Where are lymphocytes produced?
Lymphocytes are produced by haemopoetic stem cells in the bone marrow.
What happens in primary lymphoid organs? Examples of primary lymphoid organs?
Immature lymphocytes acquire receptors to recognise antigens.
Bone marrow, thymus
What happens in secondary lymphoid organs? Examples of secondary lymphoid organs?
Lymphocytes are exposed to and are activated in response to antigens.
Lymph nodes, spleen, Mucosa associated lymphoid tissue (MALT).
What are the classes of lymphocytes?
B Cells: these are derived from the bone marrow. Stimulated B cells will mature into plasma cells (antibody factories). The antibodies will be of one of five classes (Ig-A,D,E,G or M). The antibodies will then be secreted into the circulation (a proportion will remain bound to B cell membrane to act as the B cell receptor). Once activated, B cells will mitotically divide producing a mixture of plasma cells and memory B cells (capable of mounting a secondary immune response: more rapid, greater magnitude).
T Cells: these have effector and regulatory functions. T cells migrate from the bone marrow to the thymus, where they develop into mature T cells (or undergo apoptosis if they are self-reactive). T cells then move into the secondary lymphoid organs (lymph nodes, MALT), but are constantly circulating around.
What are the major classes of T cells?
- T helper cells: help other cells to perform their effector functions by secreting interleukins:
TH1 - promote a cell-mediated response
TH2 - promote humoral immunity
TH17 - promote acute inflammation - Cytotoxic T cells: kill viral and cancer cells. They require help from T helper cells to become active.
What are antigen presenting cells?
Antigen presenting cells (APCs) present antigen (normally broken down into short peptides), bound to major histocompatibilty complexes (MHCs), to lymphocytes. Contact of this MHC-peptide complex with a T cell receptor with appropriate specificity then activates the T cells.
There are two types of APCs:
Non-professional (all nucleated cells of the body): These express MHC class 1. Viral antigens, or cancer antigens would be expressed by these cells bound to MHC class I receptors, and would invoke a response by cytotoxic T cells. Professional APC (e.g. dendritic cells, macrophages, Langerhans cells): These take in external antigen, process it and present it bound to MHC class II receptors. This promotes T helper cell response, which then activates B cells.
What type of lymphocytes would you find in the follicle of a lymph node?
B-cells
What type of lymphocytes would you find in the cortex/paracortex of a lymph node?
T-cells
What type of lymphocytes would you find in the medulla?
Plasma cells
How does lymph flow through the lymph node?
- Lymph flows into the node, via afferent lymphatic vessels, on the convex surface of the lymph node. These are multiple, and contain valves to prevent back flow of lymph.
- Afferent lymphatics empty into the subcapsular sinus, which is continuous with the lymphatic (cortical) sinuses,and then into the medulla.
- Lymph flows out through medullary sinuses, to the efferent lymphatic vessel on the concave surface of the lymph node (at the hilum).
- The lymphatic vessels and sinuses are lined with lymphatic endothelial cells.
What cells are present in a lymphoid follicle?
1) B cells
- “Centroblast” (CB) (immature B cell) - large, mitotically active cells, with round nuclei found in the darker zone of the germinal centre (closer to the medulla).
- “Centrocyte” (CC) (mature B cell) - found in the paler zone of the germinal centre, towards the lymph node capsule. These cells are of variable size, and have folded irregular nuclei. These migrate to the paler capsular zone of the germinal centre to produce “immunoblasts” (memory B cells).
- Non-proliferating B cells (in the mantle region).
2) Follicular dendritic cells (FDC)
3) Macrophages (M)
What cells are present in the medullary sinus?
- Plasma cells (P) (and their pre-cursors, plasmablasts) are the major cell type in the medullary cords
- the B lymphocytes complete the final stages of maturation to form plasma cells
- plasma cells synthesise antibody that is carried by efferent lymph into the general circulation
- plasmablasts also migrate in the efferent lymph to peripheral tissues
- Sinus macrophages (M) are the main cell type in the medullary sinuses
What are the characteristic microanatomical features of the spleen?
Red pulp (RP):
- makes up bulk of the organ
- interconnected sinuses that are tributaries of the splenic vein
- blood cells enter the parenchyma from capillaries, squeeze through the walls of the sinuses and drain out via the splenic vein (open circulation)
White pulp (WP) (20% of mass)
- 0.5-1mm white nodules - lymphoid aggregations (similar to the paracortex/cortex of lymph nodes).
- T cells (mainly TH1 cells) typically form a sheath around a central artery (periarteriolar lymphoid sheath - PALS).
- B cells form follicles, usually located in the edge of the PALS. At the follicle periphery, there is a narrow zone of small lymphocytes called the mantle zone, beyond which is a broader marginal zone of medium sized lymphocytes (which contains subsets of B cells and macrophages).
- The perilymphoid red pulp (the red pulp around the marginal zone) contains lymphocytes migrating from the sinuses to the white pulp.
What are the four functions of the spleen?
1) Production of an immunological response against blood borne antigens
2) Removal of particulate matter and aged or defective blood cells from the circulation
3) Recycling iron back to the marrow
4) Extra-medullary haematopoesis in the fetus and during certain bone marrow diseases
What are the characteristic microanatomical features of the thymus?
- The thymus is a lobulated organ invested by a loose collagenous capsule (C) from which interlobular septa (S) project into the substance of the organ
- The thymic tissue is divided into two distinct zones (most obvious in childhood - as seen in this image)
outer cortex (C)
inner medulla (M) - Thymic epithelium develops into a sponge like structure containing spaces that become colonised by immature T lymphocytes derived from haematopoietic tissue
- Cortical epithelial cells promote T cell differentiation and proliferation
- The thymic epithelium forms sheaths around the blood vessels
By what 2 processes does the thymus undergo involution in the adult?
1) fatty infiltration - in the mature thymus islands of lymphoid tissue (L) are separated by areas of adipose tissue (A)
2) lymphocyte depletion (despite this, the thymus continues to provide a supply of mature T lymphocytes to the circulation and peripheral tissues)
What are the characteristic microanatomical features of the palatine tonsils?
- Discrete masses of lymphoid tissue covered in stratified squamous epithelium (E)
- Deep invaginations forming tonsillar crypts (C) allow large surface area for exposure to antigens
- Tonsillar parenchyma contains lymphoid follicles (F) similar to those found in lymph nodes
What is cardiac output?
CO is the amount of blood which is ejected from the heart in 1 minute
CO = SV x HR
CO should be 5-6L, any less suggests some dysfunction of the heart
Ejection fraction is usually 50-70%
What are some causes of heart failure?
1) Coronary artery disease
- Post MI
- Chronic ischaemia
2) Hypertension (struggling against an after load)
3) Valvular disease
- Regurgitation of a valve = volume overload
- Stenosis of a valve = extra force needed to overcome
What are some causes of myocardial disease that heart failure can be secondary to?
- Cardiomyopathies
- Arrhythmias
- Drugs (anti-arrhythmics, cytotoxics)
- Toxins (alcohol, cocaine, mercury)
- Endocrine (diabetes, thyroid disease, adrenal disease)
- Nutritional (thiamine deficiency, obesity)
- Infiltrative (sarcoidosis, amyloidosis, haemachromatosis)
- Infective (HIV)
What are some causes of high output cardiac failure?
- Anaemia
- Pregnancy
- Hyperthyroidism
What are some signs of reduced cardiac output?
- low systolic blood pressure
- narrow pulse pressure
- pulsus alterans (on ECG)
What investigations would you do for heart failure?
- ECG
- BNP (released by ventricular myocardium when stressed)
- Chest X-ray (alveolar oedema, Kerley B lines, cardiomegaly, upper lobe diversion, pleural effusion)
- Special tests: echocardiogram, cardiac MRI
How would you acutely manage heart failure?
- A-E assessment
- oxygen
- IV access and monitoring
- Furosemide IV
- Diamorphine
- Nitrates (GTN infusion)
- Non-invasive ventilation (NIV) eg. CPAP
