Inflammation Flashcards
What are acute inflammatory reactions?
Increased blood supply/capillary permeability, WBC migration. Neutrophils are the first to the site of inflammation
What cells are typically present in chronic inflammation?
Macrophages, epithelioid cells, lymphocytes
What is the classic triad of inflammation?
Pain, heat, redness
What is the chemical on the microbes used to signal the immune system?
Pathogen-associated molecular patterns (PAMPs)
What to PAMPs bind to on phagocytes?
Pattern Recognition Receptors (PRRs)
What PRR-PAMP interaction is chemotactic for macrophages and neutrophils?
fMet-Leu-Phe (and receptor)
What is the PAMP of the outer membrane of Gram NEGATIVE bacteria?
LPS (endotoxin)
What PRR does LPS bind to?
TLR4 and CD14
What PAMP is a part of Gram-POSITIVE bacterial cell wall?
Lipoteichoic Acid
What PRR does Lipoteichoic acid bind to?
TLR2 and CD14
What color does gram-positive bacteria stain?
purple
What do NLRs bind to?
DAMPs and PAMPs
Where are NOD-like receptors found?
The cytosol of leukocytes and other cell types
What can help to active IL-1β?
NLRs assembled into inflammasomes
RIG-I-like receptors (RLRs)
Cytoplasmic RNA helices that induce interferon α/β production in response to a viral infection
What it the result of pro-inflammatory cytokines IL-1?
Fever and Up-regulation of adhesion molecules
What is the major result of pro-inflammatory cytokine TNF α?
Septic shock and up-regulation of adhesion molecules
What is the major result of pro-inflammatory cytokine IL-6?
Acute phase protein release from the live
Septic shock symptoms
Drop in BP, hyper/hypothermia, weakness, tachypnea, tachycardia
Exogenous pyrogens of Gram positive bacteria
Lipoteichoic acid
What synthesis does IL-1 induce?
PGE2 (central=raise in hypothalamic set point, peripheral= myalgia/arthralgias)
What is a negative acute phase protein? (APP)
Albumin
What do APPs do?
Aid host defense via opsonins, clots, tissue repair
Complement
pathogen lysis, opsonization, chemotaxis, mast cell degranulation
CRP
Marker for inflammation and infection. Opsonization, complement lysis,
Serum amyloid A
tissue repair via ECM, chemoattractant for monocytes/dendritic cells/lymphocytes/granulocytes
Coagulation factors
Prothrombin, factor VIII, von Willebrand factor, fibrinogen (increases ESR)
Ferritin
Sequesters iron away from microbes
Extravasation
Movement of leukocytes out of the blood vessels and into the tissues
Sialyl Lewis X
CD15. Is on neutrophils. Binds to e-selectin on endothelium
Leukocyte adhesion deficiency
Certain adhesion molecules are missing, so leukocytes cannot extravasate. Results in inability to form pus and impaired wound healing.
Deficiency of CD18 that makes up part of LFA1 results in what disease sate?
LAD1
Defective fucose metabolism preventing the sialyl-Lewis X results in what disease state?
LAD2
What is the purpose of respiratory/oxidative burst?
Generates reactive oxygen species to damage protein, lipids, and DNA
What enzyme reduces H2O2 to water/oxygen?
Catalase
What disease results in NADPH oxidase deficiency and repeat catalase-positive microbe infections?
Chronic granulomatous disease
What does the DHR test diagnose?
Chronic granulomatous disease
What are signs/symptoms of CGD?
Recurrent infections, pneumonia, skin and viscera abscesses, lymphadenitis
Complement
Group of serum proteins that act in cascade to do the following activities: lysis of Gram NEGATIVE bacteria, opsonization, Leukocyte chemotaxis/activation/degranulation
3 pathways of complement
Classical, lectin, alternative
What induces the classical complement pathway?
IgG, IgM, CRP
What induces lectin complement pathway?
Mannose residues
What induces alternative complement pathways?
When C3b binds to LPS on Gram NEGATIVE bacteria/zymosan on yeast
Which complements opsonize?
C3b > C4b
Which complements are inactivated by carboxypeptidase N and cause degranulation?
C5a»C3a>C4a
What does reaction does histamine illicit?
(Released by mast cells/basophils/eosinophils) Induces smooth muscle contraction and increased capillary permeability (leads to local edema).
What complement is an activator/chemotaxin for all myeloid cells, induces PMN degranulation, and induces IL-1/IL-6 production in monocytes?
C5a
What complement in a chemotactic for eosinophils?
C3a
What does the membrane attack complex do?
Cause lysis of Gram-negative (NOT positive) bacteria
Classical complement pathway
C1q binds to CRP or Fc of IgM and IgG.
Binding activates C1r molecules (Ca-dependent).
C1r activates C1s molecules.
Lectin Pathway
MBL activates MASP1/2.
MASPs cleave C4 into a/b (C4a and C4b).
Alternative Pathway
C3b binds to LPS/endotoxin on Gram negative bacteria or zymosan in yeast
Terminal (Lytic) Pathway
MAC forms.
A combination of the 3 pathwyas occurs to form C5b678.
That complex inserts multiple C9s into the cell membrane, causing lysis
C1 esterase inhibitor (C1INH)
Disrupts C1qrs complex/MASP complex/C3bBb.
Deficiency leads to hereditary angioedema.
Edema worsens with stress/trauma/dental procedures
Decay-accelerating factor (DAF)
Binds to C4b.
Is a GPI-anchored protein.
Deficiency leads to paroxysmal nocturnal hemoglobinuria with red cell lysis (red urine in morning)
Membrane protein CD59
Interferes with MAC.
Deficiency leads to paroxysmal nocturnal hemoglobinuria.
C3 complement deficiency
Hard time fighting encapsulated bacteria (pneumococcus, influenzae, Neisseria)
MAC deficiency
Susceptible to Neisseria meningitidis/gonorrhoeae
