Antigen Processing Flashcards

1
Q

What happens if I mix an E. coli bacterium and a macrophage?

A
  1. binding
  2. engulfment
  3. Phagosome formation
    Acidification via Respiratory Burst
  4. Phagosome fuses with Lysosome to form Phagolysosome
    Digestion
  5. Membrane Disruption
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2
Q

The process of taking up a microbe, processing the antigens, and presenting it to a naïve T cell is what we refer to as

A

antigen processing and presentation.

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3
Q

Dendritic Cells

A

Phagocytic cells

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4
Q

Dendritic Cells: Minor population in the

A

blood, but:

found in skin, mucosa, lymph nodes, spleen, thymus

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5
Q

Dendritic Cells: typically express

A

MHC II molecules

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6
Q

Dendritic Cells: internalize and process

A

Ag

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7
Q

Dendritic Cells: present

A

Ag peptides within MHC II on surface

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8
Q

Dendritic Cells: important for presenting

A

Ag to T cells

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9
Q

Dendritic Cells: important for activating

A

T cells

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10
Q

Dendritic cells: PRIMARY

A

ANTIGEN-PRESENTIG CELL (Professional APC)

link between innate and adaptive immunity

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11
Q
  1. Monocytes/Macrophages: monocyte in blood —>
A

macrophage in tissue
5-10% of blood leukocytes
phagocytic cells

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12
Q
  1. Monocytes/Macrophages: characteristic
A

large nucleus

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13
Q
  1. Monocytes/Macrophages: very large
A

cell, 10 - 20 µm in diameter

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14
Q
  1. Monocytes/Macrophages: produce
A

chemotactic agents for other leukocytes

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15
Q
  1. Monocytes/Macrophages: contain arsenal of
A

lysozymes and antimicrobial proteins

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16
Q
  1. Monocytes/Macrophages: phagocytose
A

microorganisms, particles, & tumor cells

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17
Q
  1. Monocytes/Macrophages: extremely important for clearance of
A

dead cells & debris

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18
Q

Monocytes/macrophages: extremely important for

A

antigen presentation

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19
Q

B cells : a lymphocyte (part of adaptive immunity)

relatively

A

small, 6 - 10 µm in diameter

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20
Q

B cells : produce

A

chemotactic agents to attract other leukocytes

produce cytokines to activate or inactivate other leukocytes

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21
Q

B cells : can activate

A

T cells (more common in secondary (or memory) immune responses

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22
Q

Antigen presentation is a way to

A

concentrate the antigen in areas most likely to come into contact with T cells and B cells.

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23
Q

Antigen presenting cells are not limited to

A

dendritic cells, macrophages, and B cells.

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24
Q

All nucleated cells can

A

present endogenous antigens in association with MHC I molecules

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25
What is the Major Histocompatability Complex (MHC)?
- Original function was linked only to graft rejection | - Later found to be of critical importance to all immune responses involving protein antigens
26
MHC I
Found on all nucleated cells Cytoplasmic protein can be bound to MHCI Recognized by CD8+ T cells
27
MHC II
Found on antigen presenting cells Extracellular proteins will be bound to MHCII Recognized by CD4+ T cells
28
MHC II
Found on antigen presenting cells Extracellular proteins will be bound to MHCII Recognized by CD4+ T cells
29
Antigen processing is the processes by which antigens are
digested and placed on the cell surface with the correct MHC molecule.
30
Two pathways of antigen processing:
Extracellular proteins that are internalized by professional APCs into vesicles are processed and displayed by class II MHC molecules. Proteins in the cytosol of nucleated cells are processed and displayed by class I MHC molecules.
31
Often the cytosolic proteins are
viral proteins.
32
Virus enters into cell, process of
uncoating, replication, reassembly, release.
33
During entry/uncoating and reassembly there are
viral proteins in cytoplasm.
34
Proteins in the cytoplasm that are not used by the
cell get tagged for degradation.
35
Ubiquitin binds to the
proteins which targets them to the proteosome.
36
Step 2: Ubiquinated proteins are cleaved into
smaller peptides by the proteosome
37
Step 3: Peptides are transported into the
endoplasmic reticulum through the TAP transporters (TAP stands for transporter associated with antigen processing)
38
Step 4: As the peptide is being processed, Class I MHC molecule is being formed in the
endoplasmic reticulum.
39
MHCI is unstable. Peptide binding in the binding groove will
stabilize the MHCI. If no peptide, the MHCI degrades
40
Step 4: Peptide that is transferred into the ER by TAP is
trimmed to the correct size by an aminopeptidase called ERAP.
41
The correct size peptide can then bind to the
binding groove of MHCI.
42
Step 5: Once the MHCI binds to antigen, it is released from
ER (i.e., it is no longer bound to tapasin). The complex is packaged into a vesicle in the Golgi. Vesicle is trafficked to the cell surface, fused with the cell membrane resulting in expression of MHCI+Ag
43
The antigen bound to MHCI can be a
foreign protein/peptide or it can be a self peptide (i.e., from a protein from the host cell). This is one way in which the immune system is supposed to recognize self vs. non-self.
44
Antigen presentation bridges antigen recognition by
innate immune system to the activation of the adaptive immune system.
45
Antigen presentation is necessary for
T cell-mediated killing, and augments antibody production by B cells.
46
Antigen presentation is
context dependent, allowing the deployment of appropriate immune responses under different conditions.
47
CD8+ T cells are
MHC I restricted and recognize cytosolic proteins
48
CD4+ T cells are
MHC II restricted and recognize extracellular and intravesicular pathogens
49
Multiple receptors on T cells need to be engaged in order to
activate the T cell. Recognition of antigen is not enough.
50
The T cell receptor (TCR) recognizes antigen, but it does not
signal.
51
CD3 and z are non-covalently associated to the
TCR Expression of the TCR, CD3 and z chain are required for antigen recognition and signalling TCR recognizes Ag CD3 and z signal
52
Recognition of antigen (and MHC molecule) in the absence of
co-stimulation fails to activate the T cell. In fact, it leads to anergy of the T cell.
53
Multiple receptors on T cells need to be engaged in order to activate the T cell. Recognition of antigen is not enough.
TCR recognizing antigen CD4 recognizing MHCII CD28 on T cell recognizing B7 molecules on APC LFA-1 on T cell recognizing ICAM-1 on APC Together they are referred to as the immunological synapse
54
Self/Non-self vs. danger
Bacterial products such as those in the adjuvant stimulate the expression of MHC, adhesion molecules, and co-stimulatory molecules in APCs These signals provide T cells with “context” information that may determine the modality of their responses, e,g., tolerance, TH1, or TH2 response
55
Function of co-stimulatory molecules | : Absence of
co-stimulatory molecules, T cell will not be activated (anergy)
56
Function of co-stimulatory molecules | Absence of antigen-TCR interaction, T cell will not be
stimulated.
57
Function of co-stimulatory molecules | Co-reception of
both signals activate T cells
58
Function of co-stimulatory molecules | At the termination of the
immune response, CTLA-4 replaces CD28 and downregulates T cell function
59
B7 Receptors Play a Role in
Activating T cells AND Terminating the T cell Response!!
60
A. CTLA-4 can competitively inhibit
CD28 binding to B7
61
B. CTLA-4, when bound to B7, will actively
block signals from the TCR and from CD28