Adaptive Immunity 4

Question 1

which cells express MHC I molecules?

what about MHC II molecules?

Answer 1

all nucleated cells
- excludes erythrocytes (red blood cells)

professional APCs

• macrophages
• B-cells
• dendritic cells

Question 2

what is special about MHC expression in dendritic cells?

what do DCs produce?

what is cross-presentation in DCs?

Answer 2

they express MHC I and MHC II molecules

co-stimulatory molecules when they meet a pathogen

DCs can take antigens from outside the cell and present them on MHC I molecules

Question 3

what is required to activate a native T cell?

Answer 3

interaction between peptide on MHC molecule and TCR

co-stimulatory signals
e.g. B7 binds to Cd28 on T cell

Question 4

what are the features of macrophages?

Answer 4

phagocytic

have receptors for bacterial carbohydrate

inducible B7 expression

Question 5

what happens to DCs if a virus is present?

Answer 5

DCs migrate to secondary lymphoid tissue
-> present viral antigens on MHC-I to naive CD8 T-cells
= binding

if co-stimulatory signal present
-> virus-specific T cells proliferate and differentiate into CTLs

-> go and search for other cells presenting peptides on MHC-I

Question 6

how is an immature dendritic cell activated?

Answer 6

ingest antigens

• > migrate to lymph node
• > activated

Question 7

how are B cells activated?

Answer 7

1. naive B cell binds specific antigen with their surface Ig
2. antigen internalised by endocytosis and processed
3. peptides from antigen presented on its MHC-II molecules
4. an activated T helper cell forms a cognate pair with the B cell
   (TCR binds to the peptide-MHC complex)
5. naive B cell and T cell exchange signals (e.g. cytokines) that begin process of B cell activation
6. B cell proliferates

Question 8

what can IFN-gamma induce?

Answer 8

unregulated expression of MHC II molecules on cells that don’t normally produce them

-> presentation of antigen to CD4 T cells can thus be increased in inflamed tissues

Question 9

describe the genetics of the MHC complex

Answer 9

cluster of closely linked genes on Chr6

large no. of genetic variants within the human population
- BUT each individual only expresses a subset of the MHC alleles

variability evolved to enable MHC molecules to collectively bind a large variety of peptides

Question 10

is MHC I and II, which are the most polymorphic genes of the HLA complex?

Answer 10

MHC-I
= HLA-B has 250 genetic variants

MHC-II
= DRB-I in HLA II has >200 genetic variants

Question 11

how are MHC molecules selected for in a population?

Answer 11

if a population is exposed to a virus

-> may kill those with MHCs that don’t have the correct peptide selectivity

-> those with the required MHCs persist
-> reproduce
= pass on genes for MHC

Question 12

where are the polymorphisms in MHC molecules?

what does this result in?

Answer 12

the peptide binding site

different MHCs bind to different subsections of peptides

Question 13

how are MHCs involved in tissue grafts?

Answer 13

differences in MHC between donor and recipient are a major cause of graft rejection in transplants

HLA mismatches can be overcome with immunosuppressive drugs

Question 14

what is the MHC consequence of 2 closely related parents?

Answer 14

reduces peptide coverage of MHC molecules that you inherit

Question 15

where do T cells originate?

where do they mature?
what happens here?

Answer 15

from stem cells in bone marrow

thymus
(a primary lymphoid organ)

T cells rearrange TCR genes

Question 16

what can lymphoid stem cells produce?

Answer 16

lymphoblasts

-> B lymphocyte 
OR
T lymphocyte 
OR
Natural killer cell

Question 17

describe the ‘life cycle’ of the thymus

what happens once the thymus is established?

Answer 17

most active when young

increases in size up to puberty

shrinks and almost completely degenerated by 30yrs

mature peripheral T cells seem to be long lived/self-renewing

Question 18

what is required for thymocyte maturation?

Answer 18

must make contact with epithelial cells

-> as they develop they make contact with different epithelial cells

migrate towards medullary cells

• > if they survive this maturation process
• > migrate to secondary lymphoid tissue

IF NOT
= apoptosis

Question 19

what do thymocytes lack when they enter the thymus?

why is this?

what do they express?

Answer 19

TCRs, CD4 and CD8

TCR is still in germline configuration
- not yet rearranged

CD44 (adhesion molecule)
CD25 (IL-2 receptor component)

Question 20

what do signals from the cortical epithelial cells activate?

what happens next?

what are the T cells produced, called?

Answer 20

CD44 to decrease

-> T-cell rearrangements commence

beta chain locus rearranges

• > productive beta chain rearrangement
• > cell proliferation

-> then alpha chain locus can rearrange

double positive T cells (express CD4 + CD8)

Question 21

what happens in T cell positive selection?

what cell type facilitates this?

Answer 21

T cells that recognise self-MHC molecules are positively selected in the thymus

epithelial cells in the thymus

Question 22

how does positive selection control expression of the co-receptor?

Answer 22

if T cell binds to self MHC-I
= becomes CD8 positive T cell
by down-regulating CD4 expression

if T cell binds to self MHC-II
= becomes CD4 positive T cell
by down regulating CD8 expression

Question 23

what happens in T cell negative selection?

Answer 23

bone marrow derived DCs + macrophages express AIRE (autoimmune regulator)

these cells express self-MHC that present self-antigens

if TCRs bind strongly to self-MHC peptide
-> negatively selected
= removed from population

Question 24

what are cells that have undergone this selection known as?

Answer 24

self MHC restricted T cells

Question 25

when does alpha chain rearrangement stop?

where do selected cells undergo further differentiation?

what do CD8 and CD4 positive T cells become?

Answer 25

when a cell has been positively selected

secondary lymphoid tissue

CD8 = cytotoxic T cells
CD4 = TH1 cells or other types of helper T cells