Adaptive immunity 2+3 Flashcards Preview

Module 204, Theme 1: Immunology > Adaptive immunity 2+3 > Flashcards

Flashcards in Adaptive immunity 2+3 Deck (17)
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1
Q

Purpose of VDJ

A

Generates massive diversity go B and T cell receptors

2
Q

Number of splicing combinations in B cells

A

3x 10 (11)

  • 44 V
  • 27 D
  • 6 J
3
Q

Recombination signal sequence

A

Sequence of non-coding DNA that RAG 1/2 recognise in immature B and T cells.

RAG enzyme binds and flanks region of DNA at this point.

4
Q

RAG 1/2

A

Recombination activating genese

Enzymes in T and B cells that recognise RSS in DNA.

Splices introns between the RSS and V/D/J segment

5
Q

Mechanism of VDJ

A
  1. RAG1/2 binds to RSS in DNA, flanking a V/D/J gene segment
  2. RAG breaks DNA between RSS and V/D/J segment- leaving double stranded break at the end of coding segment (DNA hairpin)
  3. Loop of DNA spliced out to form signalling loop.
  4. Terminal, deoxynucleotridyltransferase (TdT) adds nucleotides to cleaved ends in a non-template fashion.
  5. DNA ligase ligates gene segments
6
Q

Terminal deoxynucleotidyl transferase (TdT)

A

DNA polymerase that adds nucleotides to cleaved hairpin end of DNA in random fashion

7
Q

Somatice hypermutation

A

Only occurs in B cells

  • Occurs after B cell has encountered antigen
  • A component of affinity maturation

Function
- Diversifies B cell receptors used to recognise foreign

8
Q

Cytidine deaminase

A

Enzyme involved in somatic hypermutation.

- Causes random mutation in V gene segment

9
Q

Somatic hypermutation process

A

Occurs in B cells, Variable (V) region.

Cytidine deaminase causes nucleotide change to uracil from cytosine, in V region of DNA.

  • Since uracil is not stable, this is fixed by base-exicison repair enzymes
  • Uracil is removed and error prone DNA-polymerases fill in the gaps with = new mutations

When B cells undergoes devision with new mutation, the cells with highest affinity are positively selected.

10
Q

Class switch recombination

- Description

A

Occurs in B cells after antigen recognition

  • Immunoglobulins switch from IgD/M isotope to another (IgA, IgG)
  • Constant region of immunoglobulin changes, whilst keeping the variable region the same

Purpose
- Allows antibody to retain affinity to antigen, whilst changing its interaction with effector molecules.

11
Q

Class switch recombination

- Process

A
  1. The first regions on the heavy chain exon are:
    - Cu (IgM)
    - C-delta (IgD)

Stimulation of B cell by T cells (CD40L) and cytokines triggers class switching.

  1. Activated cytidine deaminase is involved in breaking DNA at IgM region.
  2. Second cut is make in the isotype region that will be switched to (e.g IgG).
12
Q

MHC 1 pathway

A

Processes endogenous antigens

  1. Intracellular antigens are present and are processed in proteasome.
    - Into peptides
  2. Peptides are transported into the endoplasmic reticulum via Tap proteins
  3. Peptides are bound to MHC 1 in ER
  4. Peptides are presented on cell surface via MHC
13
Q

Mechanism of peptides binding to MHC class 1 binding

A
  1. MHC in ER originally has clanexin bound to it
    - Released when beta-microglobulin binds to it
  2. TAP proteins load peptides into ER- then MHC
  3. MHC class 1 dissociates with protein and presents peptides
14
Q

HSV and MHC 1

A

HSV can bind to Tap proteins

- Inhibits transport of peptides into ER

15
Q

MHC Class 2 pathway

A

Processes exogenous antigens.

  1. Whole antigen is taken into cell via endocytosis, into a vesicle
  2. Vesicle fuses with lysosome and undergoes acidification
    - Activates proteases to break down antigen into peptides.
  3. Vesicle fuses with another vesicle containing MHC 2
    - MHC have invariant chain blocks that initially block them, but this Is cleaved by CLIP fragment
  4. HLA-DM allows MHC to bind to peptide by releasing CLIP
  5. MHC 2 presents peptide on plasma membrane
16
Q

Adenovirus immune invasion

A

Inhibits upregulation of MHC 2 pathway

- Less MHC recognised by T cells

17
Q

Leishmania and mycobacteria immune evasion

A

Presents phagosome-lysosome fusion