Lecture 7- Antigen Recognition: Processing and Presentation

Question 1

TCRs only recognized antigens that are:

Answer 1

presented by an MCH molecule on the surface of an APC
(PROCESSED and made of PROTEINS)

Question 2

What are the 6 stages (?) of T-cell activation?

Answer 2

1 - Recognition & antigen binding
2 - Stimulation (Due to the clustering of cell surface receptors (TCRs), Polarized to one side of the cell)
3 - Clustering (Signals development inside the T cell membrane)
4 - Signal transduction (Transduction of PTKs & interaction w/ receptors)
5 - Signal is amplified (Transmitted to interior of cell)
6 - Response by T cell (Gene transcription & proliferation = clonal expansion, Production of cytokines)

Reading and Steering Cars Sometimes Seems Reasonable

Question 3

What is the first signal for T-cell activation?

Answer 3

Antigen binding and Co-stimulation

Question 4

What do co-stimulatory molecules (CD4 or CD8) do?

Answer 4

• Act as co-receptors
• Recognize the MHC 2 or MHC 1
• Aid to stabilize the TCR-MHC interaction → stronger binding

Question 5

What do accessory molecules do, and what are some examples?

Answer 5

• aid in binding TCR-APC
• CD11 [or LFA-1]——CD54 [or ICAM-1]
• CD28——-B7

Question 6

What are PTKs and what do they do?

Answer 6

protein tyrosine kinases

PTKs along with protein tyrosine phosphatases link receptors & biochemical pathways
- this happens by phosphorylation of ITAM’s and enzymes

Question 7

what is the end result/goal of signaling?

Answer 7

• proliferation
• differentiation
• expression of cytokines

Question 8

Superantigens activate T cells without ____.

Answer 8

attaching to the groove of MCH molecules

Question 9

The attachment of superantigens is ______.

Answer 9

non-specific
- attaches to the variable domain of the ß chain of TCR
- Large numbers of T cells are activated

Question 10

What is LFA?

Answer 10

Lymphocyte function-associated antigen

Question 11

Activation of naive T cells leads to their proliferation & differentiation into ____ cells.

Answer 11

effector cells

Question 12

What is the primary function of B cells?

Answer 12

antibody secretion & memory formation

Question 13

What is the primary function of dendritic cells?

Answer 13

antigen presentation

Question 14

Where are macrophages located?

Answer 14

peripherial tissues

Question 15

Where are dendritic cells located?

Answer 15

peripherial tissues

Question 16

Where are B cells found?

Answer 16

secondary lymphoid organs (SLO) and in circulation

Question 17

Which cell can internalize antigens bound to its receptor and present them?

Answer 17

B cells

Question 18

Which cell can phagocytose small amounts of extracellular debris for antigen presentation?

Answer 18

Dendritic cells (DC)

Question 19

Which cells can load foreign peptides onto both MCH class molecules (1 and 2)?

Answer 19

Professional APCs

Question 20

Which cells express MHC 1?

Answer 20

all somatic cells

Question 21

Which cells express MHC 2?

Answer 21

professional APCs

Question 22

What is an ICAM?

Answer 22

Intercellular adhesion molecules

Question 23

What is an ITAM?

Answer 23

Intracellular adhesion molecules

Question 24

The route of the antigen w/in the host determines the ________.

Answer 24

MCH selectivity
- Extracellular -> MHC2
- Intracellular -> MHC1

Question 25

What are some features of MHC 1?

Answer 25

- Expressed by all somatic cells - Cytosolic antigens - Activates cytotoxic CD8 T cells = cell death - Endogenous - Both host cell & antigen within host cell → DIE

Question 26

What are some features of MHC 2?

Answer 26

- Expressed by professional APCs - Vesicular antigens - Activates helper CD4 T cells - Aids in Humoral & Cellular immune response - Exogenous - ONLY the antigen dies

Question 27

rrrr

Question 28

Why is cross-presentation by dendritic cells needed?

Answer 28

- Non-professional APCs do NOT migrate to lymph nodes → do NOT stimulate the immune system - Infected DC can be compromised → unable to migrate to lymph node → do NOT stimulate the immune system

Question 29

What is the function of cross-presentation by dendritic cells?

Answer 29

Uninfected DC able to internalize debris from killed host cells → travel to lymph node → initiate adaptive responses

Question 30

How long does antigen processing take?

Answer 30

minutes to hours

Question 31

Cross → MHC 1-exogenous antigen via Dendritic cells [an APC] INSTEAD of via somatic cell Pathogen/antigen was exogenous = MHC 1-antigen that killed host cell = SOMATIC route Dead host cell phagocytosed by dendritic cell = MHC 1 STILL being presented but via dendritic cell CD8 will be activated b/c MHC 1 CD4 is NOT activated even though an APC is being used

Question 32

How does antigen processing work?

Answer 32

- pathogens and their proteins are degraded into smaller peptides - peptide fragments fit into/ combine with MHC 1 or MHC 2 binding grooves.

Question 33

The process by which pathogens and their products are degraded to produce peptide antigens is known as ______.

Answer 33

Antigen processing

Question 34

The MHC-peptide complex travels to the cell surface where it displays peptide fragments to T cells. This is known as _______.

Answer 34

Antigen presentation

Question 35

Antigen presentation is only required for ________.

Answer 35

Activation of T cells

Question 36

What happens during antigen presentation?

Answer 36

Generate small pieces of protein from the PATHOGEN = the epitopes i.e the antigen binding portion → can be recognized by TCR Binds to TCRs on T cells best suited to eliminate that specific pathogen Dictated by MHC selectivity & MHC restriction

Question 37

Antigen-peptides are synthesized in the _______.

Answer 37

cytosol

Question 38

What kind of antigens are processed on MHC 1? Explain the process.

Answer 38

Endogenous antigens Intracellular antigens Cytosol antigens Ag-peptide attaches to MHC 1 and moves to the cell surface Ag is recognized by cytotoxic T-cells which destroy the infected host cell

Question 39

What kind of antigens are processed on MHC 2? Explain the process.

Answer 39

Exogenous Vesicular antigen Extracellular antigen Activate humoral or cellular immune response

Question 40

What do lymphocytes do once they recognize an antigen?

Answer 40

Proliferate - some of the newly produced cells carry out the attack; others influence the activation and function of the attack cells

Question 41

Where are lymphocytes activated?

Answer 41

in lymph nodes near the site of infection

Question 42

What does IL-1 do?

Answer 42

It increases the permeability of vascular endothelium and stimulates the production of IL-6

Question 43

What does IL-6 do?

Answer 43

It acts on the liver which leads to the production of acute phase reactants (ex: C-reactive protein), causing inflammation

Question 44

What does IL-8 do?

Answer 44

It attracts & activates neutrophils, and increases the permeability of vascular endothelium

Question 45

What does IL-12 do?

Answer 45

It activates NK cells and influences lymphocyte differentiation

Question 46

Ubiquitin-tagged viral protein is processed via ________.

Answer 46

proteasome

Question 47

What contributes to the recognition and binding of exogenous antigens on professional APCs?

Answer 47

- PRR and PAMPs (pattern recognition receptor & pathogen-associated molecular pattern) - Mediated by various receptors

Question 48

What contributes to the ingestion/phagocytosis of exogenous antigens on professional APCs?

Answer 48

- receptor-mediated endocytosis - macropinocytosis by dendritic cells

Question 49

destruction within the vesicles (?) idk how to word this as a question

Question 50

What does the secretion of cytokines and chemokines do?

Answer 50

Attracts other APCs and immune cells

Question 51

What do phagolysosomes contribute to?

Answer 51

Degradation of antigens by lysosomal components = small peptide fragments produced Acid hydrolases Reactive oxygen species ROS Nitrous oxide

Question 52

What is ROS and some examples?

Answer 52

Reactive Oxygen Species - Superoxide radicals - Hypochlorite radicals - Hydroxyl radicals