Immuno exam 1 - Ag presentation

Question 1

How are lymphocytes activated?

Answer 1

Microbe taken up by APC at site of infection → APC enters lymph circulation, and into lymph node
*Naive T & B cells enter lymph node from circulation

Question 2

Describe Ag presentation

Answer 2

Antigen presentation is central to development of immune response
Processes by which MHC-antigen interacts with TH or Tc
- Bridges antigen recognition to initiation of full-blown immune response
- Enables T cell-mediated killing, or augments antibody production by B cells
- Is context dependent allowing deployment of appropriate immune responses under different conditions
- Is modulated by co-stimulatory molecules

Question 3

What is the result of antigen recognition without presentation

Answer 3

Tolerance

Question 4

Name and describe the 3 APCs

Answer 4

Dendritic cells – most efficient for initial T cell activation (priming)
Macrophages – must be activated by phagocytoses before presenting antigens
B cells – for secondary immune response
*But not limited to them… all nucleated cells can present endogenous antigens in association with MHC I molecules

Question 5

What is the meant by pathway 1 and pathway 2?

Answer 5

Pathway 1: Exogenous antigens into the cell, small peptide antigens generated & presented to TH cells together with MHC II molecule
Pathway 2: Endogenous antigens digested to small peptides & presented to CD8+ T cells

Question 6

What is antigen processing?

Answer 6

antigens digested & placed on cell surface with correct MHC molecules

Question 7

Describe the Cytosolic Pathway: Endoegenous Antigens

Answer 7

Proteins to be degraded link to ubiquitin (a small protein)
Degradation of ubiquitin-protein complex within central channel of proteasome
Peptides generated are transported into lumen of RER by Transporters associated with Antigen Processing (TAPs)
Newly synthesized MHCI binds to antigen peptide
Antigen-MHCI complex released & transported to cell surface
Extracellular antigens presented by macrophages or B lymphocytes to CD4+ helper T cells, which activate macrophages or B cells & eliminate the antigen

Question 8

Describe the Endocytic pathway: exogenous antigens

Answer 8

Endocytic pathway: exogenous antigens
Antigens internalized by enodsomes, first digested there & then in lysomoses
MHCII molecules produced at RER & associated with invariant chain protein (Ii) preventing their binding to endogenous antigens
Class II-Ii complex move into endocytic compartments
Ii digested to short fragment MHCII-associated Invariant chain Peptide (CLIP)
HLA-DM triggers exchange of CLIP & antigen peptide
HLA-DO blocks active of HLA-DM
*CD8+ cytotoxic T cell
Cytosolic antigens presented by nucleated cells to CD8+ CTLs which kill antigen-expressing cells

Question 9

What is MHC class 1?

Answer 9

MHC class I – polymorphic a chain noncovalently attached to nonpolymorphic β2 microglobulin; a chain is glycoslylated; extracellular portion of HLA-B27

Question 10

What is MHC class 2?

Answer 10

Class II - polymorphic a chain noncovalently attached to polymorphic β chain; both chains are glycoslylated; extracellular portion of HLA-DR1

Question 11

What are the 3 key roles of MHC?

Answer 11

Essential for antigen presentation to T cells
T cells constantly survey for foreign antigens
Self MHC + foreign Ag = T cell response
Self MHC + self Ag = no T cell response
Expression can be induced on almost every nucleated cell in the body
Viruses can infect any nucleated cell, MHCI function to alert the CD8+ T cells
MHC expression tells immune system that cell is a self cell
Key factor in determining tissue matching for transplant donors & receptors

Question 12

Describe MHC geners (HLA)

Answer 12

Highly polymorphic – hundreds of alleles in humans with 1013 combinations
…why difficult to find transplant donors (even among 1st degree relatives)
Concomitantly expressed – set of alleles on chromosome=MHC haplotype

Question 13

MHC hapoltypes can influence….

Answer 13

How an individual responds to certain pathogens
Susceptibility to certain diseases
Transplant success

Question 14

What are 4 characteristics of MHC-peptide interactions?

Answer 14

MHC has broad specificity for peptides (many different peptides can bind within the MHC binding cleft)
Peptides associated with MHC have a slow on & slow off rate
MHC molecules do not discriminate from self & foreign peptides
MHC haplotype determines which peptides bind & how peptides bind

Question 15

Describe MHC restiiction

Answer 15

Allows T cells to recognize foreign Ag on APC surface and to distinguish self & non self
In thymus (where T cells mature) T cells…
Are specific for foreign Ag+ MHC (positive selection)
Bind with low avidity to self peptide-MHC complexes survive
TCRs that bind with high avidity die (negative selection)
Prevents destruction of self tissue (autoimmunity)

Question 16

Describe the immunological synapse

Answer 16

• MHC-peptide complex binds to TCR
  o CD4 interacts with MHCII on APC & TCR on T cell to strengthen interaction
  o CD8 interacts with MHCI on target cell & TCR on T cells
• Co-stimulatory molecule B7 on APC binds to T cell ligand CD28
• Adhesion molecule ICAM-1 on APC binds to T cell ligand LFA-1

Question 17

What is the temporal order of multiple ligand-receptor interactions at the immunological synapse?

Answer 17

Multiple ligand-receptor interactions
Temporal order of interactions:
Non-specific, reversible binding though adhesion molecules
Antigen-MHC-TCR binding provides specific interaction & results in prolonged cell-cell contact (Ag-specific activation)
Costimulation generates a second signal that is important for the fate of cell

Question 18

Describe CD8 cell MHC restriction

Answer 18

CD8+ T cells are MHCI restricted & recognize cytosolic proteins

Question 19

Describe CD4 cell MHC restriction

Answer 19

CD4+ T cells are MHCII restricted & recognize extracellular and intravesicular pathogens

Question 20

What is the relationship b/t CD3 and TCR

Answer 20

CD3 and ζ are noncovalently associated to TCR
Expression of TCR CD3 and ζ chain are required for antigen recognition & signaling
TCR recognizes Ag, CD3 and ζ signal

Question 21

Describe the effects of co-stimulatory molecules on T-cells

Answer 21

Antigen recognition by lymphocytes provide signal 1 for activation of lymphocytes
Molecules induced on host cells during innate immune responses to microbes provide signal 2
T cell will not be activated without them (anergy – “T cells will not respond”)
T cell will not be stimulated without antigen-TCR interaction (no effect)
Co-reception of both signals activate T cells
At termination of response, CTLA-4 replaces CD28 & downregulates T cell function

Question 22

Describe the 2 different B-cell receptors

Answer 22

CD28 – before T cell activation
CTLA4 – at termination of immune response (“shuts T cell down”)
Can competitively inhibit CD28 binding
When bound to B7, will actively block signal from the TCR and from CD28

Question 23

How doe bacterial product effect MHC expression?

Answer 23

Bacterial products stimulate the expression of MHC, adhesion molecules, and co-stimulatory molecules in APCs
These signals provide T cells with ‘context’ information that determine the modality of their responses (tolerance, TH1 or TH2 response)

Question 24

Describe T cell activation following Ag presentation

Answer 24

Activation of tyrosine kinases associated with TCR/CD4(8) complex and phosphorylated cytoplasmic tails of the clustered receptors
Activation of kinase cascade follows & activation of transcription factors
Induction of IL-2 and IL-2R
Cell division after IL-2 ligation to IL-2R

Question 25

What is the effect of IL-2 receptor on T-celss in regard to ampilficaltion especially

Answer 25

Amplification of T cell response by IL-2 receptor:
Before T cell activation, T cell expresses βγ IL-2R
After, IL-2R takes the form of αβγ trimer which enhances affinity by 1000 fold → amplification
InterLeukin-2 can lead to:
T cell clonal expansion and differentiation into effector & memory cells
Regulatory T cell development, survival and function
NK cell proliferation & increased cytotoxic activity

Question 26

What cytokine drives Th1 cell development?

Answer 26

IL-12

Question 27

What cytokine drives Th2 cell development?

Answer 27

IL-4

Question 28

How do Th1 cells provide help for cell mediated response?

Answer 28

→ Microbes + APC + CD40 + IFN-γ → macrophage activation
→ Neutrophils + LT + TNF → neutrophils activation
→ B cell IFN-γ → complement binding & opsonizing antibodies

Question 29

Why is INF-gamma important to Th1?

Answer 29

→ Macrophage activation
→ isotype switching to opsonizing & complement-fixing antibodies from B cells
→ Development of TH1 effector cells (from naive CD4+ T cells)
→ increased MHC expression, antigen presentation from APCs

Question 30

How do Th2 cells help provide for a humeral mediated response?

Answer 30

→ IL-5 → eosinophil activation
→ IL-10, IL-4 → activated macrophage → suppression of macrophage activation
→IL-4 → production of neutralizing IgG; production of IgE → mast cell degranulation

Question 31

Why is IL-4 and important Th2 cytokine?

Answer 31

B cell → isotype switching to IgE & IgG4
Naïve CD4+ T cell → differentiation & expansion of TH2 cells
→ Inhibition of differentiation of TH1 cells

Question 32

What is the path for effector functions for both CD4 and CD8 Tcells (memory and effector)

Answer 32

Antigen recognition→ activation→ clonal expansion→ differentiation into effector/memory cells
→ effector functions:
Effector & memory CD4+ T cells→ activation of macrophages, B cells & other cells
Effector & memory CD8+ T cells→ killing of infected cells; macrophage activation