1 maintain fluid balance protect body from infection and disease lymphatic and immune systems
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Maintain fluid balanceMaintain fluid balance Protect body from infection and diseaseProtect body from infection and disease
Lymphatic and Immune Lymphatic and Immune SystemsSystems
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ImmunityImmunity fluids from all capillary beds are filteredfluids from all capillary beds are filtered immune cells stand ready to respond to foreign cells or immune cells stand ready to respond to foreign cells or
chemicals encounteredchemicals encountered
Lipid absorptionLipid absorption Lacteals in small intestine absorb dietary lipidsLacteals in small intestine absorb dietary lipids
Fluid recoveryFluid recovery absorbs plasma proteins and fluid from tissues and returns absorbs plasma proteins and fluid from tissues and returns
it to the bloodstreamit to the bloodstream• interference with lymphatic drainage leads to severe edemainterference with lymphatic drainage leads to severe edema
Functions of Lymphatic SystemFunctions of Lymphatic System
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Lymph and Lymphatic Lymph and Lymphatic CapillariesCapillaries
LymphLymph clear, colorless fluid, similar to plasma but much clear, colorless fluid, similar to plasma but much
less proteinless protein Lymphatic capillariesLymphatic capillaries
closed at one endclosed at one end tethered to surrounding tissue by protein filamentstethered to surrounding tissue by protein filaments endothelial cells loosely overlapped endothelial cells loosely overlapped
• allow bacteria and cells entrance to lymphatic capillaryallow bacteria and cells entrance to lymphatic capillary• creates valve-like flaps that open when interstitial fluid creates valve-like flaps that open when interstitial fluid
pressure is high, and close when it is lowpressure is high, and close when it is low
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Lymphatic CapillaryLymphatic Capillary
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Lymphatic VesselsLymphatic Vessels
Larger ones composed of 3 layersLarger ones composed of 3 layers tunica interna: endothelium and valvestunica interna: endothelium and valves tunica media: elastic fibers, smooth muscletunica media: elastic fibers, smooth muscle tunica externa: thin outer layertunica externa: thin outer layer
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Valve in a Lymphatic VesselValve in a Lymphatic Vessel
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Route of Lymph FlowRoute of Lymph Flow Lymphatic capillariesLymphatic capillaries Collecting vessels: Collecting vessels: course through many lymph nodescourse through many lymph nodes
Lymphatic trunks: Lymphatic trunks: drain major portions of bodydrain major portions of body
Collecting ducts : Collecting ducts : right lymphatic duct – receives lymph from R arm, R side of right lymphatic duct – receives lymph from R arm, R side of
head and thorax; empties into R subclavian veinhead and thorax; empties into R subclavian vein thoracic duct - larger and longer, begins as a prominent thoracic duct - larger and longer, begins as a prominent
sac in abdomen called the cisterna chyli; receives lymph sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, L arm, L side of head, neck and from below diaphragm, L arm, L side of head, neck and thorax; empties into L subclavian veinthorax; empties into L subclavian vein
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The Fluid CycleThe Fluid Cycle
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Lymphatic Drainage of Lymphatic Drainage of Mammary and Axillary RegionsMammary and Axillary Regions
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Drainage of ThoraxDrainage of Thorax
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Mechanisms of Lymph FlowMechanisms of Lymph Flow Lymph flows at low pressure and speedLymph flows at low pressure and speed Moved along by rhythmic contractions of lymphatic Moved along by rhythmic contractions of lymphatic
vesselsvessels stretching of vessels stimulates contractionstretching of vessels stimulates contraction
Flow aided by skeletal muscle pumpFlow aided by skeletal muscle pump Thoracic pump aids flow from abdominal to thoracic Thoracic pump aids flow from abdominal to thoracic
cavitycavity Valves prevent backward flowValves prevent backward flow Rapidly flowing blood in subclavian veins, draws Rapidly flowing blood in subclavian veins, draws
lymph into itlymph into it Exercise significantly increases lymphatic returnExercise significantly increases lymphatic return
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Cells are created in the bone Cells are created in the bone marrowmarrow
Lymphocytes are created in the bone Lymphocytes are created in the bone marrow. 2 types- T and B cellsmarrow. 2 types- T and B cells
B cells mature in the bone marrowB cells mature in the bone marrow T cells mature in the thymus gland by T cells mature in the thymus gland by
secretion of thymosinsecretion of thymosin
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Lymphatic CellsLymphatic Cells Natural killer (NK) cellsNatural killer (NK) cells
responsible for immune surveillanceresponsible for immune surveillance
T lymphocytes- T helper and suppressorT lymphocytes- T helper and suppressor mature in thymusmature in thymus
B lymphocytesB lymphocytes activation causes proliferation and differentiation into activation causes proliferation and differentiation into
plasma cells that produce antibodiesplasma cells that produce antibodies
Antigen Presenting CellsAntigen Presenting Cells macrophages macrophages (from monocytes)(from monocytes) dendritic cells dendritic cells (in epidermis, mucous membranes and lymphatic (in epidermis, mucous membranes and lymphatic
organs)organs) reticular cells reticular cells (also contribute to stroma of lymph organs)(also contribute to stroma of lymph organs)
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Lymphatic OrgansLymphatic Organs
At well defined sites; have CT capsulesAt well defined sites; have CT capsules Primary lymphatic organsPrimary lymphatic organs
site where T and B cells become site where T and B cells become immunocompetentimmunocompetent
red bone marrow and thymus red bone marrow and thymus Secondary lymphatic organsSecondary lymphatic organs
immunocompetent cells populate these immunocompetent cells populate these tissuestissues
lymph nodes, tonsils, and spleenlymph nodes, tonsils, and spleen
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LymphadenopathyLymphadenopathy
Collective term for all lymph node Collective term for all lymph node diseasesdiseases
LymphadenitisLymphadenitis swollen, painful node responding to foreign swollen, painful node responding to foreign
antigenantigen Lymph nodes are common sites for Lymph nodes are common sites for
metastatic cancermetastatic cancer swollen, firm and usually painlessswollen, firm and usually painless
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Lymph NodeLymph Node
Fig. 21.12 a and b
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Location of TonsilsLocation of Tonsils
Palatine tonsilsPalatine tonsils pair at posterior margin of oral cavitypair at posterior margin of oral cavity most often infected most often infected
Lingual tonsilsLingual tonsils pair at root of tonguepair at root of tongue
Pharyngeal tonsil (adenoid)Pharyngeal tonsil (adenoid) single tonsil on wall of pharynxsingle tonsil on wall of pharynx
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ThymusThymus
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SpleenSpleen
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Defenses Against PathogensDefenses Against Pathogens Nonspecific defenses - broadly effective, no prior exposure – Cell Nonspecific defenses - broadly effective, no prior exposure – Cell
mediated – T lymphocytemediated – T lymphocyte Cell mediated = T cell attacks cells that have been infected with a Cell mediated = T cell attacks cells that have been infected with a
bacteria or virusbacteria or virus first line of defensefirst line of defense
• external barriersexternal barriers second line of defensesecond line of defense
• phagocytic cells, antimicrobial proteins, inflammation and phagocytic cells, antimicrobial proteins, inflammation and feverfever
Specific defense - results from prior exposure, protects against only Specific defense - results from prior exposure, protects against only a particular pathogen – Humoral response – B lymphocyte- antibody a particular pathogen – Humoral response – B lymphocyte- antibody
third line of defensethird line of defense• immune systemimmune system
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External BarriersExternal Barriers SkinSkin
toughness of keratintoughness of keratin dry and nutrient-poordry and nutrient-poor defensins: peptides, from neutrophils attack defensins: peptides, from neutrophils attack
microbesmicrobes Mucous membranesMucous membranes
stickiness of mucus stickiness of mucus lysozyme: enzyme destroys bacterial cell wallslysozyme: enzyme destroys bacterial cell walls
Subepithelial areolar tissueSubepithelial areolar tissue tissue gel: viscous barrier of hyaluronic acidtissue gel: viscous barrier of hyaluronic acid
• hyaluronidase: enzyme used by pathogens to spreadhyaluronidase: enzyme used by pathogens to spread
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Complement SystemComplement System
Complement (C) proteins in blood that Complement (C) proteins in blood that must be activated by pathogens. Named must be activated by pathogens. Named because they “compliment” the work of because they “compliment” the work of antibodies.antibodies.
Produced in the liverProduced in the liver
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Complement SystemComplement System
Mechanisms of actionMechanisms of action enhanced inflammationenhanced inflammation phagocytosis phagocytosis
• promoted by opsonizationpromoted by opsonization cytolysis cytolysis
• membrane attack complex forms on target cellmembrane attack complex forms on target cell immune clearanceimmune clearance
• RBCs carry Ag-Ab complexes to macrophages in RBCs carry Ag-Ab complexes to macrophages in liver and spleenliver and spleen
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Membrane Attack ComplexMembrane Attack Complex Complement proteins form ring in plasma Complement proteins form ring in plasma
membrane of target cell causing cytolysismembrane of target cell causing cytolysis
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Immune SurveillanceImmune Surveillance
NK cells NK cells destroy bacteria, transplanted cells, cells destroy bacteria, transplanted cells, cells
infected by viruses, and cancer cellsinfected by viruses, and cancer cells• release perforins and granzymesrelease perforins and granzymes
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Action of NK cellAction of NK cell
Fig. 21.17
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InflammationInflammation
Defensive response to tissue injuryDefensive response to tissue injury1.1. limits spread of pathogens, then destroys limits spread of pathogens, then destroys
themthem2.2. removes debrisremoves debris3.3. initiates tissue repairinitiates tissue repair
CytokinesCytokines small proteins regulate inflammation and small proteins regulate inflammation and
immunity; includeimmunity; include• interferons, interleukins, tumor necrosis factor, interferons, interleukins, tumor necrosis factor,
and chemotactic factorsand chemotactic factors
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InflammationInflammation Suffix Suffix -itis -itis denotes inflammation of denotes inflammation of
specific organsspecific organs Cardinal signsCardinal signs
redness redness (erythema) caused by hyperemia ((erythema) caused by hyperemia ( blood flow)blood flow)
swelling swelling (edema) caused by (edema) caused by capillary capillary permeability and filtrationpermeability and filtration
heat heat caused by hyperemiacaused by hyperemia pain pain caused by inflammatory chemicals caused by inflammatory chemicals
(bradykinin, prostaglandins) secreted by damaged (bradykinin, prostaglandins) secreted by damaged cells, pressure on nervescells, pressure on nerves
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InflammationInflammation
Three major processesThree major processes1.1. mobilization of body defensesmobilization of body defenses
2.2. containment and destruction of pathogenscontainment and destruction of pathogens
3.3. tissue clean-up and repairtissue clean-up and repair
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Mobilization of DefensesMobilization of Defenses
Histamine and leukotrienes are secreted by Histamine and leukotrienes are secreted by damaged cells, basophils and mast cellsdamaged cells, basophils and mast cells stimulates vasodilation that leads to hyperemiastimulates vasodilation that leads to hyperemia
• causes redness and heatcauses redness and heat local metabolic rate, promotes cell multiplication and local metabolic rate, promotes cell multiplication and
healinghealing
• dilutes toxins, provides Odilutes toxins, provides O22, nutrients, waste removal, nutrients, waste removal
stimulates stimulates permeability of blood capillaries permeability of blood capillaries• allows blood cells, plasma proteins (antibodies, complement allows blood cells, plasma proteins (antibodies, complement
proteins, fibrinogen) into tissueproteins, fibrinogen) into tissue• clotting sequesters bacteria, forms scaffold for tissue repairclotting sequesters bacteria, forms scaffold for tissue repair
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Mobilization of DefensesMobilization of Defenses Leukocyte Leukocyte
DeploymentDeployment marginationmargination
• selectins cause selectins cause leukocytes to leukocytes to adhere to blood adhere to blood vessel wallsvessel walls
diapedesis diapedesis (emigration)(emigration)• leukocytes leukocytes
squeeze between squeeze between endothelial cells endothelial cells into tissue spaceinto tissue space
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Containment and Destruction of Containment and Destruction of PathogensPathogens
Fibrinogen Fibrinogen now in tissue clots, trapping pathogensnow in tissue clots, trapping pathogens
Heparin Heparin prevents clotting at site of injuryprevents clotting at site of injury pathogens are in a fluid pocket surrounded by clotpathogens are in a fluid pocket surrounded by clot
ChemotaxisChemotaxis leukocytes are attracted to chemotactic chemicals leukocytes are attracted to chemotactic chemicals
Neutrophils are quickest to respond Neutrophils are quickest to respond phagocytosis phagocytosis respiratory burstrespiratory burst secrete cytokines for recruitment of macrophages and secrete cytokines for recruitment of macrophages and
neutrophilsneutrophils macrophages and T cells secrete colony-stimulating factor macrophages and T cells secrete colony-stimulating factor
to stimulate leukopoiesis to stimulate leukopoiesis
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Tissue CleanupTissue Cleanup
Monocytes the primary agents of cleanup Monocytes the primary agents of cleanup arrive in 8 to 12 hours, become arrive in 8 to 12 hours, become macrophages, macrophages,
Edema Edema venous flow, venous flow, lymphatic flow that lymphatic flow that favors removal of bacteria and debrisfavors removal of bacteria and debris
Formation of pusFormation of pus mixture of tissue fluid, cellular debris, dying mixture of tissue fluid, cellular debris, dying
neutrophils and microbesneutrophils and microbes
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FeverFever Defense mechanism: can be harmfulDefense mechanism: can be harmful
promotes interferon activitypromotes interferon activity accelerating metabolic rate and tissue repairaccelerating metabolic rate and tissue repair inhibiting pathogen reproductioninhibiting pathogen reproduction
A cytokine, interleukin 1, called a pyrogenA cytokine, interleukin 1, called a pyrogen secreted by macrophages, stimulates anterior secreted by macrophages, stimulates anterior
hypothalamus to secrete PGE which resets body hypothalamus to secrete PGE which resets body thermostat higherthermostat higher
> 105> 105F may cause delirium, 111F may cause delirium, 111F- 115F- 115F, coma-deathF, coma-death
Stages of feverStages of fever onset, stadium, defervescenceonset, stadium, defervescence
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Course of a FeverCourse of a Fever
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Specific ImmunitySpecific Immunity
Specificity and memorySpecificity and memory Cellular immunity: cell-mediated (T cells)Cellular immunity: cell-mediated (T cells) Humoral immunity: antibody mediated (B Humoral immunity: antibody mediated (B
cells)cells)
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Passive and Active ImmunityPassive and Active Immunity
Natural active immunity Natural active immunity (produces memory cells)(produces memory cells) production of one’s own antibodies or T cells as a production of one’s own antibodies or T cells as a
result of infection or natural exposure to antigenresult of infection or natural exposure to antigen Artificial active immunity Artificial active immunity (produces memory cells)(produces memory cells)
production of one’s own antibodies or T cells as a production of one’s own antibodies or T cells as a result of vaccinationresult of vaccination
Natural passive immunity Natural passive immunity (through placenta, milk)(through placenta, milk) temporary, fetus acquires antibodies from mothertemporary, fetus acquires antibodies from mother
Artificial passive immunity Artificial passive immunity (snakebite, rabies, tetanus)(snakebite, rabies, tetanus) temporary, injection of immune serum (antibodies)temporary, injection of immune serum (antibodies)
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Life Cycle of T cellsLife Cycle of T cells
Stem cells in red bone marrowStem cells in red bone marrow Mature in thymusMature in thymus
thymosins stimulate maturing T cells to thymosins stimulate maturing T cells to produce antigen receptorsproduce antigen receptors
immunocompetent T cell has antigen immunocompetent T cell has antigen receptors in placereceptors in place
DeploymentDeployment naïve T cells colonize lymphatic tissue and naïve T cells colonize lymphatic tissue and
organsorgans
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Antigen ProcessingAntigen Processing
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InterleukinsInterleukins
Chemical messengers between leukocytesChemical messengers between leukocytes Used by lymphocytes to communicate with Used by lymphocytes to communicate with
one anotherone another
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Cellular ImmunityCellular Immunity T cells attack foreign cells and diseased host T cells attack foreign cells and diseased host
cellscells Three classes of T cellsThree classes of T cells
1.1. Cytotoxic T cells (TCytotoxic T cells (Tcc cells) carry out attack cells) carry out attack
2.2. Helper T cells: help promote THelper T cells: help promote Tcc cell and B cell cell and B cell
action and nonspecific defense mechanismsaction and nonspecific defense mechanisms
3.3. Memory T cells: provide immunity from future Memory T cells: provide immunity from future exposure to antigenexposure to antigen
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Attack Phase: Role of Helper T Attack Phase: Role of Helper T CellsCells
Secretes interleukinsSecretes interleukins attract neutrophils, NK attract neutrophils, NK
cells, macrophagescells, macrophages stimulate phagocytosisstimulate phagocytosis stimulate T and B cell stimulate T and B cell
mitosis and maturationmitosis and maturation
Coordinate humoral Coordinate humoral and cellular immunityand cellular immunity
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Attack Phase: Attack Phase: Cytotoxic T CellsCytotoxic T Cells
Only T cells directly attack enemy cellsOnly T cells directly attack enemy cells Lethal hit mechanism Lethal hit mechanism
docks on cell with antigen-MHC-I protein complexdocks on cell with antigen-MHC-I protein complex
1.1. releases perforin, granzymes - kills target cellreleases perforin, granzymes - kills target cell
2.2. interferons - decrease viral replication and interferons - decrease viral replication and activates macrophagesactivates macrophages
3.3. tumor necrosis factor: kills cancer cellstumor necrosis factor: kills cancer cells
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Cytotoxic T Cell FunctionCytotoxic T Cell Function
Cytotoxic T cell binding to cancer cellCytotoxic T cell binding to cancer cell
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Destruction of Cancer CellDestruction of Cancer Cell
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MemoryMemory
Memory T cellsMemory T cells following clonal selection some T cells following clonal selection some T cells
become memory cellsbecome memory cells long-lived; in higher numbers than naïve cellslong-lived; in higher numbers than naïve cells
T cell recall responseT cell recall response upon reexposure to same pathogen, memory upon reexposure to same pathogen, memory
cells launch a quick attackcells launch a quick attack
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Humoral ImmunityHumoral Immunity RecognitionRecognition
B cell receptors bind antigen, take in and digest B cell receptors bind antigen, take in and digest antigen antigen
After costimulation by TAfter costimulation by TH H cell, divide repeatedly, cell, divide repeatedly, differentiate into plasma cells, produce antibodies differentiate into plasma cells, produce antibodies specific to that antigenspecific to that antigen
AttackAttack antibodies bind to antigen, render it harmless, ‘tag antibodies bind to antigen, render it harmless, ‘tag
it’ for destructionit’ for destruction MemoryMemory
some B cells differentiate into memory cellssome B cells differentiate into memory cells
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Humoral Immunity - RecognitionHumoral Immunity - Recognition
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Antibody StructureAntibody Structure
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Antibody ClassesAntibody Classes
By amino acid sequences of C region of By amino acid sequences of C region of antibodyantibody
IgA:IgA: mucus, saliva, tears, milk, intestinal secretions, mucus, saliva, tears, milk, intestinal secretions, prevents adherence to epitheliaprevents adherence to epithelia
IgD: IgD: B cell membrane antigen receptorB cell membrane antigen receptor IgE: IgE: mast cells; stimulates release of histamines, mast cells; stimulates release of histamines,
attracts eosinophils; immediate hypersensitivity reactionsattracts eosinophils; immediate hypersensitivity reactions IgG:IgG: 80% circulating, crosses placenta to fetus, 2 80% circulating, crosses placenta to fetus, 2
immune response, complement fixationimmune response, complement fixation IgM:IgM: 10% in plasma, 1 10% in plasma, 1 immune response, agglutination, immune response, agglutination,
complement fixationcomplement fixation
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Antibody DiversityAntibody Diversity
Immune system capable of as many as 1 Immune system capable of as many as 1 trillion different antibodiestrillion different antibodies
Somatic recombinationSomatic recombination DNA segments shuffled and form new DNA segments shuffled and form new
combinations of base sequences to produce combinations of base sequences to produce antibody genesantibody genes
Somatic hypermutationSomatic hypermutation B cells in lymph nodules rapidly mutate B cells in lymph nodules rapidly mutate
creating new sequencescreating new sequences
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Humoral Immunity - AttackHumoral Immunity - Attack NeutralizationNeutralization
antibodies mask pathogenic region of antigenantibodies mask pathogenic region of antigen
Complement fixationComplement fixation antigen binds to IgM or IgG, antibody changes shape, antigen binds to IgM or IgG, antibody changes shape,
initiates complement binding; primary defense against initiates complement binding; primary defense against foreign cells, bacteriaforeign cells, bacteria
AgglutinationAgglutination antibody has 2-10 binding sites; binds to multiple enemy antibody has 2-10 binding sites; binds to multiple enemy
cells immobilizing themcells immobilizing them
PrecipitationPrecipitation antibody binds antigen molecules (not cells); creates antibody binds antigen molecules (not cells); creates
antigen-antibody complex that precipitates, phagocytized antigen-antibody complex that precipitates, phagocytized by eosinophil by eosinophil
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Agglutination and PrecipitationAgglutination and Precipitation