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HYPERSENSITIVITY/ALLERGY

Anaphylactic Rxn/Anaphylaxis : Involves ______________ antibodies which bind to Basophils/Mast cells.

1^st exposure: IgE (to the allergen) is formed and binds to Mast cells by Fc portion. (No symptoms at this point)

2^nd exposure: Degranulation (Histamine, Leukotriene and Prostaglandins released)

1) Dilates blood vessels

2) Increased permeability of capillary vessels

3) Contraction of smooth muscles

4) Increased mucus secretion

5) Increased secretion of HCl in stomach

Type I / Immediate Hypersensitivity
(10-20min)

2 Major Types

 

________________________________Anaphylaxis:

Severe , Sometimes Fatal

Develops rapidly after antigen/allergen is introduced to a sensitized individual.

e.g. Bee Sting: Shock and Asphyxia

 

Signs/Symp:

Flushing of skin

Shortness of breath

Shock

Constriction of smooth muscles in the lungs)

Asphyxia: Death due to respiratory failure

 

Treatment: ___________________________________________

 

Localized Anaphylaxis/_________________________________

More common.

 

e.g. _______________________________ ,Asthma, Hives

Ags: Plant pollen, Fungal spores

Dust, animal dander, dust mites

Foods

 

Hayfever: Involves IgE.

Allergic Rxn of Upper Respiratory system

Signs/Symp: Itchy, tearing eyes, congested nasal passages, runny nose and sneezing.

Treatment: Antihistamine

 

Asthma:

Allergic Rxn of the lower respiratory system.

Signs/Symp: Wheezing and shortness of breath.

 

Treatment: Adrenaline/Epinephrine (______________________________________ not Histamine)

 

Prevention of Anaphylactic Reactions

Skin test to identify allergens

Prevention of Anaphylactic Reactions

___________________________________________:

Carefully injecting small, repeated doses of the allergen into the skin.

Patient produces IgG antibody rather than IgE.

IgG acts as ?blocking? Ab.

Prevents binding of allergen to IgE on Mast cells g No release of histamine g No symptoms

 

 

 

 

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Type II (___________________________________) Reactions

Involve IgG or IgM antibodies and complement.

Complement activation causes cell lysis or damage by macrophages.

Transfusion Rxns & Rh Incompatibility)

 

ABO Blood Groups

Four major types based on ___________________________________antigens on surface of RBCs.

Incompatible blood types will cause clumping (Hemagglutination) of RBCs.

 

 

Rh Incompatibility (________ Ag)
Erythroblastosis Fetalis/Hemolytic Disease of the Newborn (HDN)

Results from Rh negative mother exposed to Rh positive cells by prior birth or transfusion. (Sensitized)

g Produce anti-Rh antibodies (IgG) which can cross the placenta.

g Reacts with fetal RBCs g Lysis of RBCs. g Results in release of toxins (Bilirubin) and anemia.

 

Treatment: Exchange transfusion: Removal of fetal Rh+ cells and transfusion with Rh- blood.

Prevention:

 

__________________________________: Passive immunization of Rh- mother with anti-Rh antibodies

(Blocking Ab) coats Rh+ cells and prevents sensitization.

 

Drug-induced Thrombocytopenic Purpura

 

Type III (___________________________________________) Hypersensitivity
Excess immune complexes are deposited in tissues g localized inflammation and tissue damage.

Non-self Ag: Serum Sickness

Self Ag: Autoimmune Disease

Rheumatoid Arthritis

Systemic Lupus Erythematosus

Glomeruloephritis

Type IV (____________________________________) Hypersensitivity

Contact Dermatitis

T-cell mediated response

Allergen binds to some of your own cells.

e.g. Poison Oak, Poison Ivy.

T-cells infiltrate tissue g Cytokines g activate inflammatory cells g destroy target cells.

AUTOIMMUNE DISORDERS

Production of Autoantibodies (Antibodies against ones own tissues or chemical substances) or self-reactive T-cells.
 
__________________________________________________ (Horror Autotoxicus)
The need not to react to self. Deliberately attempted to immunize animals against their own tissues.

 

EXAMPLES OF AUTOIMMUNE DISORDERS

Type I ? Due to antibodies against pathogens

Type II ? Antibodies react with cell-surface antigens

Type III (Immune Complex) ? IgM, IgG, complement immune complexes deposit in tissues

 

Type IV ? Mediated by __________________________________

 

Rheumatic Fever and Acute Glomerulonephritis

 

Follows infection with ___________________________Streptococci.
Cross-reactive Antibody can bind to heart, cartilage, muscle, and kidney tissue.
(RF ~15,000 deaths/yr US.)

 

 

 

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_____________________________________________

 

Attachment of AutoAbs to receptors for Thyroid-Stimulating Hormone (TSH) on follicle cells of the thyroid gland.
Stimulation of follicle cells g overproduction of thyroxin.

(Bypass of feedback control)
Hyperthyroidism: Goiter, increased metabolic rate, nervousness, tremor, difficulty concentrating, heat intolerance, diarrhea, and palpitations.
______________________________________________________________________________________

 

Myasthenia Gravis

 

AutoAbs bind to _________________________________________ receptors at neuromuscular junctions g

causes degradation of receptors g muscle weakness and fatigue g loss of muscle function g paralysis g respiratory failure and death
______________________________________________________________________________________

 

Systemic Lupus Erythematosis
(SLE or Lupus)
AutoAbs produced against a variety of _________________________________________________.
Most involved: Kidneys, Bone marrow, Skin, Nervous system, Joints, Muscles, Heart and G.I. tract.

 

Symptoms: Fever, skin rashes, arthritis, effusions (fluid build up) and inflammation in pleural, pericardial,
peritoneal cavities and CNS.
Can cause a life-threatening, progressive, immune complex-mediated glomerulonephritis.
90% of cases are in females of childbearing age.

Rare in males (Klinefelter?s syndrome XXY)
______________________________________________________________________________________

 

____________________________________________________
Associated with advanced age (80% of population)
Characterized by chronic inflammation of the joints.
AutoAbs (Rheumatoid factor) form immune complexes with IgG g bind to synovial membrane of joints g activates complement g scar tissue and joint destruction

______________________________________________________________________________________

 

Multiple Sclerosis (MS)

Damage to myelin sheath (____________________________________) of CNS (Brain and Spinal Cord)

T-cells attack myelin g decreased ability to conduct nerve impulses g muscular weakness, tremors, difficulties in speech and vision g paralysis.

______________________________________________________________________________________

 

Hashimoto?s/Autoimmune Thyroditis

T-cells destroy the follicle cells that produce thyroxin.

Hypothyroidism: Malaise, lethargy, pain, fever, and increased risk of pyogenic infection.
______________________________________________________________________________________

 

Diabetes Mellitus
Type I (Juvenile-onset/Insulin dependent)

T-cells attack islet cells of the ______________________________________ g inflammatory reaction g cell lyses g decreased insulin secretion.
______________________________________________________________________________________

 

 

 

 

 

 

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Acquired immune deficiency syndrome (_____________________________)

HIV: Human immunodeficiency virus (Retroviridae)

Envelope with transmembrane spikes

gp120 spikes enable HIV to attach to host cells with the CD4 receptor:

T cells, macrophages, dendritic cells, and monocytes

 

Upon entering a cell viral RNA is transcribed into DNA by the enzyme

 

_______________________________________________

Viral DNA becomes integrated into the host cell chromosome.

Integrated DNA may be active or latent.

 

Clinical Categories of HIV Infection

 

Category A: Asymptomatic or lymphadenopathy (swollen lymph nodes)

CD4 count 500/mm³ or above

 

Category B: Various symptoms & persistent infections (oral candidiasis)

CD4 count between 200-499/mm³

 

Category C: _______________________________________ AIDS.

Various opportunistic infections

Less than 14% of Tcells present are CD4 cells

CD4 count below 200/mm³

 

Transmission: Direct contact with _______________________________________________

Blood: 10-1000 IP (infectious particles)/ml

Seman: 10-50 IP/ml

Saliva: generally <1 IP/ml

 

Treatment:

Nucleoside analogs (AZT, ddI, and ddC)

Inhibit reverse transcriptase as it synthesizes DNA.

Resemble thymidine but lack the correct attachment

point for the next nucleotide.

Protease inhibitors (ritonavir, and indinavir)

Block an enzyme needed to assemble the virus.

 

Vaccine : ???

Problems: No ideal animal model,

Virus targets the immune system itself,

Mutation rate of HIV,Needs both antibody and killer T-cell response

Effective vaccine will also have to stimulate a mucosal immune response. (IgA)

Cross reactive antibodies.