Lectures 6-9 Flashcards

1
Q

B cell receptors & antibodies “BCR & Abs”

A

-directly recognize antigens
-can recognize diverse antigens - proteins, carbohydrates, lipids, nucleic acids

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2
Q

T cell receptors “TCR”

A

-can only recognize antigens presented in the context of MHC “major histocompatibility complexes” molecules
-only recognize peptide antigens

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3
Q

(TCR) Heterodimer

A

Two different chains embedded in T cell membrane that recognize antigens
-alpha + beta chains (95%)
-gamma + delta chains (5%); May recognize carbohydrate antigens

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4
Q

(TCR) Accessory Molecules

A

-closely associated w/ TCR
-needed for signal transduction
-CD4 (T helper) & CD8 (T cytotoxic)
-CD3 complex (6 peptide chains that transduce signals)
-LFA1 (CD11) = integrin that docks T cell to APC

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5
Q

(TCR Diversity) Gene rearrangement / somatic recombination

A

-during T cell development
-recombinase enzyme: coded by “RAG proteins” = Recombination Activating Genes (RAG 1 & 2) on chromosome 11
-NO somatic hypermutation
-NO class switching

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6
Q

ITAMS

A

Immunoreceptor tyrosine-based activating motifs
-activated by phosphorylation
-accessory proteins
-essential for signal transduction

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7
Q

“MHC” Major Histocompatibility Complex

A

-determinant of tissue compatibility / graft rejection
-self vs non-self
-enables immune system to recognize cells infected w/ Intracellular microbes and cancer cells
-MHC recognizes protein antigens only
-MHC is needed for T cells to recognize antigens

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8
Q

MHC I

A

-found on all nucleated cells
-present endogenous (Intracellular) peptides; includes self proteins and viral/bacterial proteins
-heterodimer = alpha + B2 macroglubulin assists w/ folding
-peptide groove in the alpha chain
-presents peptides of 8-11 amino acids
-t cytotoxic (CD8 activation)

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9
Q

MHC II

A

-found on B cells, macrophages, dendritic cells = APCs
-heterodimer = alpha & beta chains but both insert into the cell membrane
-peptide groove between alpha & beta chains
-presents peptides of 30+ amino acids
-T helper (CD4 activation)

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10
Q

MHC restriction

A

-T cells are specific for both antigen & MHC molecule
-The T cell can only react w/ its specific antigen if it is presented by a self MHC molecule
-TCR interaction with self MHC is learned in the thymus during development

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11
Q

Cell Mediated Immunity

A

-TCRs only recognize processed antigens
-Antigens must be presented by an MHC molecule on the surface of an APC
MHC I are found on nearly all cells
MHC II are found on B cells, macrophages, and dendritic cells (professionals)

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12
Q

MHC Selectivity (CD4+ = T helper)

A

-Recognize antigens presented in the context of MHC II
-MHC II is found on APCs (B cells, macrophages, Dendritic cells
-Presents exogenous peptides = extracellular
Role: produce cytokines to tell other immune cells what to do (humoral & cellular responses)

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13
Q

HMC Selectivity (CD8+ = T cytotoxic)

A

-Recognize antigens presented in the context of MHC I
-MHC is found in all nucleated cells
-Presents endogenous peptides = Intracellular
Role: kill cells with the MHC I - Antigen complex

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14
Q

Antigen Processing

A

-cleaving the proteins into smaller peptides which are the correct size for MHC I or MHC II molecules
- takes minutes - hours
-peptide fragments combine with the MHC molecules inside the cell
-MHC-peptide complex travels to the cell surface where it displays peptide fragments to T cells

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15
Q

Antigen Processing: MHC I

A

-Ubiquitin-tagged protein is processed by proteosome in the cytosol
-TAP proteins transport the peptides into the ER
-MHC I + peptide assembled in the ER
-MHC I - peptide transported to cell surface
-MHC I - peptide recognized by CD8 = T cytotoxic (kills cells)

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16
Q

Antigen processing: HMC II

A

MHC II + invariant leaves ER in vesicle
-phagolysosome cleaves protein into smaller peptides
-MHC II + peptide assembled in vesicle
Recognition & binding
-PRRs recognize PAMPS
Ingestion / Internalization
-receptor mediated endocytosis
-macropinocytosis (dendritic cells)
Destruction
-by lysosomal components within vesicles = phogolysosome
(Acid hydrolases, Reactive oxygen species ROS, Nitrous oxide (NO))

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17
Q

Antigen processing: MHC II Ag processing & presentation

A

MHC II + invariant chain leaves ER in vesicle
MHC II + peptide assembled in vesicle
MHC II - peptide transported to cell surface
MHC II - peptide recognized by CD4+ = T helper

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18
Q

Secretion of Cytokines & Chemokines

A

Attracts & stimulates other cells of immune system

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19
Q

IL1

A

Increases permeability of vascular endothelium; stimulates IL6 production

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20
Q

IL6

A

Acts on the liver to produce acute phase proteins: Inflammation

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21
Q

IL8

A

Attracts & activates neutrophils; increases permeability of vascular endothelial

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22
Q

IL12

A

Activates NK cells; influences lymphocyte differentiation

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23
Q

Assembly with MHC I or MHC II is determined by the route through the cell

A

Only peptides (= protein) are presented by MHC
TCR
-95% alpha + beta chains
-5% gamma + delta chains MAY recognize carbohydrates

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24
Q

Superantigens

A

-activate large numbers of T cells without attaching to the groove of MHC molecules
-non specific attachment & activation: binds beta subunit of MHC

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25
Q

TCR binds

A

MHC-peptide

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26
Q

Co-stimulation

A

CD4/CD8 binds MHC II/I respectively
Lck = tyrosine kinase associated with the tails of CD4/CD8 mediate the phosphorylation of ITAMs
CD11 (LFA1) - binds CD54 (ICAM 1 on APC)
CD28 - binds B7 (on APC)

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27
Q

Signal Transduction

A

CD3 complex = 6 peptide chains

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28
Q

Clonal Expansion

A

Activated T cell undergoes numerous mitotic divisions

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29
Q

Differentiation

A

CD4 = T helper
CD8 = T cytotoxic
Memory

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30
Q

Response

A

-T cell migrates to site of infection
-Production of cytokines

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31
Q

In humoral immunity

A

-naive B cells leave bone marrow -> circulation -> secondary lymphoid organs
-important against non-protein antigens

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32
Q

T-cells

A

Only recognize processed peptide antigens presented by MHC

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33
Q

B-cells

A

Recognize naive/unaltered conformational antigens
-non-protein (thymus independent antigens)
-protein (thymus dependent antigens)

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34
Q

Thymus independent = “T independent” (TI)

A

-T cells are not needed
-Non protein antigens
-Induce clonal expansion & differentiation by BCR signaling alone
-multivalent antigens cross-link many BCRs, signal for activation & proliferation, differentiation into plasma
-only IgM produced (small amounts of IgG)
-no isotype switching (needs CD40-CD40L interaction with T helper)

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35
Q

Thymus dependent = “T dependent” (TD)

A

-T helper cells are required
-Protein antigens
-BCR clonal expansion & differentiation requires additional signal from T helper
-Induce GC responses
-Isotype switching
Most pathogens contains both TI & TD antigens

36
Q

T-independent B cell activation: Initiation

A

Antigens (polysaccharide, lipid, nucleic acid)binds more BCRs

37
Q

T-independent B cell activation: co-stimulation

A

-CD21 (CR2) - binds C3d
-CD81
-CD19

38
Q

T-independent B cell activation: signal transduction - ITAMs

A

-clustering of bound receptors -> phosphorylation of ITAMs
-clonal expansion
-some memory B cells
-little / no isotype switching - IgM produced mainly
-little / no affinity maturation

39
Q

T-dependent B cell activation: B cells are APCs Initiation

A

BCR - binds antigens; Receptor - mediated endocytosis; MHC II - peptide

B cell presents MHC II - peptide to T helper -> T helper activation

MHC II - peptide - binds TCR

40
Q

CD40

A

CD40 - binds CD40L (on T helper)
-promotes B cell activation
-promotes isotype switching
-promotes other APC function
CD40L deficiency “hyper IgM syndrome” - because no class switching is taking place

41
Q

B7

A

Binds CD28 (on T helper) - T helper cytokines

42
Q

IL4

A

-B cell proliferation (+IL2)
-IL4 alone switch to IgE
-IL4 + IFN gamma switch to IgG

43
Q

IL5

A

-B cell differentiation into plasma cells
-IL5 + TGF, BAFF switch to IgA
-Activates eosinophils

44
Q

IL6

A

-B cell differentiation into plasma cells

45
Q

Isotype switching

A

-requires cytokine signal to form T helper (& CD40-CD40L)
-constant portion of heavy chain changes; effector end changes
-variable region stays the same; specificity is the same

46
Q

Affinity maturation

A

-occurs in GOs
-it is the result of somatic hypermutation followed by positive selection of high affinity B cells
-high affinity B cells give rise to long-lived plasma cells & memory B cells

47
Q

The primary Ab response

A

Generates memory B cells

48
Q

The secondary Ab response

A

-rapid recognition & Ab synthesis - memory B cells
-rapid isotype switching from IgM-IgG
-Stronger response - more IgG & higher affinity

49
Q

Memory B cells

A

-do not secrete Abs
-typically isotype switched
-typically higher affinity
-long lived

50
Q

Maternal IgG is transported by the neonatal Fc receptor

A

-across the placenta to the fetus
-across the gut epithelium to the neonate (colostrum)
-human milk contains IgA

51
Q

Passive immunity (natural)

A

-(3-4) month protection
-protection is as good as the titer of IgG in the mother against the specific organism

52
Q

IgM

A

First Ab produced

53
Q

IgA

A

Found in secretions

54
Q

IgD

A

BCR

55
Q

IgG

A

Most prevalent, crosses placenta

56
Q

IgE

A

Allergic reactions, multicellular parasites

57
Q

Agglutination

A

Clumping of particles: IgM, IgG, IgA

58
Q

Opsonization

A

Opsonins to tag foreign pathogens for phagocytic elimination ; IgG

59
Q

Neutralization

A

IgM, IgG, IgA

60
Q

Complement activation

A

IgM, IgG

61
Q

Which is false regarding MHC I?

A

Recognized by CD4 helper T cells

62
Q

What is false about Superantigens?

A

Superantigens activate T cells by attaching to the groove of MHC molecules

63
Q

What type of antigens can induce germinal center responses?

A

T-dependent antigens

64
Q

What is the role of CD40 in B cell activation?

A

Isotype switching, the constant portion of the heavy chain changes

65
Q

T cell precursors are produced in the

A

Bone marrow

66
Q

T cells develop & mature in the

A

Thymus

67
Q

T lymphocytes (T helper)

A

T helper = CD4+
-monitor the body for extracellular microbial infections
-activate/stimulate other cells of the immune system

68
Q

T lymphocytes (T cytotoxic)

A

T cytotoxic = CD8+
-destroy host cells infected with Intracellular pathogens
-destroy tumor cells

69
Q

IL-2

A

T cell growth factor
-autocrine (effects the same cell that secreted it)
-paracrine (effects other cells)

70
Q

Th cells have IL-2 receptors

A

They differentiate: influenced by cytokines

71
Q

T helper lymphocytes (CD4) effector subsets

A

TH1
TH2
TH17
TFH
TREG

72
Q

T helper CD4+: Th1

A

Th1 = Intracellular infections (bacteria, virus, protozoa) cell mediated

73
Q

Differentiation of Th1

A

Influenced by
IL-12 (from APCs)
IFN gamma (from NK cells & Th)

74
Q

Th1 secretes:

A

IFN gamma
TNF
IL-10
IL-13

75
Q

IFN gamma

A

Potent activator of macrophages, stimulates activated B cells & IgG production, stimulates Th differentiation, stimulates primed T cytotoxic to become effector cells

76
Q

TNF

A

Activated vascular endothelium to express adhesion molecules to recruit leukocytes

77
Q

IL-10

A

Reduce macrophage activation

78
Q

IL-13

A

Reduces macrophage activation, induces production of mucus in the intestine, increases peristalsis

79
Q

T helper CD4+: Th2

A

Parasites & allergies
Secretes:
IL-4
IL-5
IL-10
IL-13

80
Q

Th2 differentiation is influenced by

A

IL-4 (from mast cells)

81
Q

IL-4

A

IL-4 = stimulates primed B cell proliferation, class switching to IgE, reduce macrophage activation

82
Q

IL-5

A

Stimulates B cel differentiation into plasma cells, activates eosinophils & mast cells, class switching to IgA

83
Q

T helper CD4+: Th17

A

Fungal & extracellular bacteria

84
Q

Th17 differentiation is influenced by

A

IL-6
TGF beta

85
Q

TH17 secretes:

A

IL-17 = recruit neutrophils
IL-22 = stimulates epithelial cells to produce anti-microbial peptides to resist microbial invasion