(FE) Week 10 Infection & Vaccination Flashcards

1
Q

What are the principal mechanisms of defense against microbes?

A

1) Antibodies
- Block microbe infectivity by neutralisation

2) Phagocytes
- Phagocytosis and intracellular killing of microbes
~ With help from Ab and CD4+ T cells

3) CD8+ T cells
- Kills infected cells when infx cannot be cleared by phagocytes

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2
Q

What are the roles of Ab isotypes in host defense?

A

Bacteria, fungi, worms:
- IgM, IgG, IgA

Parasitic worms:
- IgE

Mucosal immunity:
- IgA
~ Prevents microbes from using surfaces as portals of entry for host colonisation

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3
Q

Role of cytokines in effector functions of CD4+ T cells?

A

1) Th1
- IFN-gamma + macrophage = kill intracellular bacteria

2) Th2
- IL-4 + Macrophages = expel parasites

3) Tfh (T-follicular helper cells)
- Makes IL and expresses CD40L
~ Want to make high affinity class switch b

4) Th17
- IL attracts neutrophils and induces antimicrobial peptide production

5) Treg
- Inhibits immune response
~ Prevents exacerbation of immune response

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4
Q

What cytotoxic molecules are released by T cells?

A
  • Perforin and granzyme
    ~ Proteases degrade cellular components (protein and DNA) to shut down production of viral proteins
    ~ Known as programmed cell death/apoptosis
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5
Q

How do NK cells kill infected cells?

A
  • NK cells have the ability to recognize and kill infected cells without MHC
  • Cytoplasm contains cytotoxic proteins
    ~ Perforin and granzymes
  • Perforin forms pores in cell membrane, allowing granzymes and other molecules to cause apoptosis
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6
Q

What are the specialised immune responses to extracellular bacteria?

A

1) Antibodies
- Neutralisation
- Opsonisation + phagocytosis
- Activates complement
~ Phagocytosis
- Inflammation
- Bacterial lysis

2) Helper T cells
- Cytokines induce Ab response in B cells
- Activates macrophages for pahgocytosis and bacterial killing
- Inflammation

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7
Q

What are the adverse effects of anti-bacterial immunity?

A
  • Acute inflammation and tissue damage
    ~ + system effects (fever)
    ~ Septic shock in severe cases
  • Rare late sequelae (cross-reactivity with self tissues) causing rheumatic fever, heart disease
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8
Q

What are the specialised immune responses to fungi?

A

1) Innate
- Recognition of fungal cell walls by DC, macrophages and neutrophils via PRRs
- Phagocytosis and killing via production of reactive oxygen species

2) Adaptive
- IFNgamma and IL

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9
Q

What are the specialised immune responses to parasites?

A

1) Helminths (extracellular worm)
- Triggered by Th2 cells (IL, IGE, eosinophils)
- Effect: Eosinophils kill IgE-coated parasites (Antibody dependent cell cytotoxicity ADCC)
~ Eosinophils are better at killing helminths

2) Leishmania (intracellular protoza)
- Triggered by T cells producing IFN
- Phagocytes kill parasites living in intracellular compartment

3) Plasmodium (intracellular protozoa)
- CD8+ cells secrete cytokines
- Activates macrophages, neutrophils to cheat on the mission

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10
Q

What is immunization?

A
  • Action of receiving a vaccine and becoming immune to a disease
  • Provocation of an adaptive immune response to an antigen introduced to the body

2 types: Passive and Active

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11
Q

What is passive immunity?

A
  • Immunity given to you
    ~ Naturally (from mother -> child)
    ~ Artificial (injection of PREFORMED Ab)
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12
Q

What are the pros and cons of artificial passive immunity?

A

Pros:
- Immediate protection
- Good for immunosuppressed px

Cons:
- Short protection period
- Potential allergic response

Eg. Diphtheria, tetanus, anti-Hep A,B, anti-rabies, anti-CMV

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13
Q

What is active immunity?

A
  • Immunity following exposure to antigen
    ~ Natural (following clinical infx)
    ~ Artificial (following vaccination)
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14
Q

What is the principle of cross-reaction?

A
  • 2 different viruses share some surface antigens
  • Immunization with a virus induces some Ab against its surface Ag
  • The Ab from the first virus can also bind to and neutralise the second virus with similar Ag
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15
Q

What are the immunological principles of vaccination?

A

1) Adaptive immunity must be established before infection
2) Immunity induced must be durable enough to be clinically relevant but induce little to no disease symptoms
3) Immunological mechanisms of protection by
- Ab
- Memory CD4+ and CD8+ T cells

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16
Q

What are the typical components of vaccines?

A

1) Antigens
2) Adjuvants
- Substance that enhances the immune response to a weakly immunogenic Ag
- Non-specific to pathogen
- May allow slow release of Ag to allow time for memory response to develop
- eg Alum, Liposomes, CpG

17
Q

What are the 6 main types of vaccines?

A

1) Inactivated/killed vaccines
2) Attenuated/live vaccines
3) Toxoids
4) Conjugated vaccines
5) Subunit vaccines
6) mRNA vaccines

18
Q

What are inactivated/killed vaccines?

A
  • By heat or chemical fixation
  • Needs multiple injections in its initial course
    ~ Including boosters
  • May be toxic as from toxins in killed bacteria
  • Needs adjuvant
  • Poor cell-mediated immunity, mostly CD4+

e.g. cholera, plague, influenza, rabies, polio

19
Q

What are attenuated/live vaccines?

A
  • Viruses are passaged in a non-human hosts (eg influenza virus in embryonic eggs)

Pros:
- Mimics natural infection
~ Produces large antigenic stimulus
- Generally induces T+B lymphocyte responses
~ Mostly CD8+ cells
- Long-lasting protection

Cons:
- May retain some pathogenicity
~ May revert to virulence
- Not safe enough for immunocompromised subjects
- Requires a good cold chain

e.g. polio, mmr, yellow fever, chickenpox, bcg, typhoid

20
Q

What are toxoid vaccines?

A
  • Chemically modified toxin from a pathogenic microorganism, that is no longer toxic but still antigenic
  • Intended to build immunity against toxins, not the bacteria that produces it

eg tetanus toxoid, diphtheria toxoid

21
Q

What are conjugated vaccines?

A
  • Some Ag which are not very immunogenic need to be conjugated to a protein in order to be effective

eg polysaccharides from pneumococcus and meningococcal capsules conjugated to tetanus toxoid

22
Q

What are subunit vaccines?

A
  • Presents >1 Ag to immune system without introducing pathogen particles (ie just a small bit of pathogen needed)
  • Achieved by:
    ~ Isolation of specific protein from pathogen and only administering that
    ~ Putting Ag gene from pathogen into another vector to make a recombinant virus to express the Ag

Pros:
- Cannot revert back to virulence
- Safe for immunocompromised px
- Can withstand changes in conditions (temp, humidity etc)

Cons:
- Reduced immunogenicity compared to attenuated vaccines
- Requires adjuvants
- Requires multiple booster does to provide long-term immunity
- Can be difficult to isolate specific Ag
- Costly
26
eg Hep B

23
Q

What are mRNA vaccines?

A
  • Uses a copy of mRNA to encode the specific Ag to produce an immune response
  • 3 types:
    ~ non-replicating (mRNA + liposome)
    ~ in vivo self-replicating (mRNA + viral RNA replication machinery)
    ~ in vitro dendritic cell non-replicating (DC transfected with mRNA)

Pros:
- Non-infectious (RNA does not integrate itself into host genome as RNA in vaccine is degraded as soon as the protein is made)
- Quicker production

Cons:
- May elicit unintended immune reaction
- Quickly degraded RNA
- Need to be frozen or refrigerated

24
Q

What are the routes of administration?

A
  • Deep cutaneous or IM (most)
  • Oral (oral polio)
  • Intradermal (BCG)
  • Intranasal (influenza)
25
Q

Difference in immune response if vaccine is administered orally vs IM?

A

Oral:
- Would activate mucosal immunity (in gut)
~ Mostly IgA produced

IM:
- Would activate systemic immunity
~ Mostly IgG and IgM produced

26
Q

Protection against infection vs disease?

A

P.A. infx:
- Ab protects against virus by neutralising it before it can infect the host cells

P.A. disease:
- Systemic immunity prevents viraemia and CNS infection but virus can still infect the gut