CBG Lecture 28: Effector Mechanisms in the Immune System Flashcards

1
Q

name some infectious agents that insult the immune system - in size order, largest first

A

worms - protozoa (ameoba,leishmania,trypanosome) - fungi - bacteria -viruses

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2
Q

name some infectious agents that insult the immune system - in size order, largest first

A

worms - protozoa (ameoba,leishmania,trypanosome) - fungi - bacteria -viruses

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3
Q

how do pathogens cause pathology

A

invasion
mutliplication
spread
production of diease - toxins, direct damage to host tissues,over reaction of IR - immunopathology

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4
Q

name some modes of transmission of viruses

A

respiratory - adeno,paramyxo,rhino virus
faecal-oral - HepA
contact - herpes,papillo,HIV
arthropod/animal bite - flavivirus (yellow fever, dengue). Rhabdoviridae -rabies

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5
Q

what is the mode of transmission of a virus often determined by

A

stability of virus in enviro

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6
Q

what are effector mechanisms against viral infection

A

recognition of virus particules extracellularly followed by destruction and neutralisation
preventing viral replication within host cell

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7
Q

what are viruses

A

obligate intracellular pathogens

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8
Q

what ar eIR mechanisms

A

innate barriers and complement for membrane bound viruses
ABs
cytotoxic lymphocytes and NKs

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9
Q

name an Ig thats made at mucosal surfaces

A

IgA

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10
Q

what region of AB varies between isotypes

A

Fc region

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11
Q

what is MAC

A

initiated by antibodies due to complement activation

Membrane Attack Commplex damages viral envelope by perforin enzymes; forms pore, cause lysis

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12
Q

describe structure of naive T cells

A

scanty cytoplasm
small
resting cells with condensed chromatin
synthesze lttle RNa or protein

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13
Q

what is naive T cell proliferation and differentiation driven by

A

cytokine called IL-2

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14
Q

what proteins are released by Cd8+ cells

A

perforin - deliver contents of granules into cytoplasm of target
2. granzymes - serine proteases- activate apoptosis
granulysis - antimicrobial actions, induce apoptosis
3. also release cytokines: IFN TNF

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15
Q

in what fashion are effector molecules released from T cell granules

A

polar fashion as the specified recognition redistributes cytoskeleton and cytoplasmic components of the T cell

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16
Q

why is the release of granules for CD8+ described as polar

A

because it redistributes the cytoskeleton and cytoplasmic components of the cell

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17
Q

whyich immmune response are NK cells part of

A

innate

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18
Q

how do some viruses try to avoid recognition by cytotoxic T cells

A

by downregulation of MHC - but

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19
Q

what does perforin do

A

polymerizes to form pore in target membrane

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20
Q

what do granzymes do

A

serine proteases which activate apoptosis once in cytoplasm of target cell

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21
Q

what does IFN released by CD8 cells do

A

directly inhibits viral replication and induces the increase expression of MHC1 which increases chance infected cells will be recognised for cytotoxic attACK
activates macrophages

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22
Q

when is the humoral response initiated

A

when B cells that bind antigen are sinalled by heler T cells or by certain icrobial antigens alone

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23
Q

what are the first ABs to be produced in a humoral response? why

A

IgM because IgM can be expressed without isotype switching

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24
Q

why do early IgM Abs tend to have low affinity

A

because they are produced before B cells have undergone somatic hypermutation

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25
where do MHC class 1 molecules present antigens derived from
proteins in the cytosol - bound peptides transported by MHC1 to cell surface
26
how do CD8+ cells kill
by releasing granszymes and perforin or by engagement of Fas on target cells by Fas ligand
27
which chemical do CD8+ release to cause apoptosis
granzymes
28
what type of antigens to MHC class 2 present
antigens originating in intracellula vesicles
29
which cells can T helper cells activate
macrophage and B cells
30
name an innate lymphocyte
NK cell
31
what activating receptors do NKs have - are they specific antigenic epitopes
MANY DIFFERENT - NOT SPECIFIC ANTIGENIC EPITOPES antibody viral glycoproteins stress induced ligands
32
what is the missing self hypothesis
when NKs detect a downregulation of MHCs - because viruses try to avid recognition by CTLs by downregulating MHC
33
what cells can NK cells kill - how quick
15mins | NK cells can kill virus infected or tumour cells
34
what is CD16
a low affinity IgG receptor - recognises complexed IgG antibodies signals through association with Fc receptor common gamma chain responsible for antibody-dependent cellular cytotoxicity (ADCC)
35
what receptor on NK cell is responsible for ADCC antibody dependent cellular cytotoxicity
CD16 - low affinity IgG receptor
36
outline process of ADCC
antibody dependent cellular cytotoxicity 1. ab binds antigens on surface of target cells 2. Fc CD16 receptors on NK cells recognise bound antibody 3. cross linking of Fc receptors signals the NK cell to kill the target cell 4. target cell died by apoptosis
37
how is immunity to bacteria promoted | give examples of baxteria
TB, Salmonella | ABs and complement can act to kill bacteria directly and target them to phagocytes
38
what particles do phagocytes recognise
complement or antibody opsonised particles
39
what are Fc receptors on phagocytes activated by
Abs bound to the surface of pathogens - enabling phagocytosis
40
what are the main types of antibodies that phagocytes are activated by
IgG
41
what does aggregation of immunoglobin on bacterial surface allow macrpohages to do
allows crosslinking of Fc receptors and therfore activation of macrophage leading to phagocytosis and destruction of bacterium
42
how is a bound antibody distinguishioble from free immunoglobin
by its state of aggregation and the fact only aggregated bound immunoglobins can cross link Fc receptors
43
what receptors are on macrophages that are specific for structures on pathogens
scavenger mannose LPS - lipopolysaccharide PAMPs - pathogen associated molecular patterns
44
what are phagolysosomes
fusion of phagosomes and lysosomes - where bacteria are attacked by enzymes and antimicrobial peptides
45
name some enzymes present in phagolysosomes
proteases elastase lysozyme
46
what is pH of phagolysosomes
47
what is respiratory burst of phagolysosomes mediated by
NADPH oxidase
48
outline steps of phagocytosis
1, bacteria attaches to membrane envaginations: pseudopodia 2. bacterium ingested froming phagosome 3. phagosome fuses with lysosome 4. bacterium killed and digested by lysosomal enzymes 5. digestion products are released from cell
49
what are pseudopodia
membrane envaginations
50
name some antimicrobial substances
peptides interferons granzymes perforins
51
how do pathogens cause pathology
invasion mutliplication spread production of diease - toxins, direct damage to host tissues,over reaction of IR - immunopathology
52
name some modes of transmission of viruses
respiratory - adeno,paramyxo,rhino virus faecal-oral - HepA contact - herpes,papillo,HIV arthropod/animal bite - flavivirus (yellow fever, dengue). Rhabdoviridae -rabies
53
what is the mode of transmission of a virus often determined by
stability of virus in enviro
54
what are effector mechanisms against viral infection
recognition of virus particules extracellularly followed by destruction and neutralisation preventing viral replication within host cell
55
what are viruses
obligate intracellular pathogens
56
what ar eIR mechanisms
innate barriers and complement for membrane bound viruses ABs cytotoxic lymphocytes and NKs
57
name an Ig thats made at mucosal surfaces
IgA
58
what region of AB varies between isotypes
Fc region
59
what is MAC
initiated by antibodies due to complement activation | Membrane Attack Commplex damages viral envelope by perforin enzymes; forms pore, cause lysis
60
describe structure of naive T cells
scanty cytoplasm small resting cells with condensed chromatin synthesze lttle RNa or protein
61
what is naive T cell proliferation and differentiation driven by
cytokine called IL-2
62
what proteins are released by Cd8+ cells
perforin - deliver contents of granules into cytoplasm of target 2. granzymes - serine proteases- activate apoptosis granulysis - antimicrobial actions, induce apoptosis 3. also release cytokines: IFN TNF
63
in what fashion are effector molecules released from T cell granules
polar fashion as the specified recognition redistributes cytoskeleton and cytoplasmic components of the T cell
64
why is the release of granules for CD8+ described as polar
because it redistributes the cytoskeleton and cytoplasmic components of the cell
65
whyich immmune response are NK cells part of
innate
66
how do some viruses try to avoid recognition by cytotoxic T cells
by downregulation of MHC - but
67
what does perforin do
polymerizes to form pore in target membrane
68
what do granzymes do
serine proteases which activate apoptosis once in cytoplasm of target cell
69
what does IFN released by CD8 cells do
directly inhibits viral replication and induces the increase expression of MHC1 which increases chance infected cells will be recognised for cytotoxic attACK activates macrophages
70
when is the humoral response initiated
when B cells that bind antigen are sinalled by heler T cells or by certain icrobial antigens alone
71
what are the first ABs to be produced in a humoral response? why
IgM because IgM can be expressed without isotype switching
72
why do early IgM Abs tend to have low affinity
because they are produced before B cells have undergone somatic hypermutation
73
where do MHC class 1 molecules present antigens derived from
proteins in the cytosol - bound peptides transported by MHC1 to cell surface
74
how do CD8+ cells kill
by releasing granszymes and perforin or by engagement of Fas on target cells by Fas ligand
75
which chemical do CD8+ release to cause apoptosis
granzymes
76
what type of antigens to MHC class 2 present
antigens originating in intracellula vesicles
77
which cells can T helper cells activate
macrophage and B cells
78
name an innate lymphocyte
NK cell
79
what activating receptors do NKs have - are they specific antigenic epitopes
MANY DIFFERENT - NOT SPECIFIC ANTIGENIC EPITOPES antibody viral glycoproteins stress induced ligands
80
what is the missing self hypothesis
when NKs detect a downregulation of MHCs - because viruses try to avid recognition by CTLs by downregulating MHC
81
what cells can NK cells kill - how quick
15mins | NK cells can kill virus infected or tumour cells
82
what is CD16
a low affinity IgG receptor - recognises complexed IgG antibodies signals through association with Fc receptor common gamma chain responsible for antibody-dependent cellular cytotoxicity (ADCC)
83
what receptor on NK cell is responsible for ADCC antibody dependent cellular cytotoxicity
CD16 - low affinity IgG receptor
84
outline process of ADCC
antibody dependent cellular cytotoxicity 1. ab binds antigens on surface of target cells 2. Fc CD16 receptors on NK cells recognise bound antibody 3. cross linking of Fc receptors signals the NK cell to kill the target cell 4. target cell died by apoptosis
85
how is immunity to bacteria promoted | give examples of baxteria
TB, Salmonella | ABs and complement can act to kill bacteria directly and target them to phagocytes
86
what particles do phagocytes recognise
complement or antibody opsonised particles
87
what are Fc receptors on phagocytes activated by
Abs bound to the surface of pathogens - enabling phagocytosis
88
what are the main types of antibodies that phagocytes are activated by
IgG
89
what does aggregation of immunoglobin on bacterial surface allow macrpohages to do
allows crosslinking of Fc receptors and therfore activation of macrophage leading to phagocytosis and destruction of bacterium
90
how is a bound antibody distinguishioble from free immunoglobin
by its state of aggregation and the fact only aggregated bound immunoglobins can cross link Fc receptors
91
what receptors are on macrophages that are specific for structures on pathogens
scavenger mannose LPS - lipopolysaccharide PAMPs - pathogen associated molecular patterns
92
what are phagolysosomes
fusion of phagosomes and lysosomes - where bacteria are attacked by enzymes and antimicrobial peptides
93
name some enzymes present in phagolysosomes
proteases elastase lysozyme
94
what is pH of phagolysosomes
95
what is respiratory burst of phagolysosomes mediated by
NADPH oxidase
96
outline steps of phagocytosis
1, bacteria attaches to membrane envaginations: pseudopodia 2. bacterium ingested froming phagosome 3. phagosome fuses with lysosome 4. bacterium killed and digested by lysosomal enzymes 5. digestion products are released from cell
97
what are pseudopodia
membrane envaginations
98
name some antimicrobial substances
peptides interferons granzymes perforins