L2 - Cells of the Immune Sytem
Transcript of 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
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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
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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
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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
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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