Pathology Lecture 5: Inflammation Iii; Cells Of Inflammation

Front 1

Polymorphonuclear neutrophils (PMNs)

Back 1

-represent 50-60% of total circulating leukocytes
-devel in BM takes about 2 weeks
-healthy adult 10^11/day, 10^12/day in inflam conditions;
1/2 life 4-10 h, in tissue 1-2 days

Front 2

What are the 6 morphological stages of PMNs?

Back 2

1. Myeloblast
2. Promyeloblast
3. Myelocyte
4. Metamyeloctye
5. Non-segmented (band)neutros
6. Segmented (mature cell)

Front 3

What are the 3 main types of Neutrophil granules?

Back 3

1. Primary (azurophil)
2. Secondary (specific)
3. Tertiary (small storage)

Front 4

What do Primary (azurophil) granules contain?

Back 4

1. Myeloperoxidase
2. Defensins
3. Elastase
4. Phospholipase A2

Front 5

What do Secondary (specific) granules contain?

Back 5

1. Lysozyme
2. Lactoferrin
3. Collagenase
4. Phospholipase A2

Front 6

What do Tertiary (small storage) granules contain?

Back 6

1. Gelatinase
2. Cathespins
3. Glucoronidase
4. Mannosidase

Front 7

Monocytes

Back 7

-originate in BM
-possess migratory, chemotactic, and phagocytic activities as well as PRRs and receptors for opsonins such as IgG, Fc domains, CRP, C3b

Front 8

Macrophages

Back 8

-possess migratory, chemotactic, and phagocytic activities to a greater extent than monocytes
-possess similar receptors

Front 9

What are the 4 types of normal macrophages?

Back 9

1. Histiocytes of CT
2. Kupffer's cells of the liver
3. Alveolar macrophages
4. Pleural and peritoneal macros

Front 10

What are M1 macrophages?

Back 10

-inflammatory macrophage
1. aggressively destroy micros and tumor cells
2. Release proinflamm cytokines
3. Process and present Ags

Front 11

What are M2 macrophages?

Back 11

-inflammatory macrophage
1. Remove dead/dying cells
2. Promote angiogenesis
3. Promote tissue remodeling
4. May be involved in tumor cell survival

Front 12

Mast cells

Back 12

-dev in BM from myeloid precursors
1. From CT whose granules contain heparin
2. Associated with mucosal surfaces of resp and GI system which are smaller and with granules that contain chondroitin sulfate instead

Front 13

Immune mediated (Type 1 hypersensitivity) degranulation

Back 13

IgE which is cytophilic for mast cells and basophils binds by means of its Fc domain
-Ag binding that results in cross linking of IgE molecules triggers degranulation

Front 14

Nonimmune mechanisms of degranulation

Back 14

1. Physical injury
2. Frags of the C (C3a and C5a)
3. Toll receptors binding PAMPS
4. Leukocyte derived histamine releasing proteins
5. Neuropeptides (Sub P)
6. Cytokines

Front 15

What are 3 types of production of other inflammatory mediators?

Back 15

1. Prostaglandins and leukotrienes
2. Cytokines, esp TNF
3. Platelet activating factor (PAF)

Front 16

How are basophils similar to mast cells?

Back 16

-cytophilic for IgE, granules contain heparin, histamine, and serotonin
-they syn similar secondary mediators of prostaglandins, lukotrienes, PAF, and cytokines

Front 17

How are basophils different from mast cells?

Back 17

1. basophils are normally found in circulation
2. arise from different BM progenitor cells
3. follow diff maturation pathways
4. synthesize significant amounts of IL-4

Front 18

What is a major role of IL-4?

Back 18

-The development of Th2 type immunity (humoral)

Front 19

Eosinophils

Back 19

-characteristic of IgE mediated rxns
-Type 1 hypersensitivities
-Primary defense against fungi, protozoa, parasitic worms, and pathogens that are too large to consume by endocytosis

Front 20

What do eosinophils produce?

Back 20

-prostaglandins, leukotrienes, and various cytokines such as IL-1, IL-6, IL-8, and TNF
-have granules that contain hydrolytic enzs and MBL and cationic protein

Front 21

Major basic protein (MBL)

Back 21

-toxic to parasites
-also toxic to other cells, plays a role in airway damage in asthma
-cytotoxic to tumors
-modulate allergic inflam by releasing enzymes that breakdown hist and leukotrienes

Front 22

NK cells

Back 22

-lymphocytes of null cells, part of innate immunity
-receptors called killer inhibitory receptors (KIRs) that recognize class I MHC, binding results in inhib of killing

Front 23

What does NK killing involve?

Back 23

-release of perforins
-granzymes--> enter target cell thru pores to activate apoptosis

Front 24

Activated NK cells are major sources of?

Back 24

cytokines such as IFN-Gamma and TNF
-also participates in Ab dependent cell cytoxicity (ADCC)--> killing of cells, including bact, bound with surface Abs

Front 25

Platelets

Back 25

-play a primary role in hemostatis involving the formation of the hemostatic plug and initiation and regulation of clot formation
-sources of inflammatory mediators, vasoact substances

Front 26

What are the 4 dense or delta granules?

Back 26

1. Histamine
2. Serotonin
3. Ca
4. ADP

Front 27

What are alpha granules?

Back 27

1. Fibrinogen adn various other clotting factors
2. Platelet derived growth factor--> fibroblast prolif and act in repair
3. Transforming growth factor beta (TGF-B)--> epithelial and fibroblast development

Front 28

What are 3 ways that platelet adherence, aggregation and degranulation occur?

Back 28

1. contact w/ damaged endo cells
2. contact w/ collagen following vascular injry
3. with thrombin after act of coagulation system
-release of vasoact mediators serotonin & hist* (Neg amounts)

Front 29

What do E and P selectins on endothelial cells reversibly bind?

Back 29

-leukocyte glycoproteins

Front 30

What are leukocytes activated by?

Back 30

-IL-1, IL-8, PAF and C5a

Front 31

Vascular Cell Attachment Molecule-1 (VCAM-1) on endothelial cells bind to?

Back 31

Very Late Activation - 4 (VLA-4)

Front 32

Intercellular Attachment Molecule-1 (ICAM-1) on endo cells bind to?

Back 32

1. Leukocyte Function Associated molecule-1 (LFA-1)
AND/OR
2. Myelin associated glycoprotein-1 (Mac-1)

Front 33

Emigration (diapedesis, transmigration)

Back 33

-by ameboid motion btwn endo cells at the intercellular junctions
-PECAM-1 is maj protein of process
-present on both act leukocytes and endothelial cells

Front 34

Intravascular activation of Leukocytes

Back 34

-PRRs when bound to PAMPs
-chemotactic factors, esp IL-8 that result in full expression of leukocyte cell surface integrins

Front 35

Extravascular activation of Leukocytes

Back 35

PMS are stimulated to undergo:
1. Degranulation and release of lysosomal contents
2. Gen of the oxidative burst
3. Production of eicosanoids
4. Production of cytokines

Front 36

Unenhanced attachment in Endocytosis

Back 36

-involves recognition of PAMPs such as peptidoglycan, techoic acids, lipopolysch, mannans, glucans, by surface membrane PRRs

Front 37

Enhance attachment (opsonization)

Back 37

-moleucles such as C3b, CRP and Abs IgG and IgM that attacht to and coat microbial surfaces
-phag cells have surface receptors for these molecules, so serve as points of enhanced attachement, facilitating endocytosis

Front 38

Oxygen dependent mechanism of killing

Back 38

-involves a resp/oxid burst characterized by a sudden increase in O2 consumption w/ the production of toxic reactive O2 metabolites

Front 39

What are 4 toxic reactive O2 metabolities?

Back 39

1. Superoxide (O2-)
2. Hydrogen peroxide (H2O2)
3. Hypochlorous acid (HOCL)
4. Hydroxyl radical (OH)

Front 40

What are 5 oxygen independent mechanisms of killing?

Back 40

1. Lysosomal hydroolytic enzymes
2. Bactericidal/permeability increasing protein
3. Defensins
4. Lactoferin
5. Lysozyme (G- bact resistant to its actions)

Front 41

Digestion

Back 41

1. Lysosomes (primary) w/ hydrolytic enzymes fuse w/ phagosome to form the phagolyxosome (secondary lysosome)--> digestion

Front 42

What are 4 types of tissue damage that can be caused by leukocytes?

Back 42

1. Cell death
2. Frustrated phagocytosis
3. Regurgitation
4. Autoimmune disease

Front 43

Frustrated phagocytosis

Back 43

attempts at phagocytosing targets that cannot be ingested often result in degranulation adn release of damaging substance into tissues

Front 44

Leukocyte defects

Back 44

-functional defects may affect the mechanisms of adhesion, emigration, chemotaxis, phagocytosis, or microbial killing
-characterized by overwhelming infx

Front 45

What are 5 examples of inherited leukocyte defects?

Back 45

1. Chronic granulomatous disease
2. Chediak-Higashi Disease
3. Leukocyte Adhesion Deficiency
4. Lazy Leukocyte Syndrome
5. Myleoperoxidase Deficiency

Front 46

Chronic ganulomatous disease

Back 46

microbial killing defect due to lack of NADPH oxidase necessary to produce H2O2 and the superoxide radical
-autosomal recessive and X-linked

Front 47

Chediak-Higashi Disease

Back 47

-dysfunction of the microtubules resulting in poor chemotaxis and failure of the lysosomes to fuse w/ phagosomes
-Autosomal recessive

Front 48

Leukocyte Adhesion Deficiency

Back 48

Adhesion molecule deficiencies that interfere w/ cell adhesion prior to emigration
-autosomal recessive

Front 49

Lazy Leukocyte Syndrome

Back 49

-cytoskeletal defects that interfere w/ cell movement including chemotaxis

Front 50

Myeloperoxidase Deficiency

Back 50

defect in microbial killing due to the lack of production in HOCL
-since other mechanisms compensate for this defect, ti is the least serious in nature

Front 51

Reactive Lymphadentis

Back 51

enlarged lymph nodes that are the result of delivery of APCs to the nodes by lymphatic circulation

Front 52

What are 4 possible outcomes of acute inflammation?

Back 52

1. Resolution
2. Regeneration
3. Non-function (fibrous) repair
4. Chronic inflammation