy conjugated to radionuclide, radiation kills tumor cell and neighbouring cell

Question 17

CAR-T-cells

Answer 17

T cells harvested from blood of patient with B cell tumor, retrovirus encoding anti-CD19 CAR infects T cell that are activated with antibodies, infected T cells express an anti-CD19 chimeric antigen receptor, t cells infused into patient for antitumor activity

Question 18

Immuno-oncology drugs

Answer 18

Cancer cells sense that their are under attack and increase expression of inhibitory receptors so T cells will not kill these cells

CTLA-4: Ipilimumab binds to CTLA-4, an inhibitory receptor for interaction between DCs and T cell to activate T cell response

PD-1 on T cell and PD-L1 on DCs: Pembrolizumab binds to PD-1, Atezolizumab binds to PD-L1 to decrease inhibitpry signal