Test 1-2 Flashcards
1
Q
B and T cells
A
addaptive immunity
2
Q
NK cells
A
innate
3
Q
B-lymphocyte origin
A
-plasma cell precursors from bone marrow stem cells
4
Q
B-lymphoc characteristics
A
- antigen unstimulated B-lymphs have membrane anchored IgM and IgD which bind THE SAME antigen
- each B-cell has ONE antigen specificity
- B-cell clones reactive to >10^9 antigens without the need for exposure to these antigens
5
Q
IgD helps with
A
activation of B-cells
not really meant to be secreted
6
Q
priamry immune response
A
antibody response first time see something
- 7-10 days
- mostly IgM
7
Q
secondary immune response
A
- from memory cells
- takes 2-3 days
- Most IgG
- antibody level is higher
- affinity maturation - longer immune response goes on the better the antibodies will bind
8
Q
immature b-cells only have ______ when compared to mature which have______. When immatuer b-cells come in contact with antigen they ______.
A
immature have IgM
mature have IgM and IgD
appoptize - protects us from autoimmune diseases - held in check by regulatory t-cells
9
Q
development into mature b-cell
A
- stem cells (bone marrow precursor and produce no mmunoglobulin)
- pre-b-cell-cytoplasmic mu-heavy chains (heavy chain of IgM) … not responsive to antigen
- -immature B-cell: expresses antigen-specific membrane IgM; immature b-cells tolerized if encounter antigen; present in the bone marrow*
- mature b-cell: membrane IgM and IgM specific for the SAME antigen - RESPOND to their antigen
- activated b-cell = lymphoblast: small amount of low affinity immunoglobulin; heavy chain isotope switching; differentiate into plasma cells or memory b-cells
- plasma cells - secrete one antibody isotype; found in lymph organ and bone marrow; live for a few days; secrete one antibody (evidence of LONG LIVED plasma cells too)
10
Q
plasma cell morphology
A
elongated cell, eccentric nucleus, abundant cytoplasm, perinuclear halo
11
Q
interaction b/w B and T-cells is …
A
- class II MHC restricted
- Bcell B7 interacts with T-cell CD28
- bcell CD40 binds t-cell CD40L
12
Q
b-cell antigen presentation
A
- b-cell binds antigen — internalizes it (endocytosis) Once it is processed the b-cell has fewer lysosomes and is less efficient at processing— displays it on membrane on CLASS II and activates t-cell
- usually t-cells and b-cellsbind different epitopes on an antigen
- NONPROTEINS ARE NOT REOGNIZED
13
Q
waht do secreted antibodies do when released?
A
- NEUTRALIZE ANTIGEN so it cant bind to anything
- OPSONIZE antigen so it can be phagocytosed (antibodies promote phagocytosis)
- COMPLEMENT ACTIVATION to enhance opsonization and lyse some bacteria
14
Q
protein antigens=
A
thymus dependent antigens bc (require T-cells) of T_h cell dependence
15
Q
non-prtein antigens=
A
- thymus independent bc TI dont need T-h cells
- polysaccharides, nucleic acids, lipids
- provide all necessary b-cell siganls
16
Q
TI-1 antigens:
A
- bind non-immunoglobulin receptors and promote polyclonal expansion
- best example:lipopolysaccharide (LPS)-acts as a b cell mitogen
- does not utilize antibody on surface of b-cell
- NO memory cells, NO isotype switching, NO affinity maturation
17
Q
TI-2 antigens:
A
bind through B-cell surface immunoglobulin (only activate antigen specific b-cells)
- ex) polysaccharide antigens with erpeated epitopes
- NO memory cells, NO isotype switching, NO affinity maturation
18
Q
Get memory cells, isotype switching, & affinity maturation by involving…
A
t-helper cells
19
Q
signal transduction in b-cells
A
bound antibody tails not long enough to transmit signal into cell
signalling through Igalpha and Igbeta
-same function as CD3 in tcells
20
Q
antibodies made up of (chains)
A
2 heavy chains and 2 kappa or 2 lambda light chains
21
Q
genes for antibodies organization on DNA
A
5’ —V-region gene segment —— D-region gene segment —– J-region gene segment —- C-constant region —– 3’
22
Q
variable region of heavy chain made by…
A
V,D,and J gene segemnts —> antigen binding site
23
Q
variable region of light chain made by…
A
V and J gene segments –_>antigen binding site
24
Q
ways to generate diversity in antibodies…
A
1) pairing of heavy and light chains
2) combinatorial diversity - different gene segments rearranged
3) junctional diversity - nucleotide addition/removal occurs at joints bw gene segments (TDT enzyme during DNA split it randomly inserts nucleotides in DNA=more diversity)
4) somatic mutation - point mutations in variable regions of heavy and light chain gene segments that have been rearranged
25
TDT enzyme
enzyme that inserts nucleotides at random during DNA split of introduce diversity in antibody genes.
can be used to track in leukemias and lymphomas as to ho developed the cells are
26
recombinases
loop out, excise DNA and then ligate
27
heavy chain rearrangement:
- happens first
1) Random D and J segments are brought together .. intervening DNA deleted
2) V gene segemnt randomly selected and placed 5' to the DJ segment to form VDJ segment
3) intron separates VDJ segment from c-region gene C-miu and C-delta(which remain in the primary RNA transcript
4) processing of primary RNA---> splice out introns, remove C-delta, add poly A tail
5) mRNA ---> cytoplasmic miu-heavy chain (pre-b-cell stage)
- 4 shots to make a good one
28
light chain rearrangement:
- happens second
- random J with random V-segment to makr primary RNA and make mRNA...
- kappa and lamda gene segments rearranged until a good one made... if cant kappa then lamda - kappa is preference
- 2 shots to make a good one
29
allelic exclusion
cell decides to rearrange one parents genes and not the other allele
-this makes sure that each b-cell has one specificity
30
how do b-cells express Igm and IgD for the same antigen?
both antibodies use to same VDJ region but the tail end is different.
C-miu for IgM and Cdelta region for IgD
31
secreted igMs are missing...
a transcript code for membrane anchoring protin
32
primary RnA transcript codes for....
membrane anchored and secreted form antibodies
33
isotype swithcing:
immune response starts with IgM... how do we switch to IgG and retain specificity?
keeps VDJ region but splice out any other constant regions that you dont want
34
waht class (isotype swithcing) of antibody bcell or plsma cell is not random and which is completely random?
directed by cytokines!
35
IL-4 cytokine...
calls for the production of IgG1 and IgE
36
IL-5 cytokine
calls for the production of IgA (mucosal)
37
affinity maturation of antibodies...
- happens by the accumulation of point mutations in VDJ region.
- mutations accumulate in the descendents of an indiv b-cell
- these b-cells with higher affinity are selected for and stim by t-helper cells
- low affinity b-cells die
38
primary lymphoid tissues
- generation of mature but naive T and B cells
- development of antigen recognition
- involves rearrangement of antigen receptor genes
- bone marrow and thymus
39
secondary lymphoid tissues
- where naive lymphocytes go to wait for activation
- funnel antigen to antigen-specific B and T lymphocytes to drive antigen dependent activation to effector and memory cells
- lymph nodes, tonsils, peyers patches, spleen
40
tertiary lymphoid tissues
- where the elimination of antigen occurs
- "battlefield where immune system defends tissues from microbes
- tissues have direct contact with the external environment
- skin, GI, lungs, vagina
41
bone marrow
- pluripoetent stem cells --> dev into RBC, lymphoc, granulocy, erythrocytes, platelets, monocytes
- ~5% of total body mass primarily in long bones, sternum, pelvis
- stroma - reticular stromal cells, macrophages, adipocytes
- stromal cells provide cell to cell contact + soluble factors
42
B-lymphocyte dev
- earliest B-cell precursors located near inner surface of the bone... more mature cells reside in central axis of marrow cavity
- immature to mature B cells can take place in secondary lymphoid organs
- autoreactive B-cells deleted at immature B-cell stage
43
thymus stuff
- t-lymph orig in bone marrow but mature in thymus
- stem cells --> promothymocytes ---> to thymus = thymocytes ---> dif into mature t-cells
- autoreactive cells are deleted
- mature t-cells released into periphery to populate 2ndary lymphoid tissue
44
mature t-lymphs express:
TCR, CD3, and EITHER CD4 or CD8 proteins
45
hassals corpuscles are
dead thymocyte graveyards
46
cortical epithelium i nhte thymus acts as
nurse cell providing cell to cell contact, cytokines, and peptide hromones
47
lymphatic vessels are primary responders to
tissue borne antigens
48
lymph node locations
axillary, inuinal, cervical, intestinal messentery
49
thoracic duct empties into
left subclavian vein
50
paracortical area of lymph node =
t-cells
51
germinal centers contain:
b-cells proliferating in response to antigen
52
dentritic cells in lymph nodes are found troughout
t-cell rich areas (antigen presenting cells found among t-cells
53
primary follicles =
resting b-cells
54
secondary follicles =
antigen activated b-cells
55
proliferating b-cells are found in...
germinal centers of lymph nodes
56
little antigen stimulation on lymph node...
few primary follicles and No secondary
57
much antigen stimulation on lymph node/...
numerous secondary follices and may be so big you can palpate
58
how do the lymphocytes get into lymph nodes?
- circulating and use high endothelial venules to enter lymph node
- b-cells percolate through t-cell rich areas enhancing the probability that an antigen specific b-cell will interact with an antigen specific t-cell
59
the spleen is responsible for...
blood borne antigens
- largest lymphoid tissue
- secondary lymphoid organ
60
major function of spleen=
remove particulate matter and senescent RBCs from circulation (in red pulp) and expose lymphocytes to antigens (in white pulp)
61
movement of blood spleen
splenic artery --> central arteries --> penicilliary arterioles
62
peniciliiary arterioles sinificance
small and leaky--- leak antigen into lymphoid tissue
63
periarterial lymphatic sheath (PALS) surround what and contains what?
surrounds central arteries and peniciallary arterioles
contains t-cells
64
mucosa associated lymphoid tissues are:
lungs,GI tract and GU tract
65
mucosa associaetd lymphoid tissue significance...
exposes immune system to antigens across mucosal epithelia
66
peyers patches
- localized in terminal ileum = smal intestine secondary MALT
- B-cell follicles surrounded by zone rich in T cells
- HEVs transport lymphocytes into peyers patches]
- m-cells (microfold on limunal side) transport proteins and microbes from intestinal lumen
67
why do b-cells and t-cells hang out separately?
soluble factors tell them where to migrate - factors produced by stromal cells (chemokines)
68
tertiary lymphoid tissue
- mainly skin and mucosa - pretty much anywhere that can be infected
- majority of b and t-cells are MEMORY CELLS
- cells delivered via blood stream
69
langerhams cells
- dendritic cell - samples its enviroment
- capture and transport antigen (when activated these cells retract their dendritic processes and loose adhesiveness= migrate to nearest lymph node --> present antigen to activate t-cells
70
3 ways into lymph node
- flushed into lymph node
- carried by b-lymphocytes
- carried by dendritic cells
71
immune response ina lymph node
- b-cell interact with t-cell (active now)
- tcells feed cytokines and growth factors to activate and allow b-cellto proliferate and change into plasma cell
- b-cells divide every 6-8 hours
72
plasma cells in lymph nodes migrate to... and make....
medullary cords and then to bone marrow
low affinity antibodies
73
germinal center b-cells diferentiate into.. and produce...
plasma cells
high affinity antibodies
74
bone marrow is the major site of...
antibody production (since plasma cells go to bone marrow)
75
lymphocyte homing
molecules on cells and in organ so the lymphocytes know where theyre going
if it was in the spleen it will get to the spleen
76
lymphocyte recirculation
- travel bw lymphoid organs
| - greater probabilty for rare lymphocytes to become activated if they circulate!
77
naive cell circulation
make a complete circuit (blood to lymph to blood -- these guys WANT to encounter something
78
memory cell circulation..
mainly in blood stream and move into tertiary areas to respond quickly!
-found in peyers patches
79
mucosal antigens elicit secretory
IgA and IgA secreting plasma cells by mucosal epithelia
80
serum
IgG response
81
T_reg cell functions
to prevent:
1) excessive immune response to foreign antigens
2) immune responses to self antigens missed by tolerization
82
T-reg cells are:
CD4 cells
| remember CD8 are cytotoxic t-cell
83
T-reg mechanisms of action
* **-inh cytokines (IL10, transforming growthfactor beta)***
- adsorb growth/dif factors by receptors
- cytolytic activity against helper + cytolytic t-lymphoc
84
idiotypic regulation
idiotype=antigen-binding site (hypervariable regions)
antibodies can act as antigen so an antibody for an idiotype (antiidiotypic antibody) produced which inhibits b-cells expressing idiotype antibody = b-cell could not be inhibited
85
network hypothesis
antigen stimulates antibody ---> complimentary antiidiotypic response (make antibody for the antibody for the antigen ---> decreases amount of antibody)
- antibody for antibody produced after antibody production has began
- role in immunoreg not determined
86
anti-idiotypic antibodies can
- stimulate an immune response bc they MIMIC the antigen (they need to inhibit the ANTIBODY so they bind like ANTIGEN)
- like a vaccine but dont actually need pathogen if pathogen is way to complicated
87
antibody feedback
- by secreting antibody and eliminating antigen your self downregulating the need for antibodies (antigen isnt around to bother the immune system)
- immune complex bound antibodies inhibit B_lymphocyte activation by binding to Fc receptors and b-lymph bound antibodies need to bind antigen of immune complex
88
define tolerance:
block of antigen-induced differentiation of B and T cells (antigen ignored or b and t cells remove)
--> an induced state of unresponsiveness to antigen
-tolerance against SELF so that you avoid autoimmune disease
89
characteristiics of tolerance:
- antigen specific
- acquired (not inborn)
- each of us has the capacity to dev autoimmunity
90
what kind of lymphocytes are easier to toleriza?
immature lymphocytes
91
clonal deletion
death of antigen specific lymphocytes (central tolerance bc it takes place in the primary lymphoid organs)
92
clonal anergy
functional inactivation of viable lymphocytes (peripheral tolerance bc it takes place in the periphery)
93
clonal deletion occurs in
bone marrow and thymus
94
t-lymphocyte tolerance mechnisms
-not all self reactive t-cells removed in the thymus --> need clonal anergy
1) suppressor t cells such as t_reg, Th3, and T_R1
2) t-cells-APC interaction w/out costimulatory molecules
95
t-lymphocyte tolerance is (duration?)
long lasting - protects us from self reactive t-cells
96
b-cell can see compared to t-cells
glycoproteins, proteins, lipids, nucleic acids while t-cells can only see proteins
97
receptor editing
b-cells only - that is self specific that rearrange the light chain AGAIN to produce a completely dif antigen specificit -->b-cell survives
98
b-lymphocyte tolerance is (duration?)
short lived
99
thymocyte info
- cant recognize or respond to antigen --> no TCR
| - destroyed by corticosteroids ==> state of immunodeficiency w/ chronic use
100
bw cortex and medulla of thymus thymocytes...
- rearrange renges to make TCR for antigen recognition
| - CD4 or CD8 decision
101
t lymphocytes that die are either
autoreactive or specific for foreign MHC
102
t-cells becoming CD4 or CD8...
start out as both -double positive- (80% of population) and they end up losing one
103
thymocytes need to things to mature...
1) cell to cell contact with stromal cells
| 2) soluble factors
104
positive selection in thymus
- occurs first: 1) keep cell population that recognizes self-MHC (any otherfree loaders die)
- thymocytes that bind self MHC proteins permitted to survive
- eliminates thymocytes that recognize foreign MHC proteins
- cortical epithelial cells mediate positive selection
105
negative selection in thymus
- occurs second: 2) gets rid of dangerous cells that recognize self
- thymocytes that bind self antigens and self MHC eliminated
- carried out by dendritic cells at corticomeduallary junction
106
AIRE gene (autoimmune regulator gene)
- thymus produces a lot of self reactive angitens to get rid of t-cells that recognize self
- helps with negative selection
107
mutation in AIRE gene=
widespread autoimmune disease
108
monokines produced by and regulates:
prod: macrophages
reg: phagocytotic cells
109
lymphokines produced by and regulates:
prod activated t-cells
| regulates: lymphocytes, macrophages neutrophils, eosinophils
110
colony stimulating factors produced by and regulates:
prod: lymphocytes, macrophages, bone marrow, stromal cell
regulares: granulocyte and monocyte production in the bone marrow
111
cytokine activities:
autocrine actions -
paracrine
endocrine
Positive and neg feedback on other cytokines
influences target cells by binding to specific cellular receptors
112
interferon
mediator of natural immunity
- type 1 IFN (alpha and beta) -
- paracrine action to induce resistnce to viral rep ni all cells with Mc Proteins
- increase class I (for cytotoxic t-lymphocytes)
- activate NK cells to kill viruses
113
TNF alpha actions
- activates macrophages/neutrophils
- inc adhesiveness of vascular endothelium for neutrophils
- fever generation
- neutrophilia
- DIC/shock
114
too much TNF...
body goes into shock and you die.
115
IL1 produced by and action?
-produced by macrophages, enothelial cells, and activated t-cells
-actions:
stim liver to produce acute phase proteins
induces IL6 from macrophages
high levels of IL1 generates fever and metabolic wasting
dif of B-cell into plasma cells
116
interleukin2 / IL2
produced by CD4 t-cells and autocrine and paracrine growth factor for t-cells
- inc NK cell cytotoxicity
- at high concentrations= induces NK cells to beceome lympokine activate kkiller cells
117
Interleukin 4 IL4
poduced by CD4T cells and mast cells, basophils
B-cell isotype switching to IgE
118
Tgf-Beta
produced by activated T-cells and activated pacrophages
- inhibits t cell proliferation/dif into CTL
- inhibits macrophage, b-cells, and t-cell activation
- induces b-cell to produce IgA antibody at mucosal sites
- initiates wond healig --> fibroblast migration and proliferation
119
interferon gamma
type 2 interferon or mimune interferon
-mainly produced by CD4 and CD8 t cells
```
most potent activator of macrophages
-upregulates class i and Class II MHC expression
```
120
most potent activator of macrophages:
interferon gamma
