Atopic Disease and Immune Tolerance Flashcards Preview

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Flashcards in Atopic Disease and Immune Tolerance Deck (19)
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1
Q

Which cells are responsible for adative immunity?

A
  • B lymphocytes
  • T lymphocytes
2
Q

What percentage of WBCs are lymphocytes?

A

~30%

3
Q

Where do B and T lymphocytes form?

A

In the bone marrow

4
Q

Where do B and T lymphocytes mature?

A
  • B lymphocytes mature in the bone marrow.
  • T lymphocytes mature in the thymus.
5
Q

What are BCR and TCR?

A
  • Each B and T lymphocyte has a unique surface antigen recognition receptor (BCR or TCR).
  • BCR and TCR are expressed as part of conserved surface molecules that confer function to the antigen recognition site.
6
Q

How are unique antigen recognition sites formed?

What does this result in?

A
  • Unique antigen recognition sites by recombination of a single member multiple copies of the VDJ genes - the final arrangement codes for a unique region that is aligned to constant functional gene segments (BCR shown; same principle for TCR).
  • The resulting unique antigen binding sites will capture most foreign antigens, BUT some will inadvertantly bind to host proteins.
7
Q

Which part is the variable portion?

A

The variable portion is the sum of variability on the alpha and beta sites.

8
Q

What is immune tolerance?

A

Removal of B and T cell clones that have antigen binding sites specific to self proteins / antigens.

9
Q

Describe the removal of self-reactive B cell clones in the bone marrow.

A
  • As pre-B cells develop in the bone marrow they encounter host cells and if they react they are removed.
  • If the pre-B cell surface receptor recognises host cell receptors - e.g. MHC molecules, they are eliminated.
    • Only the B cells that don’t react with anything in the bone marrow can leave the bone marrow.
  • If the pre-B cell’s surface receptor recognises soluble host proteins they are rendered anergic.
  • If a B cell looks activated it is cleaned out of the system.
10
Q

Describe the B lymphocyte maturation which occurs in the bone marrow.

A
  • B cell maturation in a radial direction with more mature cells located toward the centre of the bone.
  • Endosteal (inner) surface of bone with a layer of osteoclasts.
  • Macrophages phagocytose negatively selected cells.
  • Immature B cells travel to the spleen via the circulatory system.
11
Q

Describe the removal of self-reactive B cell clones in the spleen.

A
  • Transitional not fully mature B cells enter the periphery and pass through the spleen - a second round of removal of B cells with self-reactive antigen binding receptors in the spleen.
12
Q

Describe the removal of self-reactive T cell clones

A
  • More complex than B cell clone removal - involves 3 organs:
    • Bone marrow
    • Thymus
      • Two distinct thymocyte lineages develop in the thymus.
      • Most thymocytes die and only approximately 5% enter the periphery as CD8+ cytotoxic T cells or CD4+ helper T cells - importantly they are positively and negatively selected to recognise foreign / altered peptides presented in host MHC1 (CD8+) or MHC2 (CD4+) molecules on infected cells or APC respectively.
    • Spleen
      *
13
Q

What are MHC class I and MHC class II?

A
  • Major histocompatibility complex antigens - host specific.
  • Encoded by multiple gene families and have variable antigen presentation domains and present antigen (peptides) to T lymphocytes.
14
Q

Describe the antigen presenting site on MHC antigen grooves.

A
  • MHC antigen presenting groove variability - evolved to bind to most peptides of foreign / abnormal origin.
  • MHC class I variability in the antigen presenting groove is conferred by amino acid variability on the α 1 and 2 chain domains.
  • MHC class II antigen binding groove variability is conferred by the β1 domain. The α is invariant.
15
Q

What is T cell positive selection?

A
  • T cells with TCR in the thymus that recognise MHC I develop into CD8+ cytotoxic T cells.
  • T cells with TCR in the thymus that recognise MHC II develop into CD4+ helper T cells.
  • All others are deleted.
16
Q

What is negative T cell selection?

A
  • MHC I and II in the thymus (only) present host peptides and T cells CD8+ or CD4+ that recognise host peptides are deleted.
  • Only non-self reactive T cells enter the periphery.
17
Q

What happens to MHC class I during successful antigen presentation and T cell activation?

A

CD8 co-receptor bind to MHC class I during successful antigen presentation and T cell activation.

18
Q

What happens to MHC class II during successful antigen presentation and T cell activation?

A

CD4 co-receptor bind to MHC II during successful antigen presentation and T cell activation.

19
Q

Describe T lymphocyte antigen recognition.

A
  • B cell receptors (a cell surface copy of the antibody that will be made by plasma cells if activated) recognise soluble antigens.
  • T cells recognise processed antigens presented on the surface of host cells in MHC molecules and with the T cell co-receptors CD4 or CD8.