Inflammation Flashcards
What is released in the early response of the mast cells? Delayed response?
Early - histamine
Delayed - leukotrienes
What are the four things that attract and activate neutrophils?
C5a, leukotriene B4, IL-8, bacterial products
What are the three things that stimulate degranulation of mast cells?
Tissue trauma, C5a, cross linking of IgE molecules on the surface of the mast cell
What are the three complement pathways? How is each stimulated? What are their common products?
Classical pathway - stimulated by IgG and IgM bound to antigen
Alternative pathway - stimulated by microbial products
Mannose binding lectin pathway - mannose binding lectin binds mannose residue on bacteria surface
All pathways produce a C3 convertase, C5 convertase, and MAC complex, C3a and C5a trigger mast cell degranulation, C5a also attracts neutrophils, C3b is an opsonin for phagocytosis by macrophages
What is the common pathway for the complement cascade?
C3 convertase -> C3a and C3b -> C5 convertase -> C5a and C5b -> C5bC6C7C8C9 -> MAC complex
What cascades does the Hageman factor activate?
The coagulation and fibrinolytic cascades
The complement cascade
The kinin cascade (produces bradykinin)
What does bradykinin do?
Mediates pain, increases vascular permeability and increases vasodilation
What are the four cardinal signs of inflammation? What causes them?
Redness and heat - arteriolar vasodilation mediated by histamine, prostaglandins and bradykinin
Swelling - fluid from plasma leaks into interstitial space mediated by histamine and tissue damage
Pain - mediated by bradykinin and prostaglandin E2
Fever - macrophages release IL-1 and TNF which stimulate the cyclooxygenase pathway in the hypothalamus. The prostaglandin E2 product raises the temperature set point
What is Libman-Sacks endocarditis? Which disease is it associated with?
Libman-Sacks endocarditis is when sterile (complexes of autoantibodies) deposits form on BOTH sides of the mitral valve. Associated with SLE.
What causes DiGeorge syndrome? What are it’s characteristic symptoms?
developmental failure of the 3rd and 4th pharyngeal pouch leading to:
failure of the thymus to develop and thus a T cell deficiency
failure of the parathyroid glands to develop and thus hypocalcemia
abnormalities of the heart, great vessels and face
What are the characteristics of Severe Combined Immunodeficiency (SCID)? What are the three possible etiologies? How is SCID different from Common Variable Immunodeficiency (CVID)?
SCID = Defective of B and T cells. Common etiologies include adenosine deaminase deficiency, cytokine receptor defects, MHC class II deficiency. While SCID is the absence of B and T cells activity, CVID is characterized by defective B cells and hypogammaglobulinema. CVID carries a higher risk for lymphoma and autoimmune diseases.
What is the pathogenesis of Bruton’s agammaglobulinemia (X-linked agammaglobulinemia)? What three types of infections are these patients at high risk for?
Naive B cells cannot mature into plasma cells so the patient has no antibodies. Due to a mutation in the Bruton tyrosine kinase. Patients are at high risk for giardia, enteroviruses, and bacterial infections.
What is the most common immunoglobulin deficiency?
IgA deficiency.
What is the pathogenesis of hyper-IgM syndrome? What are the common symptoms?
Immunoglobulins cannot class switch because of defective CD40 receptor (on B cells) or CD40 ligand (on T cells). The result is low IgA, IgG and IgE levels leading to recurrent pyogenic infections, especially at mucosal sites
What are the three main symptoms of Wiskott-Aldrich syndrome?
Eczema, thrombocytopenia and recurrent infections. X linked.
What immune system deficiency is associated with an increased risk of Neisseria infections?
C5-C9 complement deficiency
What are the clinical symptoms of a C1 inhibitor deficiency?
hereditary angioedema, especially periorbital edema
What stimulates acute inflammation? What stimulates chronic inflammation?
acute - infection, tissue necrosis
chronic - persistant infection, infection with viruses, mycobacteria, fungi and parasites, autoimmune disease, foreign objects, some cancers
What cell types are associated with acute inflammation? With chronic inflammation?
Acute - neutrophils and macrophages, edema
chronic - T cells and plasma cells, no edema
What is the 2nd activation signal for CD4+ T cells? For CD8+ T cells?
CD4+ - B7 on APC binds CD28 on CD4+ cell or CD40 receptor on B cell binds CD40 ligand on CD4+ cell
CD8+ - IL-2 cytokines from CD4+ T helper cell
What cytokines do TH1 cells secrete? What cytokines do TH2 cells secrete?
TH1 - IL-2, IFN-gamma
TH2 - IL-4, IL-5, IL-10
What are the histological characteristics of granulomas?
epithelioid histiocytes (macrophages with abundant pink cytoplasm) surrounded by giant cells and a rim of lymphocytes
What is the difference between caseating and non-caseating granulomas?
caseating granulomas have central necrosis (TB, fungal infections)
non-caseating granulomas do NOT have central necrosis (foreign objects, sarcoidosis, Crohn’s disease, cat scratch fever, beryllosis)
What are the three major cell types in granulation tissue? What are their functions?
fibroblasts - deposit type III collagen
capillaries - provide nutrients
myofibroblasts - contract wound
What are the early and late phases of tissue repair in wound healing?
early - granulation tissue: type III collagen deposition
late - scar formation: collagenase and associated zinc cofactor transforms type III collagen into type I collagen
What are some of the common causes of delayed wound healing?
bacterial infection, vitamin C deficiency, zinc deficiency (collagenase requires zinc), copper deficiency, diabetes, ischemia, malnutrition or presence of a foreign body
What type of collagen is in a keloid? a hypertrophic scar?
keloid - type III collagen
hypertrophic scar - type I collagen
