L1-4 Flashcards
1
Q
PATHOGENS
A
organisms causing disease
2
Q
immune system requirements
A
recognition and response
correct reaction to benign/ self
direction of effector mechanisms to specific pathogens
adapative and innate linkage
3
Q
infection sources
A
pathogens
bacteria
fungi
parasites (worms/ protozoa)
4
Q
specific immunity features
A
lymphocyte mediation
clonal dist. of receptors
large repertoire/ low freq specific cells for antigen
slow response development of memory cells
5
Q
clonal selection theory
A
clonal deletion of self-reactive immature lymphocytes
mature naive lymphocytes proliferate and differentiate upon activation
effector cells clones
6
Q
BCR
A
expressed by B cells upon antibody activation
Ig membrane form binds free antigen
7
Q
TCR
A
membrane-form only
recognizes peptide fragment of antigen bound to MHC on APC
8
Q
bacterial infection response
A
complement activation> opsonization/ classical pathway activation/ effector cell activation
9
Q
FcR cells
A
receptor binding Fc antibody region
10
Q
antibody structure
A
4 polypeptides
paired variable regions
constant regions > form Fc regions/ receptors
heavy/ light chain
11
Q
antibody classes
A
IgM/D/A/G/E
12
Q
What are antibody classes determined by
A
heavy chain/ C region
13
Q
no. homology regions in L/H regions
A
L>2
H>4/5
14
Q
homology domain
A
110 amino acids
2 beta sheets
disulphide bridge link
paired (folded in protein)
15
Q
antibody antigen interaction
A
variable region specific to antibodies
6 hypervariable loops (3Vh/Vl) act as Ag binding sites > 12 regions
16
Q
CDR on antibody
A
complementarity defining regions
> determines specificity/ affinity for Ag
17
Q
antigen binding of CDRs
A
Ag bind amino acids in complementarity defining regions
18
Q
epitope
A
antibody recognition site on an antigen
19
Q
2 types of epitope
A
linear/ continuous
non-linear
20
Q
Ag/Ab interactions nature
A
non-covalent
21
Q
TCR
A
binds processed antigens in cleft of MHC I/II (Peptide-MHC complex)
Membrane-bound
smaller than BCR
22
Q
TCR structure
A
alpha/ beta chain heterodimer
V/C regions (V peptide bound)
4 Ig-like domains
3 CDR’s
23
Q
HLA
A
human leukocyte antigens
A/B/C alpha chains
class I/II
on ch6
7*10^6 bp
24
Q
class I MHC
A
single chain
expressed by all nuc cells
alpha/ beta 2 microglobulin
bind peptides 8-10 amino acids for TCR presentation
25
class II MHC
alpha/ beta chain heterodimer expressed on APC
expressed by immune cells
binds peptides 13+ amino acids
26
variation in MHC class I/II
highly polymorphic
limited variation in one individual
27
variation of TCR
highly variable
clonally distributed
28
antibody
H2L2
secreted/ expressed on B cells
binds free Ag
29
variability of antibodies
highly variable
clonally distributed
30
alpha 2/ beta 2 coding
Ig-like
31
alpha 1/ beta 1
peptide binding site
32
MHC 1 vs II groove length
groove II is more open than I as binds longer peptides
33
co-expression of TCR recognizing class I
CD8+ killer T
34
co-expression of TCR recognizing class II
CD4+ helper T
35
whats the V region of the heavy chain Ig encoded by
V/D/J segments
| V (Variable) D (diversity) J(joining)
## Footnote
V is biggest segment
36
What's the light chain variable region encoded by?
V/J
| less variability than heavy chain > V/d/J
37
Which T cell receptor is the heavy vs light chain?
Heavy chain = TCR alpha
light chain = TCR beta
38
B cell gene rearrangements
in bone marrow development
39
NHEJ
| Non-homologous end joining
DNA repair ligating DNA pairs
40
light chain genes
lamda/ kappa
41
Loci of H/ lamda/ kappa genes
H- 14
lamda- 2
kappa- 22
42
recombination signal sequences
sequences flanking V/D/J gene segments
| V/D/J recombinases
## Footnote
recombination activating genes 1/2 encoding lymphoid specific components of recombinase
43
RAG mutations consequences
| recombination activating gene
immunodeficiences
44
Allelic exclusion
per B> 1 rearranged H and 1 rearranged L chain per chromosomes therefore randomly generated BCR
| kappa OR lamda light chain never both
45
mechanisms for allelic exclusion
1. multiple gene segments/ chain
2. combinatorial diversity
3. H/L chain combinations
4. junctional diversity
5. somatic hypermutations
| 2. V/D/J segment recomination
46
junctional diversity
imprecise joining
N regions
| random nuc additions at junctions via terminal transferase
47
SHM
| somatic hypermutation
mutation frequency in antibody H/ lamda/ kappa genes at orders of magnitude higher than others
| in germinal centers as B recognize Ag asnd proliferate
48
AID
| Activation induced deaminase
deaminates DNA cytosine to uracil which is recognized
49
Mechanism induced by B recognition of Ag
secrete unique BCR as Ig with alternate constant region w/o transmembrane region
| both produced by alternative RNA processing
50
heavy chain constant region genes
4* gamma chain gene
2*alpha chain gene segments
| C mu closest to V/D/J gene segments
51
IgM
1st class isotype BCR/ antibody expressed by each developing B cell
| co-expressed with IgD
52
TCR gene segment rearrangement
| when/ where
## Footnote
how is it similar to Ig gene rearrangement?
During T development in thymus
## Footnote
similar to Ig gene rearrangement> RSS/ RAG enzymes involved
53
diversity of TCR rearrangement
1. multiple gene segments
2. combinatorial diversity
3. junctional diversity
| no SHM in TCRs
54
TCR alpha/beta chromosomes
alpha-14
beta- 7
55
where do TCR's recognize antigens
in groove of MHC moelcule
56
MHC diversity
| major histocompatibility complex
## Footnote
which chromosome is HLA gene found on?
no gene rearrangement
co-dominant expression
| most polymorphic genes
## Footnote
Ch 6
57
Co-dominant expression of MHC
## Footnote
Where are these expressed?
MHC I
MHC II
## Footnote
1 in all nucleated cells
II in immune cells
58
MHC I molecules
MHC class II molecules
| No. molecules if heterozygous at each loci?
MHCI> HLA-A/HLA-B/HLA-C
MHCII> HLA-DQ/DP/DR
| 6
59
MHC polymorphism
| advantages/ disadvantages
:) allows binding of peptide range presented to cells
:( ^risk of immune-mediated disease
:( lower donor organ pool
60
endogenous/ exogenous Ag-derived peptides
endo> virus (class I presented)
exo> bacterium/ fungus (class II presented)
| both processed into fragments for binding/ presentation by MHC I/II
61
MHC class I presentation
1. intra antigen synth in ctoplasm
2. Ag processed > peptide by proteasome
3. TAP transporter to ER
4. pep binding to MHC I
5. MHC I presentation at CSM
62
proteasome
inflam cytokine reception produces altered peptides
large multicatalytic protease
63
what's TAP
Multi-protein assembly / peptide loading component
| contains tapasin/ calreticulin
64
TAP functions
cytosolic protein degradation to peptide fragments by proteasome
delivers peptide to MHC Class I and folds for export
65
MHC class II molecule presentation
1. Ag endocytosed via vesicles
2. acid proteases cleave protein
3. vesicles fuse with MHC II and bind
4. complex transported to CSM
66
invariant chain complex in MHC II
| function
blocks peptide/ misfolded protein binding in groove
HLA-DM binds
| cleaved in acidified endosome > peptide fragment CLIP enzyme
67
CLIP function
blocks peptide binding ass. w binding groove
| released when HLA-DM binds to MHC II
68
what happens to peptides in normal, uninfected cells?
MHC I/ II bind and present peptides from self-proteins
69
class I/II MHC accessory molecules encoded
class I> TAP/LMP
class II> HLA-DM
70
where are B cells and plasma cells found?
in bone marrow
71
gene controlling B cell identity
Pax5
72
B cell development
1. develop from haematopoietic stem cells in bone marrow
2. express PAX5 txn factor
3. Ig gene rearrangement
4. lymphocyte then B cell- specific markers expressed
5. negative selection of self-reactive cells
73
Pre-B cell development
| immature pre-B cells
1. H chain genes rearrange to cell surface with Igalpha/beta> expressed with surrogate light chain
produces a pre B cell receptor
2. L chains rearrange > displace V pre-B / lamda 5 genes and producing IgM BCR
| H chain = mu chain
74
Pre-B cell receptor function
delivers signal to pre-B cells that H chain is functional nctional
| no antigen required
75
Pre-BCR signal
1. turns off RAG1/RAG2
2. 5-6 cell divisions
3. surrogate light chain expression stops
4. RAG1/2 turned on again
5. L chain rearrangement
## Footnote
L chain rearrangement requires RAG
76
Ig alpha/ beta function
mediate signalling of immature B cells
77
B cell names during development
stem cell> early pro B cell> pro B cell> large pre-B cell> small pre B cell> immature B cell> mature B cell
78
light chain posiibilities from pre-B cells
lamda or kappa light chain
79
kappa versus lamda expression on light chains
more kappa than lamda as kappa light chains rearraneg prior to lamda
80
where are RAG1/2 switched off?
large pre-B cell/ mature B cells
| lymphoid specific recombinase
81
no. J(kappa) genes per chromosome
5 per chromosome
| and 2 chromosomes therefore 10 rearrangements possible on same locus
## Footnote
lamda locus will then rearrange if all 10 rearrangements are out of frame
82
Ig rearrangement errors consequences
failure to productively rearrange H and L chains result in cell death
83
Ig rearrangement sequence
D-J on both chromosomes
V-DJ on 1/2 chromosomes
kappa gene rearrangement (up to 5 times) on 1/2 chromosomes> rearrangement of lamda if kappa fails on 1/2 chromosomes
mu: kappa/lamda expressed
84
Ig expressed in immature B cells
membrane IgM
85
what happens to immature B cells binding multivalent self-antigens?
clonal deletion
receptor editing
| receptor ediitng entails further light chain rearrangements/ variable ge
86
what happens to immature B cells binding soluble self-antigens?
become anergic/ unresponsive
87
T cell development
Develop from bone marrow stem cells
receptor genes rearranged in thymus
pre-T receptor expressed
negative selection of self-reactive T cells
88
T cell alternative lineages
alpha beta TCR genes (CD4+/CD8+)
gamma delta TCR genes
| cells expressing alpha beta TCR bind with self MHC expressed in thymus (
89
alpha beta T cell development
develop into thymocytes in thymus
1. beta TCR genes rearranged and express TCR
2. CD3/4/5 markers acquired\
3. +/- selection
90
thymus characteristics
bi-lobed organ in anterior mediastinum
outer cortex/ innor medulla per lobule
made up of dendritic/ macrophage/ epithelial / lymphoid cells
## Footnote
pro-thymocytes enter cortex via blood vessels from bone marrow
91
thymocyte TCR rearrangement
1. TCR beta rearranged
2. expression w pre-beta receptor
3. cell proliferationa nd TCR beta rearrangement
92
markers expressed w TCR
CD3
CD4 and CD8
## Footnote
peripheral T Cells express either CD4 or CD8
93
CD3 function
transmits signal to T cell nucleus after TCR recognition of p/ MHC
93
TCR expression requirements
CD3 complex
delta, epsilon and gamma chains
zeta chain dimer
94
gamma delta TCR
less diverse TCR
don't express CD4/CD8
in epithelial tissues at mucosal surfaces
## Footnote
lineage commitment to gamma delta/ alpha beta depends on order of intial rearrangements
95
immunity T cell recognition
recognize self-MHC + foreign Ag peptide
| positively selected and moved to medulla
96
autoimmunity T cell recognition
Recognize self-MHC + peptide from self
| positively selected and moved to medulla prior to removal by negative se
## Footnote
clonal deletion with those with highest affinity for TCR neg. selected
97
positive selection of T cells
T cells recognize MHC on cortical epithelial cells in thymus
positively selected move to medulla
| apoptosis if no recognition
97
negative selection of T cells
on thymic dendritic cells/ macrophages w high affinityTCR negatively selected
## Footnote
therefore population of T cells w low affinity for self-peptide + self-MHC
98
CD 8 + T cells
recognize MHC class I Ag
99
CD4+ T cells
recognize MHC class II Ag
100
what type of proteins are BCRs?
heterodimeric
101
Do TCRs recognise carbohydrate?
no
102
MHC I/II binding groove
I snaps shut on smaller peptides in ER following TAP translocation
II has binding groove blocked by CLIP (removed in endocytic pathway by HLA-DM)
103
which chain determines an antibody's isotype?
heavy
104
