don’t touch the poison ivy!
Post on 23-Jan-2022
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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
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