انتي عمري وكل حیاتي وانتي دنیاتي وھلياليعمرچ كل عمري انا باقي وانتي كل الچ

ابقى للكبر ویاچوانتي روحي ونبض گلبي اني حالف ألخر ایام العمر اعوفچما

عني الغالي مالي گلتيیادمع الجرح اوف مالچالغالي عفتي ھسھ

غالي غالي گلتي غالي

ما شفتھمعمت عیني علیھم احبابي من مشو ما ودعتھم وین اروح من الجروح شسوي بفراگچمدري

حبیبة انتي چنتي بجسمي روح چنتيانتي ما تغمض عیوني وعادي بفراگچ انام راح شلون

جرحي وبعد میفید الكالممن السما للگاع روحھ للتاليعفتي ورحتي

بعید عنچانتي تربیتي واعرفچ حتى لو الحچي ھذا جدیدمو حچیچ ل عرفھ ھذا

یا بعد القلبیجري دمعي چان دمعچ گبلچنتي جنتي وناري انتي

نور الزین/ الغالي مالي

4 functions of the lymphatic system

• Lymphatic capillaries absorb excess tissue fluid and return it to the bloodstream

• Lymphatic capillaries (lacteals) in the small intestine absorb fats in the form of lipoproteins and carry them to the blood

• Responsible for the production, maintenance and distribution of lymphocytes in the body

• Helps in defense against pathogens

Closely related to the CVS.

components of the lymphatic system

Lymphatic vessels

• One-way valve system that carries fluid called lymph, composed mainly of water, but also solutes (nutrients, electrolytes, gases, hormones and enzymes). It is colorless but after a meal it becomes creamy (lipid).

• Made of capillaries, vessels and ducts. Movement of lymph is *one direction* and is aided mainly by the muscle contraction.

• Functions to return tissue fluid (includes water, solutes and cell products) to the bloodstream ( Thoracic duct is the largest and collects lymph from body below the thorax, left arm and left side of head and neck into left subclavian vein, AND Rt Lymphatic duct collects lymph from the right arm, and right side of the face and neck into the right subclavian vein)

• The larger vessels are similar in structure to veins and even have valves

Elephantiasis of leg due to filariasis

Classifying lymphatic organs

• Primary– Red bone marrow– Thymus gland

• Secondary– Lymph nodes and spleen

Primary lymphatic organs

Red bone marrowSite of blood cell productionMost bones in children have red marrow and it decreases as we age (in adult, sternum, vertebrae, ribs, part of pelvic girdle, and upper ends of femur and Humerus)Produce in addition to RBC, the WBC (eosino-, baso-, neutrophils, lymphocytes and monocytes), B lymphocytes mature in bone marrow before enter circulation. T Lymphocytes mature in Thymus. Any B lymphocyte that reacts to body cells is removed in the bone marrow and not enter the circulation.

Primary lymphatic organs• Thymus gland

– Bilobed gland found in the thoracic cavity superior to the heart– Largest in children and shrinks as we age– Has TWO functions 1- Production of Thymosin2- Maturation of T lymphocytes: Immature T lymphocytes move from the

bone marrow to the thymus where they mature (By Thymosin). Only 5% leave the thymus after passing the critical test.

– Critical Test: If T lymphocytes attack the individual’s cells, they die. BUT if they have the potential to attack pathogens, they leave the thymus to circulation

Secondarylymphaticorgans• Lymphnodes

– Small,oval-shapedstructures,dividedbyconnectivetissueintocompartments(withsinuses,whicharebiggeratthecenter).LymphflowingthroughsinusesisfilteredandpurifiedbyLymphocytes (attackpathogensandcancercells),andmacrophages (engulfbacteriaanddebris).

– Commonintheneck,armpit(axillary)andgroin(Inguinal)regions

• Spleen– Intheupperleftregionoftheabdominalcavity– Composedofwhitepulpcontaininglymphocytes andredpulp (surroundvenoussinuses)isinvolvedwithfilteringtheblood.Thincapsulesoraptureeasily.

Lymphaticnodules(withnocapsule,eg.Tonsils).Peyer’sPatches,appendix

Lymphatic nodules (no capsule)TonsilsPeyer’s patches (Appendix)

Form a ring of lymphoid tissue around the entrance to the pharynx3 main sets:Palatine: Located on either side of the posterior oral cavity. Largest and infected most oftenLingual: Lie at the base of the tonguePharyngeal Found in the posterior wall of the nasopharynx. Called adenoids when infected

Tonsils

Nonspecificdefenses:Thefirstlineofdefense

• Physicalbarriers– Skin– Tears,sweat,salivaandurinephysicallyflushoutmicrobes– Mucousmembranes(ciliated)linetherespiratory,digestive,

reproductiveandurinarytracts.– Residentbacteria/normalflorathatinhabitthebodyuseavailable

nutrientsandspacethuspreventingpathogensfromtakingupresidence

• Chemicalbarriers– Secretionsoftheoilglands– Lysozymefoundinsaliva,tearsandsweat– AcidicpHofthestomachandvagina

Secondlineofdefense

1. Phagocytosis.2. Inflammation.3. Protectiveproteins.

1- Phagocyticwhitebloodcells

• Includesneutrophilsandmacrophages

• Bothleavecirculationandmoveintotissue

2- Inflammatoryresponse

• Fourhallmarksymptomsareredness,heat,swellingandpain

• Histamine isreleasedbydamagedandmastcells causesthecapillariestodilateandbecomemorepermeableincludingtophagocyticwhitebloodcells

• Increasedbloodflowtoanareaincreasesthe warmth thatinhibitssomepathogens

• Increasedbloodflowalsobringsmorewhitebloodcellstoaninjuredareawith neutrophils beingthefirstscoutstokillpathogens

• Thisresponsecanendhere,butiftheneutrophilscannotcontrolthedamagetheywillsecretcytokines(chemicals)whichwillcallinmorewhitebloodcellsincludingmacrophages

• PUS; yellow-whitesubstancecomposedofabignumberofdeadordamagedneutrophils

Summaryoftheinflammatoryresponse

Dolor (Pain)Calor (Heat)Rubor (Redness)Tumor (Swelling)Functio Laesa (Loss of function)

3- Protectiveproteins• Complement:

– Groupofbloodplasmaproteins– 1- Involvedintheinflammatory

responsebybindingtomastcellstoreleasehistamine

– 2- Attractphagocytes topathogenssites.

– 3- BindtopathogensalreadymarkedbyAbs,ensuringthattheywillbeengulfedbyneutrophils,macrophages,ordendriticcells.

– 4- Forma membraneattackcomplexthatmakeholesinsomebacteriaandvirusesthatcausesthemtoburst

• Interferon:– Proteinsproducedbyvirally

infectedcellssentouttowarnneighboringhealthycellstoproducesubstancesthatinterferewithviralreplication Activated when some Ags attached to them.

The complement proteins may also be activated by the Ag-Ab complex.

TheImmuneSystemistheThirdLineofDefenseAgainstInfection

Whatdothespecificdefensesinclude?

• Thirdlineofdefense:– Helpsprotectusagainstspecificpathogenswhennonspecificdefensesfail

– ThereexistmillionsofAg.(diversityofBandTlymphocytes)

– Helpsprotectusagainstcancer– DependsontheactionofBandTcells(lymphocytes)

SummaryofthetypesofBandTcells

Thirdlineofdefense:Antibody-mediatedimmunitybyBcells

• EachBcellhasauniquereceptorcalledaBCRthatbindsaspecificantigen

• ThisbindingandcytokinessecretedbyhelperTcellsresultinclonalexpansioninwhichthisBcellmakescopiesofitself

• Mostofthecellsproducedareplasmacellsthatsecreteantibodies

• Othercellsbecomememorycellswhichresultinlong-termimmunity

• Afteraninfectionhaspassedplasmacellsundergoapoptosis(programmedcelldeath)leavingmemorycells

• Atleast2millionsdifferentAbsareproducedbyplasmacells.

Antibody-mediatedimmunitybyBcells

CharacteristicsofBcells

Structureofantibodies• AY-shapedprotein,heavyandlight

chains.

• ThetrunkoftheYisaconstantregionthatdeterminestheclassoftheantibody.AntibodiescanbeoneYmolecules(monomer)ortwo(dimer)ormultiple(pentamers *5*,astheM-Ab)

• Theendofthearms(Y)arethevariableregionswherespecificantigensbind.

• HowAbswork?:Neutralization.(AbsurroundAg)Immune-complex(Ag-Abcomplexattackedbywbcs),whichattractsotherwbcs.

Whatarethe5classesofantibodies?

CharacteristicsofTcells

This week and next week lectures:Sundays: PhysiologyMondays and Thursdays: Anatomy

Thirdlineofdefense:Cell-mediatedimmunitybyTcells

• Each T cell has a unique receptor called a TCR that will recognize a piece of an antigen with the help of an antigen-presenting cell (APC)

• An APC engulfs an antigen, breaks it down and presents it on its surface in association with a membrane protein called an MHC *Major histocompatibility complex* (called human leukocyte antigens in humans or HLA) then presents it to T cells in the lymph node or spleen

• The T cell will specifically recognize the combination of the HLA protein and the piece of antigen

• Clonal expansion will occur leading to mostly helper T cells, cytotoxic T cells and a few memory T cells

• After an infection has passed, helper and cytotoxic T cells undergo apoptosis leaving memory cells

Cell-mediatedimmunitybyTcellsHLA I protein (presented by APC): Will activate the T cells that will form cytotoxic T cells.

If APC presents the antigen on HLA II: The activated T cell will form Helper cells.

(Helper cell is needed by both types of immunity because it secretes the cytokines). HIV infects mainly Helper T cell.

Cancer cell Presents Ag on HLA-I T-cell recognition

Formation of cytotoxic T-cell Killing the cell having the cancer

Pathogen phagocytized by Macrophage Ag presented on HLA-II Helper T cell activation

Cytotoxic T-cell B-cells clone

Plasma cells

Killing the virus or pathogen infected cell Ab against Ag

Antigen

Macrophage

Helper T - Cell

Active Cytotoxic T-Cell Active B - Cell

Kills Infected Cells Memory T- Cell Plasma Cell Memory B-Cell

Antibodies

Deactivates Antigens

Displays copy of antigen on surface of cell

Cellular Immunity Antibody Immunity

Summary Of Immune response

HelperandcytotoxicTcells

• HelperTcells:– Secretecytokinesthathelp

manyimmunecellsfunction(Bcellscannotbeactivatedwithoutit)

– HIV(aids)infectsThelpercells

• CytotoxicTcells:– Havevacuolescontaining

granzymesandperforins– Perforins punchholesin

targetcellsfollowedbygranzymes thatcausethecelltoundergoapoptosis

Immunity• Istheabilitytocombatdiseasesandcancer

• Canbebroughtaboutnaturallythroughaninfectionorartificiallythroughmedicalintervention

• Therearetwotypesofimmunity:activeandpassive

Activeimmunity• Theindividual’sbodymakesantibodiesagainstaparticular

antigen

• Thiscanhappenthroughnaturalinfectionorthroughimmunizationinvolving vaccines

• Primaryexposureisshorter-livedandslowertorespondwhileasecondaryexposureisarapid,strongresponse

• Thistypeofimmunityisusuallylong-lasting

• ItdependsonmemoryBandTcells

Examplesofimmunizations:atypeofactiveimmunity

Passiveimmunity• Anindividualisgiven

preparedantibodiesagainstaparticularantigen

• Thistypeofimmunityisshort-lived

• Thiscanhappennaturallyasantibodiesarepassedfrommothertofetusorartificiallyviaaninjectionofantibodies