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82 Cards in this Set
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Hallmarks of Hashimoto's Thyroiditis
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Most common in middle aged women
* Pt produces auto-Abs and Th1s specific for thyroid Ags ** DTH response ** Infiltration of thyroid with MACs, Th1 cells, plasma cells |
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Hashimoto's Thyroiditis - mechanism behind hypothyroidism
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Ab's prevent iodine uptake = dec. thyroid hormone production
* Ab's plus complement destroy thyroid cells --> Goiter formed by inflitration of cells |
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Symptoms of Hashimoto's Thyroiditis
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* Fatigue
* Weight gain * Hair loss * Difficulty thinking * Cold intolerance |
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Autoimmune hemolytic anemia mechanism
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IgG & IgM Abs directed at Ags on RBCs
--> leads to destruction of RBCs |
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Pernicious Anemia mechanism
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Auto-Abs to intrinsic factor produced
--> Ab blocks B12 uptake by i.f. --> impaired hematopoiesis = Low RBCs |
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Type III Hypersensitivity Mechanism
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- Immune complex-mediated
* Ag-ab complexes * Induce complement activation * Neutrophil infiltration |
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Type III hypersens. symptoms
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* Localized arthrus rxn
- Generalized rxns - serum sickness - necrotixing vasculitis - glomerulonephritis * Rheumatoid arthritis - Systemic lupus erythem |
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Hallmarks of Type IV Hypersensitivity
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Cell-mediated hypersensity
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Type IV hypersensitivity mechanism
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- Sensitized Th1 cells release cytokines
- cytokines activate MACs or Tc cels - MACs/Tc induce cellular damage |
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Type IV Symptoms
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Contact dermatitis
- Tubercular lesions * Graft rejection |
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Arthrus Reaction
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type III hypersensitivity rxn
Can follow intradermal injection of Ag (after 2nd exposure) |
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Serum Sickness
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Rxn to proteins in antiserum from animals
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Symptoms of serum sickness
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Occur after 7-10 days
- chills - fever - rash - arthritis - vasculitis - glomerulonephritis Pneumonic ** CFRAVG** |
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When is a Type III rxn most likely to occur?
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Beginning of immune response
b/c small complexes are more difficult to remove |
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Farmers lung is caused by what?
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Inhalation of moldy hay
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Type IV mechanism
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Th cells encouter Ag
Which secrete cytokines cytokines -> activate MAC/Tc which inflict celluar damage |
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Tuberculin Reaction
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Mycobacterium Tuberculosis
DTH takes 1-3 days to develop 80% MACs Red, swollen, firm lesion - MACs - not neutrophils |
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Type IV mechanism
- Sensitization phase |
Initial Ag contact --> Th cells proliferate/differentiate into Th1 cells
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Type IV mechanism
- Effector phase |
5% of participating cells are Ag specific Th1 cells by the time DTH response is fully developed
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What causes a granuloma
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Continuous activation of MACs = cause them to fuse tightly and form multinucleated giant cells displacing normal tissue
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Granuloma effects
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Double-edged sword
1) walls of organism in infected tissue 2) large amounts of lytic enzyme release causes tissue necrosis |
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How is the DTH recation detected?
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A skin test
- PPD injected intradermally --> firm,red, swollen lesion @ 48-72 hr indicates previous exposure --> positive rxn indicates presence of sensitized Th1 cells specific for that Ag. |
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Autoimmunity is sometimes caused by.....
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1) antibodies
2) T cells can mediate response to self 5% of population is affected Tissue destruction mediated by Type I, II, and III hypersensitivity mechanisms... |
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Insulin-dependent diabetes mellitus (IDDM) is produced by?
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Auto-antibody induced
--> Ag on pancreatic beta cells are attacked by auto-Ab |
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Insulin dependent diabetes mellitus is characterized by
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- loss of insulin --> diabetic
- uncontrolled blood glucose levels |
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IDDM symptoms
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!! Pneumonic!! Come back king green!
Coma - death Blindness Kidney failure Gangrene - due to impeded vascular flow |
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Grave's Disease Mechanism
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Auto-antibody to receptor for TSH
Pt makes Ab which binds to TSH receptor = uncontrolled thyroid hormone production |
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Graves disease Symptoms
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Weight loss
Heat intolerance Anxiety Irritability Insomnia Sweating Irregular heartbeat |
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Myasthenia Gravis Mechanism
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Auto-antibody to Ach receptor
Pt produces auto-Ab which binds to Ach receptors and blocks Ach binding Blocks motor end plates, blocks binding of Ach, induces complement mediated lysis |
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Myasthenia Gravis treatments
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Cyclosporin
Thymectomy Plasmapharesis |
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Continued myasthenia gravis results in...
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Antibody destruction of Ach receptor bearing cells
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Hallmarks of Lupus
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Systemic autoimmune disease
- Women 20-40 years old 10:1 ratio of females to males - Greater incidence in oriental and black populations |
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Lupus is characterized by
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Arthritis (usually a first sign)
Butterfly rash Weakness Pleurisy Kidney dysfunction |
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IgG Auto-antibodies in lupus
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Auto-Ab's are to DNA and DNA associated protein
- DNA - Histones - RNA - Nuclear Proteins - Ribosomes |
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In lupus, Auto-Ab's to RBCs cause:
...to Platelets cause: |
- Hemolytic anemia
- Thrombocytopenia |
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Mechanism of Lupus
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Type III mechanism
--> immune complex activated --> activate complement Is a relapsing/remitting disease Patients often die due to organ failure - especially kidney fail |
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Lupus diagnosis
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Average 7 years to diagnose
ANA Clinical test: - Detects Ab to DNA, histones, nuclear envelope proteins, RNA polymerase, RNA's, Etc. Sensitive for SLE |
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Other random lupus info
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Ab's against dsDNA (double stranded DNA) correlate with renal involvement - high specificity
- DNA-Ab complexes may become trapped in glomerular basement membrane of kidney through electrostatic interactions |
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What is Multiple sclerosis
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Autoreactive T cells cause inflammatory lesions along myelin sheath of nerve fibers
* Activated Th1 cells infiltrate the brain --> recruits MACs This causes inflammation that destroys myelin = neurologic dysfunction Scars form on nerves Relapsing/remitting or chronic/progressive |
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Symptoms of MS
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Mild: Numbness in limbs
Severe: Plasticity Paralysis Loss of vision |
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Who does MS affect most?!
When is MS diagnosed? If a relative has MS 1 in 50 chance of getting MS |
Women by a factor of 3!
between 20-30 years of age suggests a genetic component |
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Where is MS most prevalent?
2x incidence if live where? Risk increases if move |
Northern hemisphere (U.S mostly)
Norther of 37th parallel North of 37th parallel before age 15 |
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Cause of MS?!
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Speculation at this point...maybe -
1 failure of clonal deletion 2 neuroantigen sensitization 3 molecular mimicry to a neuroepitope following a viral infection |
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What is EAE?
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Experimental autoimmun encephalomyeletis
- model for autoimmunity - allows study investigating new treatments or how to induce tolerance to self Ag's |
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How is EAE induced?
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Induced by injection of myeling basic protein plays Freund's adjuvant
** T cell induced ** |
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How do T cells cross the BBB?
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Activated T cells express integrins allowing adhesion to vessels near brain
- activated T cells make MMP (matrix metalloproteinase) which degrades collagen in basal lamina - Once T cells gain entry into brain they are restimulated by Ag presented by microglial cells * Chemokines recruit MACs and WBCs = exacerbations following viral infection |
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Rheumatoid Arthritis hallmarks
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Type III reaction
More women than men by factor of 3 Chronic inflammation of joints |
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Rheumatoid Arthritis mechanism
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Auto-antibody to IgG (binds IgM = complex deposited in joints)
Auto-Ab's react to Fc region of IgG: these auto-Ab's are called rheumatoid factors **!! IgG-IgM complexes deposited in joints = Type III hypersensitivity reaction !!** |
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Rheumatoid Arhtritis random factoids
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Synovium normally just one cell thick
Becomes so infiltrated with WBCs that mimics lymphoid tissue = forms new blood vessels Release TNF alpha, IL-1, prostraglandins, and degradative enzymes that destroy cartilage |
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Rheumatoid arthritis causes...
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After repeated bouts of inflammation:
- Cartilate replaced by fibrous tissues - Joint fuses (ankylosis) |
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Th1 cells in autoimmunity
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Implicated in the development of autoimmunity
* transfer of Th1 cells to a syngeneic mouse transfers disease * |
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Th2 cells in autoimmunity
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Protect against development of and progression of disease
* injection of mouse with induced autoimmune disease from Th1 with myselin specific Th2 cells causes disease remission or protects from disease* |
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Initial event in Type 1 Hypersens.
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IgE-binding Fc receptors
IgE binding to receptors causes mast cell degranulation * mice with no IgE Fc receptors have no allergy |
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Histamines hallmarks
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Formed by decarboxylation of hisidine
10% of mast cells (major portion) Biologic effects seen within minutes |
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Histamines effects
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!! Induces contraction of intestinal and bronchial smooth muscles, increases vascular permeability, increased mucous!!
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Leukotrienes and prostaglandins
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Formed by enzymatic breakdown of phospholipids after mast cell degranulation
effects longer lasting than histamine mediate bronchoconstriction, vascular permeability, and mucous production |
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Cytokines in Type 1 Hypersensitivity
Mast cells produce: IL-4, actions--> IL-5 actions--> TNF-alpha actions --> |
Increases IgE production
Recruit/activate eosinophils Contributes to toxic shock in systemic anaphylaxis |
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What occurs in systemic Type I reactions?
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Within minutes of 2nd allergen exposure
Respiration becomes labored, B.P. drops, asphyxiation - anaphylactic shock |
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Treatment in Type I hypersens.reactions
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Epinephrine - counters histamine effects
- Relaxes smooth muscle constriction - dec. vascular permeability - improves cardiac output - Inc. cAMP levels in mast cells, preventing further degranulation |
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Localized anaphylaxis (atopy) includes what IgE related disorders?
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Allergic rhinitis
Asthma Dermatitis Food allergies |
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Hallmarks of allergic rhinitis
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a.k.a. hay fever
Airborne allergens interact with sensitized mast cells in nasal mucosa - causes release of mediators which induce localized vasodilation/increase capillary permeability |
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Symptoms of allergic rhinitis (hay fever)
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Sneezing
coughing watery discharge from eyes nasal mucosa upper respiratory tract |
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Allergic asthma
Intrinsic asthma |
Airborne allergens (pollens, dust, fumes, insect products) trigger an asthmatic attack
Exercise and cold air can trigger asthma; independent of Ag |
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Asthmas effects?!
Cause what? |
Contraction of bronchial smooth muscle, airway edema, mucus secretion, and inflammation
Bronchoconstriction/airway obstrction |
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Asthma is an inflammatory disease divided into two phases
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Early phase lasts minutes
Late lasts hours |
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Eosinophils role in asthma
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IL-5 contributes to differentiation/survival of eosinophils in the lung
Eosinophils express Fc receptors for IgE and bind to Ab coated Ag Degranulate to release more inflammatory mediators which cause tissue damage Contribute to chronic inflammation of bronchial mucosa which characterizes persistent asthma |
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Asthma statistics
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Effects 5% of us population
incidence increasing in developed countries mortality highest amongst africa-american population (especially inner city) |
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Some foods induce localized anaphylaxis; what is the MOA?
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Allergen crosslinking of mast cells along GI
-> induces smooth muscle contraction, vasodilation, capillary permeability ultimately = vomiting and diarrhea |
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Mast cell degranulation along the gut causes what?
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increased permeability of membranes so Ag can enter bloodf
Ag in blood cause symptoms depending on where Ag enters stream Hives if Ag carried to the skin - wheal and flare - swollen, red eruptions |
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Hallmarks of Atopic Dermatitis (Eczema)
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Inflammatory disease of the skin
Common in children !! Elevated IgE - Skin eruptions that are red and pus filled |
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How does atopic dermatitis differ from poison oak reactions?
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Lesions are infiltrated by Th2 cells and eosinophils
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Factors influencing Type I reactions
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Both parents allergic = 50% chance of child being allergic
1 parent allergic = 30% change of child being allergic Repeated low does of Ag can induce persistent IgE levels Higher doses tend to shift towards IgG |
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Mechanism of immunotherapy in Type I treatment
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Repeat injections of inc. dose of Ag
Shift from IgE to IgG and Inc IFN gammer levels IgG Ab becomes what is referred to as a blocking antibody b/c it competes for Ag, binds to it, forms a complex that can be removed by phagocytosis |
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Th1/Th2 balance
Th2 cells do what? Th1 cells do what? IL4 increase does? IFN-gamma does? |
Reduce atopy
Increase atopy Increase IgE Decrease IgE |
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Type II hypersens. is mediated by what?
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IgG or IgMs
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Mechanism of Type II hypersensitivity
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Cytotoxic cells with Fc receptors bind to Fc region of Ab's that are bound to target cells and mediate killing
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Type II reactions are typically seen in blood transfusion.
What's a transfusion reaction? |
If blood from a type A individual is transfused with blood from a type B individual --> anti-B Ab's bind to B cells = complement mediated lysis/destruction.
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What are the clinical manifestations of transfusion reactions
Symptoms of transfusion reactions |
Lysis of RBCs by Ab + complement
= free hemoglobin in the blood ==> converted to bilirubin (toxic at high levels) Fever, chills, nausea, lower back pain |
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What does repeat incompatible transfusion lead to?
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Production of IgG Ab's to foreign blood group Ag's
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Ab's specific for altered cellular components can also cause type II hypersens.
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Results in hemolytic anemia
--> Drugs (such as penicillin) can chemically alter the surface of RBCs New epitopes created in this process ** new epitopes stim IgM and IgG which bind to RBC surface = this induces complement mediated lysis and anemia |
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Hallmarks of Hemolytic disease of the newborn; aka, Erythroblastosis fetalis
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Rh+ fetus is carried by an Rh- mother
At delivery, mother exposed to large amounts of fetal cord blood -- this activates Rh specific B cells in the Rh - mothe. Next pregnancy memory cells recognize Rh- RBCs and produce IgG anti-Rh Ab causing damage to fetal RBCs |
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Rhogams MOA
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Ab's bind fetal RBCs that may have entered mothers circulation, facilitate clearance before B cell activation/ensuring memory cell production
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