Describe the fluid collection in the Lymphatic system.
- The Lymphatic System collects 3 litres per day of interstitial fluid.
- Each day 20 litres of fluid leaves the arteriolar end of the capillaries and 17 litres is absorbed back into the venular end, this leaves 3 litres a day to be returned to the venous system (region of lowest pressure in the vascular system) by the lymphatic system.
Outline the following components of the lymphatic system:
- Fluid: lymph
- Vessels: lymphatics
I. Lymphocytes (B cells, T cells and NK cells)
II. Supporting cells (follicular dendritic cells and macrophages)
I. Diffuse, mucosal associated lymphatic tissue (MALT), this includes gut-associated lymphatic tissue (GALT) and bronchus-associated lymphatic tissue (BALT)
II. Lymphatic nodules which include Tonsils, Peyer’s patches and the vermiform appendix
I. Lymph nodes
Outline the structure of lymphatic vessels.
- Lymphatics tend to lie adjacent to arteries and veins
- Like veins, lymphatic vessels are arranged into superficial and deep (deep to the deep fascia). Flow is superficial to deep.
- In the limbs, the deep lymphatics pass through muscles. Muscle contraction within the deep compartments is critical to lymph circulation.
- Larger lymphatics, in the abdomen or thorax for example contain smooth muscle in their walls. Contraction of this smooth muscle is an important contributor to lymph flow at these sites.
How is lymph propelled forward?
- Skeletal muscle movement
- Pressure changes in the thorax during breathing
- The pulsations of adjacent arteries
- Increased physical activity or passive movements really help keep that lymph flowing at a decent pace.
What is the general function of lymph nodes and what type of cells are found there?
- Serve as filters as lymph percolates on its way to the vascular system, traps antigen, processes antigen and presents processed antigen to T cells.
- Is a repository of macrophages, B cells and T cells that work together to produce an inflammatory (macrophages, neutrophils) response followed by an immune response (B cells, T cells).
How many lymph nodes are there in the human body?
Outline the blood vessels and lymphatics involved with lymph nodes.
In addition, explain the movement of lymphocytes in relation to these vessels.
- Each node has afferent lymphatic vessels that enter via the convex surface and efferent lymphatics that leave via the hilum.
- Each lymph node has a feeding artery and draining vein that enter and leave via the hilum.
- The majority of lymphocytes enter lymph nodes via the feeding artery (a few in lymph) and the majority leave in the efferent lymphatics.
- As lymph nodes fight infection, the germinal centres fill with increasing numbers of lymphocytes causing the lymph nodes to swell and this can also cause some pain
- Cancers can metastasise to lymph nodes via the afferent lymphatics
- Lymphoma often presents with lymphadenopathy
Discuss the professional Antigen Presenting Cells present in the lymph nodes
- Lymph nodes contain professional antigen presenting cells (APCs)
- Unlike B cells, T cells fail to recognize antigens in the absence of antigen presentation
- Most cells are capable of presenting antigens and activating the adaptive response. Some cells, however, are specially equipped to acquire and present antigen, and prime naive T cells.
- B cells and macrophages play a major role in the innate response, also acting as professional antigen-presenting cells (APC).
-These professional APCs are equipped with special immunostimulatory receptors that allow for enhanced activation of T cells
Outline the structure, function and location of follicular dendritic cells.
- Located in the germinal centres.
- Antigen antibody complexes adhere to their dendritic processes and the cell can retain antigen for months.
- Follicular dendritic cells cause proliferation of B cells, in particular, memory B cells.
Explain what is meant by inflammation.
- The initial reaction of the body to an antigen is an inflammatory response.
- Mediated mainly by neutrophils and/or macrophages.
- Degradation of the antigen may lead to presentation of a portion of the antigen to elicit a specific immune response.
Distinguish between humoral and cell-mediated immunity.
- The specific immune response is usually a mixture of humoral and cell-mediated.
- Humoral immunity is B lymphocyte mediated and involves antibody production by B lymphocytes that transform into plasma cells that synthesise and secrete a specific antibody.
- Cell-mediated immunity is T cell mediated.
- T cells need antigen presenting cells (macrophages, B lymphocytes) to recognise antigen.
- Cell-mediated immunity is important in defence against:
I. Viral, fungal and mycobacterial infections
II. Tumour cells
III. Transplant rejection
Outline the importance of the thymus gland in immunity.
Its role is the maturation of bone marrow derived stem cells into immunocompetent T cells. This is called thymic cell education.
Very briefly, outline the structure and function of the spleen.
- Largest lymphatic organ – very rich blood supply
- The spleen filters blood in the same way that lymph nodes filter lymph. It has functions in both the immune and haemopoietic systems
What are the immune functions of the spleen?
- Antigen presentation by APCs
- Activation and proliferation of B and T lymphocytes, production of antibodies
- Removal of macromolecular antigen from blood (macrophages do this)
What are the haemopoietic functions of the spleen?
- Removal and destruction of old, damaged and abnormal erythrocytes and platelets
- Retrieval of iron from erythrocyte haemoglobin
What are the risks associated with a ruptured spleen?
- The spleen has a very rich blood supply, it is also relatively fragile.
- A ruptured spleen can easily lead to death through exsanguination
Outline the consequences of spleen removal.
- Surgeons often remove the spleen (e.g. trauma)
- The liver and bone marrow can take over the removal and destruction of ageing red cells
- Splenectomy increases the risk of infection by encapsulated bacteria (e.g. the meningococcus) and malaria
- Splenectomy increases the risk of DVT and pulmonary embolism threefold (partly due to increased platelet count?)
Compare and contrast how the spleen and lymph nodes respond to infection.
In the same way that lymph nodes enlarge in response to infection (usually localised), the spleen may enlarge in response to systemic infection (glandular fever, malaria, septicaemia).
- Enlarged spleen = systemic infection
- Enlarged lymph node = localised infection
What is phagocytosis?
- Phagocytosis is a specific form of endocytosis by which cells internalise solid matter, including microbial pathogens.
- While most cells are capable of phagocytosis, it is the professional phagocytes of the immune system, including macrophages, neutrophils and immature dendritic cells, that truly excel in this process.
- In these cells, phagocytosis is a mechanism by which microorganisms can be contained, killed and processed for antigen presentation.
Outline the process of phagocytosis.
- The process of phagocytosis begins with the binding of opsonins (i.e. complement or antibody) and/or specific molecules on the pathogen surface (called pathogen-associated molecular pathogens [PAMPs]) to cell surface receptors on the phagocyte.
- This causes receptor clustering and triggers phagocytosis.
- The cell membrane then extends around the target, eventually enveloping it and pinching-off to form a discreet phagosome.
- This vesicle can mature and acidify through fusion with late endosomes and lysosomes to form a phagolysosome, in which degradation of the contents can occur via the action of lysosomal hydrolases.
What is meant by opsonisation?
Opsonisation is a term that refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte.
Outline the process of opsonisation.
- The process of opsonisation is a means of identifying the invading particle to the phagocyte.
- It is the molecular mechanism whereby molecules, microbes, or apoptotic cells are chemically modified to have stronger interactions with - to be more "delicious" to - cell surface receptors on phagocytes and NK cells.
- With the antigen coated in opsonins, binding to immune cells is greatly enhanced.
- Opsonisation also mediates phagocytosis via signal cascades from cell surface receptors.
- Opsonins aid the immune system in a number of ways. In a healthy individual:
I. Mark dead and dying self-cells for clearance by macrophages and neutrophils
II. Activate complement proteins
III. Target cells for destruction through the action of natural killer (NK) cells.
What is complement?
- Consists of a group of serum proteins that:
I. Activates inflammation
II. Destroys cells
III. Participates in opsonisation.
- Complement can be activated by a number of different molecules.
Outline the complement cascade.
- The complement proteins respond in a sequential manner called the complement cascade.
- The complement cascade can be activated by the Classical pathway or the Alternative pathway.
- Both pathways follow the same sequence after C3, resulting in:
III. Membrane attack complex
Compare and contrast the Classical and Alternative pathway.
- In the Classical pathway C1 is activated when it binds to an antigen-antibody complex.
- In the Alternative pathway C3b is activated when it reacts with antigens such as bacterial cell wall.
What is oedema?
Oedema is an accumulation of an excessive amount of watery fluid in cells, tissues or serous cavities.
What is lymphoedema?
- Lymphoedema – swelling (especially in subcutaneous tissues) as a result of obstruction of lymphatic vessels or lymph nodes and the accumulation of large amounts of lymph in the affected region.
- Lymphoedema is non-pitting due to the build -up of lymph and protein in the interstitial space. Fibrotic changes occur which become chronic, therefore non-pitting. Unlike the following figure:
Discuss the variations in oedema due to gravity, activity, aetiology and position.
- Oedema often appears first at the ankles. This is due to the effect of gravity on the body. Gravity in the upright human body can cause a vertical gradient of venous pressures. If someone is lying down/sitting in bed, the oedema is expected to appear in the sacral region.
- If a patient says that their ankle swelling is absent first thing in the morning and then appears during the day, this tells us that their swelling is triggered by gravity – standing up (positional, pitting oedema).
- If ankle swelling affects one side only, the implications in terms of its cause (aetiology) is local pathology/condition – cancer, lymph nodes removed.
- In patients with hypoproteinaemia (nephrotic syndrome) they often first notice oedema around the eyes (periorbital oedema) first thing in the morning. This is because lying flat at night, the skin around the eyes is flat so it is possible for the lymph to accumulate around it.
Where are there no lymphatic vessels?
There are no lymphatics in the Central Nervous System