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Immunology > Exam 3: Regulation of the Immune System > Flashcards

Exam 3: Regulation of the Immune System Flashcards

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1
Q

what needs to happen to self antigens generated by B and T cells

A

must be destroyed or turned off

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2
Q

how is adaptive immune response regulated

A

recognize and eliminate foreign invaders
kill target cells (infected/tumor cells)

autoimmunity

immunodeficiency/immunosuppression

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3
Q

what happens when excessive adaptive immune response

A

allergies

autoimmunity

amyloidosis

lymphoid tumors

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4
Q

what happens when there is a defective adaptive immune response

A

increased infections

increased cancers

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5
Q

tolerance

A

there is not an immune response to a specific antigen (self antigen)

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6
Q

when do lymphocytes become tolerant

A

immature lymphocytes become tolerant to an antigen if they first met in fetal life

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7
Q

where was tolerance observed

A

chimeric calves

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8
Q

central tolerance

A

immature self reacting lymphocytes within thymus, bursa, or bone marrow die or alter their receptor specificity

immature T and B cells in primary lymphoid organs

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9
Q

peripheral tolerance

A

mature lymphocytes that encounter self antigens are turned off, or suppressed by T regulatory cells

mature T and B cells in secondary lymphoid organs

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10
Q

what results in development of calf chimeras

A

fusion of the placentas of dizygotic twin calves

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11
Q

why is each chimera tolerant to it’s twin’s cells

will each chimera accept a skin graft from its twin despite the genetic differences

A

Hematopoietic stem cells from each animal colonize the bone marrow of the other

yes, they will accept a skin graft

recognize each others antigens as “self” because they were in contact during fetal development

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12
Q

duration of tolerance in T and B cells

A

T cells much more easily rendered tolerant than B cells

Once tolerant, T cells remain tolerant for much longer

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13
Q

why is it easier to induce tolerance in T cells

A

T cells only use gene conversion

B cells use gene conversion, somatic mutation, and gene recombination

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14
Q

central T cell tolerance

A

no functional T cells with receptors that can bind to self antigens

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15
Q

in central T cell tolerance how many gene arrangements will be out of frame

A

2/3 of possible gene arrangements will be out of frame

these will recognize self antigens

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16
Q

what happens to cells with non functional TCRs

A

apoptosis –> negative selection

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17
Q

how can T cells in thymus recognize self antigens located elsewhere

A

negative selection

thymic epithelial cells produce a transcription factor - AIRE

AIRE helps to express different proteins from different tissues

if a T cell binds to a thymic epithelial cell and recognizes self antigens –> die

AIRE – autoimmune regulator

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18
Q

positive selection in regards to central T cell tolerance

A

positive selection ensures that cells that recognize self-MHC molecules survive

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19
Q

how does thymus induce T cell tolerance

A

negative selection

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20
Q

Central T cell tolerance - positive vs negative selection

A

negative selection - makes sure T cells don’t react with self antigens

positive selection - makes sure T cells respond to foreign antigens and react with MHC

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21
Q

peripheral T cell tolerance

A

clonal anergy

T cells require multiple signals in order to respond to antigen

if these signals are insufficient or inappropriate the T cell responses to antigen will be suppressed

in secondary lymphoid organs

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22
Q

what produces activation of peripheral T cell tolerance

A

blocked CD28 - CD80 interaction

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23
Q

what is clonal anergy

A

the prolonged antigen specific suppression of T cell function

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24
Q

different doses of antigen induce peripheral tolerance differently

A

very high and very low doses of antigen - induce tolerance

high doses of antigen can induce a form of clonal anergy called immune paralysis

moderate doses of antigen - induces immune response and antibody production

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25
immune paralysis
can be induced by high doses of antigen the high dose of the antigen probably bypasses APCs and reach the Th cell receptors directly and in absence of co-stimulation they trigger anergy
26
Central B cell tolerance
primary lymphoid organs VDJ rearrangement, gene conversion, somatic mutation immature B cells can recognize self antigens (55-75%) B cell suppression at early stages in animal's development
27
Peripheral B cell tolerance
food allergies absence of co-stimulation repeated exhaustive antigen stimulation = short lived plasma cells, no memory cells = tolerance oral proteins in high doses induces clonal deletions and anergy oral proteins in low doses induces development of T regulatory cells -- why most people don't develop immune responses to most foods (why most people aren't allergic to most foods)
28
central B cell tolerance mechanism
in primary lymphoid organs immature B cell --> low dose of antigen --> clonal abortion
29
peripheral B cell tolerance mechanism
in secondary lymphoid organs mature B cell --> exhaustive antigen challenge --> clonal exhaustion mature B cell --> absence of co-stimulation --> functional deletion mature B cell --> excessive suppressor cell activity --> functional deletion mature B cell --> excessive T-independent antigen --> functional deletion and receptor blockade
30
what is the main characteristic of immune response induced by T-independent antigens
produce only 1 type of antibody --> IgM (produced by plasma cells) no participation of T helper cells no memory cells
31
what does an inadequately low immune response lead to
immunodeficiency and increased susceptibility to infection
32
what does an excessive immune response lead to
allergies or autoimmunity
33
increased antigen leads to
immune response is prolonged
34
decreased antigne leads to
immune response stop
35
``` what do these cells present antigens to Langerhans cells follicular dendritic cells DC1 DC2 ```
Langerhans cells --> T cell response Follicular dendritic cells --> B cell response DC1 --> Th1 DC2 --> Th2
36
what type of immune response are these cells involved in DC1 --> Th1 DC2 --> Th2
DC1 --> Th1 ---> cellular immune response DC2 --> Th2 ---> antibody mediated immune response (humoral)
37
how are immunoglobulins regulated
neonatal isoerythrolysis colostrum inhibitory B cell receptor (CD32)
38
what in colostrum rich in
antibodies
39
what does CD32 do
binds to antibodies and produces an inhibitory signal
40
what delays the onset of immunoglobulin synthesis in a newborn animal
presence of maternal antibody - negative feedback process
41
what happens when animal ingests maternal antibodies
takes more time to produce their own antibodies they were previously protected by ingested maternal antibodies so they didn't need to produce their own
42
what happens when an animal doesn't ingest maternal antibodies
produces own antibodies much quicker
43
what happens in cross linking between BCR and CD32
cross linkage between BCR and CD32 by antibody and antigen can turn off a B cell by activating a phosphatase that in turn blocks signaling by tyrosine kinase when crosslinking antigens, CD32 blocks activation of B cell and induces apoptosis in B cell
44
what kind of receptor is CD32
Fc receptor (antibody receptor)
45
antibody regulation: what does IgG do what does IgM do
IgG -- suppress the production of IgG/IgM IgM -- suppress the production of IgM
46
what is main function of CD80 or CD86 binding to CD152
suppression
47
regulatory T cells (Treg)
Natural Treg -- thymus Induced iTreg -- intestine suppress Th cell activity suppress CD8 T cell activity Oral Ag --- iTreg
48
what is the function of regulatory T cells
suppression of T cell and macrophage function
49
how are Treg generated
by the combined actions of IL-2 and TGF-B as well as the presence of retinoic acid
50
what to Treg produce
suppressive cytokines TGF-B IL-10 IL-35
51
what is CTLA4
cytotoxic T lymphocyte associated protein 4 CD152
52
Treg suppression of other immune responses - direct contact
1. Treg cells 2. direct contact of Treg with T effector 3. TGF-B, proteins and granzymes, galectin 1, CTLA4, TRAIL
53
Treg suppression of other immune responses - suppressive molecules
1. Treg 2. suppressive molecules 3. IL-10, TGF-B, IL-35, prostaglandin E2
54
Treg suppression of other immune responses - interference with antigen presentation
1. Treg 2. interference with antigen presentation 3. Neuropilin1, IDO
55
where does IL-10 come from
``` Th cells Treg cells dendritic cells B cells M2 macrophages ```
56
what is main function of IL-10
suppression
57
IL-10 - Suppression of macrophages
``` reduced antigen presentation reduced MHC II expression reduced co-stimulation increased apoptosis reduced IL-6, TNF-a, NO ```
58
IL-10 -- suppresses Th1 cells
reduced IL-2, IFN-y, TNF-a
59
IL-10 -- suppresses Th2 cells
reduced IL-4, IL-5
60
IL-10 -- enhances Treg cells
enhances Treg cells
61
IL-10 -- suppresses Th17 production
reduced IL-17
62
IL-10 -- suppresses NK cells
reduced IFN-y, TNF-a
63
IL-10 -- suppresses DCs
reduced MHC II expression reduced adherence molecules reduced co-stimulation
64
where does TGF-B come from
``` T cells B cells Macrophages Platelets Neutrophils ```
65
what is the main function of TGF-B
regulation
66
TGF-B -- regulates T cell activation
reduces T cell proliferation | antagonizes IFN-y and IL-12
67
TGF-B -- other cells
regulates cell proliferation regulates growth regulates differentiation regulates motility
68
TGF-B -- regulates macrophages
enhances integrin expression enhances phagocytosis reduces respiratory tone reduces cytotoxicity
69
TGF-B -- regulates B cell function
reduces B cell proliferation promotes IgA production promotes apoptosis
70
Regulatory cells - Macrophages (M2)
induce tolerance suppress inflammation inhibit dendritic cell antigen presentation
71
regulatory factors -- indoleamine 2, 3 dioxygenase
tryptophan degradation
72
regulatory cells - dendritic cells
DC1 DC2 ??????
73
regulatory cells - natural suppressor cells
suppress B and T cell proliferation | suppress immunoglobulin production
74
proinflammatory cytokines
IL-1 TNF-a IL-6 HMGB-1
75
how central nervous system and immune system interact 1
1. central nervous system releases encephalins, endorphins, somatostatin, somatotropin 2. activates immune system 3. immune system releases proinflammatory cytokines 4. induce fever, sleep, appetite which act on central nervous system
76
how central nervous system and immune system interact 2
1. central nervous system releases hormones related to stress, adrenals, and steroids 2. activates immune system 3. immune system releases proinflammatory cytokines 4. induce fever, sleep, appetite which act on central nervous system
77
how central nervous system and immune system interact 3
1. central immune system activate sympathetic nervous system and antibody formation 2. activates immune system 3. immune system releases proinflammatory cytokines 4. induce fever, sleep, appetite which act on central nervous system
78
``` what do these do Encephalins B Endorphin a Endorphin Somatostatin Somatotrophin ```
Encephalins - T cytotoxic increase B Endorphin - T cytotoxic increase, antibody production increase a Endorphin - antibody production decrease Somatostatin - immune response decrease Somatotrophin - immune response increase

Immunology (15 decks)

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