Vaccines and Diseases

Question 1

How are mucosal infections controlled?

Answer 1

-By TH2 type response
-IgA produced in MALT by B-cells and sent across the membrane to maintain barrier integrity -> binds and inhibits surface attachment
-TH2 activate ILC2, release cytokines, and IgE (by IL-4, IL-5) control pathogen on the surface

Question 2

Control of intracellular VS extracellular pathogens:

Answer 2

-Extracellular: helminths, fungi, extracellular bacteria
start with IgM, no class-switch or hypermutation yet but pentamer able to collect some pathogens
predominantly IgG in the blood

-Intracellular: recognized by cytosolic PRRs (virus), -> cytokine secretion, inflammasome activation, and induction of cytotoxic NK cells and CTLs; some bacteria hide inside vesicles

Question 3

What are ways to combat Viruses?

Answer 3

-Innate immunity: Complement, AMPs, recognition of PAMPs

-PRRs induce antiviral type I interferon expression, inflammasome complex assembly (pyroptosis), and NK cell activation

-humoral (B-cells) and cell-mediated immunity (NK sense after lack of MHC-I stress signal, virus shut down MHC-I)

Question 4

Which PRR activates inflammasomes?

Answer 4

-NLR inside the cell (viruses dsDNA (or nucleus damage), bacterias LPS)

-CLRs and TLRs detect PAMPs outside the cell or inside the vesicle, always separate from the cytoplasm
-STING is also cytoplasmic (cGMP Synthase) -> no inflammasome, just cytokine IFN to alarm neighbors

Question 5

How does an Ab combat viruses?

Answer 5

-Neutralization -> prevent it from binding to target cells
-Opsonization
-Complement activation

Question 6

How do CTLs combat viruses?

Answer 6

-CD4+ helper T cells secrete cytokines:
IFN-gamma for antiviral state -> IgG to recruit macrophages to take up the pieces after the infected cells got killed
IL-2 for CTL differentiation

-CD8+ destroy infected host cells

Question 7

How does Influenza change its surface antigens?

Answer 7

-Influenza has two primary surface proteins, hemagglutinin (HA) and neuraminidase (NA)

-error-prone ssRNA(-) genome and RNA polymerase lead to changes in HA/NA

-recombination due to segmented genome, when different viruses infect the same cell

Question 8

What is the Original Antigenic Sin?

Answer 8

-if naive B-cell binds to a mutated version of H1 and the original H1-Ag with Fc receptors -> the naïve B cells will inhibit activation -> the idea is to prevent autoimmunity (it has created Ab already, so let them do the work instead of changing and risk to create a self-reactive Ab)

-Consequence: during multiple infections the memory response is less effective as mutated antigens are produced

Question 9

What are the immune responses to bacteria?

Answer 9

-Extracellular (E.coli): TH2 response -> Ab (neutralization of toxins), Complement activation, Opsonization+Phagocytosis, Mast cells and degranulation
-Mucosal bacteria (vivia cholera): IgA response

-Intracellular (Salmonella, TB in macrophages): TH1

Question 10

Why is malaria hard to combat?

Answer 10

-Ag shifting -> B-cells don’t create new Ab, don’t adjust
-Blood cells cant be targeted no MHC-I
-Short blood circulation of the free pathogen
-outer coat shedding avoid Ab response

Question 11

How are parasitic worms attacked?

Answer 11

-Exclusively extracellular -> so TH2 response: ILC2 and IL-4 production
-IgE production and recruitment of eosinophils

Question 12

What are immune responses against fungi?

Answer 12

-Innate immunity: PRR, C-type lectin receptors (CLRs) looking for fungal carbohydrates

-Commensal fungal inhibit pathogen fungi (this is why antibacterial medications can result in oral thrush or vaginal candida due to less competition)
-fungal destruction by Phagocytosis

-Fungi can create capsules against PRR binding or escape macrophages

Question 13

Reasons for reemerging diseases:

Answer 13

-Combinations of diseases (HIV and TB bc patients get immunocompromised)
-Improper antibiotic use (MDR TB, MRSA)
-Zoonotic pathogens (Ebola - fruit bat)
-Laxity in vaccination program adherence (Diphtheria and Whooping cough)

Question 14

What are attenuated vaccines?

Answer 14

Measles, Mumps, Rubella, Rota, Tuberculose, Varicella, Yellow fever, Polio (sabin vaccine)
-Weakened (genetically, or let it replicate multiple times in a mouse and hope it got weak)

PRO: Retain their ability to replicate, promoting
both humoral and cell-mediated responses -> so no BOOSTER

Con: May mutate back (revert) to pathogenic form,
may have side effects, require cold-chain

Question 15

Pros and Cons of Killed Vaccines:

Answer 15

Cholera, Influenza, Hep A, Plague, Polio (Salk vaccine), Rabies
-Killed by heat or chemicals

Pro: No reversion to pathogenic form and easier to transport (more stable)

Cons:
-doesn’t replicate, no cell-mediated immunity (only humoral)
-need adjuvants
-dangerous if not all pathogen is
killed/inactivated

Question 16

Subunit vaccines:

Answer 16

-Toxoid: Diphtheria, tetanus
-Subunit: Hep B, Pertussis
-Conjugate: Haemophilus influenza type B

-> use purified macromolecules, Inactivated exotoxins/toxoids, surface glycoproteins, capsular polysaccharides

-Pro/Cons similar to Killed/inactivated vaccines

Question 17

Conjugated vaccines

Answer 17

non-immunogenic part combined with strongly immunogenic toxin

-Vaccine to H. influenza is a conjugate of capsular polysaccharide (non-protein) with tetanus toxoid (protein)
-> now T helper cell involved -> IgM switch to IgG and memory cells

Question 18

What are Immuno stimulating complexes (ISCOM) good for?

Answer 18

They are lipids where the Ag can be inserted -> Lipids fuse with the host cell and the Ag can be delivered into the cell -> taken up to present MHC-I for CTL response and good CTL memory cells

-if it is only on the outside DC will come and cross-present with T-helper cell and some CTL, but to get the strong CTL response the subunit must go inside the cell

Question 19

Pros and Cons of Recombinant Vector Vaccines:

Answer 19

-the attenuated Ag is placed into a live vector (bacteria, virus, salmonella transferring HIV) to carry it into the cell and express it

Pros: it replicates -> strong immune response and memory cells and no BOOSTER and it gets inside the cell for CTL response

Cons: still alive so, stability issues
if you have Ab against the vector, naive B-cells will be turned off -> Original Antigen Sin

Question 20

Pros and Cons of DNA/RNA Vaccines:

Answer 20

-DNA vaccines through plasmids into muscle
host cell takes it up and presents it with MHC-I -> CTL response

-RNA vaccines: mRNA in a liposome injected -> less stable (need cold-chain) than DNA, but cant integrate

Pros: has humoral and cell-mediated response and memory, stable and customizable (takes 1 week, flu vaccine (killed vaccine) would take 6 months

Question 21

Adjuvants:

Answer 21

-Are used to enhance the immune response when using only proteins, proteins alone don’t cause a strong immune response

-3 examples
-Alum for TH2 response
-ASO4 (alum + TLR4 agonist switches to TH1) for TH1
-Virosome viral envelope with no genes, just to get the vaccine into the cell