L4 Histocompatibility complex and antigen presentation Flashcards

1
Q

List 3 professional antigen
presenting cells (APCs)

A

Dendritic cells
Macrophages
B-cells

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2
Q

What unites microbial fragments in antigen presentation

A

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

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3
Q

MHC-microbe specific peptides present what to trigger what?

A

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

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4
Q

T-cells only see what

A

peptides in context of MHC molecoles

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5
Q

MHC prime t-cells

A

MHC activate t-cells

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6
Q

T lymphocytes only see peptides on what condition

A

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

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7
Q

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

A

host cells

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8
Q

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

A

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

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9
Q

Histo- meaning

A

tissue

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10
Q

What is the Major Histocompatibility
Complex?

A

▪ 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

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11
Q

What are some transplants rejected?

A

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.

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12
Q

Molecules responsible for transplants rejected?

A

MHC molecules that bind and present peptides to T cells.

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13
Q

Heterozygous individuals will pass down MHC to offspring explain probaility

A

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.

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14
Q

Percentage for siblings to have matching MHC haplotypes

A

25%

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15
Q

Haplotype

A

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

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16
Q

What genes are polygenic and highly polymorphic

A

MHC

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17
Q

The human MHC region is also called the

A

Human leukocyte antigen (HLA)

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18
Q

Can individuals present and respond to different microbial peptides

A

Yes

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19
Q

What is further amplifed because HLA genes are codominant

A

Variation

20
Q

Variation is further amplified because HLA genes are codominant

A

Both parental alleles of each MHC gene are expressed

21
Q

MHC-peptide: Broad Specificity

A

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

22
Q

MHC-peptide: One at a time

A

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

23
Q

MHC

A

Major histocompatibility Complex

24
Q

Proteasome

A

complex intracellular proteases that function in regulated degradation of cellular proteins

25
Q

MHC-peptide: Stable surface expression of bound peptide

A

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

26
Q

MHC-peptide: Very slow off-rate

A

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

27
Q

T-cell recognition of antigens is MHC restricted

A

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

28
Q

MHC restricted

A

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

29
Q

How are T-cells and MHC specific?

A

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.

30
Q

Explain how MHC are polygenic

A

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

31
Q

Explain how MHC are polymorphic

A

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

32
Q

Class I MHC molecules

A
  • 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
33
Q

Class I MHC molecules characteristics

A

▪ 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

34
Q

Class 1 MHC genes

A

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

35
Q

Why are CD8-T cells important wil Class 1 MHC

A

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

36
Q

Class II MHC molecules

A

▪ 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

37
Q

How do dendritic cells become activated

A

They capture antigens

38
Q

Process of dendritic activation and migration

A

▪ 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)

39
Q

How Dendritic cells work against pathogens? (Immunity)

A

▪ 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.

40
Q

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

A
41
Q

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

A

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

42
Q

MHC I pathway

A

▪ 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

43
Q

What are MHC I and II expressed by

A

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

44
Q

MHC II pathway

A

▪ 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.

45
Q

Superantigen

A
  • 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
46
Q

Antigen Cross presentation

A
  • 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