Immune System

Bio 1b ZoologyHannah NevinsImmunity: the bodys defense system

An immune cell (macrophage) engulfs a yeast cell (pathogen)Invaders : pathogensThe immune system recognizes foreign bodies and responds with the production of immune cells and proteinsTwo strategies have evolved: the innate and the acquired immune systems

2Innate Immunity of InvertebratesThe digestive system is protected by low pH and an enzyme that digests microbial cell walls called lysosomeHemocytes circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria

In insects, an exoskeleton made of chitin forms the first barrier to pathogens

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsInnate Immunity of VertebratesInnate defenses include: barrier defenses, phagocytosis, antimicrobial peptidesAdditional defenses are unique to vertebrates: the inflammatory response and natural killer cells

The immune system of mammals is the best understood of the vertebrates

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 43-7Adenoid

Tonsil

Lymphnodes

SpleenPeyers patches(small intestine)AppendixLymphaticvesselsLymphnodeMasses ofdefensive cellsBloodcapillaryLymphaticvesselTissuecellsInterstitial fluidHuman Lymphatic system5Figure 43.7 The human lymphatic systemBarrier DefensesMucus traps and allows for the removal of microbesMany body fluids including saliva, mucus, and tears are hostile to microbesThe low pH of skin and the digestive system prevents growth of microbes

Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin CummingsCellular Innate DefensesWhite blood cells (leukocytes) engulf pathogens in the bodyGroups of pathogens are recognized by Toll-like receptors (TLR)

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 43-3Microbes

PHAGOCYTIC CELL

VacuoleLysosomecontaining enzymesPhagocytosis:(=eating, =cells)engulfing pathogensExocytosis cellular debris is released8Figure 43.3 PhagocytosisPhagocytosisA white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbeThere are different types of phagocytic cells:Neutrophils engulf and destroy microbesMacrophages are part of the lymphatic system and are found throughout the bodyEosinophils discharge destructive enzymesDendritic cells stimulate development of acquired immunity

Cell Types: Red & White

Fig. 43-8-1PathogenSplinterMacrophageMast cellChemicalsignalsCapillaryPhagocytic cellRed blood cellsHow your skin keeps out pathogensRuptured mast cells (in tissue) release histamines chemical signal to other phagocytic cellsCapillaries dilate, increase blood flow increase phagocytic cellsThe clotting process also startsPlateletsClotting factors signalFibrin produced11Figure 43.8 Major events in a local inflammatory responseFor the Cell Biology Video Chemotaxis of a Neutrophil, go to Animation and Video Files.

Fig. 43-8-2PathogenSplinterMacrophageMast cellChemicalsignalsCapillaryPhagocytic cellRed blood cellsFluid12Figure 43.8 Major events in a local inflammatory responseFor the Cell Biology Video Chemotaxis of a Neutrophil, go to Animation and Video Files.

Fig. 43-8-3PathogenSplinterMacrophageMast cellChemicalsignalsCapillaryPhagocytic cellRed blood cellsFluidPhagocytosis More phagocytic cells are released Pathogenic bacteria are engulfed and destroyed Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

13Figure 43.8 Major events in a local inflammatory responseFor the Cell Biology Video Chemotaxis of a Neutrophil, go to Animation and Video Files.

Fig. 43-7Thymus

Lymphnodes

SpleenLymphaticvesselsLymphocyte maturationWhite blood cells called lymphocytes recognize and respond to antigens, foreign moleculesLymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells

14Figure 43.7 The human lymphatic systemAcquired Immunity results from B- and T-cellsT-cellsThymusCombats viruses (intracellular pathogens)B-cellsBone marrow & spleenCombats bacteria (extracellular pathogens)

Cell Types: Red & WhitePathogens have antigens, B-cells have antibodiesAntigens:Each pathogen type has unique surface moleculesAntibody binding:Causes antibodies to be secreted from B-cellAntibodies:Surface proteins of B-cellMatch antigens

Fig. 43-9 Antigen-bindingsite Antigen-binding siteAntigen-bindingsiteDisulfidebridge VariableregionsConstantregionsTransmembraneregionPlasmamembraneLightchainHeavy chainsT cell chain chainDisulfide bridgeCytoplasm of T cell(b) T cell receptorCytoplasm of B cell(a) B cell receptorB cellVVCCVVCCCCVVBoth B- and T-cells have Antigen binding sites18Figure 43.9 Antigen receptors on lymphocytes

Fig. 43-10Antigen-binding sites

Antigen-bindingsites

Epitopes(antigenicdeterminants)AntigenAntibody BAntibody CAntibody A CCCVVVVC19Figure 43.10 Epitopes (antigenic determinants)Lymphocyte DevelopmentThe acquired immune system has three important properties:Receptor diversityA lack of reactivity against host cellsImmunological memory

A Pathogen is tagged for Attack; a B-cell is selected for cloningAntibodies cause:NeutralizationAgglutinationPrecipitationruptureSelection causes rapid clonal replication

SelectionReplication

Fig. 43-14 B cells thatdiffer inantigen specificityAntibodymoleculesAntigenreceptorAntigen moleculesClone of memory cellsClone of plasma cells22Figure 43.14 Clonal selection of B cellsThe B-cells form Two cell Types:Memory CellsLong-livedAwait future encounters with specific antigenPlasma CellsSecrete many antibodies to mark and block more bacteria

SelectionReplicationSecondary Immune ResponseGet a disease, you get natural immunizatione.g. chicken poxImmunization: injecting chemical or heat inactivated antigensa.k.a vaccination

Antibodiesto AAntibodiesto BSecondary immune responsePrimary immune responseAntibody concentrationExposureto antigen AExposure toantigens A and BTime (days)1041031021011000714212835424956

Fig. 43-15

Antibodiesto AAntibodiesto BSecondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B.Primary immune responseto antigen A producesantibodies to A.Antibody concentration(arbitrary units)Exposureto antigen AExposure toantigens A and BTime (days)104103102101100071421283542495625Figure 43.15 The specificity of immunological memoryPathogens can evolve to avoid detectionSome pathogens change surface proteinsMemory cells can not recognizePathogens have shorter generation time relative to host, :. they can evolve fasterWhat does this mean for the efficacy of any given human-made antibiotic?Some pathogens like AIDS hide inside your bodys cellsIntracellular invaders are dealt with by T-cellsLike B-cells, T-cells haveDiverse antigen receptorsTwo types: Cytotoxic T-cell, Helper T-cell

Fig. 43-12Infected cellAntigenfragmentClass I MHCmoleculeT cellreceptor(a)Antigenassociateswith MHCmoleculeT cellrecognizescombinationCytotoxic T cell(b)Helper T cellT cellreceptorClass II MHCmoleculeAntigenfragmentAntigen-presentingcellMicrobe111222

Fig. 43-18-1Cytotoxic T cell

Perforin

Granzymes

TCR

CD8

Class I MHCmolecule

TargetcellPeptideantigenOnce bound to CD8 receptor, T-cell becomes an active killerCytotoxic T-cells28Figure 43.18 The killing action of cytotoxic T cellsFor the Discovery Video Fighting Cancer, go to Animation and Video Files.

Fig. 43-18-2Cytotoxic T cell

Perforin

Granzymes

TCR

CD8

Class I MHCmolecule

TargetcellPeptideantigenPore

Perforins create pores in surface of target cellGranzymes enter cell initiate apoptosis (cell death)Cytotoxic T-cells29Figure 43.18 The killing action of cytotoxic T cellsFor the Discovery Video Fighting Cancer, go to Animation and Video Files.

Fig. 43-18-3Cytotoxic T cell

Perforin

Granzymes

TCR

CD8

Class I MHCmolecule

TargetcellPeptideantigenPore

Released cytotoxic T cellDying target cellPerforins create pores in surface of target cellGranzymes initiate apoptosis (cell death)Cytotoxic T-cells30Figure 43.18 The killing action of cytotoxic T cellsFor the Discovery Video Fighting Cancer, go to Animation and Video Files.

Fig. 43-17Antigen-presentingcellPeptide antigenCell-mediatedimmunity (attack oninfected cells)Class II MHC moleculeCD4TCR (T cell receptor)Helper T cellHumoralimmunity (secretion ofantibodies byplasma cells)Cytotoxic T cellCytokinesB cellBacterium++++31Figure 43.17 The central role of helper T cells in humoral and cell-mediated immune responsesCytotoxic T-cells attack diseased of cancerous cells labeled with MHCsNormal cells make MHC (Major Histocompatibility Complex) moleculesAbnormal cells like those with viruses make MHCs which bind to viral proteinsThose antigens are presented on the surface of the infected cellThen detected by cytotoxic T-cells and the infected cell is destroyedMajor Histocompatibility Complex Genes have ~100 Alternative AllelesEach MHC type presents a different type of antigen for T-cells to recognize as alienGene polymorphism increases chances of matching antigensThus increased MHC diversity = increased disease resistanceOne study looked at male selection using old t-shirts and MHC analysis: females favor males with MHCs which differ from their own --- why is this adaptive?