Lymphoid Tissues Flashcards
What is the adaptive immune system comprised of?
primarily comprised of 2 lymphocyte populations- T cells (undergo final development in the thymus) and B cells (develop in bone marrow)
What are the hallmarks of adaptive immunity?
specificity and memory
How does the adaptive immune system achieve specificity and memory?
B and T cells have specialized receptors on their cell surface (BCR and TCR)
Each B and T cell has the ability to express only a single TCR or BCR that is unique=> both in the genetic sequence that codes it and the antigen it can recognise.
What is the lymphatic system comprised of?
lymphatic vessels
secondary lymphoid tissue
What is lymphoid tissue split into?
primary, secondary, tertiary
What are primary lymphoid organs?
The site of lymphopoiesis, where new lymphocytes are made
What are some primary lymphoid organs?
thymus, bone marrow, foetal liver
What are the lymphocytes?
B and T cells and natural killer cells
What is meant by the specificity and memory of the adaptive immune system?
specificity- provided by a vast range of unique T and B cell receptors
memory- rapid expansion in response to secondary encounter
What is the bone marrow in terms of blood cells?
primary site of hematopoiesis
What is the bone marrow in terms of B cells?
The B cell repertoire is generated in the bone marrow
Final maturation occurs in the periphery
What is the thymus in terms of T cells?
Immature T cells migrate from the bone marrow to the thymus (thymocytes)
It is the tissue of T cell selection:
- stepwise differentiation
- positive selection and negative selection of thymocytes
- final selection and exit
What happens to the thymus over time?
Thymic involution- the shrinkage of the thymus with age. Associated with a change in structure and a reduced mass.
therefore, thymic output decreases= reliant on cells already in the body and them proliferating
When does white cell production increase?
during infection
How is lymph formed?
Through the draining of interstitial fluid out of the capillaries and into the lymphatic vessels
Which part of the bone marrow does haematopoiesis occur on?
The red part
Where are B cells made in the bone marrow?
B cells in the yellow marrow in the middle
What is positive selection?
positive= can the T cell receptor signal
T cells with CD4 and CD8 proteins on surface will try bind MHC1 and MHC2. if it does, this is good as the correct proteins were expressed, and cell is not killed.
What is negative selection?
negative= does it react against our own body
Keeping the cells that don’t bind and interact with self peptides
If the TCR recognizes self peptides then apoptosis is triggered
How do the T cells differentiate into T Helper Cells and T Killer cells?
Depending on which out of CD4 or CD8 had the strongest bond, the T cell will up regulate that one
How does the thymus change with age?
Degenerates
How does the number of peripheral T cells change with age?
Remains the same - peripheral T cells numbers are maintained by the division of mature T cells
Why are older people more vulnerable to new strains of pathogens?
Due to thymic involution, the T cell numbers are maintained by the division of mature T cells outside the central lymphoid organs, therefore you get less variety of T cells
How do T cells move from their site of production?
The thymus releases chemokines initiate the chemotaxis of T cells from the bone marrow to the thymus
What happens to the thymus during infection?
No change
What are secondary lymphoid organs?
Where lymphocytes can interact with antigens and other lymphocytes
What are some secondary lymphoid tissues?
Spleen, peyer’s patches, appendix, lymph nodes,tonsils, mucosal associated lymphoid tissue
Where are lymphoid tissues and how are they connected?
Distributed around the body
Interconnected via the lymphatic system and the blood (takes drainage from large SA of body)
Can be discrete organs (e.g., lymph nodes/ adenoids) or distinct regions within a tissue (e.g., spleen)
How would you describe lymphoid tissue?
generally highly organised structures, brings cells in close proximity to antigen
What are lymph nodes?
Highly organized, encapsulated structures which are located at points of convergence of lymphatic vessels
What are germinal centers?
Anatomically restricted site where B cells undergo mutation and selection to generate high affinity antibodies
It is where antibody repertoire is enhanced against a specific pathogen
How would you describe lymph nodes?
Distinct T and B cell zones
Afferent (in) and efferent (out) lymph
Arterial and venous connection
Bean shaped
Through what vessel does lymph enter into the lymph nodes?
The afferent lymphatic vessel
What is the purpose of the spleen being connected to blood?
highly connected to blood, so filters and checks blood
What is the function of the white pulp of the spleen, and what is the other type of pulp?
there is red and white pulp
white pulp=> lymphoid tissue= areas of B and T cell segregation and there is still lymphatic drainage (just less structured)
What are the functions of the spleen?
- Store of platelets
- Reacts with blood borne antigen
- Removes defective RBCs from circulation
Why is the lymph nodes a discrete tissue?
It has no other function other than to act as a site where lymphocytes and antigen can interact
What form the first line is defense against infection?
Epithelial barriers- they are a physical barrier with an extensive lymphatic network
What is the significance of the location of lymphoid tissues?
They are spread around the body so that the lymphatic sin every part of the body can reach, allowing lymphocyte and antigen interactions
Where are Peyer’s Patches Found?
Below the epithelium of the ileum of the small intestine
What are peyer’s patches?
specialised secondary lymphoid tissues
Where are many germinal centers located?
The gut
Why is there a lot of germinal centers in the gut?
There are high levels of antigen coming from gut microbial, which are producing many foreign antigens which leads to high antibody production
What is special about the follicles in the gut?
The follicle is highly enriched with B cells, and contains a high frequency of germinal centres
What happens in the red pulp of the spleen?
Red blood cells are destroyed
What is a Periarteriolar lymphoid sheath?
An area of white pulp which surrounds the arteries running through the spleen - is highly populated with T cells
What is MALT?
Mucosa-associated lymphoid tissues
Which special cells do gut associated lymphoid tissues contain?
M cells (membrane-like) or FAE (Follicle associated Epithelial) cells
What do FAE cells do?
- take up small amount of gut antigen
- pass onto APCs
- B lymphocytes react, making type IgA antibodies which are secreted directly into the gut lumen
What do the IgA antibodies made in the gut do?
They prevent microorganisms in the gut from sticking to the gut epithelium, and can also neutralize toxins and viruses
What forms the Waldeyer ring?
The pharyngeal, tubular, palatine and lingual tonsils encircling the oral and nasal cavity
What are tonsils packed with?
continuously activated germinal centres, it is a hyperactive secondary tissue
What are the tonsils made of?
Epithelial cells that are able to phagocytosis bacteria and transfer the antigenic peptides to macrophages that act as APCs
Where are the antigen sampled from in the tonsils?
Directly from the external environment
Why is the waldeyer ring an ideal environment for the immune system to encounter antigen?
Food, bacteria and things we breath in pass the oral pharyngeal section very often, therefore more antigen
Why do lymph nodes swell during an infection?
The B cell follicles of the lymph nodes expand as the B cells proliferate to form germinal centers, amd the entire lymph node enlarges
Where do naive Lymphocytes go after they are produced?
They enter into the blood stream and migrate to the peripheral lymphoid tissues
How much lymph is returned to the blood each day and via what vessel?
2 to 3 litres of lymph are returned to the blood each day
via superior vena cava
How does fluid enter lymph?
fluid drained from between tissue cells absorbed into lymph
How long does it take for a T cell to recirculate?
24 hours- that means they don’t stay static and circulate
We have secondary lymphoid organs around our bodies where T and B cells can become activated. How do they and the antigens get there?
The secondary lymphoid organs are connected to the circulation and the lymphatics
How to lymphocytes get inside the lymph nodes?
They enter via high endothelial venules
Where are high endothelial venules found?
In T cell zones of the lymph nodes
Which organ is mainly associated with filtering antigen out of blood?
Spleen
What does it mean the extravasation of naive T cells into lymph nodes?
they can pass directly through tissue
What are the four steps of T cells getting inside the lymph nodes?
- Rolling
- Activation
- Adhesion
- Transendothelial migration
steps 1 and 2 are selectin binding
steps 3 and 4 are integrin binding
Where is the T cell entering the lymph node?
the High Endothelial Venule
What encourages the naive T cells to migrate to tissue?
any sort of inflammation or sign of inflammation the T cell will attach and enter the tissue
Encouraged to migrate via chemotaxis
What molecule on T cells results in the rolling of the T cell before it enters the T cell zone of the lymph nodes?
L Selectin on T cell
What molecules binds to L selectin?
CD34
What chemokines are involved in activating LFA-1
Recognition of CCL21 on endothelial surface of HEV by CCR7 on T cells
What happens when LFA1 is activated?
The affinity for ICAM-1 AND ICAM-2 is increased
What does ICAM allow?
The migration of the lymphocytes through the blood vessel wall
What are dendritic cells?
Potent, antigen presenting cells that pick up and bring antigen from sites if infection to secondary lymphoid organs
How to dendritic cells help with the adaptive immune response?
They pick up antigens and present them to T cells, in order to activate the T cells
How do dendritic cells display the antigens?
Through MCHII molecules
Describe the transport of lymphocytes and antigens in the lymphatics and blood stream
Free antigen and antigen bearing DC’s travel from the site of infection through afferent lymphatic vessels into the draining lymph nodes
Activate lymphocytes then undergo period of proliferation and differentiation- once mature then leave through efferent vessels
What is an example of a DC?
Langerhans cells in epidermis
Describe what is meant by ‘repertoire’ in terms of lymphocytes?
The range of genetically distinct BCRs or TRCs present in a given host
The larger the repertoire, the more threats can be recognised
Where in lymph nodes generally are the T cells found relative to B cells?
T cells - Towards inside (further from the marginal sinus)
B cells - Towards outside (closer to the marginal sinus)
What do the words afferent and efferent refer to respectively?
Afferent - the vessel the lymph enters into the lymph nodes via
Efferent - the vessel the lymph leaves the lymph nodes via
What is it that makes the spleen so good at filtering antigens from the blood?
It is highly attached to the arterial circulation via the splenic artery
So it can filter blood rapidly and in large numbers
How do specific T cells become activated by their specific antigen which is in a different part of the body?
Each naive T cell recirculates once every 24 hours
They enter Lymph nodes with antigens (lymphatic vessels)
Become activated by binding to antigens from lymphatic vessels
Leave via efferent lymphatic vessel
Travel from peripheral tissue and inflammation occurs
The lymphatic vessels enter the lymph node via the afferent lymphatic vessels
What does lymph do?
Transports dietary lipids, drains interstitial fluid and facilitates immune responses
What are the 2 steps involved in extravasation of naïve T cells into lymph nodes?
Selectin binding
Integrin binding
Define antigen presentation
The display of peptides in the major histocompatibility complex (MHC) I or II proteins such that the T cell receptor can attempt to bind them
How do dendritic cells transport antigens from site of inflammation to the secondary lymphocyte tissues?
Once dendritic cells uptake antigen
They migrate out of the inflamed tissue
Carry antigen towards the T cells and B cells
