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PHARM 310 > Cell-Mediated Immunity > Flashcards

Cell-Mediated Immunity Flashcards

1
Q

How do Macrophages use Co-stimulatory signals

A
  1. Macrophage phagocytized bacteria and break them down
  2. Induces expression of MHC class II and B7
  3. T-Cell recognizes the MHC Class II and the antigen presented
  4. T-Cell recognizes the co-stimulatory B7 signal through CD28 receptors
  5. Proliferation and differentiation of T-Cells specific for bacterial protein
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2
Q

MHC Class II
- Where are they found
- What do they form complexes with
- What receptors do they present their antigens to

A

Found in antigen presenting cells

Forms complex with exogenous antigens

Presents antigens to T-Helper Lymphocytes (CD4)

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3
Q

What are the different methods of CD8 T-Cell Activation

A

Autocrine
- Dendritic cells express high amounts of B7 which is recognized by CD28 receptors
- Dendritic cells presents antigen:MHC which is recognized by TCR
- T-cell is activated and releases its own IL-2 driving its own proliferation and differentiation

Co-Stimulatory
- Adjacent CD4 T-Cell is activated by APC
- Which in turn activates APC causing it to secrete B7
- CD8 is then activated, IL-2 is produced

Paracrine
- APC activates CD4 T-Cell, causing it to secrete IL-2
- IL-2 then activates IL-2 receptors on the CD8 T cell

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4
Q

What is B7

A

Once activated APCs express B7, the B7 ligand then riggers CD28 receptors on T-Cells

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5
Q

What is the function of a Helper T-Cell

A
  • T1 Helper Cell: Activates Macrophages using cytokines
  • T2 Helper Cell: Uses cytokines to activate B-Cells so that they differentiate into plasma cells and secrete antibodies
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6
Q

Which Human MHC Class I and Class I Isotypes are monomorphic

A

Class I
- F
- Beta 2 Microglobulin

Class II
- DO

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7
Q

MHC Class II
- Processing and Presentation process of antigens

A
  1. Extracellular material is taken in through endocytosis and phagocytosis (By phagosomes)
  2. This material is then taken into the vesicular system of the cell (Ex. Macrophages)
  3. When the phagosome fuses with a lysosome the proteases and hydrolases break down the proteins to produce peptides
  4. MHC class II are transported into these vesicles through the ER and Golgi apparatus
  5. These peptides are then bound to MHC class II
  6. The Peptide:MHC Class II complex is then transported to the cell’s surface through outgoing vesicles
  7. MHC class II presents peptide at cell surface
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8
Q

What is the CD3 Complex
- What polypeptides make up the complex

A

Facilitates signaling for the T-Cell Receptor
- Gamma
- Delta
- Epsilon
- Zeta

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9
Q

What happens when T-Cell is activated

A
  1. T-Cell synthesizes and secretes IL-2 (For autocrine and/or paracrine action)
  2. This induces T-cell proliferation and differentiation
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10
Q

How many MHC Class I Isotypes are there?
- What are they?

A

6 Isotypes

HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G

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11
Q

What kind of MHC do Kidney cells express

A

Express some Class I

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12
Q

What is the function of a Cytotoxic T-Cell

A

Will kill host cells infected by virus

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13
Q

What response does a T-Cell give if it recognizes the antigen but not co-stimulation

A

Anergy
- A non-responsive state

Helps protect against T-cells recognizing the body’s own tissue

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14
Q

What is the Antigen Processing and Presenting Process

A
  1. Ag processing:
    - Proteins are degraded into peptides
  2. Host cells then sample these peptides
  3. Host cells then assemble a MHC:Peptide complex
  4. Ag Presenting:
    - The MHC:Peptide Complex is the presented on the surface of the host cell
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15
Q

What kind of MHC do Hepatocytes express

A

Express some Class I

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16
Q

What are the 8 polypeptides that make up the whole T-Cell Receptor Complex

A
  • Alpha and Beta make up the main body
  • 2 Zeta on the bottom
  • Delta and Epsilon on the left
  • Gamma and Epsilon on the right
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17
Q
A
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18
Q

Which Human MHC Class I and Class I Isotypes are Polymorphic

A

Class II
- DP, DQ

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19
Q

Helper T-Cell Activation

A

APCs activating CD4 TH1-Cells
- Macrophage activation
- Some B-cell activation
- Production of IgG1 (Opsonizing aby)

APCs activating CD4 TH2-Cells
- B-cell activation and antibody secretion

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20
Q

Structure of a CD4 Cell
- How does the structure help stabilize MHC:TCR binding
- What does it bind to

A

4 Domains, that forms a L shape
- Leans over and binds to β2 domain of MHC Class II to stabilize it

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21
Q

T-Cell Homing Process

A
  1. Circulating Lymphocyte enters the endothelial venule of the Lymphoid tissue
  2. L-Selectin on the lymphocyte binds with addressins (GlyCAM-1 and CD34) on the blood vessel barrier
  3. Lymphocytes starts rolling across the surface of the endothelial cell
  4. Lymphocyte grips other addressin molecules and slowly becomes immobilized
  5. Starts the process of Diapedesis, where the lymphocyte is squeezed between the tissue
  6. Lymphocyte has left the blood circulation and now enters the lymph node
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22
Q

What response does a T-Cell give if it does not recognize an antigen but is co-stimulated

A

No effect on T-cell

For an effect to occur the following needs to happen:
- TCR needs to recognize the antigen and the MHC,
- CD28 needs to receive a co-stimulatory response by B7

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23
Q

What contributes to MHC diversity

A
  • Genetic Polymorphism
  • Meiotic Recombination by inter-allelic conversion
  • Segmental Exchange by Gene conversion
  • Point Mutations
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24
Q

What are the four structural classes of Leukocyte Adhesion Molecules
- What are there functions

A

Selectins
- Found on Leukocytes (Lectins), binds to addressins

Vascular on Endothelial Cells around Lymph Nodes
- Vascular Addressin (Mucin), grips the selectin and pulls in the Leukocyte

Leukocyte Integrin Receptors
- Facilitate cellular movement at the lymph node

Inter-Cellular Adhesion Molecules (ICAMS)
- Makes endothelial vessels more leaky allowing cells to enter the lymph node

CD2: Lymphocyte Antigen (LFA)

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25
Q

How do B-Cells use Co-stimulatory signals

A
  1. B-Cells bind and internalize specific antigens
  2. Once activated B-cells process the antigen and synthesize MHC and B7
  3. Antigen-derived peptides (MHC) are selectively presented on the B-cells surface
  4. B7 is expressed on Cell surface
  5. T-Cells recognize the MHC:Antigen complex
  6. T-Cells recognize the B7 ligand through CD28 receptors
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26
Q

Where are Antigen Presenting Cells

A

Meet and reside in secondary lymphoid tissues

Dendritic Cells: T-Cell Areas
Macrophage: Follicles
B-Cells: Germinal Centres

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27
Q

Where are the alpha and beta chains assembled

A

In the Endoplasmic Reticulum

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28
Q

What do TCRs recognize

A

Recognizes the presented peptide and the MHC molecule
- This co-recognition is called MHC restriction and is highly specific

Specific TCRs are specific for one isotype and for one antigen

T Cell is only activated when it recognizes both the HLA Isotype and the Peptide Antigen

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29
Q

For the TCR polypeptides which locus is located in what other locus

A

Delta locus is located within the Alpha locus

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30
Q

What are the Professional Antigen Presenting Cells
- Order them by importance

A
  1. Dendritic cells
  2. Macrophages
  3. B-Cells
31
Q

What kind of MHC do B-Cells have

A

Express both Class I and Class II

32
Q

How are T-Cells activated by APCs

A

Needs a signal from the Antigen binding to the TCR and a signal from the co-stimulatory receptors (CD28)

33
Q

What are the two primary classes of α:β T-Cells

A

Helper T-Cells (CD4 T-Cell)

Cytotoxic T-Cells (CD8 T-Cell)

34
Q

MHC and Invariant Chains

A
  1. As the MHC Class II moves from the ER to the vesicle the invariant chain blocks binding of peptides to MHC class II
  2. This invariant chain also guides the MHC class II molecule out of the ER
  3. In the vesicle the invariant chain is cleaved, however, a small CLIP fragment remains bound
  4. CLIP blocks any peptides from binding to MHC class II in the vesicles
  5. HLA-DM facilitates the release of CLIP, allowing peptides to bind to MHC class II
  6. MHC class II is then transported by the vesicle to the cell surface where it can then express the antigen
35
Q

What kind of MHC do Red Blood Cells express

A

None

36
Q

Process of Antigen Presentation in Cell Mediated Immunity

A
  1. At the site of infection Dendritic Cells and Macrophages carry antigens from site of infections
  2. Antigens are carried through lymphatics to secondary lymphoid tissues
  3. T-Lymphocytes home in on secondary lymphoid tissues and leave circulation
  4. Antigens interact with T-Lymphocytes
37
Q

How many MHC Class 2 Isotypes are there?
- What are they?

A

5 Isotypes

HLA-DM, HLA-DO, HLA-DP, HLA-DQ, HLA-DR
- The 2 stalks are represented by 2 letters

38
Q

Immature vs Mature APC

A

Immature APC have dew MHC and few B7 Costimulatory Factors
- APCs have innate immune response surface receptors that can recognize foreign microbes

Once these receptors are activated B7 expression is induced and MHC is upregulated

39
Q

Where are MHCs found

A

Major Histocompatibility Complexes are found on every cell except erythrocytes

40
Q

Cytotoxic T-Cell Activation

A

Dendritic Cells and T Helper Cells activate CD8 T-Cells into cytotoxic effector cells
- CD8 cells program apoptosis into target cells through membrane-bound FAS ligand which activates caspase enzymes causing cell death
- CD8 cells release lytic granules like perforins and granzymes that help mediate cell destruction

41
Q

What kind of MHC do Brain cells express

A

Express some Class I

42
Q

Process of Antigen being carried to Lymphoid Tissue

A
  1. Dendritic cells take up bacterial antigens
  2. Then moves into a draining lymphatic vessel
  3. Dendritic cells with the bacterial antigen settle in the T-cell areas
43
Q

What do TCRs interact with?

A

Major Histocompatibility Complex
- MHC bind to Peptide Antigens and present them to TCRs

44
Q

What kind of MHC do epithelial cells of the thymus have?

A

Express majority Class Ii and a tiny bit of Class I

45
Q

What are effects of different MHC isotypes

A

Changes the range of peptides they bind and the extent of genetic polymorphism

46
Q

What is the function of a CD Glycoprotein

A

CD4 and CD8 Co-receptors help stabilizes the interaction between MHC and TCR

47
Q

MHC and Autoimmunity

A

When no infection is present the only peptides that MHC Class I carry from the cytosol are from self-proteins
- Usually does not provoke an immune response (T-Cell Negative Selection in the Thymus)

Sometimes self-tolerance fails causing autoimmune disease

48
Q

Interallelic Conversion vs Gene Conversion

A

Interallelic Conversion:
- Recombination of alleles on the same gene

Gene Conversion
- Segmental exchange of alleles on different genes

49
Q

MHC Class I
- Where are they found
- What do they form complexes with
- What receptors do they present their antigens to

A

Found in all nucleated cells

Forms complex with endogenous antigens

Presents antigens to Cytotoxic T-Lymphocytes (CD8)

50
Q

Do MHC proteins have high or low polymorphisms
- What causes this?

A

MHC protein products are highly polymorphic due to many possible combinations of multiple genes and alleles

51
Q

Process of Inhibition of T-Cell Activation

A

CTLA4 and CD28 are both expressed by T-cells
- CTLA4 binds 20 times more strongly to B7 than CD28

CTLA4 binding inhibits B7 activation and prevents proliferation of T-cells

52
Q

Function of Antigen Presenting Cells

A

Present Antigens to naive T-Cells using surface co-stimulatory CD glycoproteins (B7)

53
Q

What is MHC incompatability

A

The leading cause of tissue graft rejection and graft-versus-host disease

54
Q

What does IL-2 do to T-cells

A

Activates them by binding to high affinity IL-2 receptors
- Inducing T-cell proliferation

55
Q

Structure of a CD8 Cell
- How does the structure help stabilize MHC:TCR binding
- What does it bind to

A

Two stalks (α and β) that are disulfide bonded together
- Line up with β2 Microglobulin and binds to α3 domain of MHC Class I

56
Q

Which Human MHC Class I and Class I Isotypes have few polymorphism

A

Class I
- E, G

Class 2
- DM, DO, DR

57
Q

What kind of MHC do T-Cells have

A

Resting T-Cells only have Class I

Activated T-Cells express Class I and a tiny bit of Class II

58
Q

MHC Class I
- Processing and Presentation process of antigens

A
  1. Intracellular antigen is processed by proteasome into peptides
  2. Transporter TAP moves peptides into the Endoplasmic Reticulum
  3. Peptides bind to MHC Class I in the ER
  4. Peptide:MHC class I complex is then transported to the cell surface through the Golgi apparatus
  5. MHC class I presents peptide at cell surface
59
Q

What contributes to TCR diversity

A

Genes that encode for the alpha and beta chains are fragmented in a germline configuration
- RAG enzymes rearrange gene segments to produce diversity and a highly specific receptor

60
Q

What kind of MHC do Macrophages have

A

Express both Class I and some Class II

61
Q

What Co-Receptors is specific for each MHC class

A

CD8 is specific to Class I
CD4 is specific to Class II

62
Q

What kind of MHC do Neutrophils express

A

Express only Class I

63
Q

What are the two classes of MHCs

A

Class I: Expressed on all nucleated cells

Class II: Found on antigen presenting cells of the immune system
- Thymus Epithelial Cells
- Lymphocytes
- Professional Antigen Presenting Cells

64
Q

Structure of MHC Class I Molecule

A

1 Protein Chain forms the peptide binding groove
- α1, α2, α3

Protein Chain is stabilized by β2 Microglobulin

65
Q

What are the two types of TCR

A

Alpha:Beta
Gamma:Delta
- Cancer Surveillance
- Determining friend and foe

T-Cells only one express on or the other

66
Q

What is the specificity of MHC?

A

Degenerate Peptide Binding Specificity
- Can bind a large range of peptides

MHCs are not receptors, they are just molecules with a peptide binding groove

67
Q

Which Human MHC Class I and Class I Isotypes have high polymorphism

A

Class I Isotypes:
- A, B, C

Class II Isotypes:
DR Beta

High amounts of specificity, can bind to a lot of derived antigens

68
Q

What kind of MHC do Other Antigen Presenting Cells have (Dendritic Cells)

A

Express both Class I and Class I

69
Q

What is the general structure of a TCR

A

Constant and Variable regions

2 Polypeptide chains that are disulfide linked
- alpha and beta chains (1 binding site)

70
Q

What facilitates the Homing process of naive T-cells to tissues

A

Leukocyte Adhestion Molecules

71
Q

TCRs vs BCRs

A

T-Cell Receptors recognize antigens presented to them from MHCs

B-Cell Receptors will bind to epitopes from antigens
- Proteins, Carbohydrate, Lipids (Macromolecules)
- Surface of organisms, soluble toxins

72
Q

What do B-Cells Express?
What do T-Cells Express

A

B-Cells:
- Surface Immunoglobulin (BCR)

T-Cells:
- T-Cell Receptor (TCR)
- Cluster of Differentiation Glycoprotein
(CD4 and CD8 that stabilize MHC)
- CD28 and CTLA4 (Receptors that receive co-stimulatory signals)

73
Q

Structure of MHC Class II Molecule

A

2 Protein Chains form the peptide binding groove
- α1, α2, β1, β2

PHARM 310 (8 decks)

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