Lecture 24: Cellular immunity and histocompatibility Flashcards

1
Q

Describe the potential cells that can be formed from the immature thymocyte that has the CD4 and CD8 receptors:

A

Immature thymocyte (CD4 and CD8) can go on to form:

-> CD8+ Cytotoxic T cells (~20% in blood)

or

-> CD4 T helper cells (~80%)

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2
Q

What are the subtypes of the CD4+ T helper cells?

A

Treg
Th1
Th2
Th17

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3
Q

What do the different types of CD4+ T Helper cells do?

A

They characterise different immune responses depending on the pathogen

(this is extra detail but to make sense of things)

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4
Q

Where is the thymus located and what does it do?

A

The thymus is located at the top of the pericardium above the heart.

Primary lymphoid organ

Site of T cell maturation

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5
Q

Describe T cell maturation in the thymus:

A

Heamopoetic lymphoid precursors migrate from bone barrow to the thymus where they mature into T lymphocytes.

Only small percentage of T cells survive the thymus as mature t cells… Most die from ‘neglect’

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6
Q

The t cells that survive the thymus have been taught to recognise what?

A

Educated to recognise self MHC molecules expressed in thymic tissue.

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7
Q

Viruses replicate inside cells, so how doe the immune system detect and kill virus producing cells?

A

Regulated by a set of highly polymorphic genes that were first identified as controlling tissue transplantation

Major histocompatibility complex (MHC) (Class one vs class two)

These genes code for human leukocyte antigens (HLA) on the cell surface.

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8
Q

How do cytotoxic T cells kill cancerous cells or viral infected cell?

A

CD8+ T cells react to own cells when there is a change in MHC class one molecules i.e when they express neoantigens picked up from inside the cell (because its cancerous or infected and fucked)

This neoantigen could be viral or altered self antigen

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9
Q

Describe MHC restriction:

A

Histocompatibility genes control viral immunity.

CD8+ cells only kill viral infected cells from the same strain i.e cytotoxic T cells only recognise self cells and when they express virus. i.e you cant transplant CD8+ cells as they wont work in another body.

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10
Q

Viral immunity requires what when it comes to MHC restriction?

A

Viral immunity requires two antigens:

Self: Antigen(s) encoded by MHC

Non-self: Antigen(s) encoded by virus

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11
Q

Describe MHC restriction in molecular / receptor terms:

A

T cell: Has T cell receptor (TcR) bound to its membrane (like Ig molecule)

Target cell: Has HLA expressed (determined by MHC genes) and they sample the cell and present peptide antigens to the T cell.

TcR recognises the HLA and presented peptide simultaneously

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12
Q

Naming is confusing for the HLA and MHC, explain these:

A

MHC = Genetic locus regulating histocompatibility

HLA: Human leukocyte antigen, referring to the six different molecules expressed on human cells

Class one MHC: A,B,C

Class two MHC: DR, DP, DQ

KNOW ALL THESE

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13
Q

compare and contrast the function of CD4 and CD8:

A

CD4 and CD8 are accessory molecules to the T cell receptors. They physically associated and are essential for function.

CD4 = T helper cells, recgonise antigens in MHC calls 2.

CD8 = Cytotoxic T cells, recognise antigens in MHC class 1.

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14
Q

Describe the intracellular signalling processes of CD4 and CD8:

A

CD4 and CD8 have intracellular tyrosine kinases associated with their cytoplasmic tails that initiate T cell signalling through phosphorylation. They are crucial for that activation of your adaptive immune system

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15
Q

Describe T helper/CD4 activation:

A

[TcR+CD4]+[MHC class+Bacterial peptide] = activation

T helper cell activates, proliferates and produces cytokines that ‘help’ other cells

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16
Q

Describe Cytotoxic T cell / CD8 activation:

A

[TcR+CD8]+[MHC class 1 + Viral peptide] = activtion

Cytotoxic T cells kill. Produce enzymes that punch holes in the target cell membrane and destroy cell viability

17
Q

What are the peptide sources for CD8 and CD4 cells?

A

CD4 cells: MHC class 2 = Peptide source is extracellular i.e bacteria

CD8 cells: MHC class 1 = Intracellular peptides i.e viruses or cancerous cells.

18
Q

Write some notes on MHC polymorphism:

A
  • MHC amino acid sequence varies greatly across the population (i.e why transplants are so difficult)
  • Polymorphism is restricted to the protein domains that form the peptide groove of the HLA
  • An individual expresses both maternal and paternal genes 2x3 MHC class one (A,B,C) and 2x3 MHC class two (DR, DP, DQ) molecules. -> Codominance
    = A total of 12 polymorphic molecules are expressed on your cells.
19
Q

What are the two important consequences of MHC polymphorism?

A
  1. Tissue transplantation is difficult between identical twins
  2. MHC polymorphisms are strongly linked to many autoimmune diseases.

[Remember MHC genes are only part of genome that is so polymorphic]