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CMMB 527 > Theme 8: Response to Pathogens and Vaccinations > Flashcards

Theme 8: Response to Pathogens and Vaccinations Flashcards

1
Q

What are the 2 initial barriers that a pathogen must face to cause an infection?

A

Physical and chemical barriers

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2
Q

Which components of the immune system control mucosal/barrier infections?

A

1) TH2-type responses
2) IgAs in sections/barrier sites bind and neutralize pathogens such that they are unable to attach and infect host cells
3) AMPs (antimicrobial products)

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3
Q

Which components of the immune system control extracellular pathogens?

A

1) Complement
2) AMPs (antimicrobial products)
3) Antibodies
4) Cytokines
5) Phagocytes

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4
Q

Which components of the immune system control intracellular infections?

A

1) TH1-type responses
2) Activation of endosomal (TLRs) and cytosolic PRRs (NLRs, RIGs) resulting in inflammasome formation, cytokine secretion
3) NKCs and CTLs

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5
Q

What is latent infection?

A

Viral DNA may be integrated into the DNA of host cells, but no infectious virus is produced

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6
Q

What is a persistent infection?

A

Bacteria can survive within the endosomal vesicles of infected cells

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7
Q

What is dangerous about latent/persistent infections?

A

If the immune system becomes compromised for any reason, the latent microbe may be reactivated and result in an infection that causes significant damage

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8
Q

Explain the concept of latent/persistent infections

A

Infections in which the immune response controls but does not eliminate the microbe, and the microbe survives without propagating the infection

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9
Q

Describe how viruses infect host cells

A

1) Viruses enter host cells by binding to cell surface molecules
2) Viral replication interferes with normal cellular protein synthesis and function (leading to injury/death)

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10
Q

How is infection against viruses prevented?

A

1) Type I interferon release by DCs (innate)
2) Neutralizing antibodies (adaptive)

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11
Q

What are measures to destroy infected cells?

A

1) NKCs (innate)
2) CTLs (adaptive)

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12
Q

Explain how type I interferons are induced and the associated effects

A

1) Recognition of viral RNA/DNA by endosomal TLRs or cytoplasmic RIGs
2) Activation of IRF TFs which stimulate interferon transcription
3) Interferons function to inhibit viral replication in both infected and uninfected cells by inducing an antiviral-state

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13
Q

Explain how antibodies act to prevent infection by viruses

A

1) Antiviral antibodies (e.g., IgA) bind to viral envelopes/capsids to prevent virus attachment and entry into cells
2) Opsonization promotes clearance by phagocytes/complement
3) Only works during extracellular stage of viruses

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14
Q

Explain how CTLs kill infected cells

A

1) Recognize antigens presented on MHC I molecules
2) Cross-presentation by DCs allows for T cells to be alerted of infection in other cells
3) Direct killing via cytotoxic release or Fas-binding, cytokine secretion, etc.

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15
Q

What is an example of virus defense mechanisms?

A

Inhibition of antigen processing (blocking TAP, MHC I production)

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16
Q

What are innate measures against extracellular bacteria?

A

1) Complement
2) Phagocytosis
3) Inflammation

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17
Q

What are adaptive measures against extracellular bacteria?

A

1) Antibodies
2) CD4+ T cells (cytokine production to enhance responses, B cell proliferation, recruitment, increased phagocytosis and antimicrobial activity)
3) TH17 response (recruitment of neutrophils and monocytes, inflammation)

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18
Q

What are some defense mechanisms of extracellular bacteria?

A

1) Genetic variation of surface antigens
2) Molecules to inactivate complement
3) Surviving within the phagocytic cell

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19
Q

What are innate measures against intracellular bacteria?

A

1) NKCs
2) Phagocytes

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20
Q

What are adaptive measures against intracellular bacteria?

A

TH-1 type response

21
Q

What are innate measures against intracellular parasites?

A

Mainly phagocytes, but many parasites are resistant and can replicate within macrophages

22
Q

Explain the infection cycle of malaria parasite

A

1) Infects RBCs (do not have MHC I)
2) Intracellular stages resist antibody-based responses
3) Extracellular stages are short-lived which prevents good immune stimulation

23
Q

Explain the infection cycle of leishmaniasis and immune responses against the intracellular parasite

A

1) Lives in macrophage phagogosomes, avoiding phagocytosis
2) Resistance to infection is mediated by an effective TH1 response
3) Individuals skewed towards TH2 type response are more susceptible

24
Q

Explain African sleeping sickness

A

1) Caused by extracellular parasites that live in the CNS
2) Parasite expresses 1 variable surface gene on its surface as a time to prevent effective immunity

25
Q

Describe immune responses against Helminths (parasitic worms)

A

1) Parasite is extracellular and capable of decreasing external Ag expression/wrapping themselves in host proteins to limit immunity
2) TH2 type response (eliminated by IgE secretion and eosinophil-mediated killing)

26
Q

What are some defense mechanisms of parasites?

A

1) Varying antigens during residence in host
2) Masking and shedding surface antigens

27
Q

What are innate mechanisms against fungi?

A

1) Macrophage phagocytosis
2) Commensal fungal organisms “crowd out” pathogenic fungi
3) Complement

28
Q

What are adaptive mechanisms against fungi?

A

Mostly TH1 responses (TH2/Treg response associated with susceptibility)

29
Q

What are some defense mechanisms of fungi?

A

1) Have capsules to prevent detection by PRRs
2) Fungi-induced expulsion from macrophages

30
Q

What are 4 factors that can contribute to reemerging diseases

A

1) Drug resistance due to improper antibiotic use
2) Zoonotic pathogens
3) Laxity in vaccination programs
4) Environmental/geographical changes

31
Q

What are useful immunogens?

A

Antigens that stimulate B and T cell response

32
Q

What are the phases of clinical trials

A

Phase I - small scale to assess safety and adverse effects
Phase II - mid-scale to assess preparation, dosage, and optimal administration
Phase III - large scale to assess safety, efficacy, and population level effects

33
Q

What are the 5 components of a vaccine?

A

1) Active ingredient
2) Adjuvants
3) Preservatives/stabilizers
4) Residual traces
5) Water

34
Q

What are RNA vaccines?

A

Introduce an mRNA sequence to host cells which codes for a specific antigen

35
Q

What are DNA vaccines?

A

Inoculation of plasmid containing complementary DNA (cDNA) encoding an antigen

36
Q

What are viral vectors?

A

Live viruses used to carry DNA into human cells

37
Q

What are recombinant vector vaccines and the pros and cons?

A

1) Vaccine vector genetically engineered to carry another pathogen’s genes and express them
2) Pros = all the benefits of an attenuated vaccine but with fewer risks
3) Cons = stability issues

38
Q

What are subunit vaccines and the pros and cons?

A

1) Purified macromolecules
2) Pros and cons similar to inactived/killed vaccines

39
Q

What is passive immunity?

A

Immunity conferred from preformed Abs, short-lived because protection lasts as long as the Ab persists

40
Q

When is passive immunity useful?

A

1) Immune deficiency
2) Toxin/venom exposure with immediate threat to life
3) Exposure to pathogens that can cause death faster than an immune response can develop

41
Q

What is an issue with passive immunity?

A

Can cause type I (IgE mediated) or type III (immune complex mediated) hypersensitivities

42
Q

What is active immunity?

A

Induction of immune memory (stimulation of B and T cells)

43
Q

What are live attenuated vaccines and the pros and cons?

A

1) Weakened pathogens
2) Pros = humoral and cell-mediated immunity, no booster
3) Cons = potential of infection, cold chain transport

44
Q

What are inactivated/killed vaccines and the pros and cons?

A

1) Heated/chemically treated pathogens
2) Pros = no risk of infection, easy storage
3) Cons = humoral immunity only, boosters, adjuvants required

45
Q

What are the pros and cons of DNA/RNA vaccines?

A

1) Pros = humoral and cell-mediated immunity, enhanced memory, stable and customizable
2) Cons = storage conditions

46
Q

What are the challenges with inducing CTL responses and how is this bypassed?

A

1) CD8+ T cells require presentation of antigens on MHC I molecules (source must be endogenous)
2) Solved by using lipid nanoparticles for delivery of vaccines (e.g., mRNA) into host cells

47
Q

What are adjuvants?

A

1) Molecules to enhance immunological response for vaccinations, such as PAMPs which can stimulate PRRs
2) Primarily targets innate response elements and helps with vaccine delivery (prolongs exposure)
3) Not antigen specific

48
Q

How is vaccine efficacy measured?

A

Measured by its ability to prevent or reduce severe disease

CMMB 527 (10 decks)

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