Pathology - Lecture 4

Front 1

Basic types and sources of inflammatory mediators

Back 1

1. exogenous mediators
2. endogenous mediators

Front 2

exogenous mediators

Back 2

1. components, products, and toxins such as endotoxin (LPS) and other toxins, unique DNA sequences, peptidoglycan, flagellin, etc of bacteria, the nucleic acids and proteins of viruses, and the DNA, proteins and other components of pathogenic fungi and protozoa
2. components & products of metazoan parasites
3. non-microbial substances such as allergens, irritants, foreign bodies, and toxic chemicals

Front 3

endogenous mediators

Back 3

1. injured or stressed cells
2. endogenous crystals, e.g. urate crystals
3. altered self components, eg oxidized low density lipoprotein (oxLDL)
4. leukocyte components and products
5. mast cells & platelet components and products
6. immune system
7. complement system
8. kinin system
9. coagulation system

Front 4

inflammasomes

Back 4

macromolecular complexes that play a crucial role in the initiation of inflammation

Front 5

some infammasomes are formed after recognition of _____s and/or _____s

Back 5

PAMP - pathogen associated molecular patterns
DAMP - damage/danger associated molecular patterns

Front 6

Caspase (ex. caspase-1)

Back 6

inflammasome assembly results in the activation of this enzyme, which then results in the formation of interleukins, like IL-1beta

Front 7

PRRs (pattern recognition receptors)

Back 7

1. circulating or secreted PRRs
2. membrane bound PRRs
3. cytosolic PRRs

Front 8

circulating or secreted PRRs

Back 8

1. C reactive protein (CRP)
2. Mannose or mannan binding lectin (MBL)

Front 9

CRP

Back 9

binds to surface phosphocholine on microbes resulting in opsonization and promotion of complement activation

Front 10

MBL

Back 10

binds to unique carbohydrates found on numerous microbial surfaces resulting in opsonization and complement activation

Front 11

Membrane bound PRRs

Back 11

1. phagocyte cell PRRs
2. toll - like receptors (TLRs)

Front 12

phagocyte cell PRRs

Back 12

phagocytic cells have scavenger receptors for mannose and other components of microorganisms, as well as infected, stressed (heat shock proteins) or injured cells (altered membrane components)

Front 13

TLRs

Back 13

Many cell types - monocytes, macrophages, mast cells, neutrophils, eosinophils, NK cells, etc have membrane receptors that recognize a number of different types of PAMPS

Front 14

How many TLRs have been identified in humans, and what do they specialize in?

Back 14

12
each specializing in a subset of PAMPs

Front 15

what are the membrane locations of TLRs

Back 15

1. endosomes
2. outer surface

Front 16

Examples of TLRs

Back 16

1. TLR-2 - recognizes peptidoglycans, bacterial lipoproteins and fungi as well as HSP70
2. TLR-3 - recognizes viral RNA
3. TLR-4 - recognizes LPS, fungal mannans, viral envelope proteins, paraside phospholipids, and several HSPs
4. TLR-5 - recognizes bacterial flagellin
5. TLR-6 - forms a heterodimer w/ ILR-2 that recognizes peptidoglycan, porins, and yeast mannans
6. TLR-9 - recognizes bacterial DNA

Front 17

Cytoplasmic PRRs

Back 17

1. NOD-like receptors (NLRs)
2. CARD containing proteins

Front 18

NOD-like receptors (NLR)

Back 18

-- cytoplasmic proteins that have a variety of functions in initiation and regulation of inflamm. response
-- 20 NLR proteins found to date: recognize cell damage or stress & microbial products in the cytoplasm

Front 19

What does binding of NLRs result in?

Back 19

activation of multiiple proinflammatory pathways to mount an effective antimicrobial response

Front 20

CARD containing proteins

Back 20

Caspase Activating and Recruitment Domain proteins like RIG-1 (retinoic acid inducible gene-1) and MDA-5 (melanoma differentiation associated gene-5) bind to viral RNA produced in viral infected cells & trigger the synthesis of interferons that block viral replication in other cells

Front 21

Major mediators of inflammation

Back 21

1. histamine and serotonin (vasoactive amines)
2. complement system
3. coagulation system
4. fibrinolytic system
5. kinin system
6. lipid mediators
7. platelet activating factor
8. nitric oxide
9. cytokines