The Immune SystemThe Immune System

An organisms’ protection from Pathogens

Video

PathogenPathogenAny infectious agent that causes diseaseAny infectious agent that causes disease

• Bacteria

•Viruses

•Fungi

•Protists/parasites

2 Divisions of Immunity in 2 Divisions of Immunity in Humans and Other MammalsHumans and Other Mammals

I.I. Innate Innate Immunity Immunity – “Non-Specific” – “Non-Specific”

This defense is not concerned with ‘what’ the pathogen is. This defense is not concerned with ‘what’ the pathogen is. This system merely prevents the pathogen from This system merely prevents the pathogen from entering the body or destroys it before identifying it.entering the body or destroys it before identifying it.

It shoots first and asks questions laterIt shoots first and asks questions later

Innate Immunity involves several layers of defense:Innate Immunity involves several layers of defense:

A.A. Barrier DefensesBarrier Defenses B. B. Inflammatory Inflammatory ResponseResponse

C. C. Cellular DefensesCellular Defenses D. D. Natural Killer CellsNatural Killer Cells

E. E. Antimicrobial DefensesAntimicrobial Defenses

A. Barrier DefensesA. Barrier Defenses

1.1. Epidermis – impenetrable barrierEpidermis – impenetrable barrier

2.2. Oil and Sweat have low pHOil and Sweat have low pH

3.3. Resident Flora – your own bacteriaResident Flora – your own bacteria

4.4. Mucous Membrane – mucus and Mucous Membrane – mucus and ciliacilia

5.5. LysozymeLysozyme

SkinSkin

EpidermisEpidermis an impenetrable barrier to an impenetrable barrier to pathogenspathogens

Oil and SweatOil and Sweat have a have a low pHlow pH that that reduces pathogen growthreduces pathogen growth

Resident FloraResident Flora your own colonies of your own colonies of bacteria that live on your skin out-- bacteria that live on your skin out-- competes with harmful bacteria for competes with harmful bacteria for spacespace

Mucous MembranesMucous Membranes Un-keritonized skin of the mocous Un-keritonized skin of the mocous

membranes have a different layer of membranes have a different layer of defensedefense

MUCUS and CILIAMUCUS and CILIA

Lysozyme

B. Cellular DefensesB. Cellular Defenses

Leukocytes – Leukocytes – phagocytic phagocytic

white blood cells have surfacewhite blood cells have surface

receptors that detect typicalreceptors that detect typical

pathogen compounds calledpathogen compounds called

antigensantigens..

Microbes/antigens

PHAGOCYTIC CELL

Vacuole

Lysosomecontaining enzymes

Groups of Groups of pathogens pathogens are are recognized recognized by by TLRTLR, , Toll-Toll-like like receptorsreceptors

EXTRACELLULARFLUID Lipopolysaccharide

FlagellinTLR4

TLR5

Helperprotein

TLR9

TLR3

WHITEBLOODCELL

VESICLE

CpG DNA

Inflammatoryresponses

A white blood cell A white blood cell engulfs a microbe, engulfs a microbe, then fuses with a then fuses with a lysosome to destroy lysosome to destroy the microbethe microbe

There are different types of There are different types of phagocytic cells:phagocytic cells:

NeutrophilsNeutrophils engulf and destroy microbes engulf and destroy microbes

Macrophages Macrophages are part of the lymphatic are part of the lymphatic system and are found throughout the bodysystem and are found throughout the body

EosinophilsEosinophils discharge destructive discharge destructive enzymesenzymes

Dendritic cellsDendritic cells stimulate development of stimulate development of acquired immunityacquired immunity

Fig. 43-7Fig. 43-7

Adenoid

Tonsil

Lymphnodes

Spleen

Peyer’s patches(small intestine)

Appendix

Lymphaticvessels Lymph

nodeMasses ofdefensive cells

Bloodcapillary

Lymphaticvessel

Tissuecells

Adenoid

Tonsil

Lymphnodes

Spleen

Lymphnode

Masses ofdefensive cells

Bloodcapillary

Lymphaticvessel

Tissuecells

Interstitial fluid

Appendix

Peyer’s patches(small intestine)

C. Antimicrobial ProteinsC. Antimicrobial Proteins

Peptides and proteinsPeptides and proteins function in innate function in innate defense by attacking microbes directly or defense by attacking microbes directly or impeding their reproductionimpeding their reproduction

Interferon Interferon proteinsproteins provide innate defense provide innate defense against viruses and help activate against viruses and help activate macrophagesmacrophages

About 30 proteins make up the About 30 proteins make up the complement systemcomplement system, which causes lysis of , which causes lysis of invading cells and helps trigger inflammationinvading cells and helps trigger inflammation

Following an injury, Following an injury, mast cells mast cells release release histaminehistamine,, which promotes changes in which promotes changes in blood vessels; this is part of the blood vessels; this is part of the inflammatory responseinflammatory response

These changes increase local blood supply These changes increase local blood supply and allow more phagocytes and and allow more phagocytes and antimicrobial proteins to enter tissuesantimicrobial proteins to enter tissues

Pus, Pus, a fluid rich in white blood cells, dead a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at microbes, and cell debris, accumulates at the site of inflammationthe site of inflammation

D. Inflammatory ResponsesD. Inflammatory Responses

Fig. 43-8-3Fig. 43-8-3

Pathogen Splinter

Macrophage

Mast cell

ChemicalSignals (Ligand)

Capillary

Phagocytic cellRed blood cells

Fluid

Phagocytosis

D. Inflammatory ResponsesD. Inflammatory Responses

Fever is a systemic inflammatory Fever is a systemic inflammatory response triggered by pyrogens response triggered by pyrogens released by macrophages, and released by macrophages, and toxins from pathogenstoxins from pathogens

Septic shockSeptic shock is a life-threatening is a life-threatening condition caused by an condition caused by an overwhelming inflammatory overwhelming inflammatory responseresponse

LymphocytesLymphocytes- are white blood cells that - are white blood cells that recognize and respond to antigens, foreign recognize and respond to antigens, foreign molecules.molecules.

Lymphocytes that mature in the Lymphocytes that mature in the thymus thymus above the heart are called above the heart are called T cellsT cells,, and and those that mature in bone marrow are those that mature in bone marrow are called called B cellsB cells

Lymphocytes have immunological memory.Lymphocytes have immunological memory.

IIII. Acquired immunity. Acquired immunitylymphocyte receptors provide pathogen-specific lymphocyte receptors provide pathogen-specific

recognitionrecognition

Fig. 43-9Fig. 43-9

Antigen-bindingsite

Antigen-binding site

Antigen-bindingsite

Plasmamembrane

T cellCytoplasm of T cell

(b) T cell receptor

Cytoplasm of B cell

(a) B cell receptor

B cell

B cells and T cells have receptor proteins that can recognize and bind to antigens

Antibody Genes

Assembled antibody molecule

VDJ

C

Gene components scattered through one chromosome

Heavy chain

Antigen-binding region

Constant region

Light chain

V

V

V

DD

JJJJ

C

Rearranged gene

components encoding a heavy chain

Markers of Self:Major Histocompatibility Complex

Antigenic peptide

Antigen-presenting cell uses MHC Class I or II

Cell membrane

MHC Class II

Antigenic peptide

Viral infection

Infected cell

MHC Class I

Antigenic peptide

MHC Class I

Body Cell with “Self-Markers called MHC

B Cells

Plasma cell

Class II MHC and processed antigen are displayed

bacteria

Antigen

Antigen-specific B cell receptor

Antibodies(Immunoglobins)

B cell

Activated helper T cell

Cytokines (Lymphokines)LIGAND

T Cells

Activated killer cellActivated helper T cell

Resting cytotoxic T cellResting helper T cell

Cytokines Released by

Helper T-Cells

Granule w/destructive

enzymes

Activated when they encounter infected cells that are presenting antigens

Killer Cells: Cytotoxic Ts

Killer cell

Target-oriented granules

Surface contact

Target cell

T cells bind to antigen fragments T cells bind to antigen fragments presented on a host cell presented on a host cell

These antigen fragments are bound to These antigen fragments are bound to cell-surface proteins called MHC moleculescell-surface proteins called MHC molecules

MHCMHC molecules are so named because molecules are so named because they are encoded by a family of genes they are encoded by a family of genes called the called the major histocompatibility major histocompatibility complexcomplex

The Role of the MHCThe Role of the MHC In infected cells, MHC molecules bind In infected cells, MHC molecules bind

and transport antigen fragments to and transport antigen fragments to the cell surface, a process called the cell surface, a process called antigen presentationantigen presentation

A nearby T cell can then detect the A nearby T cell can then detect the antigen fragment displayed on the antigen fragment displayed on the cell’s surfacecell’s surface

Depending on their source, peptide Depending on their source, peptide antigens are handled by different antigens are handled by different classes of MHC moleculesclasses of MHC molecules

Fig. 43-12Fig. 43-12

Infected cell

Antigenfragment

Class I MHCmoleculeT cellreceptor

(a)

Antigenassociateswith MHCmolecule

T cellrecognizescombination

Cytotoxic T cell (b) Helper T cell

T cellreceptor

Class II MHCmolecule

Antigenfragment

Antigen-presentingcell

Microbe

1

11

2

22

Activation of B Cells to Make Antibody

Antigen-presenting cell

Antigen

Circulating antibody

Antigen is processedClass II MHC

Antigen

Activated helper T cell

Class II MHC and processed antigen are displayed

Antibodies

Plasma cellAntigen-presenting cell

Antigen-specific B cell receptor

B cell Cytokines(LIGAND)

Fig. 43-14Fig. 43-14

B cells thatdiffer inantigen specificity

Antibodymolecules

Antigenreceptor

Antigen molecules

Clone of memory B cells Clone of plasma cells

Animation: Role of B CellsAnimation: Role of B Cells

Fig. 43-16Fig. 43-16

Humoral (antibody-mediated) immune response

B cell

Plasma cells

Cell-mediated immune response

Key

Stimulates

Gives rise to

+

+

++

+

+

+Memory B cells

Antigen (1st exposure)

Engulfed by

Antigen-presenting cell

MemoryHelper T cells

Helper T cell Cytotoxic T cell

MemoryCytotoxic T cells

ActiveCytotoxic T cells

Antigen (2nd exposure)

Secretedantibodies

Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.

Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.

+

+ +

AnimationAnimation: Helper T Cells: Helper T Cells

Fig. 43-17Fig. 43-17

Antigen-presentingcell

Peptide antigen

Cell-mediatedimmunity (attack on

infected cells)

Class II MHC moleculeCD4

TCR (T cell receptor)

Helper T cell

Humoralimmunity

(secretion ofantibodies byplasma cells) Cytotoxic T cell

Cytokines

B cell

Bacterium

+

+ +

+

Cytokines

Cytotoxic T Cells: A Cytotoxic T Cells: A Response to Infected CellsResponse to Infected Cells

Cytotoxic T cells are the Cytotoxic T cells are the effectoreffector cells cells in cell-mediated immune responsein cell-mediated immune response

The activated cytotoxic T cell The activated cytotoxic T cell secretes proteins that destroy the secretes proteins that destroy the infected target cellinfected target cell

Animation: Cytotoxic T CellsAnimation: Cytotoxic T Cells

Fig. 43-18-3Fig. 43-18-3

Cytotoxic T cell

Perforin

Granzymes

TCRCD8

Class I MHCmolecule

Targetcell

Peptideantigen

Pore

Released cytotoxic T cell

Dying target cellperforin

granzymes

B Cells: A Response to B Cells: A Response to Extracellular PathogensExtracellular Pathogens

The humoral response is characterized The humoral response is characterized by secretion of antibodies by B cellsby secretion of antibodies by B cells

Activation of B cells is aided by Activation of B cells is aided by cytokines and antigen binding to helper cytokines and antigen binding to helper T cellsT cells

Clonal selection of B cells generates Clonal selection of B cells generates antibody-secreting plasma cells, the antibody-secreting plasma cells, the effector cells of humoral immunityeffector cells of humoral immunity

Fig. 43-19Fig. 43-19

Antigen-presenting cell

Endoplasmicreticulum ofplasma cell

Secretedantibodymolecules

B cell

Class II MHCmolecule

TCR CD4

Helper T cellActivatedhelper T cell

Cytokines

Clone of memoryB cells

Clone of plasma cells

2 µm

+

Bacterium

Peptideantigen

The Role of Antibodies in The Role of Antibodies in ImmunityImmunity

NeutralizationNeutralization occurs when a pathogen occurs when a pathogen can no longer infect a host because it is can no longer infect a host because it is bound to an antibodybound to an antibody

OpsonizationOpsonization occurs when antibodies occurs when antibodies bound to antigens increase phagocytosisbound to antigens increase phagocytosis

Antibodies together with proteins of the Antibodies together with proteins of the complement system generate a complement system generate a membrane attack complexmembrane attack complex and cell lysis and cell lysis

Animation: AntibodiesAnimation: Antibodies

Fig. 43-21Fig. 43-21

Viral neutralization

Virus

Opsonization

Bacterium

Macrophage

Activation of complement system and pore formation

Complement proteins

Formation ofmembraneattack complex

Flow of waterand ions

Pore

Foreigncell

Antibodies bound to antigens on viruses can neutralize the virus

Binding of antibodies to bacteria Promotes phagocytosis of the Bactria by Macrophages

Binding of antibodies to antigens on the surface of a foreign cell activates a complex system.

Following activation the attack complex forms pores in the foreign cell’s membrane , allowing water and ions to rush in.

The Cell swells and eventually lyses.

Evolution and ImmunityEvolution and Immunity

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