Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

L12 – The Anatomy of the Immune System
Primary and Secondary lymphoid organs
Lymphoid organs can be divided into the primary lymphoid organs, where the
cells of the immune system arise and the secondary lymphoid organs, where
adaptive immune responses are generated
...

• The bone marrow is the site of generation of all the cells involved in
innate and adaptive responses from hematopoietic stem cells
...
B-cell education
occurs in the bone marrow
...

Secondary lymphoid organs
• The lymph nodes, the spleen and the mucosa-associated lymphoid
tissue (MALT) comprise the secondary lymphoid organs
...

• In general, adaptive immune responses against antigens in the tissues,
blood and mucosal surfaces are initiated in the lymph nodes, in the
spleen and in the MALT, respectively
...

• The thymus is a gland in the neck
...

• The spleen is the largest lymphatic organ and is positioned in the
superior abdomen
...
The urogenital tract is
also protected by MALT
...

Hematopoiesis
•

•

Self-renewing hematopoietic stem cells (HSC) in the bone marrow give
rise to erythrocytes, leukocytes and the megakaryocytes that produce
platelets
...


The myeloid pathway gives rise to myeloid dendritic cells, monocytes
and macrophages, neutrophils, eosinophils, basophils and mast cells,
as well as erythrocytes and platelets
...

The Thymus
•

•
•
•
•
•

•
•

•

•

A collagenous capsule surrounds the thymus
...

Each of the many lobules is separated by connective tissue septa
...

The majority of cells in the thymus are T-cells that are in various stages
of development
...

Approximately 99% die and this is because autoreactive T-cells are
being eliminated due to their TCR recognising self-antigens with high
affinity
...

A small minority of viable T-cells remain
...
The
nurse cells provide a lot of growth factors; they nurse the development
of T-cells
...

The medulla contains many macrophages and dendritic cells
...
There a also structures called Hassall’s
corpuscles, which are unique to the thymus and they seem to be
involved with the elimination of the dead and dying T-cells
...

• The fluids in the blood leak through the capillaries and into the
surrounding tissues
...

• The thoracic duct is a major lymphatic vessel that merges with the
blood vessel system at the level of the left subclavian vein to return the
lymph into the blood, ultimately replacing the volume lost from the
blood during the formation of the interstitial fluid
...
The antigen specific lymphocytes are constantly
recirculating through the blood vessels and lymphatics in order to patrol the
body for their specific antigen
...

This acts as an alert signal to slow the blood-borne lymphocytes down
allowing them to enter the inflamed tissues
...

On the other hand, naïve lymphocytes can enter the lymph nodes directly
through high endothelial venules (HEVs)
...
Once tethered, the lymphocytes
roll along the endothelial cell, followed by the process of diapedesis, allowing
them to enter the lymph nodes
...

In the spleen, which lacks HEVs, lymphocytes enter the lymphoid area (white
pulp) from the arterioles, pass to the sinusoids of the erythroid area (red pulp)
and leave by the splenic vein
...

The lymph node is comprised of a cortex, a paracortex and a medulla
...
After antigenic activation, the primary follicles enlarge into
secondary follicles, each containing a germinal centre
...

The paracortex is populated largely with T-cells and also contains
dendritic cells
...
The paracortex
is sometimes referred to as a thymus-dependent area
...

Similarly to the thymus, there is a collagenous capsule surrounding the
lymph nodes
...
The
lymph slowly moves inward from the cortex to the medulla
...

There are also blood vessels, which have HEV to allow lymphocytes in
...
The
dendritic cells will travel via the afferent lymphatics to the nearest lymph
nodes
...
The T-cell will become
activated and it will leave the lymph node via the efferent lymphatics and
migrate towards the site of infection
...
These
structures are called germinal centres
...

The Germinal Centre
Germinal centres are transient lymphoid structures appearing inside lymph
follicles after an antigenic stimulation
...

Three different areas can be identified within a germinal centre
...
Until very recently, it was
thought that lymphocytes migrate uni-directionally from the dark zone to the
apical light zone
...
The net migration is from the dark to apical light zones
...
Proliferation of B-cells, somatic hypermuation and at least
in some species and some tissues, immunoglobulin class switching
occurs in the dark zone
...
At this point,
the B-cells are referred to as non-dividing centrocytes
...
The B-cells will now differentiate via 1 of
2 pathways, to produce memory B-cells and immunoblast plasma cell
precursors
...
You do
not find plasma cells in the germinal centre, at least not in very large
numbers
...


The spleen
•

•

•

•

The spleen consists of mostly red pulp rich in erythrocytes and
macrophages, the function of the latter being to phagocytose aging
erythrocytes, and to a less extent, white pulp containing leukocytes
...

Peri-arteriolar lymphoid sheaths (PALS) containing dendritic cells and
B-cells surround the arterioles
...

You also find secondary follicles, which are where lymphocytes are
being stimulated and in addition, there is also an area called the
marginal zone extending into the red pulp containing plasmablasts and
mature plasma cells
...

During pregnancy, antibodies are passed across the placenta (mainly IgG)
and that forms a very important protection for the foetus because when we
are born, our B-cells are just about developing
...
6 weeks after birth, we
only have a quarter of the antibodies passed on by our mother
...

FcRn is synthesised by the intestinal cells of the neonate
...
0) of the gut lumen allows the binding of the receptor to the gut, which
then binds IgG from the milk
...
4)
...
However, unlike other mucosal
tissues, in both the female and male reproductive tract, the dominant isotype
is often plasma-derived IgG
...
In circulation, it is present
as a monomer, but at mucosal surfaces, it is present as a dimer, which is
joined by a cysteine-rich J chain (15kDa)
...

• Dimeric IgA binds strongly to a receptor for polymeric Ig, the poly-Ig
receptor (pIgR; also binds IgM) on the basal surface of glangular
epithelial cells
...

Cleavage of the receptor releases the secretory IgA, but still attached
to part of the receptor known as the secretory component, which is
thought to protect the secretory IgA from proteases that would
otherwise destroy the IgA in the gut environment, where there are lots
of digestive enzymes
...

• It can also can help opsonise infectious agents for phagocytosis,
because phagocytic cells express Fcα receptors to bind IgA (just like
they express Fc γreceptors for IgG)
...

IgE also plays a role, mainly as a back up mechanism if pathogens get
pass IgA
...
Upon encounter with an infectious agent, IgE activates the mast
cell, culminating in the release of vasoactive and chemotactic factors
that will recruit and allow neutrophils and eosinophils to squeeze
through the endothelial cells, along with molecules like complement
and IgG, the combinatorial effect of which would get rid of the
pathogen
...

• Specialized epithelia, M (microfold) cells sample antigen from the gut
and pass it to the immune system cells, which lie in pockets under the
M cells
...

• M cells contain small pockets, which are full of lymphocytes and
Interdigitating dendritic cells and macrophages
...

 



---