DON’T TOUCH THE POISON IVY!

Fantastic Voyage Revisited: a

conversation about the immune

system, allergic hypersensitivity, and

selected immunological issues

OUTLINE OF ACTIVITY

An overview of the immune system and

vaccination stories (45 min) followed by a 15

minute break.

Hypersensitivity (Bee stings and Poison Ivy),

Anaphylaxis and stories (45 min) followed by a 15

minute break.

Selected immune disorders [Hepatitis B, Type I

Diabetes, HIV/AIDS, & one Zoonotic Example]

(45 min) followed by discussion 15 minutes.

*Constant questioning would be appreciated, let’s

make this a conversation rather than a lecture!

LET’S BEGIN THE FANTASTIC VOYAGE

WHY DO WE NEED AN IMMUNE SYSTEM? BACTERIA, VIRUSES, FUNGI, PARASITES & NEOPLASTIC CELLS

THINGS TO REMEMBER ON THE JOURNEY!

Recognition

Specificity

Regulation

Memory

SO WHAT MAKES UP AN IMMUNE SYSTEM

WHOA!

ANTIGEN PRESENTATION AND T-CELL

HELP & MEMORY

HUMMORAL IMMUNITY B-CELL

ACTIVATION

ANTIBODY STRUCTURE

KILLING OF MICROBES BY ANTIBODY

CELLULAR IMMUNITY

KILLING OF MICROBES BY CELLULAR

IMMUNITY

VACCINATION

VACCINATION RATIONALE

Vaccine Development

Observations of natural immunity

Identification of immunological targets

Formulation and manufacturing

Clinical trials, safety, efficacy

Marketing

Expected Outcome

Elimination of clinical infection

Eradication of disease

All in the presence of evolving organisms, politics,

opinions, legal challenges, and markets

HOLD THAT THOUGHT! WE WILL BEGIN TO

ITCH IN THE NEXT HALF HOUR.

IGE-DEPENDENT IMMUNE RESPONSES &

ALLERGIC DISEASE

ACTIVATION OF TH2 CELLS AND

PRODUCTION OF IGE

Nature of Allergens

WHAT HAPPENS UPON EXPOSURE TO

ALLERGEN (ANTIGEN)

MAST CELLS, BASOPHILS, & EOSINOPHILS

MAST CELL & BASOPHIL MEDIATORS

Biogenic amines

Granule enzymes

Proteoglycans

Cytokines

Lipid mediators

Prostaglandin D2

Leukotrienes

EOSINOPHIL MEDIATORS

Granule proteins that are toxic to parasitic

organisms and may injure normal tissue.

Major basic protein

Eosinophil cationic protein

Eosinophil peroxidase

Lipid mediators

THE IMMEDIATE REACTION

The wheal and flare reaction

THE LATE-PHASE REACTION

IGE MEDIATED ALLERGIC DISEASES

Systemic Anaphylaxis

ANAPHYLAXIS

Vasodilation, fall in blood pressure (shock)

Smooth muscle constriction of upper and lower

airways, laryngeal edema, hypermotility of the

gut, outpouring of mucous in the gut and

respiratory tract, hives in the skin (respiratory

distress)

Epinephrine (adrenalin) reverses

bronchoconstriction, vasodilation and increases

cardiac output

Antihistamines may also be beneficial

OTHER IGE MEDIATED ALLERGIC

DISEASES

Bronchial Asthma

Allergic Rhinitis

Food allergies

Urticaria and Eczema

IMMUNOTHERAPY

Desensitization (allergy shots)

Shift from IgE to IgG

Specific T cell tolerance Th2 to Th1

SO WHAT IS THE VALUE OF IGE & MAST

CELLS?

Protection against parasites

Mast cells play an important protective role as part of

innate immune response to bacterial infections

Slower bleeding time in atopics, sudden cardiac arrest

less common

As a result of heightened response, protection against

arthropod vectored diseases (my speculation)

Just an unfortunate consequence of otherwise

protective responses. The price we have to pay?

Or have some organisms through evolution co-opted

hypersensitivity to there own benefit (toxins)?

CUTANEOUS “DELAYED” T-CELL

MEDIATED HYPERSENSITIVITY

Poison Ivy/Poison Oak

Contact allergens

Urushiol

ALLERGIC DISEASE IN CATTLE:

PSOROPTIC SCABIES (COWS ITCH TOO!!)

YES!!

ADDITIONAL IMMUNOLOGICAL TOPICS

Autoimmune disease, > 30 diseases or syndromes

Transplantation immunology

Neuroimmunology

Reproductive immunology

Tumor immunology

AUTOIMMUNE HEPATITIS

Infection of the liver with the hepatitis B virus

(HBV, serum hepatitis)

350 million people affected worldwide

Little cytopathology caused by the virus

Liver damage can be massive and devastating

When serious damage occurs, it is the immune

system that causes most, if not all, of the damage

Both CD4 and CD8 cells are activated and a

delayed-hypersensitivity reaction ensues.

AUTOIMMUNITY: DIABETES (TYPE I)

INSULIN DEPENDENT

Age of onset 11 to 12 years

Chronic autoimmune disease destroying the insulin producing βcells in the pancreas (CD4+TH1, Cytokine TNF and IL-1, and potentially anti-insulin antibodies)

No gender bias

Strong genetic component (HLA-DR3, DR4)

Possible onset with environmental “triggers” Viral infection, an example Serotype B Coxsackie virus

Tandem repeats within the insulin promoter (genetic)

T cells the major destructive agent with antigen being glutamic acid decarboxylase (GAD). Insulin itself also appears to be a target.

Epidemiology data suggest that repeated infection protects from diabetes. Possible reason for increase incidence in developed countries.

New Therapies: inducing immunological tolerance, generating or giving regulatory T cells to patients.

A VIRAL DISEASE AFFECTING THE

IMMUNE SYSTEM: HIV/AIDS

First reported in 1981, opportunistic infections,

Pneumocystis carinii, oral candidiasis,

tuberculosis, and Kaposi’s sarcoma

The human immunodeficiency virus (HIV) was

identified in 1983 as a retrovirus.

The coat proteins mutate at an extraordinarily

high rate.

Infects and causes a gradual loss of CD4 helper T

cells

Drug treatment is of 4 categories: nucleoside

analogs, reverse transcriptase inhibitors,

protease inhibitors and fusion inhibitors.

HIV

HIV has a surface coat protein gp 120 that specifically recognizes and binds to the CD4 molecule found on CD4 T cells

Following binding the gp 120 molecule twists and reveals a second binding molecule gp 41 that binds a second coreceptor of the CD4 cell surface, called fusin. With both binding events the virus can enter the cell.

Therapy Drug Cocktails – enfuvirtide blocks gp 41/fusin

Vaccine is available for SIV and FIV, and observe cases of natural effective immunity. DNA based vaccine/CD8 preferential stimulation

Molecular Medicine (gene therapy) antisense with target of suppression of fusin Selective expression of thymidine kinase and treatment with

acyclovir

ZOONOTIC IMMUNE DISORDER:

CATTLE GRUB, HYPODERMA LINEATUM

IMMUNE DISORDERS

Human Case of Cattle Grub Infestation

THE END

BUT STAY TUNED