Immunity

Innate & Adaptive

Immunity• Innate: response to attack is always

the same– Mechanical mechanisms– Chemical mediators– Cellular response– Inflammatory response

• Adaptive: response to attack improves with each exposure– Specific– Has memory

Innate immunity

• Mechanical mechanisms– Skin & mucus membranes form physical

barriers to prevent entry– Tears, saliva, urine wash away pathogens

from surface or body or dilute invading army of pathogens

Innate immunity• Chemical mediators: Some prevent

entry to cells, kill bacteria, or produce inflammation– Complement proteins

• ~ 20 in plasma• normally inactive; activated by combining with

parts of bacterial cells or antibodies• Leads to chain rxn activation of neighboring

compliments & inflammation, phagocytosis, or lysis

Innate immunity• Chemical mediators

– Interferons protect against viral infection• Virus-infected cells place interferons on their

surface (SOS signal)• These bind to neighboring cells & stimulate

neighbors to produce antiviral proteins• Intiviral proteins inhibit production of new viral

RNA• Some interferons activate macrophages and

NKC

Innate immunity• Cellular mechanisms

– WBC & derivatives are most important cellular components• Attracted to invading bacteria and

microorganisms through chemotaxis

– Phagocytic cells (who are these?)– Inflammatory cells (…and these?)– Natural Killer Cells (NKC)

White Blood Cells

Innate immunity• Phagocytic cells

– Neutrophils• Small; first to enter infected tissue from blood;

ingest, then die --> pus accumulation

– Macrophages• Monocytes leave blood & enlarge; arrive after

neutrophils; do most eating & cleanup• Also hang out at “entry points” (gate-keepers)

Innate immunity• Natural Killer Cells (NKC)

– 15% of all lymphocytes are NKC– Recognize tumor cells or virus-infected

cells (generalist killers)– No memory; non-specific– Kill via chemical release (cell membrane

lysis)

Innate immunity

• Inflammatory cells: activated through innate or adaptive immunity; release histamine & pyrogens– Basophils

• Motile WBC; enter infected tissue

– Mast cells• Non-motile; Located in lymph organs at “points

of entry”

– Eosinophils• Release enzymes that reduce inflammation

(control)

Inflammation is useful!

• Local inflammation: Redness, heat, swelling– caused by increased blood flow & vascular

permeability– Chemicals and swelling activate pain receptors

• Systemic inflammation– Red marrow increases neutrophil production– Pyrogens stimulate fever by increasing heat

production & conservation– Vascular permeability increases

Adaptive immunity

• Lymphocytes– Origin & development– Activation & multiplication

• Antibody-mediated• Cell-mediated

Adaptive immunity• Antigens stimulate adaptive immune

response– Self– Foreign

• MHC molecules display antigens• Lymphocytes

– Origin & development– Activation & multiplication

• Types of Adaptive Immunity– Antibody-mediated

• B cells; produce cells that make antibodies

– Cell-mediated• T cells; cytotoxic & helper T cells

Antigens

• Foreign– Components of bacteria, viruses, and

their chemical byproducts– Pollen, animal hair, foods produce allergic

response (overreaction of immune system)

• Self– Produced by our bodies

• Recognize tumor antigens

B & T-cells (Lymphocytes)

• Contain antigen receptors in their cell membranes

• We each have thousands of different populations of B & T-cells, each with unique antigen receptors

• Cells are stimulated by binding of antigens to their unique receptors

Cell Developmen

t• Red marrow produces:– Pre B-cells:

released into bloodstream

– migrate to lymph organs

– Pre T-cells: migrate to thymus & mature there

• Mature T-cells migrate to lymph organs

Lymph nodes,spleen, and

other lymphaticorgans

Final maturationof B and T cells inlymphatic organ

Viablood

T cellB cell

Viablood

Antigenreceptor

Thymus

Antigenreceptor

Immaturelymphocytes

Stem cell

Bonemarrow

Activation & multiplication• Macrophages present

antigens– Phagocytize invaders, process

& display antigens (with help of MHC molecules)

• MHC/Antigen complex binds to receptors on B or T-cells

• T-cells auto-stimulate– Produce cytokines (peptides;

e.g. interleukin) that up-regulate growth & division

B cell activation• Antibody-mediated• B-cells can also

phagocytize & process antigens– same antigen that

stimulated a Th

• Th binds to B-cell

• Interleukins are produced– stimulate B-cell division &

proliferation– Daughter (plasma) cells

produce antibodies

Effects of Antibodies

• Direct– Antibodies bind antigens = inactivation

• Indirect– Activate Complement cascade

• Inflammation (mast cells and basophils release histamine)

• Chemotaxis (attracts white blood cells)• Phagocytosis or lysis (macrophage eats

antibody & antigen

Binding of antibodies to antigensinactivates antigens by

NeutralizationAgglutinationof microbes

Precipitation ofdissolved antigens

Phagocytosis Cell lysis

Activation of complement system

Leads to

Foreign cell Hole

Complement moleculeBacteria

Antigenmolecules

Enhances

Bacterium

Virus

Macrophage

Antibody production

• Differs following first and second exposure to antigen– First exposure = primary response

• B-cells bind antigen; produce plasma cells (produce antibodies) and memory B-cells

• Response time = 3-14 days; disease symptoms develop; SLOW

Fig. 24-7aa-1

Primary immuneresponse

B cells withdifferentantigenreceptors

Antigen receptor(antibody on cellsurface)

1

Fig. 24-7aa-2

Primary immuneresponse

B cells withdifferentantigenreceptors

Antigen receptor(antibody on cellsurface)

1 Antigenmolecules

2

Fig. 24-7aa-3

Primary immuneresponse

B cells withdifferentantigenreceptors

Antigen receptor(antibody on cellsurface)

1 Antigenmolecules

2

First exposureto antigen

Cell activation:growth,division, anddifferentiation

3

Fig. 24-7aa-4

Primary immuneresponse

B cells withdifferentantigenreceptors

Antigen receptor(antibody on cellsurface)

1 Antigenmolecules

2

First exposureto antigen

Cell activation:growth,division, anddifferentiation

3

Antibodymolecules

EndoplasmicreticulumFirst clone

Plasma (effector) cells secreting antibodies

4

Fig. 24-7aa-5

Primary immuneresponse

B cells withdifferentantigenreceptors

Antigen receptor(antibody on cellsurface)

1 Antigenmolecules

2

First exposureto antigen

Cell activation:growth,division, anddifferentiation

3

Antibodymolecules

EndoplasmicreticulumFirst clone

Plasma (effector) cells secreting antibodies

4

Memory cells

5

Antibody production• Differs following first and second

exposure to antigen– Second exposure = secondary response

• Memory cells quickly induce plasma cells to produce antibodies

• Time to antibody production is reduced• More plasma cells & antibodies produced• RAPID response, no disease symptoms =

immunity

Fig. 24-7aa-6

Second clone

Plasma (effector) cells secreting antibodies Memory cells

6

Antigenmolecules

Second exposureto same antigen

Endoplasmicreticulum

Antibodymolecules

Secondaryimmuneresponse (Mayoccur long afterprimary immuneresponse.)

Fig. 24-7b

Time (days)

Second exposureto antigen X,

first exposureto antigen Y

First exposureto antigen X

Secondary immuneresponse to

antigen X

Primary immuneresponse to

antigen Y

Primary immuneresponse to

antigen X

Antibodiesto X

Antibodiesto Y

An

tib

od

y c

on

cen

tra

tio

n

5649423528211470

Cell-mediated immunity

• Cytotoxic T cells (Tc)

• Effective against viruses, bacteria

• Infected cells display antigens, and Tc binds to MHC/antigen combo– Stimulates production of more Tc

– Costimulation by Th which were stimulated by macrophage display of antigens

Fig. 24-11b

Self-nonselfcomplex

T cellreceptor

Interleukin-2stimulatescell division

Interleukin-1stimulateshelper T cell

Bindingsite forantigen

Bindingsite forself protein

HelperT cell

Antigen-presentingcell

23

4

5 6

7

B cell

CytotoxicT cell

Cell-mediatedimmuneresponse(attack oninfected cells)

Interleukin-2activates B cellsand other T cells

Humoralimmuneresponse(secretion ofantibodies byplasma cells)

Fig. 24-12-1

1 Cytotoxic T cell bindsto infected cell

Self-nonselfcomplex

CytotoxicT cell

Foreignantigen

Perforinmolecule

Infected cell

Fig. 24-12-2

1 Cytotoxic T cell bindsto infected cell

Self-nonselfcomplex

CytotoxicT cell

Foreignantigen

Perforinmolecule

Infected cell

Perforin makes holes ininfected cell’s membraneand enzyme enters

Enzyme thatcan promoteapoptosis

Holeforming

2

Fig. 24-12-3

1 Cytotoxic T cell bindsto infected cell

Self-nonselfcomplex

CytotoxicT cell

Foreignantigen

Perforinmolecule

Infected cell

Perforin makes holes ininfected cell’s membraneand enzyme enters

Enzyme thatcan promoteapoptosis

Holeforming

2 Infected cellis destroyed

3

Show “Immune Response”Mcgraw Hill

Microbe Macrophage

Self protein

Self-nonselfcomplex

T cellreceptor

Interleukin-2stimulatescell division

Interleukin-1stimulateshelper T cell

Bindingsite forantigen

Bindingsite forself protein

HelperT cell

Antigen-presentingcell

Antigen from microbe(nonself molecule)

12

3

4

5 6

7

B cell

CytotoxicT cell

Cell-mediatedimmuneresponse(attack oninfected cells)

Interleukin-2activates B cellsand other T cells

Humoralimmuneresponse(secretion ofantibodies byplasma cells)

Th stimulate both immune responses

Acquiring Adaptive immunity

Antigens, Antibodies & Vaccines

• Inject host with inactive or attenuated virus (usually bits & pieces aka antigens)

• Host immune cells grab antigens & stimulate other cells (B cells) to engineer antibodies to bind to antigens

Antigens, Antibodies & Vaccines

• B cells “remember” how to make this antibody forever

• On subsequent infection, live virus is mobbed by antibodies, targeted for termination and eaten by macrophages