HAN 202 lymhoid/immune and digestive

functions of the lymphoid system

3 main functions: fluid recovery, immune surveillance, and lipid absorption

fluid recovery of the lymphoid system

lymphatic vessels return the remaining interstitial fluid (lymph), from the interstitial spaces of tissue, back to the blood that was not absorbed by the blood capillaries

- any interference with lymphatic drainage can lead to lymphedema, swelling of body parts due to build up of interstitial fluid

immune surveillance of the lymphoid system

through fluid recovery, foreign cells and chemicals are also picked up from the tissues, the lymph nodes would detect these foreign matters and activate an immune response

lipid absorption of the lymphoid system

in the small intestine there are special lymphatic vessels, lacteals, that absorb dietary lipids that aren't absorbed by the blood capillaries

components of the lymphoid system

lymph, lymphatic vessels, lymphoid tissue, and lymphoid organs

lymph

the recovered fluid (by lymphatic vessels) that originates in the body tissue and is filtered out by the blood capillaries

- a clear and colorless fluid similar to blood plasma but is low in protein

- chemical composition varies depending on its location

- can contain macrophages, hormones, bacteria, viruses, cellular debris, or traveling cancer cells

lymphoid tissue

is composed of aggregates of lymphocytes and macrophages that populate many organs of the body and in the mucous membrane

- 2 types: diffuse lymphoid tissue and lymphoid nodules (follicles)

diffuse lymphoid tissue

the simplest form in which the lymphocytes are scattered

- is prevalent in body passages open to the external environment: respiratory, digestive, urinary, and reproductive tracts (these tissues are called mucosa-associated lymphoid tissue, MALT)

lymphoid nodules (follicles)

dense aggregations of lymphocytes and macrophages that come and go as pathogens invade the tissues and the immune system answers the challenge

- aggregated lymphoid nodules are clusters formed in the ileum, the distal portion of the small intestine

lymphoid organs

are composed of a high concentration of lymphoid tissue and is set off from surrounding organs by connective tissue capsules

- the organs are the lymph nodes, spleen, thymus, tonsils, and red bone marrow

- 2 types: primary and secondary lymphoid organs

primary lymphoid organs

are the sites where the B and T lymphocytes become immunocompetent, able to recognize and respond to one specific antigen

- these are the red bone marrow and thymus

secondary lymphoid organs

are where the immunocompetent lymphocytes migrate to after they mature in the primary lymphoid organs

- lymph nodes, tonsils. and spleen

lymphatic capillaries (terminal lymphatics)

where the beginning of lymph flow is

- has anchoring filaments and intercellular clefts

- penetrates nearly every tissue of the body except cartilage, bone, bone marrow, and the cornea

- similar to blood capillaries but differs with one end being closed and there is no through-flow of fluid

anchoring filaments

how lymphatic capillaries are tethered to the surrounding tissue and prevents the sac from collapsing

intercellular clefts

gaps between neighboring endothelial cells of lymphatic capillaries where bacteria, lymphocytes, and other cells and particles can enter along with the tissue fluid (lymph)

lymphatic vessels (lymphatics)

is a network/system that transports lymph from the capillaries -> collecting vessels -> 11 lymphatic trunks -> 2 collecting ducts -> subclavian veins

- responsible for the continual recycling of fluid from blood to tissue fluid to lymph and back to blood

- each vessel converges with the pervious one hence the changing names

collecting vessels

formed by the converging of the lymphatic capillaries

- travels alongside veins and arteries and shares a common connective tissue sheath with them

- empties into lymph nodes at irregular intervals

lymphatic trunks

are 11 types that drains a major portion of the body

- formed from the converging of the collecting vessels

- 1 intestinal trunk, pairs of jugular, subclavian, bronchomediastinal, intercostal, and lumbar trunks

- the lumbar trunks also drain the lower limbs, not only the lumbar region

collecting ducts

2 types, the right lymphatic duct and the thoracic duct, are formed from the converging of the lymphatic trunks

- these are the largest lymphatic vessels

right lymphatic duct

it receives lymphatic drainage from the head, brain, right arm, and right side of the thorax and empties into the right subclavian vein

- formed by the convergence of the right jugular, pairs of subclavian, and bronchomedistinal trunks

thoracic duct

is located on the left and is larger and longer than the right lymphatic duct because it is responsible for drainage of the rest of the body below the diaphragm, the left upper limb, the left side of the head, neck, and thorax

- formed by the joining of 2 lumbar trunks and the intestinal trunk creating the cisterna chyli sac

cisterna chyli

is a sac that collects large amounts of chyle (fatty intestinal lymph) after a meal

flow of lymph through lymphoid system

is similar to the venous return but has less pressure and is much slower

- valves of lymphatic vessels prevent back flow of fluid

what are the methods of lymph flow?

forward flow is reliant on vessel stretching via:

- lymphatic vessel contractions when the fluid stretches it (primary mechanism)

- squeezing of lymphatic vessel by skeletal muscles

- squeezing of lymphatic vessels through the pulsations from nearby arteries

- the thoracic (respiratory) pump through inhalations moves lymph from abdominal cavity to thoracic cavity

- the emptying of blood into the subclavian vein draws lymph with it

glymphatic system of the brain

are lymphatic-resembling vessels associated with neuroglia (astrocytes, who regulates the composition of the CSF-ISF mixture)

- intracerebral arteries and veins are surrounded by perivascular tunnels containing CSF and ISF (interstitial fluid)

- the veins drain the CSF-ISF mixture, residing in the subarachnoid space, via the lymphatic vessels in the meninges

- the lymphatic vessels empty into the lymph nodes in the neck

lymphoid cells

are a variety of cell types responsible for forming the different types of lymphoid tissue

- the cells are neutrophils, natural killer (NK) cells, T and B lymphocytes, macrophages, and dendritic cells

natural killer (NK) cells

are large lymphocytes that attack and destroy bacteria, transplanted tissues and host cells that have become infected with viruses or have turned cancerous

- part of innate immunity

T lymphocytes (T cells)

a lymphocyte that matures in the thymus and acts directly against antigens in cell-mediated immune responses

- dependent of thymic hormones

- part of adaptive immunity

B lymphocytes (B cells)

a lymphocyte that matures in the bone marrow and differentiates into plasma cells (connective tissue cells that secretes antibodies)

- part of adaptive immunity

macrophages

are very large, phagocytic cells of connective tissues that phagocytizes tissue debris, dead neutrophils, old erythrocytes, bacteria, and other foreign matter

- originates from monocytes

dendritic cells

are branched, mobile APCs (antigen presenting cells), found in the epidermis, mucous membranes, and lymphoid organs

- functions in alerting the immune system to pathogens that have breached the body surfaces

- engulfs foreign matter, migrate to a lymph node, and activates an immune reaction

red bone marrow

- responsible for hematopoiesis and immunity

- secretes colony-stimulating factors that stimulate HSC (hematopoietic stem cells) to produce CFUs (colony-forming units)

- is a primary lymphoid organ

- located in the axial skeleton, shoulder, hip girdle, proximal epiphysis

- is separated from osseous tissue by endosteum

thymus

a primary lymphoid organ that is a part of the endocrine and immune systems

- located in superior mediastinum and between the sternum and aortic arch

- functions in housing developing T cells/lymphocytes and the secretion of hormones to regulate them

- as one ages it involution and immunosenescene develops

involution

the degeneration and shrinking in size

- occurs to thymus with age

immunosenescene

immunity changes that occur with aging and their consequences

- older ppl increasingly become vulnerable to infections and cancer, and shows weaker responses to vaccinations

lymph nodes

is a secondary lymphoid organ and the most abundant lymphoid organ

- functions in cleansing lymph and sites of T and B lymphocyte activation

- causes lymphadenitis and lymphadenopathy

- common site of cancer

lymph node structure

and elongated, beanlike structure with

- a stroma of reticular connective tissue consisting of a capsule and trabeculae

- a parenchyma of lymphocytes and APCs with a cortex (contains germinal centers) and medulla

- lymphatic vessels: efferent (causing the hilum, indentation on one side of organ) and afferent

germinal centers of lymph node

where B cells multiply and differentiate into plasma cells

- occurs when lymph node is fighting a pathogen

afferent lymphatic vessels

Vessels that bring lymph draining from connective tissue into a lymph node

- are numerous in lymph nodes

efferent lymphatic vessels

3 vessels that transports filtered lymph away from the lymph node via the hilum

where are lymph nodes found?

they have a high concentration in the cervical, axillary, thoracic, abdominal, intestinal, inguinal, and popliteal regions

lymphadenitis

when a lymph node is under challenges by an antigen, it may become swollen or painful to touch

lymphadenopathy

the disease of the lymph nodes

cancer metastasis

cancer cells travel from the primary tumor to other sites of the body

- metastatic cells easily enter lymphatic vessels and travel in lymph to the nearest lymph node and multiply there (becomes a sentinel node)

tonsils

a secondary lymphoid organ that protects against ingested or inhaled pathogens

- located at the entrance to the pharynx

- have 3 main sets

- can cause tonsillitis

the 3 sets of tonsils

- a single medial pharyngeal tonsil (adenoids) on the wall of the pharynx behind the nasal cavity

- a pair of palatine tonsils at the posterior margin of the oral cavity

- numerous lingual tonsils that are concentrated in patches embedded in each side of the root of the tongue

tonsillitis

an acute inflammation of the palatine tonsils usually caused by a viral or bacterial infection

spleen

a secondary lymphoid organ that is largest lymphoid organ

- located inferior to the diaphragm, posterolateral to the stomach

- macroscopic structure contains the hilum (splenic artery and vein, and lymphatic vessels)

- microscopic structure consists of the parenchyma which has 2 types of tissue (red pulp and white pulp)

rep pulp

consists of sinuses filled with macrophages and erythrocytes

white pulp

consist of lymphocytes and macrophages surrounded by small branches of splenic artery

spleen function

- breaks up erythrocytes

- site of formed element production in fetus

- lymphocytes and macrophages, or white pulp, monitors blood for foreign antigens and maintains monocytes for release when needed

- stabilizes blood volume through plasma transfers to lymphoid system

immune system

defends the body against agents of disease, pathogens and some microbiomes

- it is not an organ system but exists as a cell population within all organs

- immune cells are concentrated in a true organ system, the lymphoid system

- 2 types of immunity: adaptive and innate

pathogen

A disease causing agent

- viruses, bacteria, fungi, and other microbes

microbiome

microorganisms that reside on and in the human body

- most are beneficial but some have the potential to be harmful

what are the bodies three lines of defense against pathogens?

- via the innate immunity the 1st line of defense is the external barriers and the 2nd line of defense is the internal defenses

- via the adaptive immunity the cellular and humoral immunities are the 3rd line of defense

first line of defense

consists of epithelial barriers, skin and mucosa membranes, which are impenetrable to most pathogens that assault us daily

second line of defense

consists of protections against pathogens that break through the external barriers

- leukocytes and macrophages, antimicrobial proteins, natural killer (NK) cells, fever, and inflammation

third line of defense

is via the adaptive immunity being composed of a group of mechanisms that not only defeat a pathogen but leave the body with a memory of it, enabling it to defeat it quickly in future interactions with the same pathogen

innate immunity

consists of defenses that we are born with that protects us from a broad spectrum of disease agents

- composed of the first and second line of defenses

- 3 kinds of defense: (1) protective proteins such as keratin, interferons, and complement; (2) protective cells like neutrophils and macrophages; (3) protective processes like fever and inflammation

adaptive immunity

has a capacity for immune memory by adapting the body to the presence of a pathogen so we become less vulnerable to the illness it would cause

characteristics of innate immunity

has a local effect, is nonspecific, and lacks memory

local effect of innate immunity

defends at point of invasion with little effect anywhere else in the body

- there are exceptions like fever having a systemic (whole body) effect

nonspecifity of the innate immunity

it protects against a broad spectrum of disease agents and not against just one particular pathogen

lack of memory in innate immunity

any prior exposure to a pathogen is forgotten so it is no easier to defeat that same pathogen again if exposed to it later

protective features of the skin

- toughness of keratin prevents many pathogens from penetration

- dryness and being nutrient poor prevent any support of microbial growth

- the continuous shed of the top dead layer of keratinocytes would remove any microbes adhered to it

- has an acid mantle, from sweat and sebum, composed of lactic and fatty acids that inhibit bacterial growth

- the secretion of antibacterial peptides (dermcidin, defensins, and cathelicidins) that kills microbes (bacteria, fungi, viruses)

dermcidin

an antibacterial peptide within sweat

defensins and cathelicidins

are antimicrobials secreted by keratinocytes, neutrophils, macrophages, and other cells

protective features of the mucous membranes

mucus is sticky which traps microbes and is moved by cilia to the pharynx to be swallowed and digested by the acidic enzymes of the stomach acid

- mucus, tears, and saliva contain lysozymes, an enzyme that destroys bacterial cell walls and therefore the bacteria itself

subepithelial areolar tissue of skin and mucus membranes

its ground substances contain hyaluronic acid (a giant glycosaminoglycan) which gives it a viscous (sticky) consistency that is difficult for microbes to migrate through

- some pathogens secrete hyaluronidase which breaks down the viscosity of hyaluronic acid

internal defenses

includes phagocytes, NK (natural killer) cells, antimicrobial proteins, inflammation, and fever

phagocytes

cells that engulf foreign matter

- neutrophils and monocytes

neutrophil role in immunity

wanders around in connective tissue killing bacteria

- uses neutrophil extracellular trap (NET) to trap and kill bacteria

- the degranulation of its lysozymes into the tissue fluid creates a killing zone, around the neutrophil, composed of highly toxic chemicals that destroy the bacteria

monocyte role in immunity

travels from blood and into connective tissue and transforms into macrophages that phagocytize pathogens, microbes, cellular debris, and foreign matter

macrophage system

all of the body's phagocytic cells except leukocytes

- includes monocytes, macrophages, dendritic cells and more

eosinophil role in immunity

found in mucous membranes and congregate at sites of allergy, inflammation, or parasitic infection to help phagocytize and degrade antigen-antibody complexes

- promotes the action of basophils and mast cells by stimulating them to release their substances

basophil role in immunity

they secrete chemicals that aid in the mobility and action of other leukocytes

- leukotrienes activates and attracts neutrophils and eosinophils

- histamine, a vasodilator, the inc flow of blood and delivery of leukocytes to the area

- heparin, an anticoagulant, which inhibits blood clotting that would otherwise impeded leukocyte mobility

mast cells

a type of connective tissue cell similar to basophils with its secretion of heparin, histamines, and leukotrienes

natural killer (NK) cells

are large granular lymphocytes that continually patrol the body in search for pathogens and diseased host cells

- attack and destroy microbes, transplanted cells, cells infected with viruses, and cancer cells

phagocytosis

the process in which viruses, bacteria, and other pathogens are phagocytized and digested by neutrophils and macrophages

- requires opsonization for the destruction of pathogens

opsonization

the coating of microbial cells with opsonins (proteins) that serves as a binding site for phagocyte attachment

- the "buttering up" of foreign cells to make them more appetizing to phagocytes

phagocyte mobilization

involves

- leukocytosis: WBC production

- margination, adhesion of phagocyte to vessel wall

- diapedesis: migrating through epithelial cells via their tight junctions

- chemotaxis: the attracting of phagocytes via chemicals

antimicrobial proteins

Proteins that inhibit microbial reproduction and provide short-term, nonspecific resistance to pathogenic bacteria and viruses

- interferons and complement proteins

interferons

are proteins secreted by cells infected with viruses and immune cells

- serves as an alarm to nearby cells to protect them from becoming infected

- activates macrophages and mobilize NK cells

how do interferons alert neighboring cells?

the secreted proteins bind to receptors on nearby cells, stimulating their synthesis of defensive antiviral proteins to block the viral reproduction of the viral DNA

complement system

is a group of 30+ defensive globular proteins that are synthesized by the liver, which contributes to innate and adaptive immunity

- inactive proteins continually circulate the blood system and are activated in the presence of pathogens

- outcomes: production of inflammation, immune clearance, phagocytosis, and cytolysis

complement system pathways

classical, alternative, and lectin pathways

classical pathway

requires the binding of an Ab to a microbes Ag which then changes the Ab shape and exposes the complement-binding sites

- complement C1 binds to the exposed complement-binding site which sets off a reaction cascade called the complement fixation

- requires an Ab to occur therefore is part of the adaptive immunity

alternative pathway

complement C3b binds to the microbe surface, activating a reaction cascade that leads to the accelerated splitting of more C3 into C3a and C3b

- a part of the innate immunity b/c doesn't require Ab

lectin

are plasma proteins that bind to carbohydrate

what occurs during inflammation?

C3a stimulates mast cells and basophils to secrete histamines and other inflammatory chemicals which activates and attracts neutrophils and macrophages (both are phagocytic to pathogens in inflammation) to the site

immune clearance

C3b binds antigen-antibody (Ag-Ab) complexes to RBCs

- as RBCs circulate through the liver and spleen, macrophages destroy the Ag-Ab complexes and leaves the RBCs unharmed

- this is how foreign matter is cleared from the bloodstream

phagocytosis in complement system

C3b coats microbial cells with proteins (opsonin) in order to be phagocytized by neutrophils and macrophages

cytolysis

1. C3b splits C5 (another complement protein) into C5a and C5b

2. C5b aggregates with other complement proteins to form a ring called the membrane attack complex (MAC)

3. MAC forms a hole in the target cell membrane causing electrolytes to leave the cell and water to flow rapidly in causing cell lysis (rupturing)

role of inflammation

it is a local defense response to tissue injury, of any kind, which helps to

- limit the spread of pathogens and destroys them

- remove debris from damaged tissue and initiate tissue repair

cytokines

small proteins that serve as chemical communication network among immune cells

- regulates inflammation and immunity

- alters the physiology of the receiving cell

- includes interferons, interleukins, tumor necrosis factor, chemotactic factors, and more

- involves 3 processes: mobilization of body's defenses, containment and destruction of pathogens, and tissue cleanup and repair

mobilization of defenses

this is achieved by local hyperemia (inc blood flow) which rapidly delivers leukocytes and washes toxins and metabolic wastes from the tissue more rapidly

- local vasodilation due to vasoactive chemicals (like histamines, leukotrienes, and other cytokines) which stimulate the endothelial cells to relax and widen the gaps between them (inc capillary permeability of fluid, leukocytes and plasma proteins)

- cell-adhesion molecules made by the endothelial cells aid in the recruitment of leukocytes b/c membranes are sticky causing margination of leukocytes

cardinal signs of inflammation

caused by mobilization

- redness: due to hyperemia and extravasted RBCs in the tissue

- swelling (edema): due to increased fluid filtration from the capillaries

- heat: from hyperemia

- pain: from direct injury to the nerves, pressure on the nerves from edema, stimulation of pain receptors by prostaglandins, bacterial toxins, and bradykinin

ectravasation

the leaving of cells and chemicals from the bloodstream

Lectin pathway

a lectin binds to certain sugars (carbohydrates) of a microbial cell surface and sets off another reaction cascade leading to the production of C3b

- a part of the innate immunity b/c doesn't require Ab

containment and destruction of pathogens

one priority of inflammation to prevent pathogens from spreading through the body

- fibrinogen, heparin, and neutrophils play big roles in this procedure