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Block 1 - Week 5 > Antigen Processing, Presentation, and Lymphocyte Development > Flashcards

Antigen Processing, Presentation, and Lymphocyte Development Flashcards

1
Q

MCH Restriction

A

T-cell receptors have specificity for a particular MHC/peptide compex

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2
Q

Polyspecificity of MHC receptors

A

Many different peptides can bind to MHC receptors, but not all peptides

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3
Q

Which MHC receptor can accomodate longer peptides?

A

MHC Class II molecules can accomodate longer peptides

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4
Q

MCH I peptide/complexes engage TCRs with ____ co-receptors

A

CD8+

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5
Q

MCH II peptide/complexes engage TCRs with ____ co-receptors

A

CD4+

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6
Q

Which cells express MHC I?

What is the significance of this?

A
  • All nucleated cells express MCH I
  • Can present viral peptides when infected
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7
Q

What are 2 important properties of MHC genes?

A
  • Polymorphic: many different alleles present in the population
  • Co-dominant expression: Both parental alleles of each MHC gene are expressed

This increases the number of microbial peptides that the MHC can present to T-cells

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8
Q

How do Dendritic Cells act as specialized activators of naive T-cellls?

A

Dentric cells:

  1. Process foriegn antigen
  2. Migrate to lymph nodes where they present the antigen to naive T-cells
  3. Provide addtional stimulating signals necessary for T-cell activation
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9
Q

What role does the spleen play with regards to blood-borne antigens?

A

Blood-borne antigens are captured by antigen-presenting cells in the spleed

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10
Q

Cytotoxic T-cells present T-Cell Receptors (TCRs) with

CD__ co-receptors which binds to MHC class ___

A
  • CD8+ co-receptors
  • MCH Class I
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11
Q

Helper T-cells present T-Cell Receptors (TCRs) with

CD__ co-receptors which binds to MHC class ___

A
  • CD4+ co-receptors
  • MHC Class II
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12
Q

MHC Class I Presentation Process

A
  1. Viral protein in the cytoplasm is cleaved by proteasomes
  2. Cleaved products = viral peptides
  3. Viral peptides are transported to the endoplasmic reticulum
  4. Peptides combine with MHC Class I in the ER
  5. MCH Class I/Peptide Complex is then transfered to the cell surface where it is expressed
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13
Q

MHC Class II Presentation Process

A
  1. Uptake of extracellular protein antigen via endocytosis or phagocytosis
  2. Endosome/Phagosome fuse with Lysosome
  3. Protein antigen is processed to form peptides
  4. MHC Class II is transported via a vesicle to the endosome/phagosome
  5. MHC Class II/Peptide Complex is formed and transfered to be expressed on the cell surface
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14
Q

Cross-Presentation

A
  • Endosomal antigen (normally presented by MHC II) is presented by MHC I (when the endosomal antigen is viral instead of bacterial/fungal)
  • Occurs as a result of certain viruses only infecting certain cell types, and the immune system (Ex. Dendritic Cells) still needs to be able to present these viral antigens even when the particular virus doesn’t infect Dendritic Cells
  • Follows a similar process as normal MHC I Presentation with the only difference being that the antigen source comes from endosomes instead of the cytoplasm
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15
Q

Are MHC without peptide presented on the cell surface?

A

No because MHC without peptide are inherently unstable and undergo degredation while MHC with peptide is very stable

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16
Q

Which cells express MHC II?

A
  • Dendtritic Cells
  • Macrophages
  • B-Lymphocytes
  • Thymic Epithelium
17
Q

What are the cell surface antibody associated signaling receptors?

A

Iga and IgB

18
Q

What are the T-Cell Receptor (TCR) associated signaling receptors?

A

CD3

19
Q

What does the T-Cell Receptor (TCR) recognize and bind to?

A

The MHC and peptide within the complex

20
Q

What components make up the MHC Class I peptide-binding cleft?

A

a1 and a2

21
Q

What components make up the MHC Class II peptide-binding cleft?

A

a1 and b1

22
Q

What type of molecules do MHC bind?

A

Peptides only (they do not bind lipids, carbohydrates, nucleic acids, etc.)

23
Q

Where do MHC I peptides originate?

Where do MHC II peptides originate?

A
  • MHC I peptides originate from intracellular viral proteins
    • With the exception of cross-presentation where the viral proteins come from endosomes
  • MHC II peptides originate from extraceullar pathogens
24
Q

“MHC Restricted Antigen Recognition” refers to the ability of:

A

T-cells to respond to a given antigenic peptide, only when this antigen is bound to a specific MHC molecule

25
Q

Helper T-Cell Function

A

Activate macrophages to kill phagocytosed microbes

26
Q

Cytotoxic T-Cell Function

A

Kill infected cells and eliminate reservoirs of infection

27
Q

Analogy between ab T-Cell receptor and Antibody

A
  • TCR is like the Fab fragment of an antibody
  • TCR has an a/b chain; antibody has a light/heavy chain
  • TCR is membrane anchored; antibody can be membrane anchored as a B-cell receptor or secreted
28
Q

Antibody Structure

A
  • 2 light chains and 2 heavy chains
  • Each chain has one variable domain (V) and at lesat one constant domain (C)
  • Two V domains (VL and VH) make up antigen binding site
  • The Fc region determines the antibody effector function
29
Q

Generation of combinatorial BCR diveristy

A

During B-Cell development in the bone marrow:

  • Multiple different V, D, and J gene segments are selected and combined to form the gene that codes the BCR
  • Genetic assembly of gene segments is mediated by the enzyme Recombinsase Activating Gene (RAG)

Additional diversity is generated by enzymes that semi-randomly add/remove nucleotides at the ends of different gene segments prior to assembly by RAG

30
Q

Negative Selection

A
  • Elimination of self reactive lymphocytes during their development
  • This leads to central tolerance: the immune system does not attack self
31
Q

Positive Selection of T-Cells

A

In order to complete development, mature naive T-cells must be able to weakly bind MHC/self-peptide complexes from thymust epithelial or dendritic cells

32
Q

Negative Selection (T-Cells)

A

If a T-Cell binds strongly to MHC/self-peptide it undergoes apoptosis

33
Q

Death By Neglect (T-Cells)

A
  • Failure of positive selection
  • If a T-Cell Receptor doesn’t bind MHC/self-peptide complexes at all (no binding), it undergoes apoptosis
34
Q

How does TCR gene arrangement relate to BCR gene arrangement?

A
  • They are very similar
  • TCR diversity is also generated by combination of different V, D, and J gene segments
35
Q

Double-Negative T-Cells

A

Early in development:

T-Cells do not express CD4+ or CD8+ co-receptors

36
Q

Double-Positive T-Cells

A
  • Later in development, T-Cells express both CD4+ and CD8+
  • After CD4+ or CD8+ co-receptors weakly bind MHC II or MHC I/self-peptide complexes, they stop expressing the other type of CD co-receptor
    • For example, if during development CD4+ weakly binds to MHC II, that cell will stop expressing CD8+ and become a helper T-Cell
    • This ensures that after maturation T-Cells only express CD4+ or CD8+, never both
37
Q

Where does the following generally occur:

  • T-Cell Selection
  • T-Cell Activation
  • T-Cell Effector Function
A
  • T-Cell Selection –>Thymus
  • T-Cell Activation –> Lymph Nodes
  • T-Cell Effector Function –> Site of Infection

Block 1 - Week 5 (10 decks)

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