Lecture 15 - Murooka Flashcards

(54 cards)

1
Q

What is the main purpose of a vaccine?

A

To help the immune system long-term in its defense against infections and pathogens.

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2
Q

Briefly describe variolation.
When and where was this practiced?
What was the mortality rate of this practice?

A

The practice of innoculating a small amount of dried smallpox material from pustules into a child to produce long-lasting protection against re-infection.
Practiced in India and China in the 10th century.
Fatality was approx 3%

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3
Q

Briefly describe Edward Jenner and his role in the vaccination practice.

A

Edward Jenner found that milkmaids exposed to cowpox were immune to smallpox and proved experimentally that vaccination was scientifically valid and useful.

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4
Q

Briefly describe Louis Pasteur and his role in the vaccination practice.

A

Louis Pasteur popularized the word vaccine and further developed Jenner’s work with germ theory and attenuation (rabies).

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5
Q

When was smallpox officially eradicated?

A

1979

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6
Q

Name three major pathogens that are not cooperative in succumbing to vaccination efforts.

A

Malaria
Tuberculosis
HIV

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7
Q

What are the two modern vaccination strategies?

A

Active (vaccination) and passive immunity

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8
Q

Describe in brief the basic properties and actions of a vaccine and their theory.

A

It is a modified microbe, or a component of which, that is able to stimulate the immune system without acting negatively upon it (biologically inactive but immunologically active) which is intended to trick the immune system into producing a pathogen targeted memory B and T cell response so that, once encountered, the body can recognize a pathogen a mount an appropriate response in order to prevent or lessen the disease.

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9
Q

What is the term for the process of stimulating protective adaptive immune responses against microbes?

A

Vaccination.
Trick question!
You’d better get this one right.

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10
Q

All vaccines have two parts: what are they?

A

Antigen

Adjuvant

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11
Q

How do many currently used and effective vaccines work against the pathogens?

A

They induce antibody formation against the pathogens in question.

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12
Q

What are the two protective mechanisms of vaccines which are able to induce antibodies?
How are vaccines able to do this?

A
  1. Prevent damage caused by the pathogen - pre-existing antibodies can neutralize the activity of pathogens that would cause damage to the host.
  2. Prevent secondary infections - antibody affinity, isotype, complement, and phagocyte activation all play a part.
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13
Q

Describe in brief the primary and secondary response of the immune system upon antigen presentation.

A

Primary response: Ag induces B and/or T cell responses leaving small number of memory cells.
Secondary response: Memory B and T cells rapidly expand compared to primary response resulting in higher titer of Ag specific, high affinity antibodies.

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14
Q

Why would someone receive a booster shot?

A

It increases B and T cell responses to keep memory cells alive for a particular pathogen.

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15
Q

Briefly describe the isotypes of each antibody involved in primary and secondary responses and the concentration in which they are present.

A

Primary: Early IgM response and later IgG (and/or IgA) response
Secondary: Rapid and early IgG (and/or IgA) responses

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16
Q

How do polysaccharide vaccines activate the immune system?
How long term do they work?
How can they work better?

A

PS vaccines are composed of portions of bacteria so they activate B lymphocytes through T cell independent mechanisms via induction of intermediate-affinity IgG antibodies.
No long-term memory generation.
Conjugate vaccines

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17
Q

Briefly describe how vaccines activate T cell-dependent B cell immunity.

A

Intramuscular vaccines release Ag/Adj into the muscles to stimulate DCs so that they recognize Ag and then carry it to the lymph node to activate the immune system. From there, B cells make plasma and memory cells able to stimulate T cells and create antibody.

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18
Q

How does the T cell-dependent B cell immunity act during secondary challenge via a pathogen/

A

B memory cells will be stimulated by an Ag + APC which will then clonally expand B cells to produce large amounts of IgG Abs.

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19
Q

What are the parts of an intradermal vaccine?

A

Protein or peptide

Adjuvant

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20
Q

What is the point of a peptide/antigen in a vaccine?

What is the purpose of adjuvant in a vaccine?

A

Antigen is taken up by an immature DC and able to present it to T cells.
Adjuvant activates DCs.

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21
Q

How do antibodies prevent/reduce infections?

A

Binding to enzymatic active sites of toxins/preventing diffusion.
Neutralizing viral replication
Promoting opsonization
Activating complement cascades.

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22
Q

How do CTLs reduce, control, and clear intracellular pathogens?

A

Directly killing infected cells (perforin/granzyme).

Indirectly killing infected cells through antimicrobial cytokine release.

23
Q

How do CD4+ T cells reduce, control, and clear pathogens?

A

Producing IFN gamma, TNF alpha/beta, IL2, and IL3 and supporting differentiation of B cells, CTLs, and macrophages.(th1)

Producing IL4, 5, 13, 6, and 10 (th2)

24
Q

Against which diseases have vaccinations been the most effective?

A
Diphtheria
H.influenzae
Measles
Mumps
Polio
Rubella
Smallpox
Tetanus
Varicella
25
Name the four kinds of passive immunization.
Maternal acquired antibodies Pooled human Ig preparations Specifically pooled human Ig Isolated antibodies
26
Describe passive immunization.
Administration of Ig for immediate, short-term protection.
27
Describe maternally acquired antibodies for passive immunization.
Transferred via colotrum (IgG) and milk (IgA).
28
Describe pooled human Ig preparations for passive immunization.
Intravenous Ig used for immunodeficiency patients, premature babies, patients with measles or hepatitis.
29
Describe specifically pooled human Ig for passive immunization.
From individuals selected for having high Ab titres against a certain pathogen (eg. rabies, hepatitis, and tetanus)
30
Describe isolated antibodies for passive immunization.
From immunized horses/rabbits for use as anti-toxin/anti-venom.
31
Name four of the 8 different types of vaccines. | Bonus points if you answer with the experimental vaccines.
``` Live attenuated Killed organism Subunit Toxoid Conjugate Vector DNA (experimental) Peptide (experimental) ```
32
Why are attenuated microorganisms used in vaccines? How is this accomplished?
Attenuation changes their physical biology to make them less able to grow in their natural host. This can be done by culturing in adverse conditions, passaging in non-humans, or genetic engineering.
33
Where are live-attenuated vaccines administered and what do they do? What are the potential problems with them?
Administered at site of natural infection (mucosal surfaces) and elicits antibody & CD4/CD8+ T-cell responses. Reversion of vaccine to virulent strain could happen. Cannot be safely given to immuno-compromised individuals.
34
How are killed-organism vaccines prepared and what do they do? What are the potential drawbacks to these vaccines?
Inactivated by head/chemicals and they induce strong and durable Ab responses. High doses and booster injections are required as they are not as strong as live-attenuated. T cell responses are generally absent.
35
Describe subunit vaccines. What are they made of? Describe these. What possible drawbacks do these vaccines have?
Made of only PARTS of a microbe critical for induction of immunity. Purified components: such as polysaccharides from the capsule. Recombinant forms: such as viral surface antigen from bacterially cultured viruses. Littel to no T cell responses are generated.
36
Briefly describe toxoid vaccines.
Modified toxins in the form of harmless toxoids are injected. They are changed harmless through chemical treatments without losing antigenic determinants. Anti-toxoid antibodies will react well to original toxin.
37
Briefly describe conjugate vaccines.
Covalently attaching a poor Ag to a strong Ag to enhance poor Ag response. E.g. Infants have weak polysaccharide Ag response so it is linked to tetanus toxoid to increase response.
38
Briefly describe vector vaccines.
Use of an attenuated virus/bacterium to introduce microbial DNA into cells. Vector delivers DNA to most appropriate sites. Live vectors infect slowly and keep producing antigens that can initiate Ab and cell-mediated immunity.
39
Briefly describe DNA vaccines and how they work. What could the possible drawbacks be?
Vaccination subsists of non-replicating plasmids encoding immunogen and pro-inflammatory cytokines. Injected intramuscularly = Ab and CTL responses. Immunogen transferred and processed by DCs. Weak compared to live-attenuated. Inflammatory mediators required optomization.
40
Briefly describe peptide vaccines. How are peptides chosen? What are the possible cons to this vaccine method?
Overlapping peptides from immunogenic proteins tested for immune activation. Reverse immunogenic approach by taking MHC binding peptides and recreating them via mass spec. Peptide may not bind to all MHC molecules. Direct MHC peptide exchange may induce tolerance. Cross presentation via DCs is required to laod synthetic peptides onto MHC I.
41
Why do all vaccines require adjuvant? Which adjuvant is currently in use?
To initiate the immune system. Adjuvants enhance immunogenicity via stimulation of NLRP3 pathway in DCs which activates the inflammasome initiating adaptive immunity. Alum
42
What is the depot effect?
Repository adjuvants provide long-lived reservoir of antigen
43
On what cells does alum act?
Th2 cells.
44
How do vaccine Ags get presented to the immune system?
APCs
45
How can we try to engineer Ags to better be taken up by APCs?
1. Coat vaccine Ag in mannose to enhace uptake by mannose receptors on APCs. 2. Ag delivered in form of immune complex taking advantage of Ab and complement binding by Fc and complement receptors. 3. Coupling Ags to a signal peptide that directs into lysosomes and endosomes for efficient cross presentation.
46
Describe the components of a hypothetical "all-in-one" omnipotent liposome particle adjuvant.
Would have acid resistance for stomach acid and stimulate CD8 T cells Would have multiple Ags on surface. Would have multiple adjuvants to activate multiple APCs Would have target lymphocytes (multiple cell stimulation with IL2, 4, and 12) Would have target site binding capabilities. May have additional proteins inside the liposome.
47
Name a few diseases against which effective vaccines are not yet available.
``` Malaria TB Schistosomiasis Respiratory Disease Diarrheal disease AIDS Chlamydia Ebola Zika ```
48
Why can measles not be vaccinated against world wide?
The vaccine is heat sensitive and very difficult to use in tropical countries.
49
Why is it so difficult to develop vaccines against chronic infections?
These pathogens have evolved to live in us long term and adapt to our immune system and can evade it very well. There are also distinct life cycle phases that can be targeted instead of just one target. They can usually mutate very quickly.
50
How does ebola virus affect the body?
It infects monocytes which release cytokines in a storm and die. This causes vascular instability and shock as well as epithelial detachment/release and cell death.
51
How is the current ebola vaccine in trials able to function?
The ebola Zaire RNA for the GP has been inserted into VSV so that the VSV expresses GP and tricks the immune system into mounting a response against ebola Zaire.
52
What kind of Zika vaccine is currently being researched with good preliminary results?
Antibody vaccine for secondary immunity.
53
Briefly describe the HIV STEP trial of 2007.
Attenuated adenovirus type 5 was used as a vector for gag, pol, and nef HIV genes and injected into people with high risk of HIV infection. Results: no protection and increased susceptibility likely due to previous Adenovirus immunity.
54
How can the shortcomings of the HIV STEP 2007 trial be overcome?
Instead of using a virus that humans may have contacted previously a virus like canary pox can be used as the vector with gag, pro, and recombinant GP120. So far, so good in Thailand.