B cells: lymphocyte development

Question 1

What does tolerance ensure

Answer 1

Immune system avoids destroying host tissue

Question 2

What can happen during rearrangements to create b and T cells

Answer 2

Many of random rearrangements used to create b and T cell receptors could be self reactive

Question 3

What does tolerance help do

Answer 3

Helps keep self reactive recognition molecules/cells from circulating in bloodstream

Question 4

T cell dev where

Answer 4

In thymus
T cells initially develop in bone marrow = early stages but then migrate to thymus to achieve full maturity

Question 5

Describe T cell dev in thymus

Answer 5

Developing T cells = thymocytes
Undergo rigorous selection —> mature naive T cells

Question 6

Describe anatomy of thymus

Answer 6

Cortex with cortical epithelial cells
Medulla with medullary epithelial cells
Thymocytes
Macrophages
Cortical dendritic cells

Question 7

How do T cell precursors enter thymus

Answer 7

Enter as double negative cells = do not express cd4 or cd8 co repcetros

Question 8

What happens during development in thymus to cd4 and c8 repcetros expression

Answer 8

Changes during dev in thymus
1. Double neg
2. Then double pos (express both cd4 and cd8)
3. Single pos (expresses either cd4 or cd8)

Question 9

What do T cells develop during development

Answer 9

Develop mhc restriction and undergo process to ensure self tolerance (not autoreactive)

Question 10

define positive selective

Answer 10

Selects thymocytes bearing repcetros, capable of binding self mhc molecules, resulting in mhc restriction

Question 11

define negative selection

Answer 11

Selects against thymocytes bearing high affinity receptors for self mhc/self peptide complexes, resulting in self tolerance

Question 12

Describe cortical epithelial cells

Answer 12

Express high levels fo mhc class 1 and 2 (express self peptide )

Question 13

What cna double positive T cells do

Answer 13

Browse peptide mhc on surface of these cortical Epithelial cells

Question 14

What happens if tcrs can’t bind

Answer 14

Cells die by neglect
90-96% die = why you need macrophages = clean up mess

Question 15

What happens if tcr bidns too strongly

Answer 15

Cells die

Question 16

What happens if tcrs bind low to just right

Answer 16

Positive selection to single positive stage occurs = tcr specific to self mhc but nto self peptide
= if bind mhc2 with cd4 = T cell becomes single positive cd4+ T cell
= if bind mhc1 with cd8 = T cell becomes single positive cd8+ T cell

Question 17

Describe negative selection

Answer 17

Central tolerance - in thymus - T cells

Question 18

What is negative selection

Answer 18

Needed to ensure self tolerance

Question 19

What do medullary epithelial cells express

Answer 19

Transcription factor called autoimmune regulator = aire

Question 20

Descrie aire

Answer 20

Induces expression of many tissue specific proteins in thymic epithelial cells
These are then processed and presented on mhc 1 or 2
Allows T cells to be screened against self ags safely in thymus = single pos T cell binds = means its autoreactive

Question 21

Describe cortical dcs - contribute to

Answer 21

Negative selection = cortical dcs present self peptides on mhc 1 or mhc 2
Also contribute to neg selection in cortex

Question 22

What do single positive T cells do

Answer 22

Brown self-p:mhc on surface of thymic epithelial cells and cortical dendritic cells

Question 23

Describe negative selection = if tcrs do not bind

Answer 23

Cells survive

Question 24

Describe negative selection = if tcrs bind

Answer 24

= binds self p mhc
So clonal deletion
Or clonal anergy, clonal editing

Question 25

What is clonal deletion

Answer 25

Self reactive T cells die - most cases

Question 26

What is clonal anergy

Answer 26

Autoreactive T cells inactivated

Question 27

What is clonal editing

Answer 27

Second or third chance at rearranging a non self reactive tcr gene

Question 28

Describe peripheral tolerance

Answer 28

Plan B when autoreactive t cels slip through = peripheral mechanisms of tolerance Alamo protects against autoreactive thymocytes

Question 29

Describe why peripheral tolerance needed

Answer 29

Important for self reactive T cells that escape neg selection in thymus Strong self ag signalling through tcr in absence of costimulation = may drive T cells into anergy (unresponsiveness) Regulatory T cells can help maintain peripheral tolerance

Question 30

Describe B cell development = where

Answer 30

Begins and mainly occurs in bone marrow Completed in periphery = spleen

Question 31

Describe B cell development = what type of selection

Answer 31

Only negative selection required Bc no need for mhc restriction

Question 32

Describe B cell development = describe negative selection

Answer 32

Proper gene rearrangement of h and l chain genes to give rise to ig hat shows self tolerance = negative selection (deletion) of autoreactive B cells

Question 33

What appends when B cells tested against self ags

Answer 33

3 outcomes = clonal deletion, receptor editing, anergy

Question 34

What happens when B cells tested against self ags = describe clonal deletion

Answer 34

Of strongly autoreactive cells Through apoptosis

Question 35

What happens when B cells tested against self ags = describe receptor editing

Answer 35

Reactivation of recombination machinery

Question 36

What happens when B cells tested against self ags = describe anergy

Answer 36

Induction of non responsiveness to further stimuli (even self ag stimuli)

Question 37

Compare b to T cells —> is tehre an aire equivalent

Answer 37

No aire equivalent -range of self ags available = lower Self ag are soluble protein in circulation or presented on stromal cells and other cells Any potentially self reactive B cells that’s been activated required activation from T cell (if autoreactive = cannot find tfh for signal one)

Question 38

Describe B cells exported from bone marrow

Answer 38

Still functionally immature Progress through spleen for further maturation = leave as mature naive B cells

Question 39

Describe what mature primary B cells do

Answer 39

Migrate to lymphoid follicles Express high levels of igm/igd on surface (also other other repcetros) Negative selection - peripheral tolerance here too Recirculate between blood and lymphoid organs

Question 40

Half life mature primary B cells

Answer 40

4.5 months in periphery

Question 41

Describe receptor editing of potentially auto reactive T and B cells

Answer 41

Receptor editing of potentially autoreactive repcetros occurs Recomb machinery turned back on Last ditch effor t to salvage rearrangement = depends on how many segments available - segments = upstream and downstream kept - use these

Question 42

What cna be involved in editing self reactive bcrs

Answer 42

Combinatorial diversity and junctional diversity

Question 43

What characteristics do b and T cells share

Answer 43

Rearrangement of gene segments - primary diversification Screening processes to avoid self reactivity

Question 44

Differences between b and T cell developmental pathways = name them

Answer 44

Location of matruation and screening Screening processes used Eventual outcomes of antigen receptor stimulation

Question 45

Differences between b and T cell developmental pathways = describe screeening processes used

Answer 45

Positive and neg selection in T cells Neg selection in B cells

Question 46

Differences between b and T cell developmental pathways = describe outcomes of ag repcetor stimulation

Answer 46

T cells require presentation and differentiate into helper or killer subsets B cells require T cell help and secrete abs

Question 47

Properly functioning immune system

Answer 47

Only react to dangerous non self

Question 48

What happens when properly functioning immune system breaks down

Answer 48

Can respond to safe non self= allergies Can respond to self = autoimmune disorders

Question 49

Name mechanisms of tolerance

Answer 49

Central tolernace Periphera; tolerance

Question 50

Defects in tolerance =

Answer 50

Autoimmunity

Question 51

Organ specific autoimmunity

Answer 51

Predominant injury of an organ or tissue

Question 52

Systemic autoimmunity

Answer 52

Injury of many diff tissues

Question 53

Basic mechanism of autoimmunity

Answer 53

Cell mediated autoimmunity Antibody mediated autoimmunity

Question 54

Describe cell mediated autoimmunity = basic mechanism of autoimmunity

Answer 54

Mostly T cell mediated Sensitive to thymectomy Ex= ms, type 1 diabetes

Question 55

Describe antibody mediated autoimmunity = basic mechanism of autoimmunity

Answer 55

Mostly ab mediated Ex = lupus

Question 56

Summarize central tolerance

Answer 56

Induction of immune tolerance in primary lymphoid organs = bone marrow and thymus Clonal deletion, repcetor editing, clonal anergy

Question 57

Summarize peripheral tolerance

Answer 57

Induction of tolerance outside primary lymphoid organs Anergy, deletion, immune regulation - tregs