Tissues Flashcards
What are the 2 different type of lymphoid tissues?
Primary: BONE MARROW + THYMUS
Production of functional lymphoid cells and these are found in bone marrow and thymus= actually carry out the immune response, cells form and mature
B-cells: Undergo self selection in bone marrow
T-cells: Dont mature in marrow= Migrates to thymus
Secondary: SPLEEN, LYMPH NODES
Sampling environment and initiation of immune response e.g. lymph nodes, mucosal associated lymphoid tissues and spleen- Mature cells which interact with pathogens and initiate a response= Organised to be more effective
Tertiary: Temporary and transitory= SKIN
Site of effector responses
Skin and sites of inflammation
What are some properties of bone marrow?
1) Occupies space within the structural bone-Soft tissue that fills the hollow centres of bones
Function: To produce all of the progenitors (cells which differentiate into specific types) of the haematopoietic system
2) Primary repository of haematopoietic stem cells= Where blood cells are produced
Lots of different cell types being produced
What is B cell selection?
2 types of selection to ensure proper development
Positive selection: Antigen-Independent signalling= Receptors do not bind to their ligand, B cell do not receive proper signals= Do not develop
What cells grow in the bone marrow?
B cells
Partly mature B cells are exported from the bone marrow
Pre-T cells (non functional) migrate from the marrow to the thymus
Bone marrow in health and disease
Aplastic anaemia: Shortage of blood cells, absence of production of cells= Bone marrow failure
Leukaemia: Too many haematopoietic cells
Where is the thymus located?
Just on top of sternum
It does not have any structural integrity itself= Needs to be on top of sternum to protect
What happens to size of thymus?
Greatest= Birth
Keep declining over time
Where do the T cells enter? Where do they leave?
Thymus:
Enter: Cortex= Middle bit
Leave: Medulla: outside of the main bit, in the branches
Why do most thymocytes (cells which will mature into T cells) die?
Selection: Way to ensure that self reactive T cells are eliminated- Where we learn self and non self
Involves: T cell receptor
T cell selection takes place on thymic epithelium
T cells with a TCR that has STRONG affinity for self (MHC + peptide)= Die by apoptosis
T cells with NO affinity for self (MHC + Peptide)= Dies by default
Survive: T cells with T cell Receptor that has weak affinity for self MHC
What do secondary lymphoid tissues do? What are the examples?
Make functional cells assemble in a function to make them more effective
2 types:
1) Encapsulated, systemic: Spleen and lymph nodes
2) Unencapsulated, tissue restricted: Mucosal associated lymphatic tissues (MALT) + Gut associated lymphatic tissues (GALT)
What is the structure of spleen?
Largest lymphoid organ in body
Well placed to act to filter and sample blood
Consists of organised islands of white pulp entered on arterioles, surrounded by red pulp
Red pulp: Recirculation of red blood cells
White pulp: Mainly T cells
What is the spleen’s immune function?
1) Monitor circulatory system for pathogenic insult
2) Development of immune response to circulatory pathogens
3) Organisation of T cells, B cells and phagocytes to promote the effective development of immune response
MONITORS BLOOD
What happens if you were born without a spleen?
Congenital Asplenia
Very large immune consequences, systemic blood born disease
How come you can live without a spleen at older years?
Much older age= T cell memory can still be produced if you have built up immunity
What is the lymphatic system? What does it consist of?
Blood comes out of heart at high pressure, returns at low pressure in veins
Capillaries: High pressure blood circulating, small vessels= Leakage is fluid, plasma fluid leaking out of blood vessels through gap junctions= Goes to extravascular space- How do you get liquid back into bloodstream?
Wrong: Elephantiasis= Worms block lymphatic tissues, tissues upstream will become larger and larger
Lymphatic ducts: Drains fluid back into bloodstream
Mechanism for getting fluid that leaks out, back
Every tissue in body has lymphatic which is draining it
Mechanism for whats coming downstream
DRAIN TISSUES OF LYMPHATIC FLUID WHICH LEAKS OUT OF BLOOD VESSELS BACK INTO THE BLOOD SYSTEM
Lymph nodes: Checkpoints in draining lymphatics where immune system has assembled cells to check for pathogens insult upstream of the lymphatics
1) Network of tissues and organs that help rid the body of toxins, waste and other unwanted materials.
Consist of: Small, blind ended vessels draining from tissues into lymph nodes and from lymph nodes into efferent vessels
2) The primary function of the lymphatic system is to transport lymph, a fluid containing infection-fighting white blood cells, throughout the body
3) Skin, GI and GU tacts are very well supplied with lymphatics= Places where infection tends to happen the most
4) Lymphatic system drains into circulatory system via thoracic duct
5) good system for sampling antigenic exposure of TISSUES, especially skin
How is the lymphatic system assembled?
Lymph nodes must be assembled in a fashion that will stop infections coming through, monitor what is happening upstream
Afferent vessels: Lymph is coming in from capillary
Efferent vessels: Going out= Exiting through lymph duct, into the venous side
Lymphatic vessels drain in and out, but sponge of immune cells are in middle
Lymphatic nodes= Do not have their own red blood cells= Full of leukocytes
In between: Sponge of cells of immune system, can initiate immune response if necessary
Are blood vessels: Help feed lymphatic cells
Cortex: Outside= B cells
PAracortex: Bit below= T cells
Medullar= Bottom= Activated effector cells= Plasma cells activated to produce immunoglobulin, effector cells are transiting while pump out plasma cells
Follicles= Lymph node is activated= Blob on cortex, clones of B and T cells which are responding to immune insult
What are monoclonal antibodies?
Tools to identify the molecules which particular cells express= Use as markers
Example:
Molecule called Cd20= Expressed by B cells
Monoclonal antibody which will bind to Cd20 + Enzyme which will light up= Can use as marker
How are lymph nodes assembled?- Secondary lymphoid tissues
Dynamic response= Can self assemble
Discrete assemblage which is driven by chemokine secreted by dendritic cells
Chemokine= Attracts the cells in the lymph nodes- Attracts the B cells and T cells to the lymph nodes
How do naive T cells leave the bloodstream and enter the lymph node?
1) Leave across specialised endothelial walls of blood vessels= HEV in lymphoid organs
2) Receptors and adhesion and chemoskines= lymphocyte homing to the lymph nodes in vascular endothelium
3) Initial binding of the naive T cells to the vascular endothelium= binding of chemokine on ECM
4) T cell then migrates across the endothelium, into T cell area of lymph node
5) T cell can then inspect dendritic cells in the lymph node for specific antigens
6) No recognition= T cell is no activated= passed out back into bloodstream
6) Recognition= Activate into effector cells, leave after few days
What are profile of addressins?
Naive T cells: Combination of adhesion molecules and cytokine receptors which instruct it to leave the blood stream at particular points
Tells naive T cells to get out there
Effector and Memory T cells show different addressins which are specific to the area they work on
Selectin: Allow t cells to interrogate whats happening on the surface of the blood vessel
Overall: How do naive T cells get into lymph nodes?
Profile of addressins which bind ligands on HEV in the lymph nodes
Roll along by selectins with weak adhesion= Encounters with chemokine= Strong adhesion= T cell will migrate out between endothelial cell and migrate to tissue they want
What are mucosal associated lymphatic tissue?
Almost all mucosal tissues have their own associated secondary lymphoid tissues
Peyer’s Patch: Gut
appendix= Seconday lymphoid structure
Tonsils= Address pharynx
Lung mucosal tissues
Lymphoid tissue is directly adjacent to tissue it is interrogating
Specialised epithelial cells overlying the lymphoid tissue= Grab material out of the tissue, transiting it across the epithelium directly to the lymph node= Drain off
ONLY EFFERENT VESSEL
What is lymphocyte trafficking?
T cells encounters pathogen= Triggering response in mucosal tissue= Want the T cell to go to a specific place where the infection is
Antigen –>Dendritic Cell –> Drains to lymph node –> Activating T cells , no longer naïve –> Activated T cells provide help to B cells and swells follicles –> Migrate out through lymphatic and into bloodstream –> Tissue, know where to go have different profile of addressins
Acquire different profile of addressins to naive T cells: Effector T cells now go to wound site= Know to get out of bloodstream at that point as they are addressee to different chemokines
What happens overall when a pathogen enters tissue?
1) Most pathogens kept outside by epithelial barriers= Cross at injury and establish infection at underlying tissue
2) Phagocytes such as macrophages and neutophiles engulf pathogen
3) Dendritic cells are also phagocytic, bind pathogens and leaves site of infection –> Goes to lymph node
4) Enter lymphatic vessels, collected by draining lymph node
5) T cells are activated by the antigens presented by the dendritic cells, and activate B cells= immunoglobulins
6) Activated T cells and immunoglobulins return to blood circulation= Go to site of injury
7) Inflammatory mediators have induced changes in blood vessel endothelium
8) CD4 T cells= Activate macrophages= To be more cytotoxic while antibodies recruits complements to lyse and opsonise them + CD8 T cells would kill virus cells
