6.2 T cell Development in the Thymus

Question 1

What are heavy and light chains made of in B cells?

Answer 1

Heavy - IgM, IgA, IgD, IgE, IgG

Light - kappa, and lambda

Question 2

What are the 2 main types of TCR structures?

Answer 2

alpha / beta (majority)

delta / gamma (minority)

Question 3

What happens to TCR genes during development?

Answer 3

the genes undergo random recombination, forming diverse, fully rearranged variants

Question 4

What are the 3 rough types of effectiveness with T cells,?

Answer 4

the good, expressing immunity against pathogenic cells

the bad, autoimmunity

the ugly, nothing much (death by neglect)

Question 5

How are B cells filtered?

Answer 5

immature B cells auditioned for self-antigens on the stromal bone marrow cells
if they recognise the self-antigen, they are deleted

Question 6

Why are B and T cells filtered differently?

Answer 6

T cells only recognise antigen in their presented form on MHC

Question 7

What is the structure of the thymus?

Answer 7

there are lobules with a cortex and medulla, with their own specialised epithelial cells

blood vessels and dendritic cells occupy the corticomedullary junction

Question 8

What are cells expressing both CD4 AND CD8 called?

Answer 8

double positive thymocytes

Question 9

What is the first stage of events in the thymus?

Answer 9

progenitors tested to see if they bind to MHC in the cortex, if they don’t they die by neglect

if they do they pass into the medulla

Question 10

What is the second stage of events in the thymus?

Answer 10

progenitors tested to see how strongly they bind to MHC

if too strong - negative selection

Question 11

What do cells that recognise MHC class II become?

Answer 11

CD4+ T cells

Question 12

What do cells that recognise MHC class I become?

Answer 12

CD8+ T cells

Question 13

Why do we have peripheral tolerance?

In what 4 ways is this mediated?

Answer 13

because sometimes the thymus makes mistakes

ignorance
anergy (switching off cells)
cell death
regulatory T-cells

Question 14

What do T helper cells do?

Answer 14

recognise foreign antigens to stimulate antibody production in B cells

Question 15

What do cytotoxic T cells do?

Answer 15

directly kill infected cells

Question 16

What are regulatory T cells?

Answer 16

a subset of CD4+ (also expressing CD25, the IL-2 receptor)

most importantly they express transcription factor FoxP3

Question 17

What are the 3 models for suppression of autoreactive lymphocytes that have escaped negative selection?

Answer 17

cytokine-mediated :IL-10, TGFbeta
competition for IL-2
Contact dependent negative selection (modulation of dendritic cell function)

Question 18

How does the thymus facilitate tolerance to the rest of the body, such as to insulin?

Answer 18

Auto immune regulator (AIRE), facilitating promiscuous gene expression, allowing thousands of genes to be expressed in the thymic medulla

Question 19

What does FoxP3 deficiency cause?

Answer 19

deficiency in T-reg and autoimmunity

Question 20

What does AIRE deficiency cause?

Answer 20

APECED and autoimmunity

Question 21

What happens to the thymus with age?

Answer 21

aged related thymus hypertrophy, thymus has a fair function until about the age of 40, after which it’s basically all fat

it has peak functino at about the age of 10, when it is biggest

Question 22

What might cause thymus aplasia?

Answer 22

FoxN1 deficiency
DiGeorge syndrome (complete or not)

Question 23

What would the problem be with giving an adult bone marrow transplant?

Answer 23

their thymus may not be able to cope with the amount of progenitors produced by the bone marrow, so they are more susceptible to autoimmune diseases

Question 24

How might we treat babies with DiGeorge syndrome?

Answer 24

left over thymus from paediatric cardiac surgery can be transplanted into the quadriceps femoris