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Immunology Cells of the Immune System

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


 Myeloid lineage (a stem cell)
 Lymphoid lineage (a stem cell)

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Immunology Cells of the Immune System

The Cells

Dendritic cells can have either myeloid or lymphoid lineage


They are the main antigen-presenting cells (APCs)

Erythroid progenitor cells  red blood cells


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

Megakaryocytes  platelets
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  area of infection
Also increase vascular permeability – the tight junctions between cells are loosened

Monocytes  macrophages
Monocytes have a distinctive kidney shaped nucleus
They are found in the bloodstream

Macrophages are found in tissues


Derived from a granulocyte-monocyte progenitor
Macrophages have two main functions
 Removal of particulate material by phagocytosis
 Presentation of antigens
Macrophages 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

(% in blood)
Granulocytes - Neutrophils (95%), eosinophils (~5%), mast cells (n/a) and basophils (0.2%)
All contain secretory vesicles
All have their own specific progenitors
Named on their dye staining properties

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Immunology Cells of the Immune System

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
They all have a lobed nucleus (polymorphonuclear – PMN cells)

Mast 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

Macrophages, neutrophils and eosinophils are the cytotoxic myeloid cells

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Immunology Cells of the Immune System

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
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
coated 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 (TH Cell)


See later

Cytotoxic T-Cell (TC 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

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Immunology Cells of the Immune System

 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 (MHC) that is displaying it
It will kill infected / abnormal cells
MHC = Major Histocompatability Complex
A locus that has a cluster of genes that regulate how we make immune responses

MHC 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 ‘flag’ its abnormality

MHC 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 MCH class II in a small compartment
They are then displayed on the surface

Other cells in the immune system then recognise the MHC II + antigen complex
 Specifically it is recognised by helper T-cells (TH)
 Upon interaction, the TH becomes activated
 The TH 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 MHC system is polymorphic


We all have a set of MHC 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.

MHC classes need to be taken into account when carrying out organ transplants
The MHC class I proteins are the targets for tissue rejection

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Immunology Cells of the Immune System

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

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