MICROBIOLOGY- ALCAMO

LECTURE: IMMUNE DISORDERS

IMMUNE DISORDERS

• Faulty immune system can either:

• Over-react

or

• Under-react

Introduction – Hay Fever

• Hay fever – not dangerous,

but causes great discomfort and inconvenience

• 1870’s – British scientist Charles Blackley found that pollen grains could:– When placed in the eyes of some people, cause

swelling– When rubbed into a skin scratch produce a

local reaction

Introduction Hay Fever

• Now a known disorder of the immune system

• About 35 million Americans suffer from hay fever

• Thousands more are allergic to foods, cosmetics, leather or metals, and pets

• Approximately 40-50 million people in the U.S. have some type of allergy

Introduction – Hay Fever

• The common denominator among

allergies is hypersensitivity• Hypersensitivity stems from the activity of

the immune system and involves both– Antibody mediated immunity– Cellular aspects of immunity

• Currently intense research is going on to find ways to alleviate allergy symptoms

Hypersensitivity

• Multi-step phenomenon requiring:– Initial exposure to an antigen– Dormant stage when person is sensitized– Reaction to a second exposure to antigen

• Reaction can be:– Immediate – response by antibodies within

minutes– Delayed - cell mediated response over 2-3 days

Hypersensitivity

• Early 1970’s Gell and Coombs further classified Hypersensitivities

• Immediate Hypersensitivity– 1. Type I Anaphylactic Hypersensitivity– 2. Type II Cytotoxic Hypersensitivity– 3. Type III Immune Complex Hypersensitivity

• Delayed Hypersensitivity– 4. Type IV Cellular Hypersensitivity

TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY

• Begins with entry of antigenic substance (allergens – bee venom, serum proteins, drugs, etc)

• Sensitizing Dose – smallest dose of an allergen that sensitizes a person to cause a reaction (can be as low

as 0.001 mg)• Immune system responds and

B-lymphocytes produce IgE

TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY

• IgE enters circulation and attaches to thousands of:– Mast cells (connective tissue cells with

granules)– Basophils (white blood cells with granules)

• Granules are released, flow into extracellular fluids and emit mediators:– Histamine– Serotonin

TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY

• Mediators – principal activity is to contract smooth muscles in the body - Anaphylaxis– This constricts veins and capillaries and forces

fluid out into the tissues– The skin becomes swollen around the eyes,

wrists and ankles – called edema– This is accompanied by a hive-like rash and

burning and itching of the skin as nerves are excited

TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY

• Contractions also occur in the gastrointestinal tract (causes sharp cramps) and bronchial muscles (causes shortness of breath)

• Person inhales rapidly, but can’t exhale to get rid of CO2

• Death can occur within 10-15 minutes due to asphyxiation

WHOLE BODY INVOLVEDGet medical help fast!!!!!

Medical Help

• Adrenalin – stabilizes

basophils and mast cells, opens air passages and constricts capillaries

• Muscle relaxer – opens air passages, stops cramping

• Antihistamine – competes with histamine for active sites on smooth muscle cells and inhibits histamine’s actions

• If all else fails - tracheostomy

TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY

• Desensitization – therapy used to reduce the possibility of anaphylaxis– Short-term - can inject tiny but increasing

amounts of allergen over a period of hours to induce a gradual reduction of granules rather than a later massive degranulation

– Long-term - can give a series of injections of allergen over a few weeks and the exposure causes immune system to produce IgG which can neutralize sensitized cells.

Atopic Disease/Allergy

• Also Type I Hypersensitivity,

but in localized areas• Hay Fever:

– immune stimulation by pollen antigens leads to IgE production

– sensitization of mast cells in the eyes, nose and upper respiratory tract

– Subsequent exposure causes the all too familiar sneezing, tearing and swollen mucous membranes

Asthma

• Asthma attacks are

triggered by allergic reactions• Characterized by wheezing and stressed

breathing• 15 million Americans suffer from asthma• Doctors usually prescribe bronchodilators

and/or anti-inflammatory agents (steroids)

Food Allergies• Characterized by

symptoms in the

gastrointestinal tract– Swollen lips– Abdominal cramps– Nausea and diarrhea

• May develop urticaria – rash containing hives

• Allergenic foods – chocolate, strawberries, oranges, cow’s milk and fish

Why Me????• Almost 20 % of Americans have some sort of

allergy• Allergic individuals have 100 times the IgE level

of normal individuals• Hypotheses:

– IgA levels are greatly reduced in people with allergies. In normal people IgA may shield IgE lymphocytes from antigenic stimulation

– Immune system feedback mechanisms are defective in allergic individuals (suppressor T-lymphocytes)

Type II Cytotoxic Hypersensitivity

• Cell-destroying reaction that occurs when IgG reacts with antigens on the surface of target cells

• Transfusion reaction – mixing incompatible blood types– Human Blood Types: A, B, AB and O– Each type has antigens on the surface of RBC’s– If given the wrong blood type, a person’s

antibodies will react with the antigens and agglutination (clumping) occurs

Hemolytic or Rh Disease• 85-90% of Americans’ RBC’s have a

surface antigen (Rh) and are Rh+– If an Rh- woman marries an Rh+ man, there is

a 75% chance the baby will be Rh+– A first pregnancy will stimulate the production

of Rh+ antibodies in the woman– In any subsequent pregnancies, the woman’s

body will see the baby’s blood as foreign and destroy its blood cells

– Treatment – injection of Rh antibodies within 72 hours of birth will remove Rh antigens from blood

Autoimmune Diseases – Fighting Yourself

• Thrombocytopenia – antibodies produced against thrombocytes

• Leads to impaired blood clotting and hemorrhages on skin and mouth

Goodpasture’s Syndrome

• Antibodies combine with antigens in the kidneys and lungs

• Can cause kidney and lung failure

Myasthenia Gravis

• Antibodies generated against muscle fiber membranes

• Reduces nerve impulse transfer and results in loss of muscle activity, weakness, fatigue

Graves’ Disease• Antibodies unite with receptors on the

surface of thyroid gland cells causing increased secretion of thyroxine

• This results in goiter and rise in metabolic rate

TYPE III Immune Complex Hypersensitivity

• When antibodies combine with antigens and form aggregates that accumulate in blood vessels or on tissue surfaces– Phagocytes are attracted to site and enzymes

are released that cause tissue damage– Gradual development – usually not life

threatening

• Serum sickness – IgG produced against serum proteins – can cause kidney damage

TYPE III Immune Complex Hypersensitivity

• Systemic lupus erythematosus: – as old white blood cells are – disintegrating, B-lymphocytes

produce IgG– Immune complexes accumulate

in the skin and body organs– Causes butterfly rash and lesions

in the heart, kidney and blood vessels

Rheumatoid Arthritis

• Immune complexes form in the joints causing inflammation - debilitating

• Chronic disease – may have periods with no pain, but then it returns

TYPE IV Cellular Hypersensitivity• T-cells involved• Delayed Reaction – maximal effect not seen until

24-72 hours has elapsed• Characterized by:• Induration - a thickening and drying of the skin

tissue• Erythema – surrounding zone of redness

TYPE IV Cellular Hypersensitivity

• There is a localized reaction with lumps, hives or blisters

• Contact dermatitis can develop after exposure to many different allergens (clothing, jewelry, cosmetics, fur)

• For example: Poison ivy oil on leaves is an allergen

IMMUNE DEFICIENCIES• Bruton’s Agammaglobulinemia:

– Congenital disease– B-lymphocytes fail to develop in the bone

marrow– No antibodies are made– Can’t fight infectious disease

IMMUNE DEFICIENCIES• DiGeorge’s Syndrome:

– Congenital disease– T-lymphocytes don’t develop because of failure

in thymus gland– Cellular immunity is defective– Susceptible to fungal and protozoal diseases

IMMUNE DEFICIENCIES

• Severe Combined Immunodeficiency (SCID)– Congenital disease– Defects in both antibody and cellular immunity– All immune function is suppressed– David – longest surviving victim

• Lived in a sterile, plastic bubble at Baylor College of Medicine for 12 years

• Received a bone marrow transplant from his sister but died of blood cancer

http://www.bbc.co.uk/news/health-11451810

Acquired Immune Deficiency (AIDS)

• Viral disease• Cellular immunity severely depressed• Antibody-mediated immunity also altered• Have very few T—cells• Ratio of T-cells is reversed:

– Normal 2 Helper T-cells:1 Suppressor T-cell– AIDS 1 Helper T-cell:2 Suppressor T-cells

Transplantation• 4 Types of Transplantation (Grafts)

– Autograft – a graft taken from one part of the body and transplanted to another part of the same body (never rejected)

– Isograft – a tissue taken from one identical twin and transplanted to the other twin (never rejected)

– Allograft – a graft between random members of the same species (variable degrees of success)

– Xenograft – a graft between members of two different species (rarely successful)

Transplantation• How to Make it Work:

– Tissue typing – a close match (relative) is more successful

– Immune Suppressant Drugs:• Antimitotic drugs prevent multiplication of

lymphocytes• Cyclosporin A suppresses cellular immunity• Antibodies against the lymphocytes• Steroid hormones - prednisone

Antibodies Against Lymphocytes• To obtain antibodies against lymphocytes:

– 1. lymphocytes from transplant patient are injected into a horse

– 2. later, the horse is bled to obtain antibody-rich serum

– 3. when introduced to the transplant recipient, the antibodies react with the lymphocytes

– 4. this slows the immune response and increases success rate of transplant

Monoclonal Antibodies• Antibody-secreting cells can become

cancerous• The cell will divide until it becomes a mass

of cells called a myeloma• Because it began as a single cell, all cells

are clones• The cells will produce only a single type of

antibody

Pregnancy Test

• http://www.sumanasinc.com/webcontent/animations/content/pregtest.html