Human Immune Response

Part 1: innate immunity

One of these things is not like the others..

Our bodies are under constant attack from pathogens

A pathogen is an organism that can cause disease Pathogens include:
Bacteria Viruses Protists Fungi

Review: VIRUSES
envelope

capsid nucleic acid

Review: BACTERIA

cell wall

plasma membrane cytoplasm

circular DNA

There are two types of responses to pathogens

INNATE IMMUNITY Non-specific: doesnt 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

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

External Defense: Mucous Membranes

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: Chemical Secretions

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.

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) NET formation

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 cells membrane and cause Natural Killer Cells the cell to lyse

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
Interferons

Knowledge Review
Give me: 5 types of cell involved in defense against disease 4 ways to prevent infectious agents entering the body 3 responses of neutrophils 2 types of immunity 1 antimicrobial protein

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

Major events in the local inflammatory response

Pathogen Pin Blood clot

Macrophage Chemical signals Phagocytic cells Capillary Blood clotting elements Phagocytosis

Red blood cell

1
Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable.

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

Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site.

Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals.

Internal Defense: Fever

If damage or infection is severe, a widespread nonspecific 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

Its a race
1. Pathogens are ________ that cause disease

2.
3. 4. 5. 6.

_________ have a close relationship with their host, and have a negative impact on the host
________ conditions in the stomach kill pathogens ___________ in tears and saliva are toxic to pathogens The vaginal tract contains ______ acid The _________ system is protected by goblet cells and mucus

7.
8.

________ is an example of bacteria that can infect wounds

The immune system is made up of _______ blood cells

Which of the following is NOT a "first line of defense" in the immune response?
A. B. C. D. E. F. Fever Skin Mucous membranes Lysozyme Tears Saliva

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

A. B. C. D. E. F. Natural killer Macrophage Neutrophil T cell Esinophil 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. B. C. D. E. F. Skin Neutrophil Macrophage Lymphocyte Esinophil 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. B. C. D. Lysozyme Interferons Phagocytol 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

Virus

If this is the answer, what is the Antigen question? Lactic acid

Pathogen Lymphocyte Bacteria Influenza HIV Goblet cells Phagocyte Chronic Lysozyme

Chlamydia Mucus

Parasite

Choose 3 words

Think of a question they could be used to answer

Eg. What causes flu? A = a virus

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
The feces of fleas and mites are antigenic in some people

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.
Mallow pollen SEM. Many pollens are antigens
Photo: EII

The Immune System

Phagocytes foot soldiers T-lymphocytes search team

B-lymphocytes elite attack squad

Lymphocytes
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

How do B and T cells recognize antigens? 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

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
Neutralization Clumping particulate antigens Precipitation of soluble antigens
Antibodies Antibody Bacterial cell Soluble antigens

Virus Toxin Antibodies bind to viral binding sites and coat bacterial toxins. Solid antigens such as bacteria are stuck together in clumps.

Soluble antigens are stuck together to form precipitates.

Enhances Phagocytosis

Macrophage Bacteria

Free antigens directly activate

B Cell
Gives rise to Secrete antibodies Plasma B Cells
Memory B Cells

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 cellsall 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

Division of antigen specific B cells is called CLONAL SELECTION

1. A blood stem cell undergoes differentiation and genetic rearrangement to produce: immature lymphocytes with many different antigen receptors. Those that bind to:

2.

3.

antigens from the body's own tissues are destroyed, while the rest mature into:
inactive lymphocytes. Most of these will never encounter a matching: foreign antigen, but those that do are activated and produce many clones of themselves!

4.

5.

6.

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 Ive been infectedkill 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 its 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

Humoral Response sort it out!

- 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 the macrophage - 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 the APC 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 of antibodies

Types of

Acquired Immunity

Naturally Acquired Immunity

Naturally Acquired
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.

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.

Artificially Acquired Immunity

Artificially Acquired
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.

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 Skin Mucous membranes Secretions Invading microbes (pathogens)

Internal defenses

Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells

Humoral response (antibodies)

Cell-mediated response (cytotoxic lymphocytes)

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

 Monoclonal antibodies have many

diagnostic uses:

Diagnostic Uses of Monoclonal Antibodies

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)

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).
Dipstick Antibody moves by capillary action Immobilized capture antibodies

Antibodies tagged with blue latex Colored latex in test window

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.

The HCG-antibody complexes are bound by capture antibodies. The labeled antibodies create a coloured line in the test window.

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

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 cant do metabolism, so they arent effected by antibiotics