WEEK 3: T CELL MEDIATED IMMUNITY

Question 1

What are the functions of T-cells?

Answer 1

*They carry out T-cell mediated immunity.
*They defend the body against invaders that hide inside the cells where antibodies and complement systems cannot reach them.

Question 2

Outline the 3 types of T-cells.

Answer 2

*Helper T cells (CD4+)
*Cytotoxic T cells (CD8+)
*Regulatory T- cells (T regs), (CD4+ + CD25+ T-cells)

Question 3

Describe the functions of the different T cells.

Answer 3

*Cytotoxic T cells: They destroy the host harboring anything foreign.
-Associated with CD8 coreceptor.

*Helper T cells: They modulate activities of other immune cells; they activate macrophages and lymphocytes.
-Associated with CD4 coreceptor.

*Regulatory T cells: They are small subset of CD4+ T cells but have an additional CD25 coreceptor, hence called CD4+ + CD25+ T cells

Question 4

Describe the action of a cytotoxic T cell on lysing a virus invaded cell.

Answer 4

1.Virus invades a host cell.

2.The viral antigen is displayed on the surface of the host alongside the cell self-antigen.

3.Cytotoxic T cells recognizes and binds with a specific foreign antigen in association with the self-antigen

4.The cytotoxic T cell releases chemicals that destroy the attacked cell before the virus can enter into the cell’s nucleus and start to replicate.

5.The virus is then released into the ECF where it is destroyed by phagocytic cells, neutralizing antibodies and the complement system.

Question 5

Describe the mechanism of killing by killer cells.

Answer 5

1Killer cell binds to its receptor on target cell.
2.Their perforin containing granules fuse with the plasma membrane.
3.Granules disgorge their perforin by exocytosis into a small pocket intercellular space between the killer cell and its target.

4.On exposure to the CALCIUM IONS in this space, individual perforin molecules change from spherical to cylindrical shape.

5.Remodeled perforin molecules bind to the target cell like stares of a barrel to form a pore.

6.The pore will allow salt and water to enter into the target cell which will swell up and burst.

Question 6

Outline the role of Helper T cells.

Answer 6

They secrete IL-4,5,6 that serve as B-CELL GROWTH FACTOR and contribute to B cell function.

They also secrete T-cell growth factor (IL-2) which augment the activity of cytotoxic T cells.

They secrete chemokines that lure macrophages and neutrophils to the site of infection.

They secrete MACROPHAGE INHIBITING FACTOR which keeps the large macrophages in the region of invasion and inhibit them from leaving.

They secrete IL-5 which activates eosinophils and promote development.

They secrete Il-4 which promotes the development of IgE antibodies for defense of parasitic worms.

Question 7

Describe how HIV affects the immune system.

Answer 7

*HIV selectively invades the CD4+ T-cells and destroy the cells that normally compose much of the immune response.

*It also invades macrophages.

*Enters some brain cells resulting in dementia.

Question 8

Describe how HIV affects the immune system.

Answer 8

*HIV selectively invades the CD4+ T-cells and destroy the cells that normally compose much of the immune response.

*It also invades macrophages.

*Enters some brain cells resulting in dementia.

Question 9

Outline the 4 main types of Helper T cells and their function.

Answer 9

1.T Helper 1 cells: Rally cell mediated cytotoxic T cell response for infections by microbes in the ICF.
-Helps macrophages to suppress intracellular infections.

2.T Helper 2 cells: They promote antibody -mediated immunity by B cells and eosinophil activity.
*Helps basophils, mast cells, eosinophils and B cells respond to parasite infections.

3.T Helper 17 cells:
-They produce IL-17
-They promote inflammation
-Enhance the neutrophil response to fungal and extracellular bacterial infections
-They are effector molecules in the development of inflammatory autoimmune diseases, such as multiple sclerosis.

4.T Follicular Hepler cell (TFH)
-They interact with B cells in the lymph node to help secrete antibodies on response to T dependent antigens.

Question 10

Name the cytokines that promote the formation of the different Helper T cells.

Answer 10

*IL-12: Drives naive T-cells specific for antigen to become Helper 1 T cells.

*IL-4: Favours development of naive T cells into T Helper 2, T Helper 17 and T Follicular Helper cells

Question 11

Describe the role of regulatory lymphocytes.

Answer 11

*They suppress immune response
*They inhibit both innate and adaptive immunity in a check and balance fashion to minimize harmful immune pathology.

Question 12

Name the substance found in regulatory T cells that allows them to suppress other cells and stimulate the T cells to become regulatory T cells.

Answer 12

FOXp3

Question 13

Outline the examples of antigen presenting cells under these classes.

1.Phagocytic
2.Pinolytic

Answer 13

1.Macrophage, Microglial cells, Kupffer cells
2. Cells of Langerhans, Dendritic cells and B-cells.

Question 14

How do APCs work? Dendritic cells as example.

Answer 14

1.Receptor-mediated endocytosis

-Capture bacteria and virus particles from the extracellular fluid; target them for processing in the lysosomes.

• This internalization mechanism - micropinocytosis (small volumes of extracellular fluid internalized).

2.Macropinocytosis

-nonspecific ingestion of larger volumes of extracellular fluid.
-Captures pathogens not recognized by any endocytic
receptor.
-Antigens captured enter the endosomal system, where they are processed into small peptides.

3.Cross-presentation

• Viral particles taken up by the ‘class II’ pathways can be delivered to the cytosol for processing and presentation to CD8 T cells
  -Antigens taken up by one dendritic cell can be delivered to a second dendritic cell for presentation to CD8 T cells

Question 15

Differentiate between a lysosome and an endosome.

Answer 15

1.Lysosomes, on the other hand, are primarily involved in the degradation of macromolecules. …. membrane bound vesicle containing degrading hydrolytic enzymes.

2.Endosomes relates to the transportation of extracellular material into the intracellular domain.

*Endosome refers to a vesicle/vacuole formed by the invagination and pinching off of the cell membranewhile lysosome is an organelle in the cytoplasm of.

Phagocytosis is a form of receptor-mediated endocytosis.

Question 16

NOTE: T lymphocytes only respond to antigens presented to them by APC.

Question 17

What is an MHC molecule/ self-protein?
What is a major histocompatibility complex?

Answer 17

*These are plasma bound glycoproteins.
*A group of genes that direct the synthesis of self-antigens.

Question 18

State the 2 types of MHC molecules.

Answer 18

*Class I MHC molecules
*Class II MHC molecules

Question 19

How many MHC class I molecules andMHC class II molecules does a human express on his or her cells?

Answer 19

A human typically expresses six different MHC class I molecules andeight different MHC class II moleculeson his or her cells.

Question 20

Describe the Class I MHC molecules.

Answer 20

*Are found in the surface of all cells

*They are recognized by Cytotoxic T cells

*The CD8 coreceptor links the Cytotoxic T cell and the Class MHC molecule together.

*Contain a heavy chain, non-covalently associated with an invariant molecule β-microglobulin.

Question 21

Describe the Class II MHC molecules.

Answer 21

*They are found on the surface of immune cells that the helper T-cells interact with.

APCs: [ Dendritic cells, macrophages and B-cells.])

*They are recognized by the helper T cells (CD4+)

*CD4 coreceptor links the two together.

*To be activated, helper T cells must bind with a class II MHC bearing APC (dendritic cell, or macrophage)

-To activate B cells, the helper T cells must bind with a class II MHC bearing B- cell with displayed foreign antigen.

Question 22

Describe how a dendritic cell becomes an APC when it engulfs a bacterium.

Answer 22

1.Dendritic cell engulf a bacterium

2.Large molecules of the engulfed bacterium are broken down by lysosomes to produce antigenic peptides.

3.New MHC molecules have been synthesized by endoplasmic reticulum-Golgi complex.

4.Antigenic peptides bind to newly formed MHC molecules.

5.Antigen is displayed on cell surface bound to MHC molecule.

*The cell is now an antigen presenting cell.

Question 23

How are normal body cells prevented from lethal immune attack of cytotoxic T cells?

Answer 23

The cytotoxic T cells only bind to the MHC self-antigens which in the prescence of a foreign antigen.

Question 23

How are normal body cells prevented from lethal immune attack of cytotoxic T cells?

Answer 23

The cytotoxic T cells only bind to the MHC self-antigens which in the prescence of a foreign antigen.

Question 24

Describe antigen processing for presentation to CD4+ T cells (Class II processing pathway-exogenous pathway)

Answer 24

*Pathogens endocytosed into endocytic vesicles either through pattern recognition molecules (PRR), Fc receptors (FcR), directly by endocytosis, or by surface antibody receptor in the case of B cells.

*The acidified endocytic vesicles contain endopeptidases break down peptides into linear lengths of 10–20 amino acids.

Meanwhile, MHC class II molecules, produced within the endoplasmic reticulum, have invariant chain bound into their peptide-binding sites.

This chain is enzymatically degraded to leave a smaller protein, CLIP, in the binding site. The vesicle containing MHC class II molecules with CLIP then buds off from the endoplasmic reticulum. An HLA-DM molecule attached
to the MHC molecule induces removal of CLIP.

On fusion with a vesicle containing antigenic peptides, HLA-DM facilitates their loading onto the binding sites now free of CLIP molecules.

The fused vesicles traffic to the cell surface, where they
fuse with the plasma membrane, displaying the MHC–peptide complex to CD4+ T cells

Question 25

Describe Antigen processing for presentation to CD8+ T cells (Class I processing pathway-endogenous pathway).

Answer 25

*Viruses and other microbes enter nucleated cells and escape into the cytosol where they reproduce

*Through endopeptidase activity the viral proteins are broken up into peptides, 8–10 amino acids in length in the proteasome and then transported into the endoplasmic reticulum through a channel formed by TAP1 and TAP2

Meanwhile, MHC class I molecules are assembled together with other proteins (such as tapasin to aid assembly) within the endoplasmic reticulum (ER)

(e) The transported linear peptides then attach to the binding site on the α chain of the MHC class I molecule. Vesicles pinch off from the ER containing the MHC–peptide complex and traffic to the cell surface, fuse with the plasma membrane to

(g) Display the peptide to specific T cells.

Question 26

What are proteasomes?
Where are they found?

Answer 26

*Proteasomesare protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds.

*Proteasomes are presentin the cytoplasm and in the nuclei of all eukaryotic cells.

Question 27

Describe the activation of helper T cells by antigen presentation.

Answer 27

1.A bacterium is taken up by phagocytosis and degraded in a lysosome.

2. Bacterial antigenic peptides are displayed on APC cell surface bound to Class II MHC molecules and are presented to T cells with TCRs that recognize the antigen.

3.APC secretes interleukins, which activate T cell.

4.Activated T cell secretes cytokines, which stimulate T cell to proliferate to expand clone of selected cells.

5.Cloned helper T cells are ready to activate B cells and enhance other immune activities.

Question 28

Describe the activation of B-cells responsive to T-dependent antigen.

Answer 28

1.The BCR binds to the antigen on the helper T cell.

2.2The antigen is internalized by receptor mediated endocytosis and its macromolecules degraded

*Antigenic peptidases produced are displayed on cell surface bound as class II MHC molecules

3.TCR of a helper T cell recognizes specific antigen on B cell, and CD4 coreceptor links the two cells together.

4.Helper T cell secretes interleukins, which stimulate B cell proliferation to produce clone of selected B cells.

5.Some cloned B cells become Plasma cells and secrete antibodies while the others become memory cells.

Question 29

Describe the direct activation of Cytotoxic T cells.

Answer 29

Dendritic cells infected with some types of viruses can activate a naive Virus specific T cell on their own.

1.The dendritic cell sends a sufficiently strong signal to activate the CD8+ T cell to effector status.

2.Activated Virus-specific CD8+ T-cell makes IL-2, driving its own PROLIFERATION and DIFFERENTIATION.

Question 30

Describe the activation of Cytotoxic T cells by T helper cells.

Answer 30

1.Dendritic cells infected with same virus activate virus specific CD4+ T cells to secrete IL-2 and the virus specific CD8+ to express IL-2 receptors.

2.IL-2 from the CD4+ T cell drives the proliferation of differentiation of the virus specific CD8+ T cells.

Question 31

Describe the differentiation of the alpha-beta T cell precursor.

Answer 31

It divides into two main components:
*CD4+ T: T helper 1, 2,17 and Treg
*CD8+ T: CTL