L2 - Cells of the Immune Sytem

8/7/2019 L2 - Cells of the Immune Sytem

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Immunology

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All of the cells in the immune system are derived from haematopoietic stem cells

These cells are self-renewing, a process which takes place in the bone marrow

The bone marrow is known as a primary lymphoid organ

Primary lymphoid organs are the organs where cells of the immune system are generated and differentiate.

Bone marrow (particularly long bones)

Thymus ± a small, bi-lobed organ found in the chest

Haematopoietic stem cells give rise to two different lineages of cells

M yeloid lineage (a stem cell)

Lymphoid lineage (a stem cell)

The Cells



Immunology

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Dendritic cellscan have either myeloid or lymphoid lineage

They are the main antigen-presenting cells (APCs)

Erythroid progenitor cellspred blood cells

Red blood cells carry oxygen, not important for the immunology course

M egakaryocytespplatelets

Platelets are not really cells; they are fragments of megakaryocytes (they have no nucleus)

Platelets are involved in blood clotting and inflammation

Platelets also release a number of chemoattractants when activated

Promote release of lymphocytes from blood p area of infection

Also increase vascular permeability ± the tight junctions between cells are loosened

M onocytespmacrophages

M onocytes have a distinctive kidney shaped nucleus

They are found in the bloodstream

M acrophages are found in tissues

Derived from a granulocyte-monocyte progenitor

M acrophages have two main functions

Removal of particulate material by phagocytosis

Presentation of antigens

M acrophages can ingest particulate material as well as

bacteria.They can then digest them.

Neutrophils also take up and digest microorganisms

Also derived from a granulocyte-monocyte progenitor

Very efficient at killing bacteria

Granules fuse with the phagosome, resulting in its components being deposited to the exterior

Granulocytes - Neutrophils(95%), eosinophils (~5%), mast cells (n/a)and basophils(0.2%)(%in blood)

All contain secretory vesicles

All have their own specific progenitors

Named on their dye staining properties

Called granulocytes as their cytoplasm is full of secretory granules, containing various mediators that can be

released from the cell by exocytosis

Neutrophils are predominant in the blood



Immunology

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They all have a lobed nucleus (polymorphonuclear ± P M N cells)

M ast cells are similar to basophils

Not found in the blood stream , found in tissues, especially mucosal tissues and skin

Same precursor as basophils, however during differentiation there is a split between the two

Both are involved in allergic responses

The granules contain a number of mediators that stimulate the affects of allergy when released

Contraction of smooth muscle (causes wheezing in asthma)

Vasodilation

Inflammation

Some mediators are involved in clearing parasites from the gut

Eosinophils contain a lot of toxic molecules

Good at killing organisms that are too big to be phagocytosed

e.g. a parasitic worm, many times larger than the cell

Granule components are deposited onto the surface of the parasite

M acrophages, neutrophils and eosinophils are the cytotoxic myeloid cells

Basophils are not cytotoxic, they release inflammatory mediators as well as cytokines

The growth factors that drive the immune response in a certain way

If a bacterium is coated with antibodies it is said to be opsonised



Immunology

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The same goes for the complement. Bacteria can also be coated with complement molecules

If the organism has an appropriate antibody for an antigen, it will bind to it. The antigen will be coat ed with

antibodies. The majority of the myeloid cells have receptors for antibodies, known as FC receptors. They also

have receptors for complement molecules.

When an organism is coated with these soluble components the uptake of the bacteria by phagocytosis is

enhanced. The increase in uptake efficiency is more than 1000×. Receptor mediated phagocytosis.

Antigen Presentation:

Antigen presentation is essential for priming an immune response

A part of the antigen is captured by phagocytosis

The bacterium is destroyed in a phagocytic vacuole

It contains proteases etc.

Parts of the antigen are then presented

B-cells, amongst others do this

Differentiation into more specialised cells is dependent on specific growth factors called cytokines

Hormones that operate over a short distance

Also control cell behaviour

Natural Killer Cells (NK Cells) ± very good at recognising when one of our own cells is infected or abnormal.

This can be carried out without prior exposure (innate immune system)

It will then kill this cell

Similar to cytotoxic T-cells

T Helper Cell (T H Cell)

See later

Cytotoxic T-Cell (T C Cell)

Similar to natural killer cell

Good at recognising abnormal / infected cells

T-Cell receptor (TCR) recognises antigens displayed on the surface of our cells

When cells are infected with a pathogen, antigens are displayed on the surface of that cell

The TCR recognises the antigen as well as the receptor ( M HC) that is displaying it

It will kill infected / abnormal cells

M HC = M ajor Histocompatability Complex

A locus that has a cluster of genes that regulate how we make immune responses



Immunology

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M HC Class I

Expressed on surface of all nucleated cells (almost all cells, not red blood cells)

Dimers

Display antigens ± if cell is infected then cell will µflag¶ its abnormality

M HC Class II

Found on antigen presenting cells only

Also present antigens (dendritic cell, macrophage etc.)

Dendrite takes in bacteria

Breaks it down into fragments such as small peptides

The antigen fragments are bound to M CH class II in a small compartment

They are then displayed on the surface

Other cells in the immune system then recognise the M HC II + antigen complex

Specifically it is recognised by helper T-cells (T H )

U pon interaction, the T H becomes activated

The T H will then stimulate other cells in the immune system to become activated

It helps B-cells to differentiate into plasma cells and make antibodies

This is why it is called a helper cell, it helps B-cells to make antibodies

The M HC system is polymorphic

We all have a set of M HC class I / II proteins that differs between us

They are crucial for stimulating immune responses so people react in different ways to pathogens

Some people can display antigens better than others

This polymorphic system produces an immunologically diverse population, and is beneficial to the population

as it makes some people more likely to be able to respond to new pathogens.

If everyone reacted in the same way then a new pathogen could go through the entire population, killing

everyone.

M HC classes need to be taken into account when carrying out organ transplants

The M HC class I proteins are the targets for tissue rejection

The cytotoxic T-cells will recognise that the foreign tissue is foreign

The cells will be killed

L2 - Cells of the Immune Sytem

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