Acute and Chronic Inflammation Flashcards
_____________ on macrophages recognizes lipopolysaccharide on the outer membrane of gram-negative bacteria.
CD14
What is the main result of TLR activation?
Results in an upregulation of NF-kB, a nuclear transcription factor that activates immune response genes leading to production of multiple immune mediators.
Which prostaglandings mediate vasodilation and increased vascular permeability?
PGI2, PGD2, and PGE2
REMEMBER: Increased vascular permeability takes place at the post capillary venule
Role of PGE2
mediates pain and fever
Which of the leukotrienes attracts and activates neutrophils?
LTB4
What is the role of LTC4, LTD4, and LTE4?
Leukotrienes that mediate vasoconstriction, bronchospasm, and increased vascular permeability
NOTE: These leukotrienes are known as slow reacting substances of anaphylaxis
What substances mediate and activate neutrophils?
LTB4, bacterial products, C5a, IL-8
What events activate mast cells?
- Complement proteins C3a and C5a
- Cross-linking of IgE molecules
- Tissue trauma
Compare and contrast the immediate and delayed mast cell responses.
IMMEDIATE
- Preformed histamine
DELAYED
- Arachodonic acid metabolites, particularly leukotrienes
Which complement components are anaphylaxotoxins?
C3a and C5a
Which substances are involved in opsonization?
C3b and IgG
When is hageman factor (factor XII) activates?
- upon exposure to subendothelial or tissue collagen
- In response to severe gram negative sepsis
What systems are activated post-hagemen factor activation?
- Coagulation and fribrinolytic systems
- Kinin system
- Cleavage to bradykinin
Which factors are involved in pain?
PGE2 and bradykinin
NOTE: They sensitive sensory nerve endings
What are the cardinal signs of inflammation?
- Redness (rubor)
- Warmth (calor)
- mediators: bradykinin, prostaglandin, and histamine
- Swelling (tumor)
- Mediators: histamine and tissue damage
- Pain (dolor)
- Bradykinin and PGE2
- Fever
- IL-1, PGE2 and TGF-a
Steps of neutrophil arrival and function
- Margination
- Rolling
- Adhesion
- Transmigration and Chemotaxis
- Phagocytosis
- Destruction of phagocytosed material
- Resolution
P-selectin release from __________ is mediated by histamine.
Wiebel-Palade bodies
NOTE: Wiebel- Palade bodies have proteins necessary for the fucntion of endothelial cells
What factors induce E-selectin?
IL-1 and TNF
Selectins bind _______ on leukocytes.
Siacyl Lewis X
Which factors upregulated adhesion molecules?
VCAM and ICAM (on endothelium) are upregulated by IL-1 and TGF
Which factors upregulate integrin?
Intergrins are upreguate on leukocytes (neutrophils) by C5a and LTB4.
What are the clinical features of LAD1?
- Delayed seperation of the umbilivcal cord
- Increased circulating neutrophils
- Recurrent bacterial infections that lack pus formation
What are the clinical feautures of Chediak-higashi syndrome?
- Increased risk of pyrogenic infectiosn
- Neutropenia
- Giant granules in leukocytes
- Defective primary hemostatis
- Albinism
- Peripheral neuropathy
Which enzyme catayles the conversion of oxygen to superoxide?
NADPH oxidase
Which enzyme converts superoxide to peroxide?
Superoxide dismutase
What enzyme converts peroxide to bleach?
Myeloperoxidase
What are the characteristics of chronic granulomatous disease?
- Recurrent infection and Granuloma formation with catalase-positive organisms (S. Aureus, Pseudomonas cepacia, Serratia marcescens, Nocardia, and Aspergillus)
Which test screens for chronic granulomatous disease (CGD)?
Nitroblue tetrazolium test
NOTE: Test terms blue if NAPDH oxidase can convert oxygen to superoxide
MPO deficiency results in increased risk for __________ infections.
Candida
NOTE: This deficiency prevents the conversion of peroxide to bleach
When does O2-independent killing occre?
Via enzymes present in leukpcyte scondary granules (lysozyme in macrophages and major basic protein in eosinophils)
What are the antiinflammatory cytokines?
IL-10 and TGF-b
What are the four possible next steps to the acute inflammatory process?
- Resolution and healing
- continued acute inflammation
- Abcess
- Chronic inflammation
NOTE: These steps are mediated primarily by macrophages
How is an abcess formed?
Acute inflammation surrounded by fibrosis. Macrophages mediate fibrosis via fibrogenic growth factors and cytokines
What is required for the activation of T cells?
- Binding of antigen/MHC complex
- Additional 2nd signal
- B7 binding CD28
- IL-2 from CD4 TH1 cell
What cytokine is secreted by TH1 and what is it’s function?
IFN-gamma
- Activates macrophage
- Promotes B cell class switiching from IgM to IgG
- Promotes TH1 phenotype and inhibits TH2 phenotype
NOTE: IL-10 inhibits TH1
Which cytokines are secreted by TH2 and what are their functions?
IL-4
- Facilitates B-cell switching to IgE
IL-5
- Eosinophil chemotaxis and activation, and class switching to IgA
IL-10
- Antiinflammatory
- Inhibits TH1
IL-13
What are the defining characteristics of granulomas?
-
Epithelioid histiocytes (macrophages with abundant pink cytoplasm)
- Usually surrounded by giant cells and a rim of lymphocytes
*
- Usually surrounded by giant cells and a rim of lymphocytes
Noncaseating granuloma
- lack central necrosis
- Common etiologies
- Reaction to foreign material
- Sarcoidosis
- Beryllium exposure
- Crohn disease
- Cat scratch disease
Caseating granulomas
- Exhibit central necrosis
- TB and fingal infections
- AFB stain to look for TB
- GMS stain to look for fungal infections
NOTE: A viral infetion will never give you a granuloma
What are the steps involved in granuloma formation?
- Macrophages oricess and present antigen via MHC class II to CD4 cells
- macrophages secrete IL-12, inducing CD4 to differentiate into TH1
- TH1 secretes IFN-gamma which converts macrophages to epithelioid histiocytes and giant cells
DiGeorge Syndrome
- Developmental failure of the third and fourth pharyngeal pouches
- Due to 22q11 microdeletion
- Presents with:
- T- cell deficiency
- Hypocalemia
- Abnormalties of heart, great vessels, and face
Severe combined Immunodeficiency
- Deffective cell-mediated and humoral immunity
-
Adenosine deaminase deficiency (ADA)
- Buildup of adenosine and deoxyadenosine is toxic to lymphocytes
- MHC class II deficiency
- Susceptibility to fungal, viral, bacterial, and protozoal infections
- Treatment: sterile isolation and stem cell transplantation
X-linked agammaglobulinemia
- Complete lack of immunoglobulin due to disordered B- cell maturation
- Mutated Bruton tyrosine kinase
- X-linked
- Presents with:
- Giardia lamblia infections,recurrent bacterial, enterovirus
- Live vaccines must be avoided
Common variable immunodeficiency
- Low immunoglobulin due to B-cell or helper T-cell defects
- Increased risk for autoimmune disease and lymphoma
IgA deficiency
- Low serum and mucousal IgA
- Increased risj for mucosal infection, especially viral
- Risk for Celiac disease
Hyper IgM Syndrome
- Mutated CD40L
- IL-4 and IL-5 not produced
Wiskott-Aldrich Syndrome
- Thrombocytopenia, eczema, and recurrent infections
- Bleeding disorder is a major cause of death
- Due to mutation in the WASP gene; X-linked
Patients with C5-C9 deficiences are susceptible to which infection?
Neisseria infection
C1 inhibitor deficiency
- Hereditary angioedema
- Edema of the skin and mucosal surfaces
NOTE: Overactivity of complement leads to vasodilation
__________mutations result in autoimmune polyendocrine syndrome
AIRE
___________ mutations lead to IPEX syndrome.
FOXP3
- Immune dysregulation
- Polyendocrinopathy
- Enteropathy
- X-linked
Deficency in what complement proteins result in SLE.
C1q, C4, and C2
What is the most common type of renal injury seen in SLE?
Diffuse proliferative glomerulonerphritis
Which antibodies are found in SLE?
- Antinuclear antibody (ANA)- not specific
- Anti-dsDNA or anti-Sm antibodies - highly specific
- Antiphospholipid antibody
- Against proteins bound to phospholipids
______ antibody is characteristic of drug induced lupus.
Antihistone
DRUGS: Procainamide, hydralazine, and isoniazid
NOTE: CNS and renal involvement are rare
Primary vs Seconday Sjogren Syndrome
Primary
- Sicca syndrome
Secondary
- Rheumatoid arthritis
Diagnostic criterion for Sjogren syndrome
- Dry eyes
- Dry mouth
- Lymphocytic sialadenitis
Which antibodies are found in Sjogren Syndrome?
- Antiribonucleoprotein antibodies
- Anti-SSA
- Anti- SSB
NOTE: Pregnant women with anti-SSA are at risk for delivering babies with neonatal lupus and congenital heart block
Mixed connective tissue disease
- Mixed features of SLE, systemic sclerosis, and polymyositis
- ANA along with serum antibodies to U1 ribonucleoprotein
C2 and C4 defieciency
SLE
C3 deficiency
Recurrent infections
C5-C9 deficiency
Prone to Neisseria infections
C1 inhibitor deficiency
Hereditary angioedema
C55 and CD59 deficiency
Praoxysamal nocturnal hemoglobinuria
