301 Anatomy & Physiology Flashcards
What is the lymphatic system?
An open-ended, one-direction network of vessels and nodes that convey lymph
Returns plasma-derived interstitial fluids to bloodstream
What is lymph?
Clear-to-white fluid of WBCs (mainly lymphocytes) that attack bacteria and foreign bodies in blood
When dietary fat enters lymphatic vessels, the recovered fluid is lymph
Functions of lymphatic system
- Defends body against pathogens (bacteria, viruses and fungi)
- Develop body immunity (produce lymphocytes that produce antibodies)
- Remove excess fluids from body
- Absorption & transport fats to bloodstream
- Immune cell production (lymphocytes and antibody producing cells)
What are lymphatic vessels?
Start as lymphatic capillaries
Made of overlapping endothelial cells
What happens when fluid accumulates in tissue?
Interstitial pressure increases
Pushing flaps inwards,
Opening gaps between cells,
Allowing fluid in
Why are lymphatic capillaries different from blood capillaries?
Lymphatic are so large they allow bacteria, immune cells (macrophages) to enter
Useful for large particles to reach bloodstream
Used for dietary fat absorption in intestine
What is lymph flow?
Enabled by same forces in blood flow in veins
From lymphatic capillaries to vessels and eventually drains into bloodstream via subclavian veins
Lymph flow path through the lymph node
- Afferent lymphatics carry lymph to lymph node from peripheral tissue
Afferent lymphatics penetrate capsule of lymph node on opposite side to hilum - Afferent vessels deliver to subcapsular space (reticular fibres, macrophages, dendritic cell meshwork)
Dendritic cells involved in immune initiation response - Lymph flows into outer cortex (contains B cells within germinal centres resembling lymphoid nodules)
- Lymph flows through lymph sinuses in deep cortex (dominated by T cells)
- Lymph goes into medullary sinus, region contains B & plasma cells
- Efferent lymphatics leave node at hilum, collect lymph from medullary sinus & carry to venous circulation
What are lymph nodes?
Bean-shaped structures scattered throughout lymphatic network
Most prominent in areas where vessels converge (armpits, neck, inner elbows and groin)
Contain lymphocytes (T and B cells for adaptive immunity)
Innate vs adaptive immunity
I: Body’s first line of defence against pathogens
A: Specialised response targeting specific germs, “remembering” them
What does the adaptive immune response do in lymph nodes?
Produces activated lymphocytes and antibodies specific to the invading pathogen
Then carried by lymph to bloodstream for whenever they are needed
What are the primary lymphoid organs and functions?
Thymus and bone marrow
Where immune cells develop
Sites of lymphocyte production, maturation and selection (self and non-self)
Mature lymphocytes leave primary for secondary organs
What are the secondary lymphoid organs and functions?
Lymph nodes, spleen and MALT
Lymph nodes and spleen most organised
When they encounter pathogens and become activated
All have T and B cell activity and develop lymphoid follicles
Haematopoietic stem cells in bone marrow
(Blood-forming cells) reside in bone marrow during foetal gestation
Bone marrow remains site of haematopoiesis (creating RBCs, WBCs and platelets) in adults
Where do T lymphocytes complete maturation?
Thymus
What do stem cells require to self-renew and differentiate?
Stem cell niches
Why is a bone marrow transplant used?
Treat leukaemia, lymphoma, neuroblastoma and myeloma
What are HLAs?
Human leukocyte antigens
Markers on cell surface which siblings and parents can match or need to find a donor from national bone marrow donation registry for transplant
Thymus in lymphatic system
T-cell development not complete until selection in thymus
Pass through defined developmental stages in specific thymic micro-environments to generate antigen receptors
Selected on reactivity to self MHC-peptide complexes (expressed on stromal cells)
Most T cells die here
Where do T-cell pre-cursors go from and to via what in lymphatics?
From bone marrow to thymus via blood
What are MALTs?
(Mucosa-associated lymphoid tissue)
Tonsils, Peyer’s patches (lymphoid follicles in SI, part of GALT (gut)), appendix, lymphoid follicles in mucous membranes
Important features of spleen in lymphatic system
Organises immune response against blood-borne pathogens
Supplied with antigens by splenic artery
Red pulp - RBCs destroyed
White pulp - PALS with T cells and B cells
Marginal zone - trap for antigens
What does PALS stand for?
Peri-arteriolar lymphoid sheath
Lymph node main functions
Committed to regulating immune response and 1st organised structure to face antigens
What are lymph nodes consisted of and connected with?
Packed with lymphocytes, macrophages and dendritic cells
Connected with blood and lymph vessels
4 distinct regions of lymph nodes
- Cortex - contains B lymphocytes, macrophages and follicular dendritic cells
- Follicle - microenvironment to support B cell development
- Para-cortex - T lymphocytes and dendritic cells (migrated from tissue)
Medulla - lymphocyte exit
MALT functions
Organises response to antigen entering mucosal tissues
Where are T and B cell zones and lymphoid follicles found?
Mucosal membranes
What is GALT?
Barely organised cluster of lymphoid cells
What are M-cells?
Specialised epithelial cells of MALTs that transport antigen across epithelium
What is tertiary lymphoid tissue?
Site of infection
What happens in tertiary lymphoid tissue?
Lymphocytes activate by antigen in SALT (skin associated lymph tissue) can return to lung and liver
Generate defined microenvironments organising returning lymphoid cells
What are toll-like receptors (TLRs)?
Help detect pathogens and other threats
What does TLR activation help with?
Activation in epithelia and activated macrophages help with inflammation
What do macrophages do in inflammation?
Secrete cytokines including chemokines that attract neutrophils
What happens when the body is invaded by a foreign body?
- Macrophages recognise invaders, engulf & destroy & keep markers so other cells recognise
- Macrophages release cytokines when engulfing
- Cytokines bind receptors on other macrophages to inform cells
- Macrophages can’t destroy all so travel to lymph nodes & bring info to lymphocytes
- T cells divide & help macrophages, can recognise damaged invader antigens then bind them & activate
- When activated, T cells (killer or helper) divide & increasing numbers to inflammation site so rest of invaders engulfed by macrophages
- B cells shoot out Ig’s
- B cells divide & increase in lymph nodes before moving to inflammation site
- Swollen lymph node as result of activated T & B cells
How quickly is an inflammatory response initiated?
Within hours of infection or wounding, characterised by swelling, heat, redness and pain
What 4 changes occur to local blood vessels when swelling, heat, redness and pain occur?
- Heat and redness during inflammation due to vascular diameter increase so slower blood flow
- Increased vascular permeability, endothelial cells of vessels have gaps now so fluid from blood exits accumulating in local tissue so oedema and pain
- Endothelial cells of vessels activated, cell-adhesion molecules promoting lymphocyte binding
- Microvessel clotting at infection site, pathogens stop spread to blood
In inflammation, fluid leaves blood and accumulates in local tissue, what does the fluid contain?
Plasma proteins like complement proteins and mannose binding lectin (helps defend against pathogens)
What is extravasation?
Leukocytes leaving bloodstream
They attach to endothelium and migrate into tissues where they attack pathogens
Purpose of inflammatory response
- Allow body to defend itself from invaders
- Induce local blood clotting as physical barrier
- Promote injured tissue repair
What triggers an inflammatory response?
Tissues are physically damaged or when pathogens are recognised by macrophages or later by other WBCs
After an inflammatory response occurs, what is induced?
Release of inflammatory mediators which cause response
What do macrophages and neutrophils secrete in inflammatory response?
Secrete prostaglandins, leukotrienes and platelet-activating factor (PAF) - (lipid mediators)
Why are prostaglandins, leukotrienes and PAF produced rapidly in inflammatory response?
Made from degraded membrane phospholipids
What do macrophages secrete and example?
Cytokines which are released by immune cells
Chemokines act as chemoattractants (attract cell to certain location)
What do chemokines cause?
Directed chemotaxis (movement of cells in direction with gradient of increasing/decreasing conc.)
Chemokines direct phagocytes towards chemokine source
2 cytokines which are important in inflammatory response and why?
- C5a - stimulates respiratory (oxidative burst), attracting neutrophils & monocytes
- TNF-α - produced rapidly by macrophages upon pathogen detection & activator of endothelial cells
What is oxidative burst?
What do local mast cells release in inflammatory response?
Granules containing histamines and TNF-α
Cytokines produced macrophages like TNF-α cause what?
Endothelial cells to rapidly externalise granules (Weibel-Palade bodies) containing P-selectin within minutes of pathogen detection by macrophages and P-selectin appear on local endothelial surfaces
What are important for leukocyte recruitment?
Selectins with others being intercellular adhesion molecule (ICAMs) and leukocyte integrins
Mechanism of P-selectin
Once appeared on local endothelial surface, RNA encoding E-selectin is synthesised
Both selectins interact with sulphated sialyl-Lewis X (present on neutrophil surface)
What makes up first wave of cells to cross blood vessel wall in inflammatory response and followed by what?
Neutrophils enter inflamed tissue (followed by monocytes and differentiate into tissue macrophages)
What crosses blood vessel wall later in inflammatory response?
Other leukocytes like eosinophils and lymphocytes
Where do lymphocytes like to travel and why is this a problem?
Centre of small blood vessels where blood flows fastest
Inflamed tissue has slower flow allowing leukocytes to interact with endothelial cells lining blood vessels
What 2 enzyme cascades are triggered by blood vessel injury?
Kinin (inflammatory mediator (bradykinin) production)
Coagulation (leads to fibrin clot formation)
What is bradykinin?
Vasoactive peptide that increases vascular permeability and causes pain
What are prostaglandins?
Physiologically active lipids, found in nearly all tissue (derived from arachidonic acid)
What is a lymphatic malformation?
Lymphatic system doesn’t form correctly causing parts of body to swell
Is congenital or primary condition as occurs before birth
What are other terms for lymphatic malformations?
Cystic hygroma or lymphangioma (outdated as these refer to cancer)
Cystic lymphatic malformations
Lymph piles up forming bubbles (cysts)
Microcystic (appear as small blisters near skin - blebs) or macrocystic (may tint skin blue and be painful, putting pressure on other body parts) or mixed
What are CCLAs (central conducting lymphatic anomalies)?
When central lymphatics transport chyle from intestines is malformed
Body tries to relieve pressure by finding new routes, pools & can leak into chest or abdomen
What cannot reach their destinations when CCLAs occur
Fats, proteins, immune cells and other passengers
Causing health problems
In CCLAs, what can be caused in chest and abdomen?
C: chylothorax causes cough, discomfort in chest and breathing difficulty
A: Chylous ascites, abdomen becomes large, full and painful
What is PID?
Infection of upper reproductive system including uterus, fallopian tubes and ovaries
Serious complication of PID
Infertility
Why does PID typically develop?
Bacterial infection in vagina or cervix causing inflammation of mucosal layer
60% of the time changing bacterial flora composition called bacterial vaginosis
Why does bacterial vaginosis occur?
Cervical mucus (barrier preventing bacteria entering uterus) becomes less effective
When normal balance of vaginal flora is altered and anaerobic bacteria proliferate and degrade cervical mucus
What can contribute to PID?
Retrograde menstruation (when menstrual blood flows back through fallopian tubes and into pelvic cavity)
Sexual intercourse
What is salpingitis and salpingo-oophoritis?
When PID reaches fallopian tubes
When PID also affects ovaries
What happens in PID?
Infection triggers response which sends neutrophils, plasma cells & lymphocytes into fallopian tubes
Damages tubal epithelium, tubes fill with pus
What happens when scar tissue forms to repair PID damage?
Areas with damaged epithelium tend to stick to one another, creating closed-off pockets and dead-end pouches in fallopian tubes
Scarring leads to PID complications
PID: what happens when pus builds up in tube and ovary?
Can turn into tubo-ovarian abscess which can be life-threatening if ruptured
PID: what happens when fluid builds up in a pocket?
Pocket created by scar tissue in tubes called hydrosalpinx
Can cause affected area to become swollen
Structural damage of fallopian tubes tends to cause difficulty getting pregnant, risk of ectopic pregnancy and chronic pelvic pain
Complication (syndrome) of PID
Fitz-Hugh-Curtis syndrome
Inflammation from PID spreads to peritoneum and to Glisson’s capsule which surrounds liver
Results in “violin string” adhesions of scar tissue attaching liver to peritoneum