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LC Respiratory week 4 > Immunology 1 > Flashcards

Immunology 1 Flashcards

1
Q

Why should we vaccinate individuals?

A

Vaccination is effective at reducing or preventing disease
Certain pathogens cause life-threatening or life-altering disease
After clean water, vaccination is the most effective public health intervention in the world

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2
Q

In basic terms what is vaccination?

A

Deliberate exposure to an antigen

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3
Q

In basic terms why do we vaccinate people?

A

To induce immunologically-mediated resistance to a disease

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4
Q

In basic terms how does vaccination work?

A

Through the induction of memory

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5
Q

What does immunological memory require?

A

The stimulation and maturation of the immune response after exposure to an antigen such that it is able to respond immediately and robustly upon re-exposrure to that antigen.

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6
Q

What cells are involved in immunological memory?

A

Memory CD4+ T cells
Memory B cells
Memory CTLs
Long lived plasma cells

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7
Q

When are the long lived memory T and B cells generated?

A

During primary adaptive immune responses

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8
Q

How long can memory T and B cells survive?

A

They can survive in a dormant state for many years after the antigen had been eliminated

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9
Q

What do memory T and B cells do rapidly in response to a second encounter with a specific antigen?

A

They re-activate, go into colonial proliferation and expansion, differentiation and into effector cells.

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10
Q

Describe the IgM and IgG antibodies etc on primary infection?

A

IgM peaks early and is down by 14 days

IgG raises over months and years and peaks after 14 days, leading to clinical disease

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11
Q

Describe the IgM and IgG antibodies etc on secondary infection?

A

IgM - peaks early and is down by 14 days

IgG - peaks very early, very high levels and the clinical features are aborted

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12
Q

What does pre existing IgG antibody result in, in terms of the secondary antibody response?

A

Results in ability to clear infection during incubation periods

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13
Q

More specifically what does the pre existing IgG antibody result in, in terms of the secondary antibody response?

A

Direct ability to neutralise bacteria and bacterial products
Rapid mobilisation of phagocytes and complement
Preformed IgA blocks bacterial attachment to mucous membranes
Diphtheria: an individual may clear the toxin through anti-toxin antibodies, but remain a carrier of microorganism

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14
Q

What is the secondary antibody response mediated by?

A

Long lived plasma cells

  • Reside in the bone-marrow where they continually secrete antigen specific antibodies of the IgG type (and other Ig classes)
  • They have already undergone an Ig class switching reaction during the Germinal centre reactions of the primary immune response
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15
Q

Where do the long lived plasma cells reside?

A

In the bone marrow

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16
Q

How can vaccination also generate memory T and B cells?

A

Vaccination simulates rare naive T and B cells
Induces a strong T cell and B cell response in 14–21 days
Some become effector cells, which:
- Mostly die by apoptosis in the absence of persisting antigen
Smaller number become memory cells and are maintained at low frequency

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17
Q

What happens after the removal and destruction of the initiating pathogen or antigen? (in terms of effector and memory cells)

A

The effector cells die (via apoptosis)

The memory T and B cells persist in the body for a long period of time

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18
Q

What does the increase in cell number due to the increase of memory T and B cells mean?

A

This increase in cell number means that the system is primed to respond better and faster upon a second exposure to the initial antigen.

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19
Q

Describe some characteristics of memory T and B cells?

A

Make a more effective immune response:

  • Memory cells are present in greater numbers than the original parent lymphocyte
  • Memory CD8+ T cells are able to kill immediately upon antigen stimulation - No requirement for help from Th cells
  • Memory CD4+ T cells are able to produce cytokines immediately upon antigen stimulation - No requirement for co-stimulation
  • Memory B cells have already undergone Ig class switching and hypermutation - Produce IgG and other Ig classes, Produce high affinity antibodies
  • Memory cells have enhanced properties of cell adhesion and chemotaxis - they can access non-lymphoid tissues effectively (i.e. where the bugs actually are)

Longevity
- Memory Cells are long-lived, persisting in the absence of antigen

20
Q

What are CD8+ T cells able to do?

A

Kill immediately upon antigen stimulation - No requirement for help from Th cells

21
Q

What are CD4+ T cells able to do?

A

Produce cytokines immediately upon antigen stimulation - no requirement for co-stimulation

22
Q

Memory cells have enhanced properties of cell adhesion and chemotaxis, which means they can?

A

they can access non-lymphoid tissues effectively (i.e. where the bugs actually are)

23
Q

What is immunisation?

A

Immunisation is the process through which an individual develops immunity/memory to a disease
Includes both deliberate and natural infection

24
Q

What is vaccination?

A

Vaccination is the deliberate administration of antigenic material to produce immunity to a disease

25
Q

What is active immunity?

A

Protection produced by the person’s own immune system
Can be stimulated by vaccine or naturally acquired infection
Usually permanent

26
Q

what is passive immunity?

A

Protection transferred from another person or animal

Temporary protection that wanes with time

27
Q

How does active vaccination work?

A

It stimulates an immune response to antigen through the same pathways as natural infection.
Generates immunity and immunologic memory similar to natural infection

In general, the more similar a vaccine is to the disease-causing form of the organism, the better the immune response to the disease

28
Q

What are some methods for generating immunological memory?

A

Exposure of an individual to the infectious organism
Exposure to a similar but less virulent pathogen (cowpox protects from smallpox)
Exposure to the inactivated pathogen

29
Q

What are the key features of inactivated vaccines? (Killed/attenuated vaccines)

A

Cannot replicate
Generally not as effective as live vaccines
Immune response primarily antibody based (not T cells)
Antibody titer may diminish with time
Require multiple doses to stimulate immune response

30
Q

What are the problems from making an inactivate vaccine from a live pathogen?

A

Under-inactivation
- Leaves viable pathogens or toxins within organism
Over-inactivation
- Loss of tertiary structure and conformational antibody binding sites loss of antigenicity

31
Q

What are the pros of inactivated vaccines?

A

Advantages

  • Can be made quickly (prevent epidemics)
  • May elicit good antibody responses
  • Easy to store - no refrigeration required
  • Usually safe
  • Can be given to immunocompromised individuals
32
Q

What are the cons of inactivated vaccines?

A

Disadvantages

  • May be very difficult to stimulate an immune response to many killed organisms
    • Doesn’t replicate or disseminate
    • Often require adjuvants to improve immunogenicity
  • Poor at eliciting T cell responses
  • Memory variable
    • Require multiple injections
    • Booster immunisation required
33
Q

What are adjuvants?

A

Mixture of inflammatory substances required to stimulate immune responses to coadministered peptides, proteins or carbohydrates

  • Aluminium hydroxide
  • Toxins eg tetanus toxoid
  • Other pathogens
    • Bordetella pertussis
34
Q

Why do adjuvants work?

A

Create inflammatory environment
Bind to macrophages and signal the unequivocal presence of a microbial invader
Activate the innate immune system to stimulate development of antibody and T cell responses

35
Q

What are the problems of adjuvants?

A
  • Toxic
  • Alter the immune response
    • Immune response is generated to vaccine:protein conjugates rather than vaccine itself
    • CD4+ T cells may recognise the carrier only
    • Therefore infection challenge will not necessarily elicit a secondary response
36
Q

What are fractional vaccines, like subunit vaccines used in Hep B?

A

Only part of the organism used in the vaccine

37
Q

Describe the Hep B vaccine?

A

Its a subunit vaccine
Consists of Hepatitis B surface antigen only
Produced by recombinant DNA technology
Stimulates protection in 85% of individuals
No risk of infection
First of the anti-cancer vaccines
Protects against Hepatitis B associated hepatocellular cancer

38
Q

Describe polysaccharide vaccines?

A
  • Polysaccharide sugars from the outer capsule of some bacteria determines pathogenicity and antigenicity
  • However polysaccharides are not good at stimulating response,
  • Generates antibody with less functional activity
    especially in immature immune system
  • Immunogenicity can be improved by conjugating to an adjuvant (“conjugate vaccines”)
39
Q

Describe live attenuated vaccines?

A

Attenuated (weakened) form of the “wild” virus or bacterium
Immune response similar to natural infection
Organism must replicate to be effective
Usually generate immunity with single dose

Examples - BCG (bacterial) Measles, mumps (viruses)

40
Q

What are the pros to live attenuated vaccines?

A

Very similar to natural infection, so relevant effector mechanisms elicited (antibody + activated T cells)
Localised, strong response
Memory good, therefore boosting not usually required

41
Q

What are the cons to live attenuated vaccines?

A

Immune response can be interfered with by circulating antibody
Safety
- May acquire new mutations and revert to virulence (eg vaccine associated poliomyelitis)
- May cause infection in immunocompromised host
Fragile – must be stored and handled carefully i.e. depends on cold chain

42
Q

In passive immunity describe transfer of material antibody?

A

Maternal antibody
- Crucial to protection of infant in first 6 months of life
- Active transport of maternal IgG in third trimester
- Breast milk, especially colostrum, contains IgA: important for colonisation of infant GI tract
Maternal antibody also important in enabling subsequent memory
- Exposure to an antigen while under cover of maternal antibody may result in an less severe illness, but nonetheless memory to the antigen is generated

43
Q

What are some sources of passive immunity?

A 
Naturally acquired passive immunity
 - Transplacental transfer of antibody (IgG)
 - Breast milk (sIgA)
Therapeutic passive immunisation
 - Pooled normal human immunoglobulin
 - Hyperimmune globulin 
 - Heterologous hyperimmune serum 
 - Monoclonal antibody against specific pathogen
44
Q

Describe pooled immunoglobulin?

A

Transfer of antibody from an unrelated individual

Pooled normal immunoglobulin from immune humans
- Previously used for protection against hepatitis A (now superceded by inactivated Hep A vaccine)

Hyperimmune globulin

  • Administered after specific exposure
  • Immunoglobulin from an individual known to have high antibody levels against a specific pathogen
    • Rabies (post exposure)
    • Snake venom anti-toxin
45
Q

Why is it so difficult to develop vaccines for some organisms?

A 
Chronic or latent infections
 - Immune system doesn’t normally generate a response that clears organism
     - Tuberculosis  
     - Hepatitis C
     - HIV
     - Herpes viruses:  CMV, HSV, EBV
Rapidly evolving infections
 - Pathogens highly adept at immune evasion
     - HIV
     - Influenza

LC Respiratory week 4 (6 decks)

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