L4 Histocompatibility complex and antigen presentation

Question 1

List 3 professional antigen
presenting cells (APCs)

Answer 1

Dendritic cells
Macrophages
B-cells

Question 2

What unites microbial fragments in antigen presentation

Answer 2

glycoproteins – major histocompatibility (MHC) proteins and presented at the cell surface

Question 3

MHC-microbe specific peptides present what to trigger what?

Answer 3

The MHC-microbe-specific peptide complex will then be presented to T lymphocytes, triggering adaptive immune responses

Question 4

T-cells only see what

Answer 4

peptides in context of MHC molecoles

Question 5

MHC prime t-cells

Answer 5

MHC activate t-cells

Question 6

T lymphocytes only see peptides on what condition

Answer 6

T lymphocytes can see only peptide fragments of protein antigens, and only when these peptides are displayed on host cell surfaces bound to MHC molecules

Question 7

T cell–mediated immune responses is generated only against protein antigens that are either produced in or taken up by what?

Answer 7

host cells

Question 8

what do Naive T lymphocytes see to initiate clonal expansion and differentiation

Answer 8

Naive T lymphocytes see protein antigens presented by dendritic cells to initiate clonal expansion and differentiation of the T cells into effector and memory cells

Question 9

Histo- meaning

Answer 9

tissue

Question 10

What is the Major Histocompatibility
Complex?

Answer 10

▪ Collection of genes encoding proteins that enable the host to distinguish self and non-self
▪ MHC molecules were first discovered as proteins encoded by the murine MHC locus involved in graft rejection - hence histo (tissue) compatibility (to get along)
▪ The MHC complex includes more than 200 genes and have many possible variations

Question 11

What are some transplants rejected?

Answer 11

Transplantation of cells or tissues from one individual to a genetically nonidentical individual invariably leads to rejection of the transplant because of adaptive immune responses.

Question 12

Molecules responsible for transplants rejected?

Answer 12

MHC molecules that bind and present peptides to T cells.

Question 13

Heterozygous individuals will pass down MHC to offspring explain probaility

Answer 13

offspring will receive one of four possible combinations of the parental MHC haplotypes. Siblings are also likely to differ in the MHC alleles they express, there being 1/4 chance that an individual will share both haplotypes with a sibling.

Question 14

Percentage for siblings to have matching MHC haplotypes

Answer 14

25%

Question 15

Haplotype

Answer 15

a set of DNA variants along a single chromosome that tend to be inherited together.

Question 16

What genes are polygenic and highly polymorphic

Answer 16

MHC

Question 17

The human MHC region is also called the

Answer 17

Human leukocyte antigen (HLA)

Question 18

Can individuals present and respond to different microbial peptides

Answer 18

Yes

Question 19

What is further amplifed because HLA genes are codominant

Answer 19

Variation

Question 20

Variation is further amplified because HLA genes are codominant

Answer 20

Both parental alleles of each MHC gene are expressed

Question 21

MHC-peptide: Broad Specificity

Answer 21

Different peptides can bind to the same MHC molecule but not at the same time

Question 22

MHC-peptide: One at a time

Answer 22

A t-cell only response to a single peptide bound to an MHC molecule

Question 23

MHC

Answer 23

Major histocompatibility Complex

Question 24

Proteasome

Answer 24

complex intracellular proteases that function in regulated degradation of cellular proteins

Question 25

MHC-peptide: Stable surface expression of bound peptide

Answer 25

Only the peptide loaded MHC molecules are expressed on the cell surface for recognition by T-cells

Question 26

MHC-peptide: Very slow off-rate

Answer 26

MHC molecules displays bound peptide for long enough to be located by T-cel;

Question 27

T-cell recognition of antigens is MHC restricted

Answer 27

T-cells depend on the presence of MHC molecule in the APC and co-recognisiton of foreign peptide and MHCm called MHC restriction

Question 28

MHC restricted

Answer 28

Co-recognition of a foreign peptide and an MHC molecule is known

Question 29

How are T-cells and MHC specific?

Answer 29

A T cell recognises antigen as a peptide bound by a particular allelic variant of an MHC molecule and will not recognise the same peptide bound to other MHC molecules.

Question 30

Explain how MHC are polygenic

Answer 30

The genes of the MHC exhibit genetic variability; and the MHC has several genes for each class hence it is polygenic.

Question 31

Explain how MHC are polymorphic

Answer 31

The MHC is also polymorphic, meaning a large number of alleles exist in the population for each of the genes.

Question 32

Class I MHC molecules

Answer 32

* Identify all nucleated cells of the body as “self” * No RBC * Class I MHC molecules span the membrane of almost every cell in an organism

Question 33

Class I MHC molecules characteristics

Answer 33

▪ Bind to normal (self) peptides and antigens extracted from intracellular pathogens (e.g., viruses) – signalling to the immune system that it is an infected host cell ▪ Smaller binding pocket ▪ Endogenous antigen processing

Question 34

Class 1 MHC genes

Answer 34

Class I: HLA-A, HLA-B, and HLA-C.

Question 35

Why are CD8-T cells important wil Class 1 MHC

Answer 35

Class I MHC molecules are recognized by CD8+ cytotoxic T-lymphocytes (Tc cells) * Tcyt Cell (cytotoxic T cell) has specificity towards cells containing peptides associated with Class I MHC due to the presence of CD8 antigen on the surface of Tcyt Cell. * CD8 Recognize peptides on infected cells presented by MHC-I

Question 36

Class II MHC molecules

Answer 36

▪ Expressed by professional antigen presenting cells ▪ Bind to antigens degraded as a consequence of phagocytosis or receptor mediated endocytosis (extrinsic or exogenous antigen) ▪ Larger and deeper pocket ▪ Exogenous antigen processing

Question 37

How do dendritic cells become activated

Answer 37

They capture antigens

Question 38

Process of dendritic activation and migration

Answer 38

▪ Dendritic cells (DCs) capture antigens and become activated ▪ Upon activation, DCs lose adhesiveness for epithelia & peripheral tissues and begin to migrate through lymphatic vessels to the lymph nodes where it collects antigens ▪ During migration DCs start to mature by increasing synthesis and stable expression of MHC molecules, and other costimulatory molecules like CD80/CD86 (B7-1/B7-2)

Question 39

How Dendritic cells work against pathogens? (Immunity)

Answer 39

▪ Immature DCs undergo maturation in presence of antigens (or cytokines) ▪ activates its metabolic, cellular and gene transcription causing it to move (MIGRATE) from peripheral tissues to Lymphoid organs. ▪ Loose adhesiveness to epithelia and peri-tissues and increase motility ▪ increase expression of MHC-II and costimulatory molecules.

Question 40

Antigen presentation to naïve T cells in the initiation of T cell responses to protein antigens

Question 41

Numerous cytoplasmic processes and high surface area allows intimate contact with many surrounding cells - e.g.,

Answer 41

experimentally, only one mature DC is required to stimulate 100 - 3000 T cells

Question 42

MHC I pathway

Answer 42

▪ cytosolic protein antigens are degraded in the proteasome, and transported from the cytosol to the ER, ▪ where MHC-I molecules receive peptides and bind. ▪ Stable complexes of MHC-I molecules with bound peptides move out of the ER, through the Golgi complex, to the cell surface. ▪ For recognition by CD8 + T cells

Question 43

What are MHC I and II expressed by

Answer 43

[1] by all nucleated cells and interact with CD8+ T cells. [2] by APCs and interact with CD4+ T cells.

Question 44

MHC II pathway

Answer 44

▪ protein antigens are internalised into endosomes, and proteolytically cleaved by enzymes in lysosomes and late endosomes. ▪ protein antigens that are degraded in lysosomes bind to class II MHC molecules for recognition by CD4 + T cells ▪ MHC-II molecules are transported from the ER to endosomal vesicles. ▪ The peptides generated from extracellular proteins bind to class II MHC molecule ▪ the complex moves to and is displayed on the surface of the cell.

Question 45

Superantigen

Answer 45

* Toxins that can directly interact (w/o prior processing) with MHC-II molecules * Will lead to massive T-cell activation and cytokine release (can cause inflammation) * Toxic shock syndrome toxin-q and staphylococcal enterotoxins

Question 46

Antigen Cross presentation

Answer 46

* DCs transport ingested antigens (that were going to go through the MHC-II pathway) into the cytosol. * Antigens are processed and mounted on MHC-I molecules * Cross-presentation is essential for the initiation of cytotoxic CD8+ T cell responses when DCs are not directly infected ▪ Dendritic cells are able to ingest infected host cells, dead tumour cells, microbes, and microbial and tumor antigens