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73 notecards = 19 pages (4 cards per page)

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Lecture 11

front 1

What are the tenets of clonal selection theory?

back 1

Each lymphocyte has a unique receptor, receptors are made before infection, antigen selects the matching cell, the cell proliferates, clones become effector and memory cells, and self-reactive cells are eliminated

front 2

Why is clonal selection theory relevant?

back 2

Explains specificity, immune memory, and how vaccines work

front 3

What is the difference between stem cells and stromal cells?

back 3

Stem cells become immune cells, stromal cells support development

front 4

How do stromal cells support development?

back 4

Through physical contact and soluble factors (cytokines)

front 5

What are examples of stromal support?

back 5

SCF–Kit (contact) and IL-7 (cytokine)

front 6

What happens in the Pro-B cell stage?

back 6

Heavy chain rearrangement

front 7

What happens in the Pre-B cell stage?

back 7

Heavy chain made, pre-BCR forms, proliferation

front 8

What happens in the immature B cell stage?

back 8

Light chain rearrangement and IgM expression

front 9

What happens in the mature naïve B cell stage?

back 9

IgM and IgD expression, leaves bone marrow

front 10

What is a pre-B cell receptor?

back 10

A test receptor for the heavy chain

front 11

What is the purpose of the surrogate light chain?

back 11

Tests if the heavy chain works

front 12

What are the surrogate light chains?

back 12

VpreB and λ5

front 13

How is the heavy chain tested?

back 13

Forms pre-BCR with surrogate light chain and must signal

front 14

What is a productive rearrangement?

back 14

Functional receptor with correct reading frame and no stop codon

front 15

What is a non-productive rearrangement?

back 15

Nonfunctional receptor due to frameshift or stop codon

front 16

What determines if rearrangement is productive?

back 16

In-frame sequence, no stop codon, full protein

front 17

What is the relationship between rearrangement and allelic exclusion?

back 17

Productive rearrangement stops the other allele; non-productive leads to trying the second allele

front 18

What is the difference between heavy and light chain rearrangement?

back 18

Heavy chain has one chance; light chain can retry and edit

front 19

What are the checkpoints of B cell development?

back 19

Heavy chain checkpoint, light chain checkpoint, self-tolerance checkpoint

front 20

What proteins are expressed early in B cell development?

back 20

CD19 and IL-7 receptor

front 21

What proteins are expressed mid-development?

back 21

Pre-BCR

front 22

What proteins are expressed later?

back 22

IgM and IgD

front 23

How does the heavy chain variable region attach to the constant region?

back 23

By RNA splicing

front 24

What is recombination vs splicing?

back 24

Recombination is DNA-level VDJ joining; splicing is RNA-level joining to constant region

front 25

Why is the order of constant regions important?

back 25

Determines antibody class

front 26

What is the role of alternative splicing?

back 26

Allows IgM and IgD expression

front 27

What happens during negative selection of B cells?

back 27

Self-reactive cells undergo apoptosis, anergy, or receptor editing

front 28

What is apoptosis?

back 28

Programmed cell death

front 29

What is anergy?

back 29

Cell becomes inactive

front 30

What is receptor editing?

back 30

Light chain is changed to avoid self-reactivity

front 31

Why can receptor editing only occur in light chains?

back 31

Heavy chain rearrangement is complete and cannot be redone

front 32

What is central tolerance?

back 32

Removal of self-reactive cells in bone marrow

front 33

What is peripheral tolerance?

back 33

Control of self-reactive cells outside bone marrow

front 34

Why is peripheral tolerance needed?

back 34

Not all self-antigens are in bone marrow

front 35

What are B1 and marginal zone B cells?

back 35

Innate-like, fast responders

front 36

What are B2 cells?

back 36

Conventional adaptive B cells

front 37

Where does T cell development begin and end?

back 37

Begins in bone marrow, ends in thymus

front 38

What is a thymocyte?

back 38

Developing T cell

front 39

What is the difference between cells entering and leaving thymus?

back 39

Entering are immature; leaving are CD4 or CD8 mature cells

front 40

What is the role of the Notch receptor?

back 40

Drives T cell development

front 41

What happens to the thymus over time?

back 41

Shrinks after puberty (involution)

front 42

What are the regions of the thymus?

back 42

Cortex and medulla

front 43

What happens in the cortex?

back 43

Positive selection

front 44

What happens in the medulla?

back 44

Negative selection

front 45

What are the stages of T cell development?

back 45

DN → DP → SP

front 46

How long does T cell development take?

back 46

About 2–3 weeks

front 47

What does the CD4

back 47

CD8 flow plot show? / None → both → one

front 48

What does the CD44

back 48

CD25 flow plot show? / 44 → both → 25 → none

front 49

What are double negative cells?

back 49

No CD4 or CD8

front 50

What are double positive cells?

back 50

Both CD4 and CD8

front 51

What are DN1 cells?

back 51

Earliest stage, entry into thymus

front 52

What happens in DN2 cells?

back 52

TCR rearrangement begins

front 53

What happens in DN3 cells?

back 53

β chain rearrangement and pre-TCR checkpoint

front 54

What happens in DN4 cells?

back 54

Proliferation and CD4/CD8 expression

front 55

What are αβ T cells?

back 55

Most common, adaptive

front 56

What are γδ T cells?

back 56

Less common, innate-like

front 57

What is the pre-TCR made of?

back 57

β chain + pTα + CD3

front 58

What is β-selection?

back 58

Checkpoint testing β chain function

front 59

What is positive selection?

back 59

Keeps T cells that recognize self-MHC

front 60

What is self-restriction?

back 60

T cells must recognize antigen with self-MHC

front 61

What is the goldilocks model?

back 61

Binding must be just right

front 62

What happens with weak binding?

back 62

Death by neglect

front 63

What happens with strong binding?

back 63

Apoptosis

front 64

What happens with intermediate binding?

back 64

Survival

front 65

What happens with slightly high affinity?

back 65

Treg formation

front 66

What is lineage commitment?

back 66

Becoming CD4 or CD8 T cell

front 67

What determines CD4 vs CD8?

back 67

Type of MHC recognized

front 68

What is negative selection?

back 68

Removal of self-reactive T cells

front 69

What is self-tolerance?

back 69

Immune system ignores self

front 70

What are mechanisms of negative selection?

back 70

Apoptosis, anergy, Treg formation

front 71

What is AIRE?

back 71

Protein that presents self-antigens in thymus

front 72

What is positive selection characterized by?

back 72

Cortex location, self-MHC recognition, ~5% survival

front 73

What is negative selection characterized by?

back 73

Medulla location, removal of self-reactive cells