4. Major Histocompatibility complex Flashcards

1
Q

Major Histocompatibility Class (MHC) II

A

Function:

to present peptide antigens

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2
Q

Major Histocompatibility Complex

A

MHC Class I & II (and III)

Human Leucocyte Antigen (HLA) main
classes:
- HLA - A, B, C = MHC Class I
- HLA - DR, DP , DQ = MHC Class II
- MHC Class I present on nucleated cells of body
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3
Q

How many MHC molecules does a cell express?

A

MHC Class I – probably 6

  • co-dominant expression of paternal and
    maternal HLA – A, B & C loci

NB - Minor Histocompatibility Complex Antigens too

MHC Class II – at least 6

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4
Q

Structure of MHC I vs. MHC II

A

MHC I – transmembrane alpha chain (3 domains) + β2-microglobulin

MHC II – heterodimer of 2 transmembrane chains (2 domains each)

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5
Q

MHC variability determines peptide specificity

A

-

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6
Q
  1. Cytosolic pathogens
A
  • > degraded in cytosol
  • > peptides bing to MHC class I
  • > presented to effector CD8 T cells
  • > effect on presenting cell - cell death
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7
Q
  1. Intravesicular pathogens
A
  • > degraded in endocytic vesicle (low pH)
  • > peptides bind to MHC class II
  • > presented to effector CD4 T cell
  • > effect on presenting cell - activation to kill intravesicular bacteria and parasite
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8
Q
  1. extracellular pathogens and toxins
A
  • > degraded in endocytic vesicle (low pH)
  • > peptides bind to MHC class II
  • > presented to effector CD4 T cell
  • > effect on presenting cell - activation of B cells to secrete Ig to eliminate extracellular bacteria / toxins
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9
Q

MHC class I

A

Intracellular antigen

Proteasome - antigen processing to peptides in proteasome

peptide transport into endoplasmatic reticulum (ER)

peptide binding by MHC class I

MHC class I present peptide at cell surface

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10
Q

MHC class II

A

extracellular antigen -> endocytic vesicle

peptide production in phagolysosome

peptide binding by MHC class II

Golgi -> MHC class II in vesicle

MHC class II presents peptide at cell surface

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11
Q

CD8 T-cells + MHC class I

A

Cytotoxic killer T cells

CTL kill virus infected cell -> apoptotic cell

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12
Q

CD4 T-cells = peptides + MHC class II

A

TH1 cells:

  • > IFN gamma and macrophage containing intracellular bacteria
  • > deas intracellular bacteria

TH2 cells:

  • > IL 4 / 5/ 13
  • > eosinophil, mast cell, plasma cell

TH17 cells:

  • > IL 17 -> fibroplasts, epithelial cells + chemokinse
  • > neutrophil

TFH cells:

  • > B cell with IgM
  • > B cell with IgG, plasma cell (isotope switching and affinity maturation)

T reg cells

  • > T reg inhibit immature dendritic cell
  • > CD4 T cell (lack of T cell activation)
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13
Q

Key facts - Why have 2 types of MHC?

A

MHC I present Intracellular antigen, e.g viruses.

MHC I - antigen complex recognised by CD8+ve T cells
(T cytotoxic)

CD8+ve T cells kills presenting cell

MHC II present Extracellular antigen, e.g. bacteria

MHC II - antigen complex recognised by CD4+ve T cells
(T helpers)

CD4+ve T cells produce cytokines that promote antibody production (humoral)

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14
Q

Antigen can “swap” & additional T cells recruited

A

Helper T cell antigen – but now recognisable by Cytotoxic T cell

Cytotoxic T cell antigen – but now recognisable by Helper T cell

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15
Q

Monoclonal Antibodies

A

An immunological reagent that underpins medicine and is commercially valuable

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16
Q

Production of monoclonal antibodies (mAb)

A

Hypoxanthine:guanosine Phosphoribosyl Transferase HGPRT

  • > Spleen cels producing antibody from mouse immunized with antigen A
  • > Myeloma cells (immortal) lacking sntibody secretion and the enzyme HGPRT

Hypoxanthine aminopterin - thymidine (HAT)

  • > Mix and fuse cells with PEG
  • > Transfer to HAT medium (immortal hybridomas poliferate; mortal spleen cells and infused HGPRT - myeloma cells die)

-> Select hybridoma that makes antibody specific for Antigen A

-> Clone selected hybridoma
(Hybridomas can be frozen + 1000s of key tools available)

17
Q

Production of polyclonal antibodies (pAb)

A
  • > inject antigen into animal
  • > B-lymphocytes produce antibodies to antigen
  • > Remove blood sample containing antibodies
  • > isolate antibodies from blood in laboratory
18
Q

Monoclonal antibodies

A

These have been made against many cell surface molecules – check the Appendix of the textbooks.

They are a cataloguing system. NB. A cell surface molecule can have lots of different names reflecting functions, and the CD naming system (nomenclature) just uses monoclonal antibodies