Immunology Flashcards
1
Q
What are the 5 major subtypes of T cells
A
Th1 Th2 Th17 TFH Treg
2
Q
What are the cytokines that create Th1, Th2, and Th17 cells
A
Th1 = IL-12 Th2 = IL-4 Th17 = Il-6
3
Q
What is the cytokine that create TFH cells
A
IL-6
4
Q
What is the cytokine that create Treg cells
A
TGF-beta
5
Q
What major cytokines do Th1 cells produce
A
IFN-gamma
IL-2
6
Q
What major cytokines do Th2 cells produce
A
IL4,5,13
7
Q
What major cytokines do Th17 cells produce
A
IL-6,7
8
Q
what major cytokines do TFG cells produce
A
IL-21 and 17
9
Q
what major cytokines do Treg cells produce
A
TGF-beta and IL-10
10
Q
Main roles of Th1 cells
A
promote macrophage recruitment and phagocytosis
promote IgG isotype switch
pro-inflammatory
promote neutrophil activation
11
Q
main roles of Th2 cells
A
allergy and parasitic infection
- IgE production
- eosinophil activation
- macrophage activation
12
Q
main roles of Th17 cells
A
neutrophil migration and activation
13
Q
main roles of TFH cells
A
B cell proliferation and differentiation
14
Q
what is the order of antibody isotype switching
A
IgM –> IgG –> IgE –> IgA
15
Q
Which cytokine promotes IgE isotype switching
A
Il-4
16
Q
which cytokine promotos IgA isotype switching
A
TGF-B
17
Q
what cytokine promotes IgG isotype switching
A
IFN-gamma
18
Q
what is the difference between an antigen and a pathogen
A
pathogens cause disease
antigen is a protein that is recognised by the immune system
19
Q
what does the innate and adaptive immune systems recognise and respond to
A
innate - recognise PAMPs (TLR, DAMPs) by PRRs
adaptive - antigens
20
Q
which TLRs are intracellular
A
3, 7, 9
21
Q
which blood cells are from the myeloid progenitor lineage
A
RBCs basophils eosinophils neutrophils monocytes - macrophages dendritic cells
22
Q
which blood cells are from the lymphoid progenitor lineage
A
T cells
B cells
NK cells
23
Q
what is the difference between a cytokine and a chemokine
A
cytokine - interacts with and affects the behaviour of nearby cells bearing the appropriate receptors
chemokines - attracts cells bearing the appropriate receptors
24
Q
what are the two receptors for chemokines
A
CCR
CXCR
25
where do leukocytes develop
primary lymphoid organs
26
what are the secondary lymphoid organs
spleen, lymph nodes, MALT
27
what stimulates the innate immune system to enter tissues
infection and trauma - innate cells enter infected tissues through interactions with endothelial cells -> then bind PAMPs --> activated
28
where do cells of the adaptive immune system interact with antigens initially
in the secondary lymphoid tissues (lymph nodes) --> activated --> proliferated --> blood --> tissues
29
explain the organisation of lymph nodes
cortex - B cells
paracortex - T cels
medulla - macrophages and plasma cells
30
how do the lymphocytes enter into the lymph node
through highly structured endothelial cells (HEV)
31
function and outcome of neutrophils
phagocytosis --> removes EXTRACELLULAR pathogens
32
function and outcome of monocytes/macrophages
phagocytosis and releases cytokines --> removes EXTRACELLULAR pathogens
33
function and outcome of NK cells
binds and kills infected cells, releases cytokines --> removes INTRACELLULAR pathogens
34
function and outcome of eosinophils
binds and kills parasites --> removes parasites
35
function and outcome of basophils
release inflammatory mediators and cytokines --> boosts response, especially for parasites
36
function and outcome of dendritic cells
phagocytoses, presents antigen to T cells and releases cytokines --> stimulates T cells
37
function and outcome of B cells
secrete antibodies --> block adhesion of EXTRACELLULAR pathogens
38
function and outcome of CD8 T cells
binds cells infected with INTRACELLULAR pathogens, release cytokines --> kills infected cells
39
function and outcome of CD4 T cells
help macrophages, B cells and CD8T cells, releases cytokines --> better activation of these cells
40
which PAMPs do mucosal epithelia recognise
peptidoglycan
LPS
flagellin
41
what does the mucosal epithelia do if it recognises PAMPs
releases antimicrobial peptides
42
what are the 6 outcomes of the C' cascade
```
Inflammation
chemotaxis
opsonisation
lysis
MAC
activation of B cells
```
43
what are the 3 pathways that can activate C'
alternative
lectin
classical
44
what is the common step of the C' cascade that is common to all 3 pathways
the activation of C3 to C3a and C3b by C3 convertase
45
what is the action of C3a
mediator of inflammation and phagocyte recruitment
46
what is the action of C3b
- binds with C3a and C4b to form C5 convertase
| - powerful mediatory of opsonization of the pathogen
47
what is the action of C5a
mediator of inflammation and phagocyte recruitment
48
what is the action of C5b
binds with C6,7,8,9 --> MAC --> lysis
49
how is the alternative pathway of C' activated
it isn't "activated" - it is the result of spontaneous hydrolysis of C3 to C3a and C3b
50
what activates the classical pathway of C'
IgM and IgG bound pathogen --> activates C1 complex
51
explain the steps of the classical pathway of C' up to the activation of C3
antigen-antibody interaction with C1q activates C1r --> activates C1s --> activates C2 and C4 --> C2a + C4b complex (C3 convertase) --> activation of C3
52
how is the mannan binding lectin pathway of C' activated
the mannon-binding lectin binds to mannose and other sugars on microbes --> captures MASP-2 --> activates C4 --> activates C2 --> C3 convertase
53
which outcome does not occur with the MBL pathway of C'
MAC formation
54
the MAC outcome of C' is essential in the control of which organism
Neisseria
55
what do extracellular TLRs recognise
structural components of bacteria (eg. flagellin, LPS, peptidoglycan)
56
what do intracellular TLRs recognise
genomic components of bacteria
57
what is the major molecule associated with TLR activation and signalling
MyD88
58
what are the inflammatory cytokines produced by macrophages and what are their functions
```
IL-1 = activates vascular endothelium
TNF-alpha = increases cell migration
IL-6 = increases acute phase proteins
```
59
what are the antiviral cytokines produced by macrophages
IFN-alpha
60
what are the stimulatory cytokines produced by macrophages and what are their functions
```
IL-12 = stimulates T cells and NK cells
GM-CSF = stimulates myeloid cell production
```
61
what are the suppressive cytokines produced by macrophages
IL-10
| TGF-beta
62
what are the chemokines produced by macrophages
CXCL-7 (IL-8)
63
what are the 3 phases of phagocytosis
attachment - binding to opsonised organism
ingestion - formation of phagosome
killing - fusion of phagosome-lysosome
64
PAMPs binding to macrophages results in...
- phagocytosis
| - chemokine and cytokine release
65
PAMPs binding to DCs results in
- activation
- chemokine and cytokine release
- initiation of adaptive immunity
66
what is the first stage of neutrophil migration from blood to tissue
- microbial activation of C' and macrophages and DC --> induces endothelial receptors such as E selectin and ICAM-1 and release CXCL8
67
what is the 2nd stage of neutrophil migration from blood to tissue
CXCL8 attracts neutrophils that express CXCL8-R
68
what is the 3rd stage of neutrophil migration from blood to tissue
neutrophils bind to E-selectin on endothelial cells and then LFA-1 of neutrophil binds to ICAM-1
69
what is the 4th stage of neutrophil migration from blood to tissue
migration of neutrophil through the endothelial cells and into the tissue --> chemotaxis to site of inflammation
70
what cells are cytotoxic cells
NK cells
eosinophils
macropahges
71
what is the major cytokine released by NK cells
IFN-gamma
72
what is the difference between epitope and antigen
epitope = part of the antigen that binds the TCR or BCR
antigen = the target of an immune response
(one antigen may have many epitopes)
73
what is the difference between the conformation of epitopes that T and B cells recognise
T cells only recognise linear epitopes
| B cells can recognise both linear and discontinuous epitopes
74
what part of the B cell recognises antigen
the BCR/antibody/Ig
75
what are the 2 forms of antibody
```
surface antibody (IgG or IgM) - the B cell Receptor
secreted/soluble antibody
```
76
what part of the antibody is involved in binding of the antigen
the variable region of the H and L chains
77
what is the importance of the constant region of the antibody
determines whether the Ab is IgM, IgG, IgA, IgD or IgE
78
what are the functions of the constant region of the antibody
- mediate effector function
- activation of classical C' cascade
- delivery of Abs
79
where are our antibodies made
in the bone marrow during B cell development
80
what are the 4 main stages of antibody diversity production
1. V region
2. junctional diversity
3. Combinatorial diversity
4. somatic hypermutation
81
explain the variable regions of the heavy and light chains of an Ab
heavy - has 3 regions: variable, diversity and joining regions (VDJ)
light - has 2 regions: variable and joining regions (VJ)
82
explain the 1st step of antibody diversity (V region)
RANDOM SOMATIC GENE REARRANGMENTS
heavy chain gene rearrangements in B cells
- D onto J and the DJ onto V
light chain gene rearrangements in B cells
- J onto V
- kapp and gamma rearrangment
83
what is gene rearrangement during antibody diversity mediated by
RAG enzymes
84
explain the junctional diversity stage of antibody diversity
during the joining process of the V region gene segments, deletions and insertions of nucleotides occur - mediated by TdT
85
explain the combination diversity stage of antibody diversity
join a particular heavy chain with a particular light chain
86
what gives the multipotent progenitor cell for haemopoietic cells the signal to transform into the common lymphoid progenitor cell
Flt3L expressed by bone marrow stromal cells tells the MPC to differentiate into CLP
87
what is the role of IL-7 in B cell development
helps the process along
| - if you dont have IL-7 - you dont have development
88
explain the 4th step of antibody diversity production (somatic hypermutation)
after antigen binds to B cell in secondary lymphoid tissue --> genomic mutation occurs to help increase affinity
89
what are the two fates of B cells
plasma cells --> pump out Ig (no longer have surface Ig)
| memory B cells
90
what are the 3 processes that underpin vaccination
- stronger and faster proliferation of B cells
- affinity maturation - stronger and more powerful
- isotype switching
91
which enzyme helps facilitate isotype switching
AID
92
where does isotype switching occur
in secondary lymphoid tissues only after B cells have been stimulated
93
what determines isotype switching
- dependent on T cell help
| - cytokines released (microenvironment)
94
which Ig are more specialised for neutralisation
IgG and IgA
95
which Ig are more specialised for opsonization
IgG1>IgG3>IgG4=IgA
96
which Ig are more specialised for ADCC
IgG1=IgG3
97
which Ig are more specialised for degranulation
IgE
98
which Ig are more specialised for C' activation
IgM>>IgG1=IgG3>IgG2=IgA
99
explain what neutralisation by Abs is
Ab binding to, and blocking proteins that are essential for attachment to the host cell --> blocking infection
100
explain what opsonization by Abs is
Ab bind to and coat pathogen --> targets them for phagocytosis
101
explain the process of NK cell killing of a cell
- Ab binds to target cell via variable region
- Ab binds to NK cell
- cross linking of FcR triggers NK cell killing
102
which Ig is associated with mucosal lymphoid tissue
IgA
103
what is affinity maturation
the process by which a B cell increases its affinity for a particular antigen as the immune response progresses through somatic hypermutation
- as the infection continues, only high affinity surface Ig are selected for survival (clonal selection)
104
what do you need for activation of T cells
presentation of the peptide antigen by the MHC
105
which cells are the professional Antigen presenting cells (APCs)
dendritic cells
macrophages
B cells
106
what is different between the antigens presented to B and T cells
- Antibodies bind to epitopes in whole protein complexes
| - T cells recognize short linear epitopes only that have to be presented by MHC
107
explain the T cell R
- has alpha and beta chains
- -> alpha has V, J and C gene segments
- -> beta has V, J, C and D regions
108
what protein do all T cells have
CD3
109
what is the difference in roles between CD8 and CD4 T cells
CD8 - kill tissues infected with IC pathogens and neoplastic cells
CD4 - produce cytokines that augment and specialise adaptive and innate responses
110
where are MHC class 1 and 2 molecules found
1 - on almost all nucleated cells of the body
| 2 - on antigen presenting cells only
111
which 3 molecules do MHC class 1 and 2 molecules have
1 - HLA A, B and C
| 2 - HLA DR, DP and DQ
112
why is the antigen diversity larger for MHC class 2
```
because the binding cleft is open and therefore can fit longer peptides in there
(MHC class 1 has a cleft with closed ends - can only fit small peptides)
```
113
how are antigens held in the cleft of MHC molecules
held in place by specific anchor residues
114
```
polymorphism:
which genes within MHC class 1 and 2 vary most between different individuals
```
```
MHC class 1 - the alpha 1 and alpha 2 chains
MHC class 2 - the alpha 1 and beta 1 chains
```
115
how many alleles are there for MHC
6
116
the polymorphism of MHC confers what property
different specificities for peptide
117
what are the 2 pathways to get antigen presented on MHC
```
cytosolic pathway --> MHC class 1
endosomal pathway --> MHC class 2
```
118
explain the stages of the cytosolic pathway to get an antigen presented on MHC
- protein in the cytoplasm (endogenous) -> through proteosome --> peptides
- peptides actively transported to ER by TAP
- MHC class 1 loaded onto peptide in ER = stabilisation of MHC
- transported to Golgi --> expressed on cell surface
- recognised by CD8 T cells
119
explain the stages of the endosomal pathway to get an antigen presented on MHC
- uptake of peptide by endocytosis (exogenous)
- synthesis of MHC class 2 in ER --> cytoplasm with a stabilisation chain
- MHC and peptide intersect in endosome
- expressed on cell surface
- recognised by CD4 T cell
120
how can exogenous antigens find their way into the cytosolic pathway
cross presentation
121
why are superantigens special
they do not need to be processed by the cell and presented via MHC
122
how do superantigens activate the immune system
they bind directly to conserved regions of MHC Class 2 Beta1 chains together with the variable-beta chain of many T cell receptors
(they cross link the MHC of APC to CD4 T cells) --> large number of T cells activated --> significant pathology
123
what "activates" DCs
the recognition of PAMPs or DAMPs by the PRR
124
explain the early maturation events of DCs
signalling via TLRs results in:
- loss of anchor molecules
- increase in chemokine receptor expression (CCR7) --> migration to lymph nodes
- increase in secretion of cytokines - to attract precursor DC and monocytes to infected site for more antigen uptake
125
explain the late maturation events of DCs
- increased surface expression of MHC class 2
- increased antigen processing
- increased adhesion molecules
- secrete new chemokines
- loose ability to capture angtigen
- expression of costimulatory molecules
- secrete cytokines
126
which costimulatory molecules do mature DCs express
CD80 and CD86 - signal two for T cell activation
127
explain the early events of DC to T cell interaction
- initial adhesion involves LFA-1 (T cell) adhesion to ICAM-1 (DC)
- stabilised when T cell R binds to peptide in MHC (signal 1) --> conformational change in LFA-1 to increase binding affinity
128
what is signal 2 of Tcell-DC interaction
CD28 (T cell) to CD80/86 (DC)
129
without costimulation (signal 2) - what happens to the t cell
in becomes anergic (inactivated)
130
what is signal 3 of T cell-DC interaction
cytokines produced by DC - directs the differentiation of T cells
131
which B cell responses are NOT dependent on T cells
- activation by polysaccharides and most lipids
132
explain the antibodies produced by T cell independent activation of B cells
- exclusively IgM
- low affinity
- no memory
133
what molecule expressed by T cells is essential for T cell dependent B cell activation and differentiation
CD40L
134
when do T cells express CD40L
when they are activated by APCs
135
what happens if you dont have CD40L
B cells cannot differentiate and therefore you are stuck with IgM
136
where does the activation of B cells by T cells occur
in the paracortex/follicle junction in lymph nodes
137
what is in the germinal centres of lymph nodes
sites of intense B cell proliferation and affinity maturation
138
what are follicular dendritic cells
they are resident cells of the lymphoid follicle that capture immune complexes and drive B cell activation and affinity maturation (somatic hypermutation) by presenting the antigen all the time
(long term antigen depot)
139
CD8 T cells require an additional activator (aside from the DC signal 1,2,3) - what it is
needs help by CD4 T cells - must recognise the same antigen
140
how are CD8 T cells activated via CD4 T cells
CD4 T cells interact with the APC via CD40L and therefore allow the DC to induce CD8 T cell activation
141
what are the two pathways for Cytotoxic T lymphocyte killing
- granule exocytosis --> activation of caspases --> apoptosis
- FasL-Fas mediated target cell apoptosis
142
CD8 T cells kill tissues recognition of antigen in which MHC molecule
class 1
143
how are B cells activated via C'
activated via the complement receptor CR2 (CD21)
| - further boosted by T cells
144
which cytokines by macrophages promote
- increased vascular endothelial permeability
- increased neutrophil migration
- chemokines
- vascular endothelial permeability = IL-1
- increased neutrophil migration = TNF-alpha
- chemokines = CXCL-8
145
what are the steps of IC pathogens activating NK cells
- pathogen interacts with PRR on macrophages --> inflammatory cytokines
- interact with IC PRR in infected epithelial cells and macrophages --> IFN --> blocks neighbouring cells translation of viral mRNA
- upregulate Class 1 MHC
- induce influx and activation of NK cells --> kill infected cell
146
when do APCs present CD80/86
only when activated by recognition of PAMPs/DAMPs by PRRs
147
two outcomes of the failure of CD28-CD80/86 interaction
- anergy of T cells
| - binding of alternate T cell ligands to CD80/86 following activation may lead to suppression of T cell proliferation
148
what alternate T cell ligands (other than CD28) can CD80/86 bind to, and when are they expressed
CTLA-4 - only expressed when the T cell has already been activated --> T cell suppression
149
where do long lived plasma cells live
in the bone marrow
150
which cytokine is essential for CD4 T cell proliferation
IL-2
151
how does cyclosporine affect the immune system
inhibits IL-2 production --> therefore no T cell proliferation
152
how does rapamycin affect the immune system
blocks signalling through IL-2R --> inhibits T cell proliferation
153
which has the stronger interaction with CD80/86?
| - CD28 OR CTLA-4
CTLA-4
