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

Exam 3: Regulation of the Immune System Flashcards

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
Q

immune paralysis

A

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

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26
Q

Central B cell tolerance

A

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

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27
Q

Peripheral B cell tolerance

A

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)

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28
Q

central B cell tolerance mechanism

A

in primary lymphoid organs

immature B cell –> low dose of antigen –> clonal abortion

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29
Q

peripheral B cell tolerance mechanism

A

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

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30
Q

what is the main characteristic of immune response induced by T-independent antigens

A

produce only 1 type of antibody –> IgM (produced by plasma cells)

no participation of T helper cells

no memory cells

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31
Q

what does an inadequately low immune response lead to

A

immunodeficiency and increased susceptibility to infection

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32
Q

what does an excessive immune response lead to

A

allergies or autoimmunity

33
Q

increased antigen leads to

A

immune response is prolonged

34
Q

decreased antigne leads to

A

immune response stop

35
Q 
what do these cells present antigens to 
Langerhans cells
follicular dendritic cells
DC1
DC2
A

Langerhans cells –> T cell response
Follicular dendritic cells –> B cell response
DC1 –> Th1
DC2 –> Th2

36
Q

what type of immune response are these cells involved in
DC1 –> Th1
DC2 –> Th2

A

DC1 –> Th1 —> cellular immune response

DC2 –> Th2 —> antibody mediated immune response (humoral)

37
Q

how are immunoglobulins regulated

A

neonatal isoerythrolysis
colostrum
inhibitory B cell receptor (CD32)

38
Q

what in colostrum rich in

A

antibodies

39
Q

what does CD32 do

A

binds to antibodies and produces an inhibitory signal

40
Q

what delays the onset of immunoglobulin synthesis in a newborn animal

A

presence of maternal antibody - negative feedback process

41
Q

what happens when animal ingests maternal antibodies

A

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
Q

what happens when an animal doesn’t ingest maternal antibodies

A

produces own antibodies much quicker

43
Q

what happens in cross linking between BCR and CD32

A

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
Q

what kind of receptor is CD32

A

Fc receptor (antibody receptor)

45
Q

antibody regulation:

what does IgG do

what does IgM do

A

IgG – suppress the production of IgG/IgM

IgM – suppress the production of IgM

46
Q

what is main function of CD80 or CD86 binding to CD152

A

suppression

47
Q

regulatory T cells (Treg)

A

Natural Treg – thymus
Induced iTreg – intestine

suppress Th cell activity
suppress CD8 T cell activity

Oral Ag — iTreg

48
Q

what is the function of regulatory T cells

A

suppression of T cell and macrophage function

49
Q

how are Treg generated

A

by the combined actions of IL-2 and TGF-B as well as the presence of retinoic acid

50
Q

what to Treg produce

A

suppressive cytokines

TGF-B
IL-10
IL-35

51
Q

what is CTLA4

A

cytotoxic T lymphocyte associated protein 4

CD152

52
Q

Treg suppression of other immune responses - direct contact

A
  1. Treg cells
  2. direct contact of Treg with T effector
  3. TGF-B, proteins and granzymes, galectin 1, CTLA4, TRAIL
53
Q

Treg suppression of other immune responses - suppressive molecules

A
  1. Treg
  2. suppressive molecules
  3. IL-10, TGF-B, IL-35, prostaglandin E2
54
Q

Treg suppression of other immune responses - interference with antigen presentation

A
  1. Treg
  2. interference with antigen presentation
  3. Neuropilin1, IDO
55
Q

where does IL-10 come from

A 
Th cells
Treg cells
dendritic cells
B cells
 M2 macrophages
56
Q

what is main function of IL-10

A

suppression

57
Q

IL-10 - Suppression of macrophages

A 
reduced antigen presentation
reduced MHC II expression
reduced co-stimulation
increased apoptosis
reduced IL-6, TNF-a, NO
58
Q

IL-10 – suppresses Th1 cells

A

reduced IL-2, IFN-y, TNF-a

59
Q

IL-10 – suppresses Th2 cells

A

reduced IL-4, IL-5

60
Q

IL-10 – enhances Treg cells

A

enhances Treg cells

61
Q

IL-10 – suppresses Th17 production

A

reduced IL-17

62
Q

IL-10 – suppresses NK cells

A

reduced IFN-y, TNF-a

63
Q

IL-10 – suppresses DCs

A

reduced MHC II expression
reduced adherence molecules
reduced co-stimulation

64
Q

where does TGF-B come from

A 
T cells
B cells
Macrophages
Platelets
Neutrophils
65
Q

what is the main function of TGF-B

A

regulation

66
Q

TGF-B – regulates T cell activation

A

reduces T cell proliferation

antagonizes IFN-y and IL-12

67
Q

TGF-B – other cells

A

regulates cell proliferation
regulates growth
regulates differentiation
regulates motility

68
Q

TGF-B – regulates macrophages

A

enhances integrin expression
enhances phagocytosis
reduces respiratory tone
reduces cytotoxicity

69
Q

TGF-B – regulates B cell function

A

reduces B cell proliferation
promotes IgA production
promotes apoptosis

70
Q

Regulatory cells - Macrophages (M2)

A

induce tolerance
suppress inflammation
inhibit dendritic cell antigen presentation

71
Q

regulatory factors – indoleamine 2, 3 dioxygenase

A

tryptophan degradation

72
Q

regulatory cells - dendritic cells

A

DC1
DC2
??????

73
Q

regulatory cells - natural suppressor cells

A

suppress B and T cell proliferation

suppress immunoglobulin production

74
Q

proinflammatory cytokines

A

IL-1
TNF-a
IL-6
HMGB-1

75
Q

how central nervous system and immune system interact 1

A
  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
Q

how central nervous system and immune system interact 2

A
  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
Q

how central nervous system and immune system interact 3

A
  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
Q 
what do these do
Encephalins
B Endorphin
a Endorphin
Somatostatin
Somatotrophin
A

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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