Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/76

Click to flip

76 Cards in this Set

  • Front
  • Back
5 cardinal signs of inflammation?
Rubor (red), dolor (pain), calor (hot), tumor (swelling), functio laesa (loss of fn)
3 families of adhesion molecules involved in acute inflammation?
Selectins, immunoglobulin-family adhesion proteins, integrins
What are the steps in neutrophil margination and adhesion during inflammatory response?
1) Margination
2) Rolling
3) Activation
4) Adhesion
5) Transmigration
What occurs during "margination"?
neutrophils line vessel walls due to increased blood viscosity due to fluid extravasation
What occurs during "rolling"?
E- and P-selectins on endothelial cells bind weakly to neutrophils
What occurs during neutrophil "activation" and "adhesion"?
neutrophils are stimulated by chemokines to express their integrins, which firmly adhere to immunoglobulin-family adhesion proteins on endothelial cells (ICAMs)
What occurs during neutrophil "transmigration"?
leukocytes move between endothelial cells, and migrate through basement memb towards inflammatory stim (chemotaxis)
What is chemotaxis?
when leukocytes are attracted to and move toward an injury, moves along a chemical gradient
Chemotactic factors?
Chemokines (IL-8), C5a, finbrinopeptides, leukotriene B4 (LTB4), formyl methyl peptides
Hemodynamic changes in acute inflammatory response?
1. Transient initial vasoconstriction, followed by massive vasodilation
2. Increased vascular permeability (due to endothel cell contraction or injury) -> leakage of proteinaceous fluid -> edema
3. Blood stasis due to increased viscosity -> facilitates neutrophil margination
Causes of NEUTROPHILIA?
BACTERIAL infections, and other causes of ACUTE INFLAMMATION, such as infarction (usu w/in 1st 24hrs); EARLY RELEASE from bone marrow reserve pool
Causes of MONOCYTOSIS?
TB, brucellosis, typhus, salmonella (seen w/CHRONIC INFLAMMATION)

Replace neutrophils after 2-3 days, are longer lived, can divide/proliferate in tissue
Causes of LYMPHOCYTOSIS?
VIRAL infections (influenza, mumps, rubella, infectious mononucleosis)

BACTERIAL infections (whooping cough and TB)

**prominent in CHRONIC INFLAMMATION
Causes of EOSINOPHILIA?
ALLERGIC reactions and PARASITIC infections, also in polyarteritis nodosa and Hodgkin lymphoma
Causes of BASOPHILIA?
chronic myelogenous leukemia and other myeloproliferative diseases

(mast cells and basophils are source of histamine)
Key steps in phagocytosis?
1. engulfment of opsonized particle by macrophage or neutrophil, forming phagosome
2. fusion with lysosome to make phagolysosome
3. digestion
What are the most important opsonins in phagocytosis?
IgG subtypes and C3b
Types of intracellular microbial killing in phagocytosis?
Oxygen dependent:
1. NADPH oxidase-dependent
2. myeloperoxidase-dependent

Oxygen independent:
1. lysosome-dependent
Basic mechanism of killing in oxygen-dependent microbial killing during phagocytosis?
H2O2 (and other free radicals) are produced/activated, and disrupt cell walls
Endogenous mediators of acute inflammation?
1. Vasoactive amines
2. Arachidonic acid metabolites
3. Cytokines
4. Kinin system
5. Complement system
6. Nitric oxide
Effects of HISTAMINE?
vasodilation and increased vascular permeability
Where is histamine released from?
Basophils, mast cells, platelets
What triggers release of histamine from PLATELETS?
is liberated by platelet aggregation and release reaction, which is triggered by 1)endothelial injury and thrombosis, or 2)platelet activation factor (PAF)
What triggers the release of histamine from MAST CELLS or BASOPHILS?
1. antigen binds to IgE on mast cell/basophil
2. C3a or C5a (ANAPHYLATOXINS) bind to receptors on mast cell/basophil
3. physical stimuli (heat/cold)
4. IL-1 (cytokines)
What substances does PAF release, and what other effects does it have?
1. releases histamine and 5HT from platelets
2. vasoactive and bronchospastic effects
3. activates arachidonic acid
What does VASOACTIVE mean?
causing constriction or dilation of blood vessels
What is a VASOACTIVE AMINE?
acts on blood vessels to alter permeability or to cause vasodilation

e.g. histamine and 5HT
What are the 2 ARACHIDONIC ACID PATHWAYS?
1. cyclooxygenase pathway
2. lipooxygenase pathway
What are the general effects of arachidonic acid metabolites?
short range hormones that rapidly decay, they mainly affect inflammation and hemostatis via vasodilation/vasoconstriction, platelet aggregation, etc
What 2 enzymes catalyze the cyclooxygenase pathway?, and which one is expressed in gastric mucosa?
COX-1 (in gastric mucosa) and COX-2
What substances inhibit the catalysts of the cyclooxygenase pathway, and via what mechanism?
aspirin and other NSAIDs inhibit prostaglandin synthesis (prostaglandin is the intermediate between arachidonic acid and TXA2,PGI2,PGD2,PGE2,PGF2)
What might be the benefit of selective COX-2 inhibitors?
actions of COX-1 in gastric mucosa are preserved, thus avoiding anti-inflammatory effects in gastric mucosa, and preventing gastric ulceration
What are the three classes of products of the cyclooxygenase pathway?
1. (Platelet) Thromboxane A2 (TXA2)
2. (Endothelial) Prostacyclin (PGI2)
3. PGD2, PGE2, PGF2
What are the opposing functions of TXA2 and PGI2?
TXA2: IN PLATELETS, promotes platelet aggregation and vasoconstriction

PGI2: IN ENDOTHELIUM, inhibits platelet aggregation and causes vasodilation
What are the functions of PGD2, PGE2, and PGF2?
vasodilation (plus pain for PGE2)
Products of lipooxygenase pathways?
leukotriene B4 (LTB4), LTC4, LTD4, LTE4
What is the function of LTB4?
neutrophil chemotaxis
What is the function of LTC4, LTD4, LTE4?
vasoconstriction, bronchospasm, increased permeability

"slow-reacting substance of anaphylaxis" (SRS-A)
Common cytokines involved in inflammation?
IFN-gamma (activates monocytes), IL-1 & TNF (s/c by monocytes)
Main cytokine effects on inflammation?
1. Systemic effects (fever, leukocytosis)
2. Hepatic synthesis of acute phase proteins
3. Synthesis of adhesion molecules
4. Neutrophil degranulation
5. Promote thrombosis
What is the important peptide product of the kinin system that plays a role in inflammation?
bradykinin
What are the 2 cascade reactions necesesary to create bradykinin?
1. Hageman factor (factor XII) converts prekallikrein -> kallikrein

2. Kallikrein converts high molecular weight kininogen (HMWK) -> bradykinin
What are the effects of BRADYKININ?
increase vascular permeability, pain, vasodilation, bronchoconstriction
Which complement proteins participate in inflammatory response?
C3a & C5a, C3b, C5b-C9
What is an ANAPHYLATOXIN?
mediate degranulation of basophils and mast cells w/release of histamine (e.g. C3a and C5a)
What are the 4 functions of C5a?
1. anaphylatoxic effect
2. chemotactic effect on neutrophils
3. induces expression of leukocyte adhesion molecules
4. activates lipooxygenase pathway of arachidonic acid metabolism
What is the function of C3b?
opsonization of invader for phagocytosis by neutrophil/macrophage
What is the function of C5b-C9?
Forms membrane attack complex (MAC) = lytic agent for bacteria and other cells
What are the 3 main functions of the complement cascade?
1. opsonization of pathogens (C3b)
2. recruitment of inflammatory cells (C3a, C5a)
3. killing of pathogens (C5b-C9)
What are the effects of NITRIC OXIDE during the inflammatory process?
produced by endothelial cells; smooth muscle relaxation (controls vasc tone), inhibits platelet aggregation, increased vascular permeability

aka endothelium-derived relaxing factor
What triggers the ALTERNATIVE PATHWAY of complement activation?
bacterial surface
What triggers the CLASSICAL PATHWAY of complement activation?
antigen-antibody complex (IgG or IgM)
What molecules are unique to the alternative pathway?
C3, factors B and D -> C3 converatse
What molecules are unique to the classical pathway?
C1, C2, C4 -> C3 convertase
3 potential outcomes of acute inflammation?
1. restoration of tissue and function
2. tissue destruction and persistent acute inflammation
3. conversion to chronic inflammation
4 ways that tissue destruction from acute inflammation can manifest itself?
1. abscess
2. ulcer
3. fistula
4. scar
What are the characteristics of an ABSCESS?
filled w/pus (neutrophils, monocytes, liquefied cellular debris), walled off by fibrous tissue, results from tissue destruction by lysosomal products, usu caused by bacterial infections
What is the "final result" of tissue destruction?
Scar, w/resultant distortion of structure, and sometimes altered function
What histological changes occur when acute inflammation becomes chronic?
replacement of neutrophils and monocytes w/lymphocytes, plasma cells, and macrophages; proliferation of fibroblasts and new vessels, w/scarring and architectural distortion
What are the 3 major diseases caused by defects of neutrophils?
1. Chronic granulomatous disease (CGD)
2. Chediak-Higashi syndrome
3. Leukocyte adhesion deficiency (LAD)
Molecular defect in CHRONIC GRANULOMATOUS DISEASE (CGD)?
deficiency of NADPH OXIDASE, thus failure to generate superoxide anion and other O2 radicals -> oxygen-dependent microbial killing cannot proceed
Histologic marker of CGD?
phagocytes that ingest but do not kill certain microorganisms
Symptoms of CGD?
recurrent infections w/catalase-positive bacteria and fungi
Why is a person w/CGD still protected from catalase-negative organisms?
catalase-negative organisms produce sufficient H2O2 to permit oxygen-dependent microbicidal mechanisms to proceed (catalase negative organisms destroy H2O2)
Molecular defect in CHEDIAK-HIGASHI SYNDROME?
granule structural defect
Markers for CHEDIAK-HIGASHI SYNDROME?
abnormal white blood cells:
-chemotactic defects
-degranulation defects
-large cytoplasmic granules caused by impaired fusion of lysosomes
Symptoms of CHEDIAK-HIGASHI SYNDROME?
absent NK activity, partial albinism, cranial/peripheral neuropathy, repeated infections
Molecular defect of LEUKOCYTE ADHESION DEFICIENCY (LAD)?
absence of CD18--common beta chain of leukocyte integrins; interferes with neutrophil adhesion and transmigration
Symptoms of LEUKOCYTE ADHESION DEFICIENCY (LAD)?
recurrent chronic infections, failure to form pus, does not reject umbilical cord stump
2 major patterns of CHRONIC INFLAMMATION?
Chronic nonspecific inflammation, granulomatous inflammation
Chronic inflammation commonly arises in what 3 settings?
1. persistent infections
2. autoimmune diseases
3. prolonged exposure to toxic agents
3 common histologic markers of chronic inflammation?
1. collection of chronic inflammatory cells (macrophages, lymphocytes, plasma cells)
2. tissue destruction
3. repair involving angiogenesis and fibrosis
Who activates what in CHRONIC NONSPECIFIC INFLAMMATION?
-MONOCYTES recruited by chemotactic factors
-MONCYTES/MACROPHAGES secrete cytokines, which activate LYMPHOCYTES
-LYMPHOCYTES then secrete additional cytokines that activate MONOCYTES/MACROPHAGES
-MACROPHAGE presents antigen to activate B LYMPHOCYTE, which forms antibody-producing PLASMA CELLS
What is a GRANULOMA?
collection of activated macrophages that have an enlarged, squamous cell-like (EPITHELIOD) appearance
What disease is characterized by CASEATING GRANULOMAS?
TB
What disease is characterized by NONCASEATING GRANULOMAS?
sarcoidosis