Immunity

Overview

Barriers help animals defend against many dangerous pathogens they encounter.

The immune system recognizes foreign bodies and responds with the production of immune cells and proteins.

Two major types of defence have evolved:

Innate immunity and acquired immunity

Innate immunity

Present before exposure to pathogens and is effective from birth.

Involves nonspecific responses to pathogens.

Innate immunity consists of external barriers plus internal cellular and chemical defences.

Acquired immunity

Acquired or adaptive immunity develops after exposure to agents such as microbes, toxins, or other foreign substances

It involves a very specific response to pathogens

Innate immunity

Recognition of traits

shared by broad ranges

of pathogens, using a

small set of receptors

Rapid response

Barrier defences: skin,

mucous membranes,

secretions

Internal defences:

Phagocytic cells,

antimicrobial proteins,

inflammatory response

Natural killer cells

Acquired immunity

Recognition of traits specific to

particular pathogens, using a

vast set of receptors

Slower response

Humoral response:

Antibodies defend against

infection in bodily fluids

Cell-mediated resonse:

Cytotoxic lymphocytes defend

against infection in body cells

Barrier defences include the skin and mucus membranes of the respiratory, urinary, and reproductive tracts.

Mucus traps and allows for the removal of microbes

Many body fluids including saliva, mucus, and tears are hostile to microbes

The low pH of skin and digestive system prevents growth of microbes

White blood cells (leukocytes) engulf pathogens in the body

Groups of pathogens are recognized by receptors

After the WBC (white blood cell) engulfs a microbe, then it fuses with a lysosome to destroy the microbe

• There are different types of phagocytic cells:

• Neutrophils engulf and destroy microbes

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

• Eosinophils discharge destructive enzymes

• Dendritic cells stimulate development of acquired immunity

• These white blood cells engulf microbes, then to destroy the microbe they fuse with a lysosome

• Antimicrobial peptides and proteins function in innate defence by attacking microbes directly or stopping their reproduction

• Interferon proteins provide innate defence against viruses and help activate microphages

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

Inflammatory response occurs following an injury. Mast cells release histamine, which promotes changes in blood vessels.

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

Pus is a fluid filled with white blood cells, dead microbes, and cell debris, that builds up at the site of inflammation

Inflammatory response• 1.Tissue injury -> release of histamine

• 2.Causes dilation and increased leakiness in local blood vessels and movement of phagocytes to

area• 3.Phagocytes consume bacteria and cell debris,

and tissue heals

Inflammation can either be local or systemic (throughout body)

Fever is a systemic inflammatory response triggered by macrophages (one type of WBC) and toxins from pathogens

• Septic shock is a life threatening condition caused by an overwhelming inflammatory response.

• Natural Killer Cells

Almost all cells in the body have a receptor on their surface

Cancerous or infected cells no longer display this receptor, and natural killer cells attack these damaged cells

Some pathogens avoid destruction by modifying their surface to prevent recognition or resisting breakdown by phagocytosis

Tuberculosis is an example

Acquired immunity

White blood cells called lymphocytes recognize and respond to antigens, or foreign molecules

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

Lymphocytes contribute to immunological memory, an enhanced response to a foreign molecule encountered previously

B cells and T cells have receptor proteins that can bind to foreign molecules

Each individual lymphocyte is specialized to recognize a specific epitope, or antigenic determinant, on an antigen

An antigen is any foreign molecule to which a lymphocyte responds

A single B or T cell has about 100,000 identical antigen receptors

Antigen binding siteAntigen binding site

Antigen receptor on a B cellAntigen receptor on a T cell

B cells give rise to plasma cells, which make proteins called antibodies or immunoglobulin

Antibody 1

Antibody 2

Antibody 3

Antibody 4Antigen

binding sites

Epitopes

Antigen

B cell receptors bind to specific, intact antigens

Secreted antibodies, or immunoglobulins, are the same shape as B cell receptors and consist of two identical heavy chains and two identical light chains

The tips of the chains form a constant (C) region, and each chain contains a variable (V) region.

T cells bind to antigen fragments presented on a host cell

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

In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, called antigen presentation

A nearby T cell can then detect the antigen fragment that is being displayed

If the MHC is presented on a normal body cell the antigen is displayed for cytotoxic T cells

If the MHC is presenting on an immune system cell such as a macrophage, or B cell the antigen is displayed for cytotoxic T cells, and helper T cells

Normal body

cell Immune cell

The acquired immune system has three important properties:

1. Receptor diversity (T cells and B cells can bind to any foreign particles)

2. A lack of reactivity against host cells (T cells and B cells never bind to normal cells, or proteins in the body)

3. Immunological memory (B cells remember coming in contact with a foreign particle)

Infected cell Antigen B cell

Cytotoxic

T cell

Cytotoxic T cell

Helper T cell Helper T cell

Helper T cell

Plasma B cell Memory B cell

Antibody

production

Antigen receptors are generated randomly

As lymphocytes mature in bone marrow or thymus, they are tested for self reactivity

Lymphocytes with receptors specific for the body's own molecules are destroyed by apoptosis

In the body there are a few lymphocytes with antigen receptors for any particular epitope

The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly

This is called clonal selection

Two types of clones are produced: short-lived activated plasma cells and long-lived memory cells

Antigen

Proliferation

Memory B cellPlasma B cell

The first exposure to a specific antigen represents the primary immune response

During this time, plasma cells are made, and T cells are activated

In the secondary immune response, memory cells allow a faster, more efficient response to the same specific antigen

Acquired immunity has two branches: the humoral immune response and the cell-mediated immune response

Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies

Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

Helper T cells aid in both responses

Helper T cells respond to nearly all antigen

Helper T cells bind to antigen presenting cells

Helper T cells secrete chemical messages that stimulate other lymphocytes

Cytotoxic T cells interact the MHC on infected cells and become activated killer cells

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

Antibody Classes

• The five major classes of immunoglobulins (antibodies) differ in function and body location

• Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen

• Monoclonal antibodies are prepared from a single clone of B cells grown in culture

Fig. 43-20a

DistributionClass of Immuno-

globulin (Antibody)

IgM

(pentamer)

J chain

First Ig classproduced afterinitial exposure toantigen; then itsconcentration inthe blood declines

Promotes neutraliza-tion and cross-linking of antigens;very effective incomplement systemactivation

Function

Fig. 43-20b

Distribution FunctionClass of Immuno-

globulin (Antibody)

IgG

(monomer)

Most abundant Igclass in blood;also present intissue fluids

Promotes opsoniza-tion, neutralization,and cross-linking ofantigens; less effec-tive in activation ofcomplement systemthan IgM

Only Ig class thatcrosses placenta,thus conferringpassive immunityon fetus

Fig. 43-20c

Distribution FunctionClass of Immuno-

globulin (Antibody)

IgA

(dimer)

J chain

Secretory

component

Present insecretions suchas tears, saliva,mucus, andbreast milk

Provides localizeddefense of mucousmembranes bycross-linking andneutralization ofantigens

Presence in breastmilk conferspassive immunityon nursing infant

Fig. 43-20d

Distribution FunctionClass of Immuno-

globulin (Antibody)

IgE

(monomer)Present in bloodat low concen-trations

Triggers release frommast cells andbasophils of hista-mine and otherchemicals that causeallergic reactions

Fig. 43-20e

Distribution FunctionClass of Immuno-

globulin (Antibody)

IgD

(monomer)

Trans-membraneregion

Present primarilyon surface ofB cells that havenot been exposedto antigens

Acts as antigenreceptor in theantigen-stimulatedproliferation anddifferentiation ofB cells (clonalselection)

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

Antibodies attached to antigen increase phagocytosis by macrophages called opsonization

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

Fig. 43-21

Viral neutralization

Virus

Opsonization

Bacterium

Macrophage

Activation of complement system and pore formation

Complement proteins

Formation of

membrane

attack complex

Flow of water

and ions

Pore

Foreign

cell

Fig. 43-21a

Viral neutralization

Virus

Fig. 43-21b

Opsonization

Bacterium

Macrophage

Fig. 43-21c

Activation of complement system and pore formation

Complement proteins

Formation of

membrane

attack complex

Flow of water

and ions

Pore

Foreign

cell

Three types of immunity• Innate immunity

Everyone is born with a general type of

protection. Many of the germs that

affect other species don’t harm us. For

example the virus that causes

leukemia in cats doesn’t affect

humans.

Innate immunity includes the first line

of defense – external barriers of the

body

And non-specific defenses such as

fever and inflammation.

Adaptive Immunity and Passive Immunity

• The second kind of defense is

active immunity which develops

through our lives. This involves

lymphocytes and develops only as

people are exposed to diseases or

immunized by vaccines.

• Passive immunity is “borrowed”

from another source and lasts for a

short time. For example,

antibodies in a mother’s breast milk

provide a baby with temporary

immunity to diseases the mother

has been exposed to.

Tissue and Organ Transplants

• MHC molecules are different among genetically non-identical individuals

• Differences in MHC molecules stimulate rejection of tissue grafts and organ transplants

• Chances of successful transplantation increase in donor and recipient have MHC tissue types that are matched closely

• Immunosuppresive drugs facilitate transplantation

Immunity • Everyone’s immune system is

unique. Some people never seem

to get infections, whereas other

seem to be sick all the time. As

people become older they usually

become immune to more

pathogens. This is why adults and

teens tend to get sick less often

then kids.

Problems of the Immune System

• Disorders of the immune system fall into four

main categories:

1. Immunodeficiency disorders (primary or

acquired)

2. Autoimmune disorder (in which the body’s

own immune system attacks it own tissue as

foreign matter)

3. Allergic disorders (in which the immune

system overreacts in response to an

antigen)

4. Cancers of the immune system

Immunodeficiency Disorders

• Immunodeficiencies occur when a

part of the immune system is not

present or is not working properly

• A person can be born with an

immunodeficiency, although the

symptoms might not occur until

later in life, or it can be acquired

through infection or produced by

drugs

• Immunodeficiencies can affect B

lymphocytes, T lyphocytes, or

phagocytes.

Innate Immunodeficiency:• Severe combined

immunodeficiency

(SCID) also known

as “bubble boy”

disease after a boy

who lived in a

microbe free

bubble.

SCID is a serious immune system disorder

that occurs because of a lack of both B and

T lymphocytes, which makes it almost

impossible to fight infections.

Acquired Immunodeficiency• Usually develop after a disease,

although can also be the result of

malnutrition, or medical problems.

Can be caused by certain

medications.

Latency

• Some viruses may remain in a host in an inactive state called latency

• Herpes simplex viruses can be present in a human host without causing symptoms

HIV

• Human immunodeficiency virus (HIV) infects helper T cells

• The loss of helper T cells impairs both the humoral and cell-mediated responses and leads to AIDS

• HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA

Immunodeficiency caused by medication• Some medications suppress the

immune system. One of the

drawbacks of chemotherapy for

treatment of cancer, is that it attacks

many fast growing, healthy cells,

including immune cells.

• As well people who have had organ

transplants may need to take

immunosuppresant medications.

Autoimmune Disorders

• In an autoimmune disorder, the immune system mistakenly attacks the body’s healthy organs and tissues as though they were foreign invaders. Examples:

• Lupus – chronic disease marked by muscle and joint pain and inflammation (may involve attacks on kidneys and other organs)

• Juvenile rheumatoid arthritis – a disease in which the immune system attacks certain body parts ( such as joints of the knee, hand, and foot)

Allergic Disorders

• Occur when the immune system overreacts to exposure to antigens in the environment. The substances that provoke such attacks are called allergens. The immune response can cause symptoms such as swelling, inflammation, watery eyes, sneezing. Medications that are antihistamines can relieve symptoms.

• In some cases, allergies can be life threatening if they cause anaphylaxis – which is a systemic allergic response.

• Allergic disorders include asthma, eczema, and allergies

• In localized allergies, including hay fever IgEantibodies produced after first exposure to an allergen attach to receptors on mast cells

• The next time the allergen enters the body, it binds to mast cell-associated IgE molecules

• Mast cells release histamine and other mediators causing vascular changes leading to typical allergy symptoms

Cancers of the immune system

• Cancer occurs when cells grow out of control. This can happen with cells of the immune system.

• Lymphoma involves the lymphoid tissue.

• Leukemia involves abnormal growth of leukocytes, is the most common childhood cancer.

• Both types of cancer in kids are curable.

Vaccines

• A vaccine is a biological preparation that provides active acquired immunity to a particular disease.

• Vaccines are typically made of an agent that resembles the disease causing microorganism, or its toxins, or one of its surface proteins.

• The agent stimulates the body’s immune system, to produce B memory cells, so that if the immune system encounters these microorganisms in the future it will easily recognize and destroy them.

What are vaccines made of?

• There are several types of vaccines:• Inactivated – a previously virulent microorganism that

has been destroyed with chemicals, heat, radioactivity or antibiotics.

• Examples: Influenza vaccine, bubonic plague

• Attenuated – live, attenuated microorganisms.• Many of these are active viruses that have

been cultivated under conditions to disable their virulent properties, or that are closely related but less dangerous organism that produce a broad immune response.

• Examples: viral – measles, bacterial - typhoid

• Typically produce more durable immunological response, but may not be safe for immunocompromised individuals. (May rarely mutate to a virulent form and cause disease.)

• Toxoid – made from inactivated toxic compounds that cause illness rather than the microorganism.

• Examples: tetanus and diptheria

Subunit – protein subunit

• Rather than introducing a “whole-agent” vaccine, a fragment can be used to create an immune response.

• Example: Hepatitis B virus – only the surface proteins of the virus

Conjugate

• Certain bacteria have polysaccharide outer coats that are not good at causing an immune response.

• But, by linking these outer coats to proteins (e.g. toxins) the immune system can be led to recognize the polysaccharide as a protein antigen.

• Example – Haemophilus influenzae type B vaccine

How the vaccine works

• The agent stimulates the body’s immune system, to produce B memory cells, so that if the immune system encounters these microorganisms in the future it will easily recognize and destroy them.

Schedule

• For the best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to the particular vaccines.

• Later on “booster” shots are required to achieve “full immunity”.

History

• Edward Jenner (1700s) learned that dairy workers never got the disease small pox, which was deadly and disfiguring.

• Instead the dairy workers got cowpox, a much milder disease.

• Jenner took pus from the hand of a milkmaid with cowpox and scratched it into the arm of an 8-year-old boy.

• Six weeks later he inoculated (inserted smallpox fluid) the boy with smallpox, but the boy did not catch smallpox.

• Smallpox was eradicated worldwide by the 1960s and 70s. There are no human cases, and smallpox is not found in any other organisms.

• This achievement was hoped to be the first for many disease’s eradication.

Herd Immunity

• The form of immunity that occurs when a significant proportion of the population is vaccinated.

• Provides a measure of protection for individuals who have not developed immunity, such as babies, and immunocompromised individuals.

Are vaccines harmful?

Myth: MMR causes autism

• MMR is a vaccine for mumps measles and rubella given to toddlers.

• Symptoms of autism usually become apparent around the same time as MMR is given – no causality proven.

• Autism probably has multiple components including genetics.

Myths about vaccines

• Myth: Thimerosal causes autism• Thimerosal – is a compound that contains mercury, and

was used as a preservative in vaccines

• There was no evidence of harm, but it has been taken out of vaccines as a precaution

• Thimerosal has not been used in any routinely recommended childhood vaccines since 2001

• Multiple studies have shown that thimerosal in vaccines does not cause autism when comparing children who received thimerosal-containing vaccines and those who received thimerosal free vaccines.

Myth: vaccines contain harmful chemicals• Vaccines contain aluminum as an adjuvant – an

ingredient that improves immune response. This allows for less antigen to be used.

• Aluminum is a very common metal found in nature, and infants get more of it through breast milk than in vaccines.

Continued chemicals

• Formaldehyde – used to detoxify diphtheria and tetanus toxins or to inactivate a virus.

• There is a very small amount left over in the vaccine, but it is safe.

• Humans normally have formaldehyde in their bloodstream at levels higher than found in vaccines.

Myth Vaccines are not effective

• Most childhood vaccines are very effective when properly administered (~80% - 100%), but no vaccine claims to be 100% effective.

• Some adult vaccines are not as effective as childhood vaccines.

Myth: Natural Infection is better than immunization• Natural infection usually does cause better

immunity than vaccination.

• However the price paid for natural disease can include paralysis, permanent brain damage, liver failure, liver cancer, deafness, blindness, pneumonia or death.