A&P 3: Exam 1

Lymphatic (lymphoid) system

(A set of tubes) circulatory system that drains and removes excess interstitial fluid (prevents edema)

• includes lymphatic vessels that penetrate most tissues, with lymphoid tissues/organs that produce immune cells

• prevents fluid accumulation in tissues

• the immune system is it’s second part (immune surveillance)

Lymphoid system: lymph (fluid)

clear, colorless fluid, similar to plasma, but low in protein

• can help return plasma proteins to the blood

• flows at low pressure

• stretching - stimulates contraction

• moved down the tubes by rhythmic contractions of lymphatic vessels, squeezing of skeletal muscles, rhymthic pulsations of nearby arteries, a thoracic (respiratory pump; breathing in/out), and rapod blood in subclvain veins draws lymph down the tubes

Fluid Recovery:

interstitial fluid that enters the lymphatic capillaries (fluid comes out of capillaries into interstitium, then goes from intersititum into the lympathic system)

• classified as ECF (extracellular fluid)

• ultimately returned to venous circulation (venous system)

• 1) maintains fluid balance between the blood and interstitial space

• 2) returned to the blood at the same rate it is produced

Lymphoid system: lymphatic capillaries

microscopic vessels that penetrate nealry every tissue, taking interstitial fluid by it’s gaps

• flow like the venous system (driven by skeletal mmuscle pump)

• contains one way valves (keeps flow in one direction)

• High pressure causes valves to shut pushing interstital fluid to the lymph nodes. low pressure opens them allowing fluid to come in (not on exam b/c confusing)

• assisted by the tunica media

• Absent from cartilage, cornea, osseous tissue, and bones/bone marrow (b/c they dont have lymphatic draining)

• very similar to how blood moves thru veins (skeletal muscle squeezing it)

• fluid comes out of gaps (some sources call it intercellular clefts)

• arteriole/venule capillaries secrete fluid and enter these capillaries

Lymphoid system: lymphatic vessels

made from lymphatic capillaries that penetrate nearly every tissue by transporting lymph to the lymph nodes. These vessels converge to form larger (11) lymphatic trunks (on test)

• made of: tunica interna, media and externa (thinner) much weaker structure compared to veins/can barely see them

Converges into two collecting ducts:

1) Right lymphatic duct: half of the system drain into the subclavian veins ( right arm, right thoracic region, and right side of the head, and a little bit of the liver) and lymph them become plasma, and empties into the subclavian vein (right side)

• right upper wuadrant of body drains to right subclavian vein via lympahtic duc

• 2) Thoracic duct: larger and longer, begins as a sac in abdomen called (cisterna chyli) receives lymph node from digestive system & rest of the body (whole bottom of the body, left side of the body, left side of the head, neck, and thorax) drain into the left subclavian vein via thoracic duct

lympahtic system: immune system & lymph nodes

lymph nodes flow thru lympathic nodes ( important for immune function)

• full of reticular tissue: helps filter out, trap, and detect foreign matter found in the lymph

• nodes are loaded with lymphocytes & macrophages *forms a gauntlet

Infection in the lympathic sysmtem?

infection occurs in the tissue first

• pathogens will go into the lymph nodes and flow thru a lymph node

• provides surveillance of the interstital fluid draining tissue that allow immune system to mount a defense against the infection

Edema in tissues

where rate of capillary filtration is greater than lymphatic removal causing accumulation of excess interstitial fluid

Two main causes:

1) Too much filtration (inflammation/trauma):

• increased Filtration coefficient (Kf) b/c increase in hydraulic conductivity of capillarly wall → capillaries become “leaky”

• increase Net filtration pressure (NFP) due to vasodilation and increase capillary pressure

• Seen in inflammation (“inflammatory soup”) and tissue injury

2) Lymphedema (next slide)

ALSO helps with tissue clean up:

• swelling compresses veins/reduces venous drainage

• forces open valves of lymphatic capillaries, promoting lymphatic drainage of bacteria, dead cells, and debris

immune system

not an organ system, but cell population that defends against pathogens/diseases and in concentrated in the lymphoid system

Two divisions:

• four primary categories of pathogens: bacteria, viruses, fungi, parasties

system must differentiate from “self” to “non-self” in order to destroy potential pathogens (based on surface proteins/cells/free substances that are normall found in our “self” cells/body fluids)

• include foreign markers called “antigens (immunogens)

Important: helps guard between mutations of our own cells (ex; tumors; cancer)

• everywhere in the body except avascular tissue

• confines infection to one region (smart) makes it easier to battle w/

lymph nodes

bean/kidney shaped struture that cleanse lymph (debris), are is site of lymphocyte activation.

• enclosed w/ fibrous capsule w/ trabeculae tha devide inferior into compartments

• parenchyma divided into cortex & medulla

• has ferminal center in cortex: where b-cells multiple and differencial in plasma cells

• several afferent lymphatic bessels lead into the mode along its convex surface

• lymph leaves node thru 1-3 efferent lymphatic vesells thay leave the hilum

• simplest organ and we see them in the neck, armpits, groin, gut!

• most numerous organ (apprx. 450 in trypical adult)

• picks up foreign chemicals in tissues that passes thru the nodes (organ), samples to see if theres anuthign fangerous

• helps isolate infections! (doesn;t allow infections to spread)

• contains lymphocytes and macrophages

lymphatic tissue

high density of lymphocytes (but scattered) in connective tissues of mucous membranes/organs

• ex of mucosa membranes: respiratory, digestive, urinary, and reproductive tract

• MALT: mucosa-associated lymphoid ___ or GALT if in gut

• macrophages are found densely here too (helps ingest & clean up (destory) pathogens, sending debris to the general circulation)

lymphocytes

lymph cells that have 11 of three branches?

• one of the top 5 WBC

• more associated w/imme system than other WBC

Lines of defenses against pathogens (immune system)

this division prevents pathogens (viruses, bacteria, fungi, & parasites) from producing diseases in body initially by physical barriers like…

1) First line defense: skin/mucous membranes as a barrier

2) Second line defense: protects when pathogens break thru skin/mucous membrane barriers (leukocytes & macrophages, antimicrobial proteins, natural killer cells, fever, & inflammation)

3) Third line defense: adaptive immunity, mechanisms that defeat a specific pathogen & leave body with memory of it.

• includes processes that react to a lot of “common markers”

• includes the 4 types of WBCs (myeloid): neutrophils, eosinophils, basophils, and monocytes as well as the macrophages (monocytes)

lymphoid organs

organs where lymphoid cells/tissues are concentrated

1) Primary organs: thymus, and bone marrow

• site where B & T cells become immunocompetent (able to recognize and respond to antigens)

2) Secondary organs: tonsils, lymph nodes, and spleen

• locations where immunocompetent cells migrate and populate (these take place in early embryonic development and move around to other sites living ur whole life)

• ex: mucosa (invaginations of the body) where pathogens are most likely to enter (ex: digestive tract, respiratory tract, and urogenital; urinary and reproductive tracts)

Lymphedema

A blockage in lymphatic system (lymphatic insufficiency) due to external compression and closing of lympathic vessels

• ex: when tumor grows and squishes lymphatic vessel

• primary lympathic insufficiency: congenital malformation

• secondary lymphatic insufficiency: due to trauma, tumor, surgery, etc

immune cells

found in the lymphatic tissues distributed to many areas of the body

• circulate thruout bloodstream and tissues of the body

• can move back and forth between capillaries & surrounding interstital fluids of the tissues into the lympathic circulation

• found everywhere except avascular tissues

Adaptive immunity: (immune system)

third line defense system that, recognizes and reacts to very specific pathogens, developed only w/ exposure and maintains immune memory (systemic effect)

• two types cellular and humoral

• ex: getting measles

• important to combat pathogens not removed by the innate immune system

• B & T cells are associated

• other two (non-myeloid) type of lymphocytes

cellular (cell-mediated) adaptive immunity

specfic defense where T lymphocytes directly attack/destory foreign cells/diseased host cells

• rids body of pathogens that reside inside human cells (parasitic worms, cance cells, transplanted cells) where theu are inaccessible to antibodies

• 4 classes of T-cells: Cytotoxic, Helper, Regulatory, Memoru

General stages: recognition, attack, and memory

cytotoxic T (tc) cells

carry attack out on another cell when the cell displays its antigen

• when it recognizes the complex of antigen/MHC-1 protein on the diseased/foregin cell it “docks” on that cell

• after docking it delivers a lethal hit of chemicals: perforin and granzymes (kill cells)

• interferons: inhibit viral replication activating/recruiting macrophages

• tumor necrosis factor (TNF) aid in macrophage activation and kills cancer cells

• only respond to MHC - 1 proteins

once it finishes its job it turns into a memory cell

Helper T (Th) cells

promote activites of other immune cells

• only respond to MHC-2 proteins

Regulatory T (Tr) cells

limit the immune response

Memory T (Th) cells

responsibe for immune primary response in celllular imunity

• long-lived

• more numerous than naive T cells

• fewer steps to be activated so they respond faster (T cell recall response)

humoral (antibody-mediated) adaptive immunity

mediated by antibodies that do not directly destory a pathogen but tag it for destruction

• useful for extracellular viruses, bacteriam yeasts, protzoans, and molecular (noncellular) disease agents like toxins and venoms

• ex: B-cells

Has Primary and Secondary responses

Normal Immune Physiology

when operating normally, pathogens are found and eliminated successfully

Natural active immunity

Production of one’s own antibodies/T-cells as a result of infection or natural exposure to antigen

• catching a cold

• innate immunity

Artifical active immunity

Production of one’s own antibodies or T-cells as a result of vaccination against disease

Vaccine

consists of dead/attenuated (weakened) pathogens that stimulate the immune response without causing the disease

• booster shots: given to restimulate immune mmeory to maintain high level of protection

Natural passive immunity

temporary immunity that results from antibodies produced by another person

• fetus acquires antibodies from mother thru placenta, baby acquries thru breast-feeding

• no memory

Artificial passive immunity

Temporary immunity that results form the injection of immune serum (antibodies) from another person or animal

• emergency treatment for snakebite, botulism, tetanus, rabies, etc.

• no memory

Pathological Immune Physiology

involve either excess activity or insufficient activity

• excess activity: exemplified by autoimmune disorders (system over-reacts/attacks itself) ex: allergies

• Insufficient activity: excess disease. ex: immunosuppression: immune function is unnatrually supresed and pathogens get out of control (ex: glucocorticoids; cortisol causes immunosuppression and excess secetion/administration causes pathogen invasion)

• ex: bone marrow stem cell disorder: lack of WBC production (leukopoiesis)

Physical barriers of the innate immune system

The epithelia (skin) is the first defense to prevent pathogenic entry into the tissues of the body

• integument made of a thick stratified epidermis that is kertinized (tough) have tight junctions and desmosomes making it difficut to be penetrated

• if penetrated, we have adipocytes of the hypodermis that secete anti-pathogenic secretons for prevention of pathogens

• weak barriers (not as thick): epithelial linings of the GI, respiratory or urogenital tracts (good target for pathogens)

• nose hairs, glandular secretions (antibacterial eye secretions): help filter out pathogens

• etc: mucus, coughing, or sneezing

Inflammation

a local defensive response to infection from pathogen.

• Due to trauma (physical damage, burns, etc)

purposes:

• helps remove debris from damaged tissue to initiate tissue repair

• helps promote repair and healing, preventing infection (b/c body is notifiyinh you to treat it).

• limiting spread of pathogen (then destroys)

• basophils and mast cells are activated

• involves LOTS of cytokines including interferon, interleukins, chemotactic factors, etc

Inflammation & fibrinogen

it filters into tissue fluid, clots to forma a sticky mesh that walls of microbes

• heparin prevents clotting at injury site

• here, pathogen is in a fluid pocket surorunded by clots

• it is then attacked by antibodies, phagocytes & other defenses

• after an hour, neutrophils come exhibiting chemostaxis when they leave: attracts bradykinin and leukotrienes

Cardinal signs of inflammation ON EXAM.

1) Redness (ruber): due to hyperemia

2) Swelling (tumor/edema): due to increased fluid filtration from capillaries

3) Heat (calor): due to hyperemia

4) Pain (dolor): injury to nerves creating prostaglandins

Inflammatory soup

includes heparin and histamine

mobilization of inflammation

The immediate requirement after tissue injury is to get defensive leukocytes to the site quickly (bc capillary gaps increase)

• due to hyperemia (increase in blood flow meaning more WBC & washes toxins/metabolic waste from site rapidly)

• vasoactive chemicals causes = local vasodilation (more WBC/filtration)

• includes histamine, leukotrienes, and other cytokines which are secreted by basophils, mast cells, & cels damaged by trauma, toxins, or organisms, triggering inflammation

Diapedesis (emigration) inflammation

leukocytes crawl through gaps in the endothelial cells *that are widened and enter tissue fluid

• extravasated: cells and chemicals that have left the blood stream

margination (inflammation

the ability of WBC to stick to the capillary wall easily, where it senses that inflammation is going on and near source of infection

Cytokines

small proteins that function in chemical communications between cells

• alter physiology of receiving cell (both local and systemic)

• includes interferons, interleukins, chemotactic factors

Basophils (leukocyte)

activated during inflammation, and reside in every tissue, they secrete most of the inflammatory “soup” (grp of mediators: cytokines) more associated with mucosa

1) local effects they secrete include:

• Prostaglandins: causes elevated sensitivity to paid (hyperalgesia)

• Bradykinin: causes pain directly (color)

• Histamine: causes vasodilation of local arterioles, increasing blood flow causing redness and heat, can lead to edema

• Heparin: inhibits coagulation (clot formation). Causes leakyness of capillary plasma (increase in hydraulic conductivity).

• leukotrienes: activate/attract neutrophils/eosinophils when infection involved

• cytokines: increase immune activity (stimulation of non-specific WBCs, macrophages & defenses) lots of positive feedback

Mast cells have similar functions to basophils but found in connective tissue and ARENT leukocytes!

Resolution: immune system

when the battle is won and damaged has repaired, inflammation shuts down.

• if this fails, chronic inflammation can occur leading to long lasting pathologies

Chemotaxis

ability of WBCs to move (taxis) torwards a source of infection where signals are concentrated (chemo)

Fever (pyrexia)

an abnormal elevation of body temperature due to a release of endogenous (produced from within) pyrogens targeting hypothalamus, a cytokine from an inflamed area, that circulate and target the hypothalamic thermoregulator

• due to trauma, infections, drug reactions, brain tumors, etc

• promotes interferon activity

• elevates metabolic rate to accelerate tissue repair

• inhibits reproduction of bacteria/viruses

• Interleukins-1: a cytokine that contributes to this effect

• stages are “onset”: temp begins to rise and “stadium” where it remains elevated

• exogenous pyrogens, byproduct of bacterial infection can cause same increase in temp (however, not adaptive)

• recovery is faster when not taking fever reducing medications (antipyretics)

Endogenous pyrogens

fever-producing agents originating from within body (peptides secreted by neutrophils, macrophages)

• These raise hypothalamic set point for body temperature

Exogenous pyrogens

fever-producing agents originating outside the body

• Examples: glycolipids on bacterial and viral surfaces

• Stages of fever: onset, stadium, defervescence

Phagocytes

A cellular defense, includes 2 types: microphage/macrophage cells that ingest foreign cells/debris by phagocytosis (internalized and broken down).

• attracted by inflammatory cytokines

• functions when leukocytes/macrophages don’t do their thing

microphages

Attack and engulf smaller pathogens and takes/cleanup debris

ex: defined as neutrophils and eosinophils (2/5 WBC)

• microfaded (can’t engulf)

• part of the innate system

macrogphages

These larger cells attack larger pathogens (parasites)

• Larger phagocytes derived from monocytes (a type of WBC)

1) Two types: Wandering & Fixed

• wandering: freely move thru tissues, patrolling for pathogens (attracted by cytokines signaling for an infection)

• fixed (dendritic cells): remain in a specific tissue (waits for pathogens to come) most dense at points of entry into the body (ex: Kupffer cells(stellate); liver, Langerhans cells; skin, histiocytes; connective tissue, microglial cells; central nervous system, microfold cells: gut)

Natural Killer (NK) Cells

Cells patrol body for pathogens/diseased host cells by attacking/destroying microbes, transplanted cells, cells infects by virus, cancer cells.

• attacks by secreting perforins (grp of proteins that lyse “punch a hole in” the plasma membrane of bacteria or pathogen)

• perforins inject granzymes into cell that help degrade cellular machinery & speed cell’s death.

• reliant on the expression of external markers to detect problems, bacteria

• type of lymphocyte a component of the innate immune system

Deficiency in these cells: higher rates of cancer & viral infections

• innate immunity

Interferons (antimicrobial Proteins)

class of cytokines that act locally (paracrine effector) and are secreted with two situations

1: common) secretes when a cell is infected by a viral infection (causes nearby cells to upregulate their antiviral defenses that interfere with viral replication) doesn’t prevent entry of viruses

• attract and increase activity of NK cells and macrophages to destroy cells/nearby cells that are also infected

Interferons: cancer

Secretes when fighting against certain cancers by promoting inflammation which promotes healing

• destroy the cell WE DO NOT HEAL IT

Complement activation

group of 30 or more globular proteins that contribute to both innate/adaptive immunity

• synthesized mainly by liver

• circulate in the blood when inactive (soluble) but turns (insoluble) when performing a pore that punches thru a cell (loses lots of electrolytes and H2O will get into the cell)

• can be activated by antibodies bound to antigens (helps indicate a foreign cell:inflammation) or common markers

• not normally confined to plasma but can enter interstital spaces during inflammation

Complement activation pathway

Includes:

1) classical pathway

2) Alternative pathway

3) Lectin pathway

Outcomes of complement activation

1) Inflammation: C3a stimulates mast cells/basophils to secrete histamine/other inflammatory chemicals

• activates and attracts neutrophils/macrophages

2) Immune clearance: C3b binds w/ antigen-antibody (Ag-Ab) complexes to RBC that circulate thru liver and spleen

macrophages of those organs strip off and destroy the (Ag-Ab) leaving RBCs unharmed

3) Phagocytosis: C3b coats microbial cells (opsonization) & attract and serve as binding sites for phagocyte attachment

3) Cytolysis: complement C3b initiates formation of C5b

• C5b aggregrates w other complement proteins within plasma membrane of microbe

• form membrane attack complex (a hole in the target cell membrane where elctrolytes leak out and water fows in rapidky, cell then ruptures: cytolysis)

• MAC (Membrane Attack Complex) forms this

classical pathway (complement activation)

Antibody binds to microbe, which changes antibodys shape exposing compleemt-binding sites

• binding of the complement C1 sets off a reaction cascade called “complenent fixation”

• macrophage punches hole into the ex: “bacterium”

Alternative pathway (complement activation)

complement C3b binds to microbe surface, activating reaction cascade

Lectin pathway (complement activation)

Lectins are plasma proteins that bind to carbohydrates

• iin the blood they bind to certain sugars on microbe surface, activating reaction cascade

B & T lymphocytes

A very small minority of cells that ciriculate in the bloodstream in order to exchange between lymphatic tissues and to access all vascular tissues

• found in the primary lympathic organs: Thymus and Red Bone Marrow

• limited in blood but we do blood test to figure out the amt #

• eflects the overall activity of the adaptive immune

  system.

antigen presenting cells (APCs) IMPORTANT

antigen cells that only present T cells interact with and can only recognize antigens on here (so T-cells disregard it)

• present via dendritic cells, macrophages, and B cells

• if ABC displays a non-self antigen the appropriate T cell will intiate an immune response against the source of the antigen.

• function depends on MHC proteins encoded by major histocompatability (MHC) complex genes

• acts as cell “identification tags” that label every cell of your body as belonging to you

• structurally unique to each individual, except for identitcal twins

Never let monkeys eat bananas (NLMEB)

• only these cells have MHC-2

Antigen processing

APC encounters antigen, internalizes it by endocytes, and digests it into fragments

• display fragments (epitopes) in the grooves of the MHC protein

MHC molecule/protein

interleukins

how APCs, T-cells and lymphocytes communicate with cytokines

• T-cells recognizes Ag-MHC complex then secretes it which then…

1) attract neutrophils and NK cells

2) Attract macrophages, stimulate their phagocytic activity, and inhibit them from leaving the area

2) stimulate T and B cell mitosis and maturation

Primary lymphatic organs: Thymus and Red Bone Marrow

involved in maturation of lymphocytes where they develop immunocompetence

• Red Bone Marrow: responsible for production of all formed elements of blood, including B & T lymphocytes (they mature here)

• T - cells exit and circulate and taken up by thymus where they undergo their final maturation

Secondary Lymphatic Organs and Tissues: Lymph Nodes

destinations for already immunocompetent lymphocytes

• lymph filters for detection of pathogens within interstital fluid. Infections generally occur in tissues and lympathic overflow from these regions

• indirectly monitor all tissues drained by lymphatics (ex: nervous tissue drained by lymphatics) everywhere! except avascular tissues

• approx. 450 nodes in a typical human

• placed on groin, axilla, and neck are extended to confine any infection to the limb or head and can’t expand to other regions

• A LOT found in the digestive organs to protect against pathogens (most vulnerable)

• swelling indicates exposure to a pathogen and response includes active division of the lympocytes within (hence why increase in size)

Spleen: Lymphatic system

The body’s largest lymphoid organ. It’s a lymphatic filter to monitor blood passing through.

• The sinusoid capillaries here are very leaky

• surrounding immune cells detect pathogens (infections) in blood

• also occasionally removes/recycle RBC (red pulp)

• first place to detect blood infection!!

• more organized than other diffuse lymphatic tissue (tonsils, lymph nodes)

Parenchyma *two types of tissue:

• red pulp: sinuses filled w/ erythrocytes

• white pulp: lymphocytes, macrophages surrounding small branches of splenic artery (monitors foreign antigens)

• medial hilum for passage of the BIG splenic artery, vein and lymphatic vessels

• if you lose this organ the liver can take over bc it has similiar functions (BUT highe risk of immune system failure)

Diffuse Lymphatic tissue

found within the mucosal that lines the lympathic tissue (MALT) of the gut, respiratory, and urogenitcal tracts

• dividing lymphocytes found here

• minimal organization here

Tonsils

patches of lymphoid tissue near the entrance of the pharynx that guard against inhaled/ingested pathogens (food/air), encapsulated by limited connective tissue

• considered an organ however less complex and organized

• covered by epithelium and lined by lymphoid nodules

• three main sets: single pharyngeal, palatine, and lingual

Antigen (immunogen) receptors

Any molecule (protein) that can bind an antibody

• most have large molecular weights (over 10,000 amu) and some structural complexity

basis of the specific immune system (SIS) associated with B &T lymphocytes

• it is antigenic (immunogenic) when it provokes an immune response from the SIS

• markers that have a unique shape nd form that usually involves a

  protein component (may involve carbs/lipids)

• provoke an immune response b/c it is “non-self”

• expressed on external surfaces of pathogens/byproduct (excretion) of a pathogen)

neutral debris (ex. animal hair, pollen) not harmful, can also provoke an immune response (allergic response)

Epitopes (antigenic determinants):

• expressed by B & T lymphocytes and consist of proteins thay bind to antigens w/ a “lock and key” specifivity based on shape and charge distributions of the antigen to enable an immune repsonse. (huge diversity of antigen receptors derived from DNA)

• only the light chain and part of the heavy chain has a antigen binding site

antibody classes

called GAMED five classes of antibodies

• anti-G’s

• anti-A’s

• anti-M’s

• anti-E’s

• anti-D’s

Thymus: Lymphoid Organ

Where t-cells mature in the epitherlial cells: secretes signaling molecules like thymosin, thymopoietin, thymulin, interleukins, and interferon (on exam)

• the 2nd lymphoid organ

• practically degenerates/gone by age 65 (b/c it’s js a bunch of fatty cells) meaning u stop producing t-cells (immune system decreases)

• has a fibrous capsule, gives off trabeculae that divides glands into several lobes

• lobes have cortex and medulla populated w/ t cells

Antigen receptor maturation

After maturation, immunocompetent cells travel through the blood stream and lymphatics to “seed” the

lymphatic tissues. From there further division can produce more copies of each clone containing that

unique antigen receptor and those copies can continue to mobilize and travel via the bloodstream to seed

other lymphatic tissues

• final cell lines are referred as “immunocompetent” (usually completed by 6 months of age; fetal stage)

B & T lymphocyte activation

1) Encounter and Recognition: antigen receptor binds to matching antigen; due to expression of the pathogen

• when lymphocyte binds it is activated

• starts dividing repeatedly. some copies form memory cells to enchance memory to recognize future antigen of the pathogen in the future (a repeated invasion)

• contribute to evenetrual response to pathogen (varies by type)

B - lymphocytes (B-cells)

responsible for antibody mediated aka humoral (adaptive) immunity

• develop in red bone marrow

• antibodies that maybe be free or bound to B-cells (also called immunoglobulins)

• composed of multiple proteins

• has specifice shape and charge distribution for non-self antigens

• self-tolerant cells synthesize antigen surface receptors, divide rapidly, produce immunocompetent clones

• leave bone marrow and colonize same lymphoid tissues and organs like T-cells

• if these cells react to self-antigens (they are go thru clonal deletion)

T lymphocytes (T cells)

cell in adaptive immunity

Three developmental stages:

• Birth in bone marrow

• Training in the thymus

• Deployment = to locations to carry out immune function ( shuffle thru bloodstream to lymphnodes, spleen, etc)

Proper development = immunocompetent: capable of recognizing antigens presented to them

• however can fail by reacting to the self-antigen whcih they are then eliminated (ensures that it’s “self-tolerant” meaning it wont attack one’s own tissue)

Responds to two classes of MHC protein:

1) MHC-1 Protein

2) MHC-2 Protein

T-cell activation

Beings when Tc or Th cell binds to a MHC protein displaying an epitope that the T cell is programmed to recognize

Constimulation: additional signaling process required for this activation

• MHC and antigen binding, T cells must also bind signaling proteins on surface of APC’s in damged, infected tissues

• helps ensure the immune system does not launch an attack in the absense of an enemy

Successful costimulation: triggers clonal selection

• activated t cell undergo mitosis

• creates identical T cell programmed against the epitope

• some cells become effector cells and carry out the attack

• other cells become memory cells

MHC-1 Protein

Occur on all nucleated cells, internal peptides are presented on cell surface

• ex: a liver cell (b/c it can easily get infected)

• RBC do not have MHC-1 bc not nucleated

• test question

MHC-2 Protein

occur on APCs, external (phagocytosed, foregin antigens are presented on cell surface

• test question

naive lymphocytes

T-cells that migrate to secondary lymphoid tissues and await their antigen

• haven’t been tested yet (not exposed to the real *bloodstream etc thing)

Free Type antibodies

these are release from extracellular fluids (humors) and bind to antigens causing: Neutralization, Agglutination, Antibody Opsonization, and Complement Activation

• humans have approx. 100 million floating in the body (ask) (we need this b/c a lot of things attack us our entire life)

• accomplished by: somatic recombination & tolerated hypermutation (bc we only have 20,000 genes)

somatic recombination: antibody

DNA segments shuffled and form new combinations of base sequences to produce antibody genes

Tolerated hypermutation: antibody

B cells in lymphoid nodules rapidly mutate creating new sequencies

Neutralization

A bound pathogen is often a disabled pathogen that cannot perform its pathogenic function.

• (toxin, virus, microbial cell)

Agglutination

Some types especially bind (clump) many pathogens together and these large clusters are easier to remove by the spleen and liver and the macrophages within the tissues.

Antibody Opsonization

When bound, the constant region of the antibody changes configuration

and allows macrophages to more easily recognize, bind, and ingest the antigenic pathogen or toxin (similar to complement opsonization).

• Unbound antibodies are invisible to the macrophages.

Antibody Classes: IgG

dominant monomer form, include approx. 80% of the circulating free antibodiesmin the body.

• found primarily in plasma and heavy region is excellent at activating complement and opsonizing bacteria. They are the class that is most able to transfer across the placenta into fetal tissue from maternal blood.

• dominate in secondary immune response, capable of complement fixation

• donating plasma to ppl who don’t have a lot

Antibody Classes: IgE

monomer associated w/ activation of basophils/mast cells and initiating and amplifying inflammation.

• IMPORTANT: involved pathologically in allergies and hypersensitivity reactions.

• stimulates release of histamine/chemical mediators of inflamamtion & allergies

• stimulates eosinophils defensive actions against parasites

Antibody Classes: IgM

forms a pentamer of antibodies (10 antigen binding sites) and are especially good at agglutination (causes things to stick tgt)

• This class also activates complement well.

Antibody Classes: IgA

associated with secretions (tears, saliva, vaginal, prostatic, bronchial, and gut secretions, mothers’ milk; coats internal digestive tract of newborn providing protection before the infant’s immune system is fully functional.

• good at blocking ability of a pathogen to adhere to epithelia

• tougher and more resistant to damage that might occur in these areas where they are secreted (pH fluctuations for example).

Antibody classes: IgD

expressed on the surface of B cell transmembrane antigen receptor - lymphocytes (cells)

• an immunoglobulin

B-cell activation

has antibodies attached to their cell surfaces (IgD) and when a matching antigen binds to these membranebound antibodies, the cell is “activated”.

• when activated, cell begins to divide and produce two cells of the same clonal cell line

1) Memory Cells

2) Plasma Cells

Also activate “Helper” T-Cells aplifying processes (secretes interleukins)

• acts as antigen presenting cells (APCs) simialar to macrophages when they encounter a pathogen.

• has thousands of surface receptors for one antigen

• antigen binds to several of these receptors, links them tgt, and is taken into the cell b yreceptor-mediated endocytosis

• cell processes (digests) the antigen, then displays antigen fragments with MHC-II on its surface

• DOESNT KILL CELL triggers clonal selection

• B cell mitosis gives rise to clons of identical B cells programmed agains same antigen

• mosy differentiaye into plasma celss

• plasma cells secrete antibodie sat a rate of 2,000 molecules per second during their life span of 4 to 65 days

• - firs exposure to antigen triggers production og IgM antibodies later exposures to the same antigen, IgG

• antibodies travel thru body in blood other body fluids

Memory Cells: B cells

These are copies of the same cell line that do not do anything immediately.

• may respond more immediately to more of the pathogen and amplify the other effects below after being

activated, or they may wait for another invasion of the same pathogen. They may remain dormant

for more than 20 years providing enhanced “memory” of that pathogen which is the basis of

acquired immunity (below).

• secreted from B-cells

Plasma Cells: B cells

These copies begin production of the antibodies that match the encountered

pathogen. Many antibody copies will be formed and secreted to the tissue and enter the

bloodstream for distribution throughout the body, though they will be most concentrated in the

same region where the pathogen was encountered. The free antibodies will attack that pathogen as

above through neutralization, etc.

• secreted from B-cells

microbiome

microorganisms that reside on/in the body

• can be beneficial/harmful

• constantly exposed to potential harmful microrganisms from external/outside environment

• protected by the immune system

Lymphoid system: Lacteal

these are in the small intestines and absorbs dietary lipids (vitamins and fat-soluble ADEK) that aren't absorbed in blood capillaries

subclavian veins: lymphatic vessels

where the fluid gets funneled from collecting ducts into the subclavian vein

• low pressure system

• one way flow builds up (gets pushed) fluid to get from vessels to veins

lymphoid nodules (follicles): lymphoid tissue

where lymphocytes and macrophages gather in dense masses

• can be temporary/permanent on some tissues

• pyres matches: lymphoid nodules in the small intestine

Red Bone Marrow: Lymphoid Organs

soft, loosely organized, high vascular material seperated from osseous tissue by endosteum of bone

• involved in hematopoiesis (blood formation) and immunity

• blood-forming cells attached to reticular cells/other elements of marrow stroma

• secretes colony-stimulating factors that stimulate stem cells to produced formed elements (erythropoietin)

• as blood cells mature (B-cells), they push their way thru the reticular/endothelial cells to enter sinu and flow away in blood stream

• doesn’t have lymphatic draining

Pharyngeal tonsil (adenoids)

A single tonsil on the wall of the pharynx

Palatine tonsils

a pair of tonsils at the posterior margin of oral cavity

• the standard tonsils you get removed if you have a tonsillectomy/adenoidectomy

Linguinal tonsils

numerous tonsils concentrated on each side of the base of the tongue

Tonsillitis

acute inflammation of palatine tonsils