Human Immune Response

8/2/2019 Human Immune Response

1/102

Human Immune Response

Part 1: innate immunity


2/102

One of these things is not like theothers..


3/102

Our bodies are under constantattack from pathogens

A pathogen is an organism that can causedisease

Pathogens include:

Bacteria

Viruses

Protists

Fungi


4/102

nucleic acid

capsid

envelope

Review: VIRUSES


5/102

cell wall

plasmamembrane

cytoplasm

circular DNA

Review: BACTERIA


6/102

There are two types ofresponses to pathogens

INNATE IMMUNITY

Non-specific: doesntdistinguish oneinfectious agent fromanother

Rapid response topathogens

Is present before anyexposure to pathogens

Is effective from the timeof birth

ACQUIRED IMMUNITY(AKA Adaptive response)

Specific response to aparticular antigen

Slower response topathogens

Requires previousexposure to the pathogen

Built over a life time ofexposure to pathogens


7/102


8/102


9/102

Two types ofInnate Immunity

First Line of Defense

External defenses

Skin

Mucous membranes

Chemical secretions

Second Line of Defense

Internal defenses

Phagocytic cells

Natural killer cells

Antimicrobial proteins

Inflammation

Fever


10/102

External Defense: Skin

Cannotnormally be

penetratedby bacteriaand viruses


11/102

Secretions fromsebaceous and

sweat glandskeep the skin ina pH range of 3

to 5 (acidic)which kills mostmicrobes

External Defense: Skin


12/102

Line digestive,respiratory, and

genitourinary tracts

Trap microbes andparticles

External Defense:Mucous Membranes


13/102


14/102

In the trachea, ciliatedepithelial cells sweepout mucus andtrapped microbes

Prevents these fromentering the lungs

Swallowing exposesthem to the acidicenvironment of thestomach

External Defense:Mucous Membranes


15/102


16/102

Microbialcolonization is alsoinhibited by saliva,

tears, and mucussecretions

All of thesesecretions containantimicrobialproteins

External Defense:Chemical Secretions


17/102

An example is lysozyme, an

enzyme that digests the cell walls of

many bacteria.

External Defense:Chemical Secretions


18/102


19/102



External defenses

Skin

Mucous membranes Chemical secretions


Internal defenses

Phagocytic cells

Natural killer cells Antimicrobial proteins

Inflammation

Fever

Link to video clip
http://intro%20to%20second%20line.mp4/http://intro%20to%20second%20line.mp4/


20/102

Internal Defense:Phagocytic cells

White blood cells (leukocyctes) that ingestinvading organisms

3m


21/102


22/102


Three types:

1. Macrophages

2. Esinophils

3. Neutrophils


23/102


Macrophages Large, long-lived

phagocytes

Cells extend longpseudopodia, engulf themicrobe into a vacuolewhich fuses with alysosome.

Some microbes have outercapsules to whichmacrophages cannotattach


24/102

Link to animation
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.html


25/102


26/102


Esinophils

Help fight large parasiticinvaders

Position themselvesalongside the parasite

and dischargedestructive enzymesthrough exocytosis


27/102


Neutrophils

Most abundant whiteblood cell

Recruit and activateother cells of theimmune system


28/102

Internal Defense:Phagocytic cellsNeutrophils

Have three strategies for directlyattacking micro-organisms

phagocytosis (ingestion)

release of anti-microbial proteins

generation of neutrophil extra cellular traps(NETs)

NET formation
http://www.youtube.com/watch?v=ZWXBViH86NE&feature=relatedhttp://www.youtube.com/watch?v=ZWXBViH86NE&feature=related


29/102


30/102


31/102

Internal Defense:Natural Killer Cells

Do not attack microbes directly

They destroy infected cells (typically thoseinfected with viruses)

Also attack abnormal body cells that could

become cancerous

They attack the cells membrane and cause

the cell to lyse Natural Killer Cells
http://www.youtube.com/watch?v=HNP1EAYLhOshttp://www.youtube.com/watch?v=HNP1EAYLhOs


32/102


33/102

I l D f


34/102

Internal Defense:Antimicrobial Proteins

A variety of proteins that attack microbesdirectly or impede microbe reproduction

Example: Lysozyme

Example: Interferons

Secreted by virus-infected cells

Do not benefit the infected cell but induceneighboring cells to produce chemicals thatinhibit viral reproduction

Interferons
http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_2.htmlhttp://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_2.html


35/102

Knowledge Review

Give me:

5 types of cell involved in defense againstdisease

4 ways to prevent infectious agentsentering the body

3 responses of neutrophils

2 types of immunity

1 antimicrobial protein

I l D f


36/102

Internal Defense:Inflammation Tissue damage leads to a localized

inflammatory response

Could be injury

Could be invasion by microbes Capillaries respond by:

Increased dilation

Increased permeability

Enhanced delivery of clotting elements

Enhanced migration of phagocytic cells

Leads to increased redness, heat, and swelling

Inflammatory Response
http://www.youtube.com/watch?v=suCKm97yvykhttp://www.youtube.com/watch?v=suCKm97yvyk


37/102


38/102

Major events in the local inflammatory response

Pathogen Pin

Macrophage

Chemical signals

Capillary

Phagocytic cells

Red blood cell

Bloodclottingelements

Blood clot

Phagocytosis

Fluid, antimicrobial proteins,and clotting elements movefrom the blood to the site.Clotting begins.

2

Chemical signals releasedby activated macrophagesand mast cells at the injurysite cause nearby capillariesto widen and become morepermeable.

1Chemokines released by variouskinds of cells attract morephagocytic cells from the bloodto the injury site.

3Neutrophils and macrophagesphagocytose pathogens andcell debris at the site, and thetissue heals.

4

I t l D f


39/102

Internal Defense:Fever

If damage or infection issevere, a widespread non-specific response may occur

Increased body temperature

Inhibits growth of somemicrobes

Facilitates phagocytosis

Speeds up repair of tissue


40/102



External defenses

Skin

Mucous membranes Chemical secretions


Internal defenses

Phagocytic cells

Natural killer cells Antimicrobial proteins

Inflammation

Fever


41/102

Its a race1. Pathogens are ________ that cause disease

2. _________ have a close relationship with their host, andhave a negative impact on the host

3. ________ conditions in the stomach kill pathogens

4. ___________ in tears and saliva are toxic to pathogens

5. The vaginal tract contains ______ acid

6. The _________ system is protected by goblet cells andmucus

7. ________ is an example of bacteria that can infect wounds

8. The immune system is made up of _______ blood cells

Whi h f h f ll i i NOT "fi


42/102

Which of the following is NOT a "first

line of defense" in the immune

response?A. Fever

B. Skin

C. Mucous membranesD. Lysozyme

E. Tears

F. Saliva


43/102

Which of the following is NOT a cellof the innate immune system?

A. Natural killer

B. Macrophage

C. NeutrophilD. T cell

E. Esinophil

F. Skin

A

B

C

D

E

F


44/102

Which cell type is part of the innateimmune system?

A. Lymphocyte

B. LeukocyteA

B

C

D

E

F


45/102

pH of the skin is:

A. Basic

B. AcidicA

B

C

D

E

F


46/102

Which molecule disrupts the viral


47/102

Which molecule disrupts the virallife cycle by preventing the

replication of DNA in infected cells?A. Lysozyme

B. Interferons

C. PhagocytolD. NETs

A

B

C

D

E

F


48/102

Review

Second line defenses Pathogen Acquired Virus Skin

Phagocytic cells Natural killer cells Antimicrobial proteins Inflammation Fever

Macrophages Esinophils Neutrophils Interferons

Bacteria Innate First line defenses Mucous membrane Sebaceous gland

Sweat gland Cilia Trachea Lysozyme Leukocyte

Pseudopodia Lysosome Exocytosis NETs


49/102

Human Immune Response

Part 2: acquired immunity

aka adaptive immunity

If thi i th h t i th


50/102

If this is the answer, what is thequestion?

Lymphocyte

Bacteria

Lysozyme

Chlamydia

Chronic

Antigen

VirusLactic acid

Mucus

Parasite

Choose 3 wordsThink of a question they could be used toanswer

Eg. What causes flu? A = a virus

Phagocyte

HIV

Influenza

Goblet cells

Pathogen


51/102


52/102

Acquired Immunity

The third line of defense

The key cells of the third line of defense arelymphocytes B cells

T Cells

Lymphocytes recognize and respond tospecific microbes and the molecules on the

foreign cells membrane (antigens)


53/102

Antigens include:Potentially damagingmicrobes and

their toxins.

Substances such as pollenand flea and dust mite feces.

Blood cell surface proteins.The surface proteins oftransplanted tissues andorgans.

Photo:EII

Mallow pollen SEM.

Many pollens are antigens

The feces of fleas and mitesare antigenic in some people

Antigens


54/102

The Immune System

Phagocytes footsoldiers

T-lymphocytes search

team

B-lymphocytes elite attacksquad


55/102

Lymphocytes originatefrom pleuropotent stemcellsin the bone marrow

or liver of a developing fetus If they migrate to the

thymus to mature, theybecome T cells

If they stay in the bonemarrow to mature, theybecome B cells

Lymphocytes

H d B d T ll


56/102

B and T cells haveantigen receptors

A single B or T cellshas about 100,000receptors, all with

exactly the samespecificity

How do B and T cellsrecognize antigens?

H d B d T ll


57/102

There is anenormous variety ofB and T cells in the

body, each withdifferent specificity

This allows

response to millionsof potentialpathogens

How do B and T cellsrecognize antigens?


58/102

While B cells and T cells are developing, their antigenreceptors are tested for potential self-reactivity

Will I attack cells of my own body?

If YES: rendered non-functional or destroyedby apoptosis

This leaves only lymphocytes that react toforeign substances

Autoimmune diseases result when thisself-reactivity check malfunctions


59/102


60/102

How do T and B cells differ?

B cells: HUMORAL IMMUNE RESPONSE

T cells: CELL MEDIATED IMMUNE RESPONSE


61/102

B ll


62/102

B cells:HUMORAL IMMUNE RESPONSE

1.Antigen floating in the blood binds toreceptor on B cell surface

2.B cell divides into two cell types:

Plasma B cells: Memory B cells:

HUMORAL IMMUNE RESPONSE


63/102


Plasma B cells

Secrete antibodiesinto the bloodimmediately



64/102


Plasma B cells

Antibodies areproteins that attach tospecific pathogen

antigens

Tip of antibodies

become specialized forspecific antigens
http://en.wikipedia.org/wiki/File:Antibody.svg


65/102

Antibody Molecule

antigenbinding sites


66/102



67/102


Plasma B cells

The antibody / antigencomplex makes themicrobe easier targets

for phagocytes

Inactivation of Antigens


68/102

Inactivation of AntigensClumping particulate

antigens

Solid antigens such as

bacteria are stuck together in

clumps.

Bacterial cell

Neutralization

Antibodies bind to viral

binding sites and coat

bacterial toxins.

VirusToxin

Antibody

Enhances Phagocytosis

Macrophage

Bacteria

Soluble antigens are stucktogether to formprecipitates.

Precipitation ofsoluble antigens

Solubleantigens

Antibodies


69/102



70/102


Memory B cells Memory B cells:

Long-lived cells bearing receptors for the samespecific antigen

Eventually, a few cells give rise to thousands ofnew cellsall clonesof the original and all specificto original invading antigen

Memory cells will continue to divide and createantibodies for the rest of the life of the organism

Division of antigen specific B


71/102

1. A blood stem cell undergoes differentiation andgenetic rearrangement to produce:

2. immature lymphocytes with many differentantigen receptors. Those that bind to:

3. antigens from the body's own tissues aredestroyed, while the rest mature into:

4. inactive lymphocytes. Most of these will never

encounter a matching:

5. foreign antigen, but those that do are activatedand produce

6. many clones of themselves!

cells is calledCLONAL SELECTION


72/102

B Cells

antibodies


73/102

Activation of B Cells by

Antigenantigen

Clonal Selection


74/102

Clonal Selection

Clonal Selection


75/102

Clonal Selection

plasma cells memory cells

antibodies


76/102

T cells:


77/102

T cells:CELL MEDIATED IMMUNE RESPONSE

A viral infected cell exposes the antigen on its owncell surface, to say Ive been infectedkill me

Helper T cell binds to the antigen exposed on thesurface of an infected cell

Helper T cells release chemicals called cytokinesthat activate macrophages, natural killer cells, andkiller T cells

These cells respond by destroying the infected cell


78/102


79/102

The rate of the immune response is different


80/102

depending on if the body has seen the antigen

before

If its the first exposure:

About 10 to 17 days required for peakplasma B cell response


81/102

The rate of the immune response is different


82/102

depending on if the body has seen the antigen

before

Second (and subsequent) exposure:

Response is faster (2 to 7 days)

Magnitude is greater

Duration is longer


83/102

Humoral Response sort it out!


84/102

- and in response to stimulation by cytokines released by the T cell,

clonal selection of B cells occurs.

- macrophages move to engulf and digest the antigen.- and memory cells which are able to deal with the antigen if

encountered again

- Fragments of the antigen are presented on the surface of themacrophage

- clonal selection of more identical T cells.

- An antigen enters blood stream and

- to form antigen presenting cell (APC).

- Specific T cells attach to the antigen fragments presented by theAPC and release cytokines which stimulate

- Then a specific B cell binds with one of the T cells

- This produces plasma cells which make large quantities ofantibodies


85/102

Types of


86/102

Acquired

Immunity

Naturally Acquired Immunity


87/102

y q y

Naturally Acquired

Active

Antigens enter the body

naturally, as when:

Microbes cause the person

to catch the disease.

There is a sub-clinical infection

(one that produces no evident

symptoms).

The body produces specialized

lymphocytes and antibodies.

Passive

Antibodies pass from the mother

to the fetus via the placenta

during pregnancy or to her infant

through her milk.

The infant's body does not produce

any antibodies of its own.

Artificially Acquired Immunity


88/102

y q y

Active

Antigens (weakened or dead

microbes or their fragments) are

introduced in vaccines.

The body produces and

specialized lymphocytes and

antibodies.

Passive

Preformed antibodies in an

immune serum are introduced

into the body by injection

(e.g. anti-venom used totreat snake bites).

The body does not produce

any antibodies.

Artificially Acquired


89/102

A summary of innate and acquired immunity

INNATE IMMUNITYRapid responses to a

broad range of microbes

ACQUIRED IMMUNITYSlower responses to

specific microbes

External defenses Internal defenses

Skin

Mucous membranes

Secretions

Phagocytic cells

Antimicrobial proteins

Inflammatory response

Natural killer cells

Humoral response(antibodies)

Cell-mediated response(cytotoxic lymphocytes)

Invading

microbes(pathogens)


90/102

Immune Technologies

Monoclonal Antibodies


91/102

A monoclonal antibody is anartificially produced antibodyfor a specific antigen.

Monoclonal antibodies areuseful for 3 reasons:

They are totallyuniform (i.e. clones).

They can be produced in largequantities.

They are highlyspecific.Monoclonal antibodies

chemically linked to a

fluorescent dye to detect the

presence of gonorrhea

Monoclonal Antibody Production


92/102

Monoclonal Antibody Production

Stimulate the production of B-cellsin mice by injecting them with theantigen.

These B-cells produce an

antibody against the antigen. B-cells isolated and fused with

immortal tumor cells.

Immortal cells cultured indefinitelyin a suitable growing medium.

Antibodies isolated via proteinchromatography

Diagnostic Uses of


93/102

gMonoclonal Antibodies

Monoclonal antibodies have manydiagnostic uses:

Detecting the presence of pathogens such as Chlamidiaandstreptococcal bacteria, distinguishing between HerpesvirusI and

II, and diagnosing AIDS.

Measuring protein, toxin,or drug levels in serum.

Blood and tissue typing.

Detection of antibioticresidues in milk.

Detecting pregnancy.

Direct treatment of disease (i.e. rabies)

How Pregnancy Tests Work


94/102

Dipstick

Antibody moves

by capillary action

Antibodies

tagged

with blue

latex

HCG bound to

free antibody

HCG in the urine of a pregnant women binds to

the color-labeled antibodies. The antibodies

then travel up the dipstick by capillary action.

g yThe test area of the dipstick contains two types ofantibodies: free monoclonal antibodies and capturemonoclonal antibodies, bound to the substrate in thetest window (arrowed).

Immobilized

capture antibodies

Colored latex in

test window

The HCG-antibody complexes are bound by

capture antibodies. The labeled antibodies

create a coloured line in the test window.

Vaccination


95/102

Vaccination

Vaccination is the purposefuladministration of antigenic material toproduce immunity to a disease.

live but weakened forms of pathogens

killed or inactivated forms of pathogens

purified material such as proteins

Vaccination


96/102

Vaccination

The vaccine stimulates clonal selectionand development of memory cells, butwithout developing the disease symptoms.

Vaccination


97/102

Vaccination

If an infection of the disease occursnaturally after vaccination, the body reactsas if it is the second exposure to the

disease

Vaccination


98/102

Vaccination

Vaccination is generally considered to bethe most effective and cost-effectivemethod of preventing infectious diseases.

Vaccination


99/102

Vaccination

BENEFITS

Eradication of diseasefrom a population (i.e. smallpox)

Reduced deathfromdisease (i.e. measles)

Reduced disabilitiesfromdisease (i.e. polio)

Decreased loss of workdays due to disease (i.e. flu)

DANGERS

Vaccine immunity lesseffectivethan naturalimmunity

Side effectsof vaccination

Antibiotics


100/102

Antibiotics

Antibiotics are substances that killsbacteria or inhibits its growth

Antibiotic Action


101/102

Antibiotic Action

Antibiotics block metabolic pathwaysand structures found in bacteria

the bacterial cell wall

bacterial ribosomes enzymes that are specific to bacteria

Viruses cant do metabolism, so theyarent effected by antibiotics


102/102

Human Immune Response

Documents

Transcript of Human Immune Response