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IHO Week 4 > Antigen Presentation and Processing - Diebel > Flashcards

Antigen Presentation and Processing - Diebel Flashcards

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1
Q

Define Anergy

A

Self-tolerance; T-cell binds to APC without CD28 binding CD80/86 => T-cell inactivated or may die

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2
Q

What 3 receptors need to bind for a T-cell to be activated?

A 
TCR = MHC
CD4/8 = MHC
CD28 = CD80/86 (B7-1/2)
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3
Q

When a T-cell is activated, what happens next?

A

IL-2 produced with IL-2R (high affinity) to promote division, differentiation, effector functions

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4
Q

What happens to T-cell activation 24 hours after an event?

A

CTLA-4 binds CD80/86, blocking the stimulatory effects that the T-cell gets from CD80/86; shuts off the signal

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5
Q

Which has a higher affinity for the CD80/86 complex?

CD28 or CTLA-4

A

CTLA-4 will outcompete and bind better to CD80/86 leading to T-cell activation inhibition

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6
Q

What is the main function of CTLA-4 (broad picture)?

A

Prevent overstimulation of T-cells

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7
Q

ACP LFA-3 binds to…

A

CD2 on T-Cell

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8
Q

APC MHC II binds to…

A

TCR-CD3 on T-Cell

CD4 on T-Cell

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9
Q

APC CD80/86 binds to…

A

CD28 on T-Cell (Activating)

CTLA-4 on T-Cell (Inhibiting)

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10
Q

APC ICAM-1 binds to…

A

LFA-1 on T-Cell

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11
Q

What is the BCR made up of?

A

Membrane bound IgM or IgD

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12
Q

How do T-cells recognize antigen?

A

Cannot recognize free antigen - must first be processed and presented on an MHC molecule

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13
Q

How many different Class I MHC molecules could each cell express?

A

6

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14
Q

How many different Class II MHC molecules could each cell express?

A

12 (DP, DQ, DR)

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15
Q

What cell type is the most effective professional antigen presenting cell?

A

Dendritic Cells

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16
Q

Describe the MHC presentation on immature and mature dendritic cells.

A

Immature DCs = LOW MHC II
Mature DCs = HIGH MHC II (primary presenters of antigen via phagocytosis and endocytosis)
- Constitutively express CD80/86

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17
Q

How can macrophages express MHC II molecules?

A

Activated by phagocytosis and cytokines to express MHC II

Activated to express co-stimulatory molecules

18
Q

If B-Cells constitutively express MHC II, how are they activated?

A

By antigen binding to antibody to express co-stimulatory molecules

19
Q

Describe the types of antigens presented by DCs, Macrophages, and B-Cells.

A 
DCs = peptides, viral antigens, allergens
Macrophages = particulate antigens
B-Cells = soluble antigens, toxins, viruses
20
Q

What is the cytosolic pathway for antigen presentation?

A

Requires intracellular protein synthesis of the endogenous antigen for presentation on MHC I
* Key for presenting damaged DNA or proteins to receive apoptotic signal from CD8+ T-Cell

21
Q

What is the endocytic pathway for antigen presentation?

A

Requires the endocytic uptake of exogenous antigen and degradation in phagolysosomes or endosomes for presentation of antigen on MHC II

22
Q

What two ways can cellular proteins be degraded?

A

Constitutive proteasome: 20S proteasome or 26S proteasome (Ub required 20S proteasome with 19S regulator

Immunoproteasome: stimulated with INF-y or TNF-a to efficiently load peptides into MHC I through better TAP protein complex association

23
Q

What is the TAP protein and what is it used for?

A

TAP = Transporter Associated with Antigen Processing with affinity for peptides 8-16 amino acids long

A transporter protein heterodimer complex of TAP1 and TAP2 extends across the RER membrane to facilitate the passage of peptides into the lumen of the RER to be loaded onto MHC I

24
Q

What is the optimal binding size of the MHC Class I Molecule?

A

9 amino acids

25
Q

What enzyme is responsible for the final trimming of the amino acid peptide sequence and where does this trimming occur?

A

In the ER by ERAAP (ER-associated aminopeptidase)

Can also occur in MHC I grove in ER

26
Q

What are DRiPs?

A

Defective Ribosomal Products are proteins that are synthesized incorrectly

27
Q

What do virus-infected cells contain and how did it get there?

A

A distinct 20S proteosome induced by INF-y and TNF-a, which degrades and presents viral proteins on MHC I

28
Q

What two ways can CD8+ activated T-cells induce apoptosis?

A 
Release of cytotoxic molecules
  - Perforin
  - Granzymes
  - Granulysin
Binding of Fas ligand to Fas receptor (death receptor)
29
Q

What does chromosome 6 encode?

A

HLA Class I, II, & III and TAP

30
Q

What does chromosome 15 encode?

A

Beta2-microglobulin

31
Q

What is the normal ratio of CD4:CD8 T-Cells?

A

65% CD4+ to 35% CD8+ T-Cells

32
Q

MHC Class II molecules are synthesized in the RER as trimers. What makes up the trimer?

A

Alpha and Beta chain coupled with an invariant chain, CD74.

33
Q

What is the role of the invariant chain?

A

Assist in folding of MHC Class II, binds to peptide-presenting site, assists in transport from Golgi to cytoplasmic vesicles

34
Q

What non-classical MHC Class II molecule releases the CLIP invariant chain remnant from the peptide binding site of MHC Class II molecules?

A

HLA-DM exchanges CLIP for the antigenic peptide, which is regulated by HLA-DO

35
Q

What is the function of Th1 T-Cells?

A

Recognize peptide bound to MHC Class II to activate macrophages and destroy intravesicular pathogens

36
Q

What is the function of Th2 T-Cells?

A

Recognize peptide bound to MHC Class II to cause B-Cell proliferation and differentiation to plasma cells and antibody production

37
Q

What is the normal nutrophil and lymphocyte counts in a WBC differential?

A

Neutrophils: 40-60%
Lymphocytes: 22-44%

38
Q

How is MHC Class II deficiency inherited?

A

Autosomal Recessive with health problems in early infancy

39
Q

What is typically seen in dividuals with a MHC Class II deficiency that are deficient in CD4+ T-Cells?

A

Moderate to Severe Hypogammaglobulinemia

40
Q

What is the treatment for MHC Class II deficiency?

A

Hematopoietic Stem Cell Transplant

41
Q

What is the cause of MHC Class II Deficiency?

A

Defects in the transcription factors required to regulate expression of MHC Class II genes

42
Q

What induces the expression of MHC Class II on APCs in normal people?

A

IFN-y

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