T lymphocytes and antigen recognition

Question 1

summarise the origins and functions of T lymphocyte subsets

Answer 1

generated in the bone marrow and mature in the thymus
Subsets have different receptors
CD4 - Th
CD8 - Tc
stem cell has neither - double negative
attempt to make TCR - beta chain first with surrogate alpha - preTCR
then double positive in medulla
Co-receptors bind MHC, increase avidity of T cell target cell interaction and important in signalling.
Whether the T cell is CD4+ or CD8+ depends on which MHC molecule it meets in thymus (cortex)
Whether Th 1/2 depends on what cytokines it releases
check that T cell is functional and safe - if not it is killed by apoptosis - needs to bind to MHC weakly.

Question 2

T lymphocytes and CD3

Answer 2

Charged residue in TCR membrane binds to CD3 polypeptide constant – marker of T cells and activate TCR – deliver signal from TCR so when TCR bind antigen, cytoplasmic tails of CD3 polypeptide become tyrosine phosphorylated – activated T cell. CD3 integral part of TCR

Question 3

CD8 T cells

Answer 3

cytotoxic - apoptosis
cytokines
recognition of an infected cell - polarisation and release of granules
perforin, granzymes and granulysin
FasL - interact with Fas on cell wall - death

Question 4

CD4 T cells

Answer 4

Th cells 
cytokines - downstream response 
recruit effector cells
activate macrophages
amplify Tc and B cell

Question 5

T cell circulation

Answer 5

bone marrow - thymus (cortex and medulla)

mature T cells - blood, lymph and secondary lymphoid tissue

Question 6

what process generates TCR

Answer 6

gene recombination
B similar to heavy
a similar to light

Question 7

How does HLA-B mutation affect HIV infection

Answer 7

chronic infection, some HLA better at protecting against some than others. HLA-B protection against HIV it kills virus better than other complexes. Virus out of their body it is weaker but if re-infects another host back to wild type strength.

Question 8

CD4 - activating macrophages

Answer 8

o T cell macrophage interaction
o Inflam t cells
o Th1 produce INF-gamma and TNF this activates the macrophage
o Get anti-TNF the macrophages stop working
cross talk between T cells and macrophages with cytokines

Question 9

Delayed type hypersensitivity - Th

Answer 9

o Defence against intracellular pathogens
o If source antigen not eradicated – chronic stimulation – granular formation
o In contact hypersensitivity – tissue damage with no benefit
o When first exposure causes no damage but 2nd exposure when see the CD4+ cells causes pathology. Need lay down of immune memory first. Dendritic cell present antigen to T cell so next time T cells cause immune response
o React to things that are normally in env, eg pollen – stimulate eosinophils, release mediators that cause pathology.

Question 10

Th - B cell activation

Answer 10

o Dendritic and B cells take up pathogen
o Process – MHC2
o Tfh talk to DC, activated – talk to b cell with same antigen – stimulate to produce more antigens

Question 11

memory T cells

Answer 11

o Consequence of clonal selection
o T cells no isotope switching or affinity maturation
o Less stringent activation (less licencing and lower Ea), express different chemokine receptors.
o Sometimes in excess – too many T cell in lung affect why O2 transferred into blood or in wrong anatomical department
o Trm – retain in tissue where infection is
o Tem – circulate

Question 12

pathological reactions of T cells

Answer 12

autoimmunity - self protein

rejection - self protein of donor

Question 13

Outline structure of MHC molecules

Answer 13

immunoglobulin superfamily 
class 1 - heavy and light chain - light is myobectin - 1 transmembrane part - antigen biding part at top 
class 2 - 2 heavy chains - 2 transmembrane sections

Question 14

Class 1 outline structure

Answer 14

heavy and light chain - non-covalently linked 
3 domains a 1, 2, 3 
between domain 1 and 2 peptide binds 
light is beta 2 myoglobulin 
1 transmembrane part 
there are 2 a helixes on top of B pleated sheets 
peptide is shorter 
a 3 - non-variable - where CD8 binds

Question 15

class 2 outline structure

Answer 15

2 chains
chains the same size
2 transmembrane sections

Question 16

Function of class 1

Answer 16

transplantation antigens

Question 17

function of class 2

Answer 17

control ability to mount immune response.

Question 18

Generic function of MHC molecules

Answer 18

present antigen to TCR

Question 19

How does TCR bind to antigen in MHC

Answer 19

TCR bind non-variable region
hypervariable roots in TCR bind to antigen
Anchor residue is highly conserved AA residue
Other peptide binding motif binds to TCR

Question 20

What is HLA

Answer 20

human MHC

human leukocyte antigens

Question 21

Class 1 HLA

Answer 21

o A B C
o Only heavy chain encoded in MHC
o B-myoglobulin same in all molecules so not encoded in MHC
o Expressed on all nucleated cells – interferon or infection upregulate antigen presenting in MHC

Question 22

Class 2 HLA

Answer 22

o DP DQ DR
o Both chains encoded in MHC
o They’re on cells that activate naïve T cells (professional APC) – upregulated by interferon

Question 23

MHC gene expression

Answer 23

MHC polygenic – several loci
Large population variation but 1 haplotype in individuals – co-dominant
Group alleles on 1 chromosome is a haplotype
Lead to different immune response between people
Alleles not evenly distributed in population and segregate with race.

Question 24

Examples of APC

Answer 24

activated macrophages
DC
B lymphocytes

Question 25

Class 2 APC

Answer 25

``` exogenous antigen class 2 MHC bind to invariant chain endocytic vesicles protease chop up invariant chain clip chain left in MHC CLIP swapped for antigen go on surface ```

Question 26

location of APC

Answer 26

macrophage and B lymphocyte - secondary lymphatic tissue | DC - circulates

Question 27

Class 1 APC

Answer 27

endogenous antigen protein chopped up with protease - peptides ER - associate with Class 1 heavy chain and B - 2 - myoglobulin (TAP) Golgi surface