T Cells And Cell Mediated Immunity

Front 1

What is Cell Mediated Immunity?

Back 1

Immune response that does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

Front 2

What are some key features of cell mediated immunity?

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- For immunity to be transferred to other inbred animals by cells it requires direct contact between cells and the infection
- Provides help for the development of humoral immunity

Front 3

What is humoral immunity?

Back 3

The aspect of immunity that is mediated by macromolecules (as opposed to cell-mediated immunity) found in extracellular fluids such as secreted antibodies, complement proteins and certain antimicrobial peptides.

Front 4

What are some key features of humoral immunity?

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- Immunity that can be transferred to another inbred animals by antibodies
- Involves B cells which recognise antigens due to receptors on their surface when they bind to the antigen
- Provides protection against extracellular microbes e.g. Things outside the cells.
- It may also be affective against viruses before they enter the cells.
- It is part of the adaptive immune response.
- Main component is immunoglobulin

Front 5

In cell mediated immunity and in certain instances not only are CD4 and CD8lymphocyte responses desired but what else is specifically targeted?

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It may be more advantageous to specifically target Th1 or Th2 responses

Front 6

How does cell mediated immunity decide which cells to target?

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The cell that is targeted is determined by thepresence of the foreign protein in association with MHC class I molecules.

Front 7

What is the role of CD4 cells?

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Directors of theimmune response – interact with foreign antigen expressed with MHC class IImolecules and then provide soluble or membrane bound signals for B cells,macrophages or CD8 T cells to help them obtain their full effector cellfunctions

Front 8

Cell mediated immunity is a function of two distinct T cell populations- what are these?

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T helper cells and cytotoxic T cells

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What is the role of T helper cells?

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They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses.

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What is the role of cytotoxic T cells?

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A cytotoxic T cell is a T lymphocyte that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways. They directly kill cells infected withintracellular microbes. ·

Front 11

What are B cells?

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Responsible for producing antibodies

Front 12

How do B and T cells Differ?

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Unlike B cells, T cells need to interactdirectly with the cells that they are going to kill / help.

Front 13

What are T lymphocytes?

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- Derive their name from the thymus

- Like B lymphocytes, they have membrane receptorsfor antigen.

- Unlike membrane bound antibody, the T-cellreceptor recognises antigen only when associated with MHC molecules- they canonly recognise the antigen when it is being presented.

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What is the Major Histone Compatibility complex?

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A set of cell surface molecules encoded by a large gene family which controls a major part of the immune system in all vertebrates.

Front 15

What is the role of the Major Histocompatibility complex?

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The T Cell receptor interacts with an antigen only when afragment of the antigen is on the surface of a cell bound to a MHC molecule. As far as the TCR is concerned there are twoimportant classes:- MHC class I (found on all nucleated cells)- MHC class II (found on specialised antigen presenting cells)

Front 16

What is the thymus and what is its role?

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A lymphoid organ situated in the neck of vertebrates which produces T-lymphocytes for the immune system. The human thymus becomes much smaller at the approach of puberty.

Front 17

How are T cells derived?

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Derive from the bone marrow and migrateto the thymus where 99.9% of them are killed off
-Aselection process kills off all of the T cells with the potential to attacktheir own tissues e.g. Type 2 diabetes, thyroid disease, lupus, rheumatoidarthirits are all auto immune diseases.

- In the thymus the T cells take on characteristicsto be able to kill foreign bodies and react with antigens.

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How are T cells activated?

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1) Microbe is present in body

2) This activates dendritic cells or macrophages (APCs)

3) The microbe is presented on the cell surface via MHC class 2 molecules - this is part of the humoral response

4) T helper cells are then activated from here creating an adaptive response

5) Antigen specific T cells are primed and Cytokines are released leading to the activation of T killer cells to kill the infection

Front 19

What are T cell Receptors?

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- Each T cell has a surface two-chain moleculethat interacts with antigen known as a receptor
- The T cell receptor is clonally distribute –thus when the T cell recognises an antigen it rapidly divides producingdaughter cells all of which produce the same antibody·

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What are accessory molecules?

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- The T cell receptor (TCR) is expressed on thesurface with accessory molecules (CD4 or CD8) - T cells are either CD4 positive/ negative or CD8positive / Negative
- In the blood the ratio of CD4 + : CD8 + cells is2:1

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What are CD4 and CD8 molecules?

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CD4 and CD8 molecules are adhesion molecules that help to tighten the binding of T cell receptors to antigen presenting cells.

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What is the co-receptor and MHC restriction of T helper cells?

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Co receptor: CD4

MHC Restriction: ClassII, as Class II Only found on specialisedantigen presenting cells e.g. Macrophages and dendritic cells

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What is the co-receptor and MHC restriction of cytotoxic T cells?

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Co receptor: CD8

MHC Restriction: Only bind to antigens that have been presented by class 1 MHC molecules. These are on every molecule / cell in the human body apart from RBC.

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How do cytotoxic T cells recognise infection?

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- Peptides from the intracellular microbe arepresented on the infected cell surface of MHC class I molecules ·
- This marks the cell as being infected andenables the T cells to recognise it and target it

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Through which two mechanisms do cytotoxic T cells kill infected cells?

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1. Release of lytic granules containing perforinand granzymes

2. Interaction of FasL with Fas on the TC cell andthe target cell.

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What happens to any cell in the body following antigen presentation?

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- ERis a membrane bound organelle within which the MHC molecules are embedded –these bind to the peptides of the microorganism.
- This complex then goes off to the golgi and budsoff where it fuses with the membrane.
- It opens and what is inside is then released outside.
- Thecytotoxic T cell bound to the infected cells triggers a rise in calciumgranules.

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How do T helper cells work?

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These express CD4.

They interact with the cells which express MHCclass II (they are a lot more restricted in the types of cells that they caninteract with) · Theyproduce cytokines which activate or modulate the functions of other cells ofthe immune system e.g. B cell class switching on proliferation

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There are two specific types of T helper cells that help tailor theimmune system further to create a particular type of response, what are they?

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Th1: Inflammatory and act when there is a lot of tissue damage. They lead to the activation of macrophages and the production of IFN gamma and TNF alpha

Th2: Involved in humoral Immunity. They lead to the activation of B cells IL-4, IL-5 and IL-6 they produce different cytokines in order to do this.

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How do T cells Differentiate in the thymus?

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- Several consequences of T celldifferentiation in the thymus
- T cells emerge from the thymus that recognise antigen only when associatedwith MHC molecules this is known as MHCrestriction
-T cells emerge that do not respond to self components (They are self tolerant). This is referred to as thymic education

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What are super antigens?

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Class of antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system.Superantigens can activate cells irrespective of the TCR specificity.

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In what infections may super antigens be produced?

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- Staphylococcal and streptococcal infections leading to TSS.
- May also be involved in food poisoning, scarlet fever, rheumatic fever, arthiritis and sudden infant death syndrome.

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How do super antigens work?

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They bind to different regions of the MHC and the positive cell receptor ·
- Upto 0.5% of the cells are activated and the response it much bigger.
- It is not the infection that causes the damage – it is the process that does

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How does TSS cause cytokine production?

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- Clinical manifestation of TSS are a consequenceof massive cytokine production
- IL-1 and TNF alpha are involved in the acutephase response and fever ·
- TNF alpha activates the vascular endothelium andvascular permeability- fluids leak from the vascular space leading tohypertension, shock and multiple organ failure.