Inflammation

Front 1

Acute inflammation

Back 1

a. Beneficial
b. Directs elements of the immune system
c. Tissue repair
d. PMNs, macrophages/monocytes

Front 2

Chronic

Back 2

a. Harmful
b. Tissue destruction or fibrosis
c. Contributes to heart disease, Alzheimer’s, diabetes, arthritis, cancer
d. Macrophages/monocytes, lymphocytes, fibroblasts

Front 3

Inflammation inducers

Back 3

a. Infections
b. Allergies
c. Neoplasms
d. Necrosis
e. Fractures
f. Cuts
g. Burns
h. Ischemia

Front 4

Inflammation local signs

Back 4

a. Pain
b. Redness
c. Immobility/loss of function
d. Swelling
e. Heat

Front 5

Systemic signs of inflammation

Back 5

a. Fever
b. Cytokine release
c. Acute phase protein release

Front 6

Leukocyte recognition of pathogens

Back 6

a. Microbes express conserved pathogen-associated molecular patterns (PAMPs)
b. Phagocytes bind to PAMPs via PATTERN RECOGNITION RECEPTORS (PRRs)

Front 7

PAMP-PRR interactions

Back 7

i. Enhance phagocytosis
ii. Up-regulate adhesion molecule expression to aid leukocyte extravasation and migration
iii. Enhance cytokine production by phagocytes

Front 8

PAMPs

Back 8

i. Bacterial cell wall components
1. LPS/endotoxin from G-
2. Peptidoglycan and lipoteichoic acid from G+
ii. Mannose
iii. Nucleic acids from bacteria and viruses
iv. Flagellin
v. fMet-Leu-Phe
vi. Glucan from fungi

Front 9

PRRs

Back 9

i. Toll-like receptors, especially TLR-4
ii. Mannose receptors

Front 10

LPS/endotoxin on G- bacteria...

Back 10

....binds to phagocyte TLR4/CD14

Front 11

LPS/endotoxin on G- bacteria binds to phagocyte TLR4/CD14-->

Back 11

g. Stimulates IL-1 and TNFa release from phagocyte
i. Increase adhesion molecule expression
ii. Increase acute phase proteins from liver

Front 12

Gram-positive bacteria-- production of IL-1 and TNFa

Back 12

Recognition of lipoteichoic acid on G+ bacteria by the phagocyte TLR2/CD14 induces release of IL-1 and TNFa by phagocyte

Front 13

TNFa

Back 13

1. Induces septic shock
2. Drop in blood pressure
3. Hyper/hypothermia
4. Shaking chills
5. Weakness
6. Tachypnea and tachy cardia
iv. IL-1 is a pyrogen

Front 14

Oxygen-independent killing

Back 14

i. Lysozyme
ii. Defensins

Front 15

Oxygen-dependent killing

Back 15

i. Requires NADPH oxidase

Front 16

Respiratory/oxidate burst

Back 16

Early, short lived

1. ROS damge DNA, proteins, lipids
2. Neutralized by catalase
Oxygen-dependent

Front 17

Nitric oxide

Back 17

Later, sustained
Oxygen-dependent

1. Inducible nitric oxide synthase
2. Arginine+oxygen→ NO
3. Reversible inhibition of bacterial replication
4. Important against intracellualar pathogens→ Listeria

Front 18

Chronic granulomatous disease (CGD)

Back 18

1. Granulomas
2. Abscesses
3. Pneumonia
4. Lymphadenitis
5. Catalase+ bugs
a. Staphylococcus
b. Serratia
c. Aspergillus

Front 19

PAMP-PRR interactions induce pro-inflammatory cytokines

Back 19

1. IL-1
2. IL-6
3. TNFa
4. All pyrogens

Front 20

Pro-inflammatory cytokines are responsible for...

Back 20

...fever and acute phase protein release from liver (systemic signs)

Front 21

Il-1 and TNFa aid extravasation by....

Back 21

enhancing adhesion molecule expression

Front 22

Extravasation

Back 22

1. Induced by IL-1 and TNFa

Front 23

Leukocyte adhesion deficiency

Back 23

i. LAD1: no CD18, so no LFA-1
ii. LAD2: no sialyl Lewis X
iii. No extravasation
iv. Leukocytosis, especially neutrophilia
v. No pus, poor healing
vi. Chronic/repeated bacterial infections of mouth and GIT

Front 24

Positive APPs _____ during inflammation

Back 24

Increase

Front 25

Complement

Back 25

i. Group of 30 serum proteins (zymogens) that act in a cascade
ii. Inactivated by heating serum to 56 C for 30 min.
iii. Activities
1. Lysis of G- bacteria
2. Gram+ cell walls are too chick for lysis
3. Opsonization
4. Leukocyte chemotaxis, activation, degranulation

Front 26

C3b>C4b

Back 26

i. Opsonization
ii. Recognized by complement receptors CR1, CR2, CR3 and CR4 on macrophages

Front 27

C5a>>C3a>C4a

Back 27

i. Anaphylatoxins
ii. Inactivated by carboxypeptidase N
iii. Cause degranulation of mast cells, basophils, and eosinophils
iv. Histamine release by basophils and mast cells→ smooth muscle contraction→ increases capillary permeability→ local edema

Front 28

C5a

Back 28

i. Activator and chemotaxin for all myeloid cells
ii. Induces PMN degranulation
iii. Induces IL-1 and IL-6 production in monocytes
iv. Most potent anaphylatoxin
v. Most potent chemotaxin

Front 29

C3a

Back 29

i. Chemotactic for eosinophils

Front 30

MAC

Back 30

g. C5b6789n
ii. Causes lysis of gram- bacteria but not gram+ bacteria

Front 31

Classical pathway

Back 31

i. Globular domains of C1q bind to CRP or the Fc fragment of IgM and IgG
ii. Binding induces Ca-dependent autoactivation of two C1r molecules
iii. C1r activates two C1s molecules

Front 32

Lectin pathway

Back 32

i. Similar to classical pathway→ initiated by mannose-binding lectin (MBL)
ii. MBL analogous to C1q
iii. MASP1 and MASP2 (mannose-associated serine proteases) are analogous to C1r and C1s
iv. MASPS cleave C4 into C4a and C4b
v. From there onward, lectin pathway is identical to classical pathway

Front 33

Alternative pathway

Back 33

i. C3b bins to LPS/endotoxin on Gram- bacteria or zymosan in yeast
ii. C3b can come from
1. Classical pathway
2. Lectin pathway
3. Spontaneous hydrolysis of C3 in serum

Front 34

Terminal (lytic)pathway

Back 34

i. Formation of membrane attack complex (MAC) C5b6789n
ii. Culmination for all three complement pathways
iii. Deposition of C5b678 promotes insertion of 10-15 monomers of C9 into the target cell membrane
iv. Polymerization of C9 forms pores that cause cell lysis
v. Similar to perforin

Front 35

Regulation of complement pathway

Back 35

a. Regulated to prevent autoreactive lysis of human cells

Front 36

C1 esterase inhibitor (C1INH)

Back 36

i. Disrupts C1qrs complex, the MASP complex, and C3bBb
ii. C1INH deficiency leads to hereditary angioedema

Front 37

Decay-accelerating factor

Back 37

i. Bind to C4b, disrupt C4b2a
ii. DAF is a GPI-anchored protein
iii. DAF deficiency leads to paroxysmal nocturnal hemoglobinuria (PNH) with red cell lysis

Front 38

Factor H

Back 38

i. Protects human cells from Factor B

Front 39

Factor I

Back 39

i. Inactivates C4b and C3b
ii. Requires co-factors

Front 40

Proteins that interfere with MAC

Back 40

i. Membrane protein CD59
ii. Plasma proteins S-protein (vitronectin), clusterin
iii. CD59 deficiency leads to PNH

Front 41

C3 deficiency

Back 41

i. Results in profound susceptibility to infections by encapsulated bacteria
ii. SHINS

Front 42

C5-C9 deficiency (MAC)

Back 42

i. Components increase susceptibility to Neisseria spp.

Front 43

Deficiency in C1INH

Back 43

i. Causes hereditary angioedema (HAE)
ii. Unchecked activation of the classical complement pathway
iii. Cutaneous angioedema
iv. Abdominal pain
v. Airway obstruction
vi. Stress

Front 44

Anaphylatoxin

Back 44

cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability.
also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals.

Front 45

Diapedesis adhesion molecule on epithelium

Back 45

PECAM-1 (adhesion molecule on both epithelial cells and leukocytes)

Front 46

Chemotaxis adhesion molecules

Back 46

fMet-Leu-Phe (bacteria)
C5a, IL-8, leukotriene B4, kallikrein (mnenomic: CILK) (host products)