Lecture 8

Question 1

What kind of transplantation (grafting) are there?

Answer 1

1. Autograft- same person
2. Syngeneic graft - genetically identical
3. Allograft: between unrelated animals of same species
4. Xenograft: animals of different species

Question 2

For allograft (unrelated animal but same species), what is the outcome?

Answer 2

Graft rejection

Repeated grafting from same donor = accelerated graft rejection

Survival of graft can be prolonged by immunosuppressive drugs

Question 3

What are the drawbacks of taking immunosuppressive drugs to prolong graft survival?

Answer 3

higher incidence of cancer

Question 4

What is the full form of MHC?

Answer 4

Major Histocompatibility Complex

Question 5

What does the organ transplantation success correlate to?

Answer 5

the degree of MHC matching (mainly MHC class 1 antigens)

Rejection due to T cells, not antibodies

Question 6

Why is nude mouse used to study the development of the immune system?

Answer 6

• lack T cells, do not reject allografts and xenografts

-used to study tutor growth, imagine and study the effect of drugs

Question 7

Where are MHC class 1 expressed?

Answer 7

All cells except erythrocytes

Question 8

Where are MHC class II expressed?

Answer 8

B cells, macrophages and dendritic cells

Question 9

What is the structure of MHC class 1?

Answer 9

alpha chain (a1, a2 and a3 domains) and beta-micro globulin

Question 10

Where is the gene for beta-microglobulin located?

Answer 10

chromosome 15

Question 11

What is the structure of MHC class II?

Answer 11

alpha chain: a1 and a2 domains

beta chain: beta1 and beta2 domains

Question 12

Where are the human major histocompatibility complex genes (MHC) located?

Answer 12

chromosome 6

Question 13

What Is the regions on chromosome 6 that codes for MHC class II called?

Answer 13

DP, DQ and DR

each of these 3 regions codes for beta chain and alpha chain

Thus, 6 gene products

Question 14

What Is the regions on chromosome 6 that codes for MHC class I called?

Answer 14

B, C and A

gene products: HLA-B, HLA-C and HLA-B

one gene product for each as they only produce the alpha chain of MHC class 1

Question 15

Which gene , MHC class 1 or II, comes first in chromosome 6?

Answer 15

class II (DP, DQ and DR)

Question 16

What is the characteristic of MHC genes?

Answer 16

Highly polymorphic and polygenic

Question 17

Which MHC class is more polymorphic than the other?

Answer 17

MHC class 1

Question 18

What is meant by polymorphic and polygenic?

Answer 18

Polymorphic: multiple alleles (e.g single locus, 2 possible alleles, one on each chromosome)

Polygenic: multiple genes that encode the same protein (more than 1 loci)

Question 19

What is a haplotype?

Answer 19

A haplotype (haploid genotype) is a group of alleles in an organism that are inherited as a single unit from a parent.

Question 20

What are the odds that there is a complete MHC class I match between 2 siblings?

Answer 20

1/4

Question 21

What is the % match of MHC class I between parents and progenies?

Answer 21

50%

Question 22

Apart from B cells, Macrophages and dendritic cells, where else could MHC class II antigen be found?

Answer 22

T cells and thymic epithelial cells

Question 23

Why is there a different expression profile of MHC class I and MHC class II antigens?

Answer 23

due to their unctional differences

Question 24

What is the function of MHC class I?

Answer 24

MHC Class-I antigens are for the identification of self. They serve as to
present foreign epitopes (to be defined later) for cytotoxic T cells to
mediate their killing activity – for example, of viral infected cells

–> MHC restriction

Question 25

What is meant by MHC restriction?

Answer 25

MHC Class-I antigens are for the identification of self. They serve as to present foreign epitopes (to be defined later) for cytotoxic T cells to mediate their killing activity – for example, of viral infected cells

Question 26

What is the function of MHC class II antigens?

Answer 26

MHC Class-II antigens are for antigen presentation

Question 27

How many different MHC class I antigens can be expressed on the same cell (for humans)?

Answer 27

6

Question 28

Cytotoxic T cell specificity

Answer 28

T cells are specific for virus A-infected cells expressing a specific MHC genotype. They cannot kill MHC cells infected with virus B, or C, etc or another MHC genotype infected with virus A

Question 29

What is the major difference between the expression of TCR by T cells and expression of antibodies by B cells?

Answer 29

TCR only exists on T cells as membrane proteins In contrast, for B cells, could be membrane bound or secreted form antibody

Question 30

What T cell has MHC I with viral peptide as target?

Answer 30

Cytotoxic T cell TCR with CD8

Question 31

What are the 2 types of TCRs called?

Answer 31

αβ type γδ type

Question 32

Are there soluble form TCR?

Answer 32

No Though single spanning transmembrane segment, with no cytoplasmic segment

Question 33

Describe the structure of a TCR

Answer 33

-alpha-chain and beta chain -each chain consists of a variable region and a constant region --> 4 domains -carbohydrate on each domain -1 disulphide bind between the hinge regions of the 2 subunits

Question 34

Do the 2 chains of TCR have a cytoplasmic domain?

Answer 34

almost no cytoplasmic domain but it has a cytoplasmic tail

Question 35

What is holding the 2 chains of TCR together?

Answer 35

a disulphide bond at the hinge region

Question 36

How many CDRs on each chain of TCR?

Answer 36

3 CDRs ( namely 1,2 and 3)

Question 37

What are the subtle differences between Ab and TCR?

Answer 37

There is no Fc region for the TCR. Whereas the Ab needs the Fc to recruit other molecules to deliver its function, the TCR has the whole cell already, which may be viewed as the “Fc”. instead of different Fc, there are different T cells

Question 38

How many positively charged residues in transmembrane segments of alpha chain and beta chain of TCR respectibely?

Answer 38

2 and 1 respectively

Question 39

Are there any cytoplasmic domains of TCR?

Answer 39

almost No cytoplasmic domains

Question 40

For TCR, what does the a-chain and the beta-chain locus resemble?

Answer 40

a-chain: kappa chain of Ig beta-chain: heavy and lamda of Ig beta-chain can have 1 of 2 constants

Question 41

For TCR, does somatic hypermutation occue?

Answer 41

No

Question 42

What is somatic hypermutation in B cells?

Answer 42

Somatic Hypermutation is a process that occurs in mature B cells, particularly in the germinal centers of secondary lymphoid organs. -->introduces random point mutations in the variable region of the immunoglobulin genes post-antigen encounter to enhance antibody affinity.

Question 43

Which of the TCR chains is synthesized first?

Answer 43

beta-chains

Question 44

the binding affinity of the TCR to the MHC-peptide complex is VERY low, but the number makes up for high avidity.

Answer 44

Yes

Question 45

Membrane bound Ab has almost no cytoplasmic segment, so how does it signal to the B cell for “activation”?

Answer 45

It relies on the Igβ and Igα for signaling. They have an Ig domain on the outside, and ITAM in the cytoplasmic side

Question 46

What is the full form of ITAM?

Answer 46

Immunoreceptor tyrosine- based activation motif

Question 47

What are the 4 CD3 chains?

Answer 47

two ε one δ one γ

Question 48

What are the CD3 chains for?

Answer 48

for the cell-surface expression of the antigen-binding chains and for signaling.

Question 49

What are the ζ (zeta) chains for?

Answer 49

signal to the interior of the cell upon antigen binding

Question 50

For TCR, what is each 'complete receptor complex' composed of?

Answer 50

two α:β heterodimers associated with the six accessory chains (4 CD3 chains and homodimer of zeta chains)

Question 51

For each TCR, zeta chains exist as a ________________.

Answer 51

homodimer

Question 52

CD4 and CD8 are _______ proteins.

Answer 52

type-1

Question 53

Describe the structure of CD4

Answer 53

a type-1 membrane protein with 4 extracellular Ig domains

Question 54

Describe the structure of CD8

Answer 54

two type-1 membrane proteins each with one Ig domain

Question 55

Where are T cells made and where do they mature?

Answer 55

-originate in bone marrow -mature in thymus

Question 56

What is a double positive thymocyte?

Answer 56

intermediate stage of T cell maturation in thymus --> express both CD4 and CD8 co-receptors on their cell surface

Question 57

What is a double negative thymocyte?

Answer 57

specific type of developing T cell that lacks the expression of both CD4 and CD8 co-receptors on its surface

Question 58

Where are MHC molecules translated, processed and expressed?

Answer 58

tranalated: Rough ER processed: golgi apparatus expression: plasma membrane

Question 59

How does proteolysis of protein take place in proteosome?

Answer 59

A protein has to denature and the polypeptide threads through the central cavity where proteolysis take place.