Memory and vaccination Flashcards

1
Q

primary immune response

A

first time individual’s immune system is exposed to a pathogen
before exposed to antigen they are referred as naive
this is response to infection or vaccination

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2
Q

secondary immune response

A

second, third, fourth etc time an individuals immune system is exposed to the pathogen
cells are antigen experienced and have immunological memory
is qualitatively and quantitatively improved
often asymptomatic or mild disease

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3
Q

what does immune memory involve

A

T cells
b cells
antibodies
can last decades

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4
Q

activation of B cells

A

3 signals:
1. antigen and mhc
2. costimulation
3. cytokines

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5
Q

characteristics of memory B cells

A

produce higher affinity antibody than plasma cells
produce class switched antibody
produce antibody quickly
can re-enter germinal centres and undergo another round of somatic hypermutation and affinity mutation
higher levels of MHC and costimulatory molecules to attract T cell help

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6
Q

unimmunized donor
primary response

A

frequency of antigen-specific B cells 1:10^4/10^5
more IgM than IgG
low antibody affinity
low somatic hypermutation

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7
Q

immunised donor
secondary response

A

frequency of antigen-specific B cells 1:10^2/10^3
IgG and IgA produced
high antibody affinity
high somatic hypermutation

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8
Q

2 subsets of memory T cells

A

central
effector

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9
Q

molecules that naive T cells make

A
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10
Q

molecules effector T cells make

A
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11
Q

molecules memory T cells make

A
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12
Q

what activates naive T cells

A

dendritic cells in the lymph nodes
have CCR7 and CD45RA on surface

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13
Q

what happens after naive T cell activation

A

effector T cells differentiate and secrete cytokines, express cytokine receptors
memory cells derive directly from some effector T cells

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14
Q

what happens to most effector T cells

A

die by apoptosis

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15
Q

what do some memory T cells seem to be

A

quiescent or anergic
can’t respond to antigen

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16
Q

how do memory T cells survive

A

because they can respond to survival signals from cytokines IL-7 and/or IL-15

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17
Q

central memory T cells

A

express CCR7
remain in lymphoid tissue
behave more like naive cells
need antigen presented to them again
long lived precursors that take longer to respond
not committed to Th1 or Th2 type

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18
Q

effector memory T cells

A

lack CCR7 and migrate to tissues
immediate expansion on re-infeciton
express receptors for inflammatory chemokine so can be recruited to inflammation rapidly
produce IFN gamma, IL-4 or IL-5 quickly

committed to a lineage Th1,17 or 2

19
Q

trained immunity

A

innate immune system may display memory
not antigen specific and is shorter lived
innate memory= trained
involved epigenetic changes, metabolic changes and improved effector functions

20
Q

how can memory be induced by vaccination

A

as a surrogate for primary infection
seek to generate antibodies to prevent damage by pathogen toxins or neutralise pathogen to stop infection
vaccine needs to incorporate antigen that the body will recognise as foreign and drive B cell activation and antibody production

21
Q

vaccines and T cells

A

best vaccine also triggers T cell immunity
essential in effective vaccination against viruses
if antigen isn’t cleared by innate immune system then vaccine won’t work

22
Q

measles percentage vaccinated for herd immunity

A

93-95%

23
Q

vaccine requirements

A

safe-mustnt cause illness or death
protective- must protect against illness caused by live pathogen
sustained protection-ideally last several years

24
Q

practical considerations for vaccinations

A

low cost per dose
biological stability
ease of administration
low side effects

25
Q

types of vaccine

A

mRNA
live attenuated pathogen
subunit or toxoid
synthetic or conjugated
whole inactivated pathogen

26
Q

live attenuated pathogen

A

typically viral vaccines e.g. rotavirus and MMR
can replicate which. provides strong stimulation to the immune system

27
Q

1st way live attenuated vaccines are produced

A
  1. pathogenic virus is isolated and cultured in human cells
  2. used to infect a different animals cells e.g. monkey
  3. virus acquires mutations to allow it to grow well
    in monkey cells
  4. mutations then reduce its ability to grow in human cells when used as a vaccine
28
Q

2nd way live attenuated vaccines are produced

A

isolate the pathogenic virus
identify the virulence genes (receptor binding proteins, virulence proteins, core structural proteins)
mutate OR delete the virulence genes to attenuate the virus

29
Q

inactive pathogen

A

whole pathogens are inactivated/dead e.g. flu and polio

30
Q

how are inactive pathogen vaccines produced

A
  1. isolate the live pathogenic organism
  2. inactivate the pathogen with either heat or formaldehyde
  3. pathogen is structurally intact but inactive, can’t replicate in the body
31
Q

conjugate vaccines

A

some antigens can’t effectively induce a memory response on their own, specifically in children
combine and antigen recognised by the B cell (polysaccharide)
second antigen that will induce T cell help (protein toxoid)

meningitis C

32
Q

producing conjugate vaccines

A
  1. B cell recognises polysaccharide and takes up whole vaccine molecule
    presents polypeptides of this and the toxoid on MHC2
  2. T cell recognises the toxoid being presented by B cell and provides stimulation to cause B cell activation and class switching
  3. B cell produces antibodies to polysaccharide that its receptor recognised and develops a memory response
33
Q

pathogen components

A

include subunit and toxoid vaccines
use small pieces of pathogens combined with adjuvant to induce immunity

34
Q

toxoid vaccines

A
  1. some bacteria exert their harmful effects through toxin production
  2. toxins are purified from the bacteria and inactivated
  3. now referred to as toxoids nd can induce immune system to produce antibodies against toxin without causing disease

tetanus

35
Q

subunit vaccines

A
  1. pathogenic bacteria are isolated
  2. specific protein from the organism which causes immune response is isolated
  3. used in a vaccine to stimulate dendritic cells to take it up and present antigen

whooping cough (pertussis)

36
Q

DNA/RNA vaccines

A
  1. produce RNA/DNA strand which codes for pathogenic protein and inoculate it into the body’s cells, usually muscles
  2. cells take up nucleic acid, produce protein and express it on their surface and/or secrete it
  3. immune system recognises this as foreign and mounts a response (often both CD8+ and CD4+)

COVID-19 and prostate cancer

37
Q

advantages of DNA/RNA vaccines

A

potentially effective against cancers
antigen presentation by MHC1 and MHC2
long term persistence of the antigen

38
Q

disadvantages of DNA/RNA vaccines

A

possibility of inducing tolerance (switching immune responses off) if insufficient adjuvant is given

39
Q

adjuvants

A

compounds used to enhance immune response e.g. alum, bacterial cell wall components and mineral salts

40
Q

what are adjuvants mixed with antigens to do

A

enhance immunogenicity by giving a danger signal
reduce amount of antigen needed
aid delivery at the mucosa

41
Q

future of vaccination

A

reverse vaccinology (meningitis B vaccine)
CAR T cells (in leukaemia)
dendritic cell vaccines (in rheumatoid Arthritis and cancer)

42
Q

reverse vaccinologu

A
  1. examine the genome of the pathogen and try and identify novel antigens (usually surface proteins)
  2. synthetically produce the protein
  3. test for an effective immune response and antibody production
43
Q

current approved covid-19 vaccines in the UK

A

moderna- mRNA
pfizer- mRNA
nuvaxovid- protein subunit
AstraZeneca- non replicating viral vector
Janssen- non replicating viral vector
valneva- inactive virus