THE IMMUNE SYSTEM

operates on a series of biological structures and processes which help protect the body from foreign molecules through the following steps:

1. Recognition

The immune system differentiates between self and non-self molecules.

Identifying self

Natural Killer cell

=)

T cell

=)

A self marker (MHC) labels the body's cells as a 'friend' and are tolerated by the immune system.

Identifying non-self

Natural Killer cell

=(

T cell

An antigen is a molecule that the immune system recognises as a foreign (non-self) and treats as a 'foe'.

2. Activation

After the immune system successfully recognises harmful invaders, it will activate white blood cells to ingest or kill the foreign substance.

The 5 main immune cells involved in activation are:

YY

Y

Natural Killer (NK) cells

Y

Killer T cells

Y

Macrophages

Y

Eosinophils

Antibodies

Natural Killer Cells

They are innate immune cells that kill foreign substances directly without prior stimulation.

Granule-dependent killing

1. NK cell binds to cancer cell via receptors and ligands.

YY

Y

Receptor

Ligand

Cell surface complex

NK cell

Cancer cell

Killing by death ligands

TNF Release

The cell receptors and ligands come into contact and initiate apoptosis directly.

Perforin

2. Perforin secreted by the NK cell makes holes in the cell membrane and granzymes enter the cancer cell.

Granzyme

Y

YY

Hole formation

3. Infected cell is then destroyed.

Y

YY

Destroyed

Killer T Cells

They are one of the major components of the adaptive immune system. Their roles include directly killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response.

1. Killer T cell binds to cancer cell via receptors and ligands.

Cell surface complex

Y

Foreign antigen

Killer T cell

Cancer cell

2. Perforin secreted by the killer T cell makes holes in the cell membrane and granzymes enter the cancer cell.

Y

Hole formation

3. Infected cell is then destroyed.

Y

Destroyed

Macrophages

A macrophage is a large white blood cell that has the ability to locate and 'eat' particles, such as bacteria, viruses, fungi, and parasites. They are born from white blood cells called monocytes.

1. The macrophage interacts with the pathogen.

Y

Receptor

Surface proteins

2. The macrophage then envelopes the pathogen.

Y

3. The pathogen is then digested.

Y

Phagosome

4. The pathogen is then broken down into proteins and other molecules, with the formation of the Major Histocompatibility Complex (MHC).

MHC and antigen

5. It then presents the antigens with the MHC on the cell surface to other immune cells such as T cells.

Eosinophils

Eosinophils are a specific type of white blood cell that protect the body against certain kinds of germs, mainly parasites.

Antibodies

Antibodies are specific Y-shaped proteins which can flag pathogens or neutralise its target directly. They are part of the adaptive immune system.

1. Interaction between the receptor and immunoglobulin triggers the release of granular proteins.

Receptor

Immunoglobulin E/G

Y

Eosinophil

Granular proteins

2. Release of granular proteins directly damage the worm.

Flagging

1. Antibody binds to antigens on surface of cancer cell.

2. Antibody sends out signals (amplified) to other immune cells to attack the cancer cell.

Neutralisation

1. Antibodies prevent viruses from attaching to healthy cells.

Healthy cell

2. If attached, antibodies also promote detachment from healthy cells.

Healthy cell

3. If virus is able to get attached to healthy cell and enter it, the antibody is able to stop the virus from fusing its membrane with the healthy cell and releasing toxins into the cell.

3. Regulation

Regulatory T cells (Treg) are the master regulatory cells and serve as the brakes of the immune system by suppressing it when the pathogen is cleared.

Exerts suppressive effects through 4 mechanisms:

Note: effector cells are immune cells involved in defending the body, such as killer T cells and B cells.

1. Suppression by inhibitory cytokines

Inhibits effector cells such as killer T cells to stop

Regulatory T cell

Inhibitory cytokines

Inhibits

Y

Killer T cell

2. Suppression by cytolysis

Kills effector cells via Granzyme and Perforin production

Regulatory T cell

Granzyme

Perforin

Killer T cell Apoptoses

3. Suppression by metabolic disruption

Produces metabolites to increase the likelihood of suppression

IL-2 receptor

Regulatory T cell

IL-2 cytokine

Y

IL-2 receptor

Killer T cell

Free cytokines in the body activates Treg cells rather than killer T cells due to higher levels of expression of the IL-2 receptor by the Treg cells.

4. Suppression by modulation of dendritic cell maturation/function

CTLA-4 receptor

CD80, CD86 receptors

Dendritic cell

Regulatory T cell

Naive T cell

CTLA-4 receptor on regulatory T cells interact with the receptors on dendritic cells, preventing them from activating naive T cells.

4. Resolution

Once the immune cells halt their action, the white blood cells then self destruct and the body retains memory cells to ensure it is better prepared to respond to the same foreign substance in the future.

Naive T cell

Memory T cell precursor

Memory T cell

Effector T cell

Cell death

One model for memory T-Cell formation proposes that the precursor cells that give rise to memory T Cells and effector T Cells both arise independently from naive T Cells

Naive T cell

Pathogen encounter and cell division

In another model, a subset of effector cells gives rise to memory T Cells

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