Human Immune Response

Part 1: innate immunity

Our bodies are under constant

attack from pathogens

• A pathogen is an organism that can cause

disease

• Pathogens include:

– Bacteria

– Viruses

– Protists

– Fungi

nucleic acid

capsid

envelope

Review: VIRUSES

cell wall

plasma membrane

cytoplasm

circular DNA

Review: BACTERIA

There are two types of

responses to pathogens INNATE IMMUNITY

• Non-specific: doesn’t

distinguish one infectious agent from another

• Rapid response to pathogens

• Is present before any exposure to pathogens

• Is effective from the time

of birth

ACQUIRED IMMUNITY (AKA Adaptive response)

• Specific response to a

particular antigen

• Slower response to pathogens

• Requires previous exposure to the pathogen

• Built over a life time of exposure to pathogens

Two types of Innate 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

External Defense: Skin

• Cannot normally be penetrated by bacteria and viruses

Secretions from sebaceous and sweat glands keep the skin in a pH range of 3 to 5 (acidic) which kills most microbes

External Defense: Skin

Line digestive,

respiratory, and

genitourinary tracts

Trap microbes and

particles

External Defense:

Mucous Membranes

• In the trachea, ciliated epithelial cells sweep out mucus and trapped microbes

• Prevents these from entering the lungs

• Swallowing exposes them to the acidic environment of the stomach

External Defense:

Mucous Membranes

• Microbial colonization is also inhibited by saliva, tears, and mucus secretions

• All of these secretions contain antimicrobial proteins

External Defense:

Chemical Secretions

• An example is lysozyme, an

enzyme that digests the cell walls of

many bacteria.

External Defense:

Chemical Secretions

Two types of Innate 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

Link to video clip

Internal Defense:

Phagocytic cells

White blood cells (leukocyctes) that ingest

invading organisms

3m

Internal Defense:

Phagocytic cells

Three types:

1. Macrophages

2. Esinophils

3. Neutrophils

Internal Defense:

Phagocytic cells Macrophages

– Large, long-lived phagocytes

– Cells extend long pseudopodia, engulf the microbe into a vacuole which fuses with a lysosome.

– Some microbes have outer capsules to which macrophages cannot attach

Link to animation

Internal Defense:

Phagocytic cells

Esinophils

– Help fight large parasitic

invaders

– Position themselves

alongside the parasite

and discharge

destructive enzymes

through exocytosis

Internal Defense:

Phagocytic cells

Neutrophils

• Most abundant white

blood cell

• Recruit and activate

other cells of the

immune system

Internal Defense:

Phagocytic cells Neutrophils

• Have three strategies for directly attacking micro-organisms

– phagocytosis (ingestion)

– release of anti-microbial proteins

– generation of neutrophil extra cellular traps (NETs)

Link to video clip

Internal Defense:

Natural Killer Cells

• Do not attack microbes directly

• They destroy infected cells (typically those infected with viruses)

• Also attack abnormal body cells that could become cancerous

• They attack the cell’s membrane and cause the cell to lyse Link to video clip

Internal Defense:

Antimicrobial Proteins

• A variety of proteins that attack microbes

directly or impede microbe reproduction

• Example: Lysozyme

• Example: Interferons

– Secreted by virus-infected cells

– Do not benefit the infected cell but induce

neighboring cells to produce chemicals that

inhibit viral reproduction

Link to website

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

Link to video clip

Major events in the local inflammatory response

Pathogen Pin

Macrophage

Chemical signals

Capillary

Phagocytic cells

Red blood cell

Blood

clotting

elements

Blood clot

Phagocytosis

Fluid, antimicrobial proteins,

and clotting elements move

from the blood to the site.

Clotting begins.

2

Chemical signals released

by activated macrophages

and mast cells at the injury

site cause nearby capillaries

to widen and become more

permeable.

1 Chemokines released by various

kinds of cells attract more

phagocytic cells from the blood

to the injury site.

3 Neutrophils and macrophages

phagocytose pathogens and

cell debris at the site, and the

tissue heals.

4

Internal Defense:

Fever • If damage or infection is

severe, a widespread non-specific response may occur

• Increased body temperature

• Inhibits growth of some microbes

• Facilitates phagocytosis

• Speeds up repair of tissue

Two types of Innate 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

6.3.1 Define pathogen.

6.3.3 Outline the role of skin and

mucous membranes in defense

against pathogens.

6.3.4 Outline how phagocytic

leucocytes ingest pathogens in

the blood and in body tissues.

Assessment Statements

Which of the following is NOT a "first

line of defense" in the immune

response?

A. Fever

B. Skin

C. Mucous membranes

D. Lysozyme

E. Tears

F. Saliva

Which of the following is NOT a cell

of the innate immune system?

A. Natural killer

B. Macrophage

C. Neutrophil

D. T cell

E. Esinophil

F. Skin

A

B

C

D

E

F

Which cell type is part of the innate

immune system?

A. Lymphocyte

B. Leukocyte A

B

C

D

E

F

pH of the skin is:

A. Basic

B. Acidic

A

B

C

D

E

F

Which of the following cells acts by

killing cells that have been infected

by a virus?

A. Skin

B. Neutrophil

C. Macrophage

D. Lymphocyte

E. Esinophil

F. Natural Killer

A

B

C

D

E

F

Which molecule disrupts the viral

life cycle by preventing the

replication of DNA in infected cells?

A. Lysozyme

B. Interferons

C. Phagocytol

D. NETs

A

B

C

D

E

F

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

Human Immune Response

Part 2: acquired immunity

aka adaptive immunity

Acquired Immunity

• The “third line of defense”

• The key cells of the third line of defense are

lymphocytes • B cells

• T Cells

• Lymphocytes recognize and respond to

specific microbes and the molecules on the

foreign cells membrane (antigens)

• Antigens include:

Potentially damaging

microbes and

their toxins.

Substances such as pollen

and flea and dust mite feces.

Blood cell surface proteins.

The surface proteins of

transplanted tissues and

organs.

Photo

: E

II

Mallow pollen SEM.

Many pollens are antigens

The feces of fleas and mites

are antigenic in some people

Antigens

• Lymphocytes originate

from pleuropotent stem

cells in the bone marrow or liver of a developing fetus

– If they migrate to the

thymus to mature, they

become T cells

– If they stay in the bone

marrow to mature, they

become B cells

Lymphocytes

• B and T cells have

antigen receptors

– A single B or T cells

has about 100,000

receptors, all with

exactly the same

specificity

How do B and T cells

recognize antigens?

– There is an

enormous variety of

B and T cells in the

body, each with

different specificity

– This allows

response to millions

of potential

pathogens

How do B and T cells

recognize antigens?

While B cells and T cells are developing, their antigen

receptors are tested for potential self-reactivity

• “Will I attack cells of my own body?

– If YES: rendered non-functional or destroyed

by apoptosis

• This leaves only lymphocytes that react to

foreign substances

• Autoimmune diseases result when this

self-reactivity check malfunctions

How do T and B cells differ?

• B cells: HUMORAL IMMUNE RESPONSE

• T cells: CELL MEDIATED IMMUNE RESPONSE

HUMORAL IMMUNE RESPONSE

“challenge and response” • The immune system needs to "challenged" by

a disease

• The immune system “responds” by producing

a clone of "B" cells which produce large

amounts of antibodies to fight and eliminate

the pathogen.

B cells: HUMORAL IMMUNE RESPONSE

1.Antigen floating in the blood binds to

receptor on B cell surface

2.B cell divides into two cell types:

• Plasma B cells:

• Memory B cells:

HUMORAL IMMUNE RESPONSE

Plasma B cells

• Secrete antibodies

into the blood

immediately

HUMORAL IMMUNE RESPONSE

Plasma B cells

• Antibodies are

proteins that attach to

specific pathogen

antigens

– Tip of antibodies

become specialized for

specific antigens

Antibody Molecule

antigen binding sites

HUMORAL IMMUNE RESPONSE

Plasma B cells

• The antibody / antigen

complex makes the

microbe easier targets

for phagocytes

Inactivation of Antigens Clumping 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.

Virus Toxin

Antibody

Enhances Phagocytosis

Macrophage

Bacteria

Soluble antigens are stuck

together to form

precipitates.

Precipitation of

soluble antigens

Soluble

antigens

Antibodies

Free antigens directly activate

B

Cell

Gives

rise

to

Plasma

B Cells

Memory

B Cells

Secrete

antibodies

HUMORAL IMMUNE RESPONSE

Memory B cells • Memory B cells:

– Long-lived cells bearing receptors for the same

specific antigen

– Eventually, a few cells give rise to thousands of

new cells—all clones of the original and all specific

to original invading antigen

– Memory cells will continue to divide and create

antibodies for the rest of the life of the organism

1. A blood stem cell undergoes differentiation and

genetic rearrangement to produce:

2. immature lymphocytes with many different

antigen receptors. Those that bind to:

3. antigens from the body's own tissues are

destroyed, while the rest mature into:

4. inactive lymphocytes. Most of these will never

encounter a matching:

5. foreign antigen, but those that do are activated

and produce

6. many clones of themselves!

Division of antigen specific B

cells is called

CLONAL SELECTION

B Cells

antibodies

Activation of B Cells by

Antigen

antigen

Clonal Selection

Clonal Selection

plasma cells memory cells

antibodies

T cells: CELL MEDIATED IMMUNE RESPONSE

– A viral infected cell exposes the antigen on its own

cell surface, to say… ”I’ve been infected…kill me”

– “Helper T cell” binds to the antigen exposed on the

surface of an infected cell

– “Helper T cells” release chemicals called cytokines

that activate macrophages, natural killer cells, and

“killer T cells”

– These cells respond by destroying the infected cell

The rate of the immune response is different

depending on if the body has “seen” the antigen

before

• If it’s the first exposure:

– About 10 to 17 days required for peak

plasma B cell response

The rate of the immune response is different

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

Types of

Acquired

Immunity

Naturally Acquired Immunity

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

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 to

treat snake bites).

The body does not produce

any antibodies.

Artificially Acquired

A summary of innate and acquired immunity

INNATE IMMUNITY

Rapid responses to a

broad range of microbes

ACQUIRED IMMUNITY

Slower 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)

Assessment Statements

6.3.5 Distinguish between antigens and antibodies.

6.3.6 Explain antibody production.

11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity.

11.1.3 Define active and passive immunity.

11.1.4 Explain antibody production.

Immune Technologies

Monoclonal Antibodies

• A monoclonal antibody is an

artificially produced antibody

for a specific antigen.

• Monoclonal antibodies are

useful for 3 reasons:

– They are totally uniform (i.e. clones).

– They can be produced in large quantities.

– They are highly specific.

Monoclonal antibodies

chemically linked to a

fluorescent dye to detect the

presence of gonorrhea

Monoclonal Antibody Production

• Stimulate the production of B-cells

in mice by injecting them with the

antigen.

• These B-cells produce an

antibody against the antigen.

• B-cells isolated and fused with

immortal tumor cells.

• Immortal cells cultured indefinitely

in a suitable growing medium.

• Antibodies isolated via protein

chromatography

Diagnostic Uses of

Monoclonal Antibodies • Monoclonal antibodies have many

diagnostic uses:

Detecting the presence of pathogens such as Chlamidia and

streptococcal bacteria, distinguishing between Herpesvirus I and II, and diagnosing AIDS.

Measuring protein, toxin, or drug levels in serum.

Blood and tissue typing.

Detection of antibiotic

residues in milk.

Detecting pregnancy.

Direct treatment of disease (i.e. rabies)

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.

How Pregnancy Tests Work The test area of the dipstick contains two types of antibodies: free monoclonal antibodies and capture monoclonal antibodies, bound to the substrate in the test 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.

Assessment Statement

11.1.5 Describe the production of

monoclonal antibodies and their

use in diagnosis and in treatment.

Vaccination

• Vaccination is the purposeful

administration of antigenic material to

produce immunity to a disease.

– live but weakened forms of pathogens

– killed or inactivated forms of pathogens

– purified material such as proteins

Vaccination

• The vaccine stimulates clonal selection

and development of memory cells, but

without developing the disease symptoms.

Vaccination

• If an infection of the disease occurs

naturally after vaccination, the body reacts

as if it is the second exposure to the

disease

Vaccination

• Vaccination is generally considered to be

the most effective and cost-effective

method of preventing infectious diseases.

Vaccination

BENEFITS

• Eradication of disease

from a population (i.e. small

pox)

• Reduced death from

disease (i.e. measles)

• Reduced disabilities from

disease (i.e. polio)

• Decreased loss of work

days due to disease (i.e. flu)

DANGERS

• Vaccine immunity less

effective than natural

immunity

• Side effects of vaccination

Assessment Statements

11.1.6 Explain the principle of vaccination.

11.1.7 Discuss the benefits and dangers

of vaccination.

Antibiotics

Antibiotics are substances that kills

bacteria or inhibits its growth

Antibiotic Action

Antibiotics block metabolic pathways

and structures found in bacteria

– the bacterial cell wall

– bacterial ribosomes

– enzymes that are specific to bacteria

Viruses can’t do metabolism, so they

aren’t effected by antibiotics

Assessment Statement

6.3.2 Explain why antibiotics are effective

against bacteria but not against

viruses.