Hypersensitivity Reactions (additions to Dr. Miller) Flashcards
What are the two phases to a Type I Immediate Hypersensitivity Reaction?
- Time frame?
- Cells?
Early phase (minutes): - Mast Cells
Late phase (2-8 hours):
- Eosoinophils
- T cells
Define the role of the following in the type I hypersensitivity reaction, including what phase you see them in.
- IL-4
- IL-5
- IL-13
Early Phase: IL-4 - B cell class switching to IgE
Late Phase:
IL-5 - Eosinophil recruitment to late phase rxn
IL-13 - Epithelial Cell Mucus Secretion
What is the role of eotaxin?
- type of hypersensitivity reaction that its associated with?
- Recruits Eosinophils and T-cells
- This is in the LATE PHASE of type I hypersensitivity reaction
What mast cell mediators induce Vasodilation and increased vascular permeability?
- Histamine
- PAF
- Leukotrienes
- Neutral Proteases that activate complement kinins
- Prostaglandins D2
What mast cell mediators induce smooth muscle spasm?
- LTC-4, D-4, E-4
- Histamine
- Prostaglandins
- PAF
What is the most important prostaglandin that induces bronchospasm?
Prostaglandin D2
What mast cell mediators induce cellular infiltrations?
- TNF, Chemokines
- Leukrotriene B4
- Eosinophil and Neutrophil Chemotactic factors
What is the ultimate effect of the mediators that induce cellular infiltrates in type I hypersensitivity reactions?
- what do the cellular infiltrates consist of?
SUSTAIN AND AMPLIFY THE RESPONSE EVEN IN THE ABSENCE OF AN ALLERGEN
- TH2 cells and Eosinophils
How do you differntiate between acute and chronic rhinitis on H and E stain?
- cellular as well as other things
- Chronic will show Eosinophil Presence
- Eosinophil granules may combine to make SHARP LIPIN crystals that are also eosinophilic
What is intrinsic factor?
- what does a IgG binding this cause?
Intrinsic Factor:
- secreted by the stomach and is necessary for B12 absorption
Lack of Intrinsic Factor:
- Pernicious Anemia
Why does lacking intrinsic factor cause anemia?
B12 is necessary for thymidylate synthetase function, without it you get slowed DNA synthesis
What is a common problem associated with given too much antivenom?
- what type of reaction is this?
- describe why it causes issues.
Too much antivenom = Serum Sickness
Rxn:
- Type III hypersensitivity Reaction
Issues:
- Abs from the anti-venom create small immune complexes that can’t be cleared, this causes inflammation, joint pain, vascularitis, and glomerulonephritis
What are the steps leading to vasculitis?
- Ab (endogenous or exogenous) binds Antigen
- Immune complex deposits in the endothelium and complement binds it
- C5a and C3a released from complement attract neutrophils that then degranulate on your vessels leading to their death
What is the Arthus Reaction?
- Non-self substance is injected into a person who has made IgG Abs. against the substance
- Local immune-complex forms and activates complement and C5a is released
- 5a binding to a C5a receptor on a mast cell
- Binding of Immune compex to FcgammaRIII on mast cell induces degranulation
- Granules induce inflammatory reaction
Suppose you do a lung biopsy on a patient with caseating granulomas showing Mycobacterium TB and they come back 5 years later and you do a TB test and they don’t test positive.
- Explain.
- Cells involved?
Patient could have aquired HIV in the past 5 years
- Immunosuppressed individuals will not respond to a TB skin test because they lack CD4 T cells (SPECIFICALLY TH1 cells that are needed to form granulomas)
Stimulation by what hormone can cause the formation of Giant cells (epitheloid histiocytes).
IFN-gamma
T or F: a positive test for anti-nuclear antibody (ANA) is a definitive test for the presence of lupus.
False, other disorders also show the presence of anti-ANA antibodies
**Additionally, about 20% of the population tests positive for ANA
In what years and in what group of people is lupus most likely to manifest?
- Reproductive Years
- African American FEMALES
What are some of the Clinical Criteria for Lupus?
- which of these is typically the MAIN (lethal) problem lupus patients have?
- Acute Cutaneous Lupus
- Chronic Cutaneous Lupus
- Oral or Nasal Ulcers
- Arthritis
- Serositis
- Renal****
- Neurologic
- Leukopenia
- Non-scarring alopecia
What are some of the imuunologic Criteria for Lupus?
- ANA
- Anti-DNA
- Anti-Sm
- Antiphospholipid Ab*****
- Low complement (C3, C4, CH50)
- Direct Coomb’s
What antibodies lead to the following aspects of systemic lupus erythema?
- Cytopenias
- Thrombosis
- Neuropsychiatric complications
Cytopenias:
- Autoantibodies for Red Cells, White Cells, and Platelets
Thrombosis:
- Autoantibodies against phospholipids (e.g. CARDIOLIPIN)
Neurophsychiatric:
- Autoantibodies against Neurotransmitters
What are LE bodies?
- what causes them to form?
Neutrophils where nucleus is pushed to the edge of the cells because they have engulfed a lymphocyte that has been damaged so that their chromatin in homogenous
- Homogeneous chromatin of Lymphocytes is causes by ANAs (anti-nuclear antibodies)
What causes the wire loop appearance of in the glomerulus of SLE patients? - What level/class of damage does this represent?
Loop appearance caused by SUBENDOTHELIAL deposits of DNA-ANTI-DNA-COMPLEXES
- Class IV damage is classified by this wire loop pattern
What causes Libman-Sacks endocarditis?
- how is this related to SLE?
- Relationship to bacteria?
- Mononuclear Infiltrates attack heart valves causing Warty and Bumpy Lesions
- SLE patients sometimes have this as a side Effect
- NO RELATIONSHIP TO BACTERIA, it is a NONBACTERIAL VERRUCOUS ENDOCARDITIS
What is the most common cause of death in SLE patients?
1 Renal Failure
- Cardiovascular Disease also Plays a role
What is the Difference between a primary and secondary Amyloidosis?
- Examples given in class?
Primary amyloidosis arises because of monoclonal plasma cell proliferation (AL - light chain amyloidosis)
Secondary Amyloidosis - arises from long term inflammatory processes and/or tissue damage
(IL-1 and IL-6 induced SAA formation leading to AA deposits in tissue)
What is Transthyretin?
Binds and Transports Thyroxine and Retinol
What is a plasmacytoma?
- location
- It is a discrete solitary Mass of Neoplastic MONOCLONAL plasma cells
Found in:
- Bone
- Soft tissue
