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Pathophysiology > Immunology: mechanism of self defense > Flashcards

Immunology: mechanism of self defense Flashcards

1
Q

Innate immunity definition

A

the basic resistance to disease that a species possesses - the first line of defense against infection

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2
Q

characteristics of the innate immune response

A
  • Broad-Spectrum (non-specific)
  • no memory or lasting protective immunity
  • limited repertoire of recognition molecules

Not equipped to fight something major – just general traffic, maintaining integrity

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3
Q

Antigen

A

Foreign Invader, Intruder

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4
Q

Antibody

A

Your Fire-power

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5
Q

Leukocytes

A

Your Soldiers

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6
Q

Phagocytes

A

Eaters - We eat our enemies

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7
Q

Macrophages

A

Big Eaters

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8
Q

Opsonization

A

Coating (coating surface of antigen, so possibly dealt w/later in various ways)

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9
Q

1st, 2nd, and 3rd line of defense

A
  • First line of defence
    • Innate resistance
  • Second line of defence
    • Inflammation
  • Third line of defence
    • Adaptive (acquired) immunity. Very Specialized soldiers/specific reactions
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10
Q

What is our 1st line of defense?

A
  • physical and mechanical barriers
  • biochemical barriers
  • anatomic barriers
  • physiologic barriers
  • chemical factors
  • Endocytic and phagocytic barriers
  • biochemical barriers
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11
Q

Why do smokers develop respiratory infections, chronic bronchitis?

A

Failure in 1st line of defense: loss of ciliary action –> inflamed and chronically inhabited by bacteria

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12
Q

Physical and mechanical barriers

A

1st line of defense

  • skin
  • lining of GI, GU, respiratory tracts
    • sloughing off of cells
    • coughing & sneezing
    • flushing
    • vomiting
    • mucus & cilia
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13
Q

Biochemical barriers

A
  • Synthesized and secreted saliva, tears, earwax, sweat, and sebum
    • sebaceous glands in skin secrete antibacterial and antifungal FAs and lactic acid
    • perspiration, tears, saliva contain lysozome, which attacks cell walls of gram-positive bacteria (= acidic skin surface)
  • Normal Flora – bacteria that live w/us, prevent other invaders. Our health depends on them in addition to our own genetic material *
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14
Q

What causes an “opportunistic infection”?

A

infection - taking advantage of weakened immune system

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15
Q

biochemical barriers and opportunistic infections

A

Antibiotics: subsequent vaginal infection, etc – b/c normal flora has been changed along w/ridding body of problem. in vaginal infections, protective lactobacillus is diminished leading to growth of other bacteria and yeast

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16
Q

Antimicrobial Peptides

A
  • Biochemical barriers: proteins secreted by epithelial surfaces of body.
  • 2 classes: Cathelicidins & Defensins
    • class division based on structure
    • high local concentrations. Toxic to several bacteria, fungi, viruses
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17
Q

Cathelicidins

A
  • small cationic peptides that possess broad-spectrum antimicrobial activity
  • linear alpha-helical shape
  • only one known to function in humans
  • stored in neutrophils, mast cells, variety of epithelial cells
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18
Q

Defensins

A
  • Defensins are a family of small cationic, antibiotic peptides that contain six cysteines in disulfide linkage
  • abundant in phagocytes and small intestinal mucosa
  • about 50 different defensins ID’d thus far
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19
Q

Defensin structure

A
  • triple-stranded ß-sheet structures
  • 3 intrachain disulfide bonds
  • Carboxy end and NH2 end
  • Subdivided depending on how many cystein residues are connected in formation of disulfide linkages
    • into alpha (at least 6 in humans) and beta (at least 10, but maybe up to 40) types
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20
Q

alpha vs beta defensins

A
  • alpha
    • often require activation by proteolytic enzymes
    • esp in granules of neutrophils, paneth cells lining sm intestine
      beta defensins: variety of epithelial cells lining respiratory, urinary, intestinal tracts, & skin.
  • beta defensins
    • synthesized in active forms
    • Have antibacterial properties AND
    • may also help protect epithelial cells from HIV!
  • Both classes can activate cells of innate and adaptive immunity
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21
Q

how antimicrobial peptides kill bacteria

A

bacteria have cholesterol-free cell membranes - may allow cathelicidins to insert selves into and disrupt membranes

Defensins have similar chemical charge to cathelicidins and may work in same way

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22
Q

Physiologic Barriers

A

1st line of defense

  • Temperature
  • pH
  • Oxygen Tension
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23
Q

1st line of defense: Temperature

A
  • normal body temperature inhibits growth of most microorganisms.
  • Elevated body temperature (fever) can have a direct effect on pathogenic microorganisms.
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24
Q

1st line of defense: pH

A

low pH of stomach, skin, & vagina (inhibits microbial growth)‏

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25
Q

1st line of defense: Oxygen Tension

A

particularly damaging to group of bacteria that prefer anaerobic environment. **e.g., diabetes –> poor circulation –> infection by anaerobes –> poor wound healing

Why chronic wound clinics use hyperbaric O2 chambers –> several hundred percent oxygen concentration to tissues

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26
Q

1st line of defense: chemical factors

A

a number

  • Fatty acids, lactic acid
  • Pepsin (digestive enzyme which hydrolyzes proteins)
  • Lysozyme
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27
Q

1st line of defense: endocytosis

A

endocytic & phagocytic barriers

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28
Q

Lectins: definition

A
  • proteins which specifically bind (or crosslink) carbohydrates
  • involved in a variety of recognition processes
  • exhibit considerable structural diversity.

  • like flags sticking out of cell membranes*
  • 2nd line of defense*
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29
Q

Types of lectins

A
  • *Collectins**: Collectins are a family of collagenous calcium-dependent defence Lectins.(respiratory tract)
  • *Selectins**: an important family of Lectins!

antimicrobial lectins: intestinal epithelium, against gram+ bacteria

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30
Q

Lectin forms & shapes

A

a variety!

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31
Q

Lectins & inflammation

A
  • Release of Mediators into blood stream
  • Release of Lectin like substances from the endothelial cells (b/c they sense inflammation)
  • Lectin like substances slowing down the circulating leukocytes (expressed like little flags (lectin flag), slow leukocytes down – to come fight inflammation)
  • Leukocytes get attached to the blood vessel wall near the site of inflammation
  • Leukocytes leave the vessel and go to the site
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32
Q

Selectin: A Modified Lectin

A
  • During an inflammatory response, some of the inflammatory mediators (such as histamine and thrombin) cause endothelial cells to mobilize P-selectin from stores inside the cell to the cell surface.
  • P-Selectin has low affinity for a protein on the surface of leukocytes by the name of P-selectin glycoprotein ligand-1 (PSGL-1)
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33
Q

Putting it together: you step on a nail. How do leukocytes know to come and participate/attack the invader?

A

Antigens invade. Area hot/red/inflamed. Inflammation causes endothelial cells to produce selectin flags (P-selectins). P-selectin-leukocyte interaction brings leukocytes

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34
Q

What is the selectin roll?

A
  • Leukocytes are able to “roll” along the blood vessel wall during their adhesion cascade!
  • As the leukocyte rolls, the distal Lectin-like domain of the Selectin binds to certain carbohydrate groups presented on proteins on the leukocyte (PSGL-1)
  • Selectin attachment slows the leukocytes and allows it to leave the blood vessel and enter the site of infection.
  • The “rolling action” is because of Selectin’s low affinity. (they’re able to attach, but then they let them go fight infection)
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35
Q

innate immunity: 2 lines of defense

A

natural barriers & inflammation

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36
Q

cells involved in first line of defense

A

epithelial

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37
Q

Cells involved in 2nd line of defense

A

inflammation:

mast cells, granulocyte (neutrophils, eosinophils, basophils), monocytes/macrophages, natural Killer cells, PLTs, endothelial cells

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38
Q

Cells involved in adaptive immunity

A

T lymphocytes, B lymphocytes, macrophages, dendritic cells

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39
Q

Peptides involved in 1st line of defense/barriers

A

defensins, cathelicidins, collectins, lactoferrin, bacterial toxins

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40
Q

Peptides involved in inflammatory response

A

complement, clotting factors, kinins

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41
Q

Peptides involved in adaptive immunity

A

antibodies, complement

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42
Q

Where does inflammation occur?

A

tissue that has a blood supply

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43
Q

Cardinal Signals of inflammation

A

**redness: **vasodilation & increased BF

**heat: **” “

swelling: exudate (fluid & cells) accumulate

**pain: **PGs, bradykinin, pressure of exudate

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44
Q

Inflammation: 3 characteristic changes in microcirculation (arterioles, capillaries, venules)

A
  1. Vasodilation
  2. increased vascular permeability
  3. WBC adherence to inner walls of vessels and their migration through vessel walls to site of injury (diapedesis)
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45
Q

Describe Acute Inflammatory Response

A
  • (usually) Cellular injury > mast cell degranulation / activation of 3 plasma systems / release of subcellular components from damaged cells.
  • Interdependent systems: e.g., mast cell degran can result in other two
  • leads to dvpt of microscopic changes in inflamed site AND characteristic clinical manifestations
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46
Q

What causes edema?

A

cap permeaility, leakage of plasma (also > viscous blood in microcirculation)

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47
Q

What causes warmth and redness of inflammation?

A

increased blood flow and increase in RBCs

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48
Q

What stimulates endothelial cells lining capillaries to retract during inflammation and what is the effect?

A

biochemical mediators (e.g., histamine, bradykinins, leukotrienes, PGs)

Effect: spaces at junctions btwn cells, allowing leukocytes and plsma to enter surrounding tissue

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49
Q

Inflammation: what do the cells and chemicals do together once in the tissues

A
  1. prevent infection/further damage
  • contaminate microorganisms through
    • influx of fluid to dilute toxins produced by bacteria and released by dying cells
    • influx & activation of plasma protein systems that help destroy and contain bacteria (e.g., complement, clotting)
    • influx of “eater” cells (neutrophils, macrophages) to destroy cell debris & infectious agents
  1. ​LImit & control inflammatory process (prevent spread)
    * ​through influx of plasma protein systems (e.g., clotting), plasma enzymes, cells (e.g. eosinophils)

​3. Interact with components of adaptive immune system to elicit specific response

  • through influx of macrophages and lymphocytes
    4. Prepare area of injury for healing
  • through removal of bacterial products, dead cells, other products of inflammation
  • and initiation of mechanisms of healing & repair
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50
Q

Role of lymph nodes in adaptive immunity

A

microbial Ags in lymphatic fluid activate B & T lymphocytes

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51
Q

Phases of inflammation and repair

A
  • cell injury
  • Acute inflammation
  • healing or chronic inflammation
  • healing or granuloma formation
  • healing
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52
Q

Type of cell does most work in inflammatory response

A

leukocyte

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53
Q

Types of leukocytes

A

neutrophils, monocytes, eosinophils, lymphocytes, macrophages, mast cells, and basophils.

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54
Q

What is an inflammatory mediator?

A

molecules inside and outside your body that play a role in inflammation.

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55
Q

endotoxin

A
  • an “exogenous” inflammatory mediator, called endotoxin, or lipopolysaccharide (LPS).
  • present in the outer covering of some types of bacteria, and signals to immune cells that there are bacteria present, causing an increase in inflammation.
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56
Q

Selectin Roll image (good to know)

A

PMN: neutrophil

Rolling: L-selectin, P-selectin, E-selectin

Margination: Integrin alpha4beta1 (VLA4) & alpha4beta7, VCAM-1

Diapedesis: integrin aLB2 (LFA-1), integrin aMB2 (MAC-1), PCAM-1, ICAM-1, ICAM-2, PCAM-1

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57
Q

Neutrophil Adhesion and Chemotaxis in inflammatory response (image)

A

Selectin mediates neutrophil attraction & attachment

Rolling & sticking initially mediated by selectin then integrins

CAM molecules help enter tissue, spread, extravasate

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58
Q

How does the body recognize inflammatory mediators?

A

Toll-like receptors: on surface of our cells. Can sense presence of several different microbial stimuli

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59
Q

How are macrophages activated during inflammation?

A

by various immune system molecules (such as cytokines, including interferons, or IFNs), endotoxin, or by other microbial signals.

chemical message! not selectin like leukocytes

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60
Q

How do active macrophages differ from non-active?

A
  • develop different properties, e.g., capacity to stop dividing and phagocytosis. “Make war not love”
  • vigorous production of inflammatory molecules such as TNF and interleukins, clotting factors, prostaglandins, free radicals, nitric oxide, and tissue remodelling enzymes (i.e. enzymes promoting bone resorbtion) and growth factors
  • promote the growth of new blood vessels. NOT just destruction
61
Q

Macrophage overview (image)

A

Monocytic cells give rise to resident and recruited macrophages w/functional heterogeneity

Clockwise from top left

  • 1st of defense against intracellular pathogens by
    • generating an inflammatory and respiratory burst and
    • initiating antigen presentation to activate adaptive immunity; (unlike neutrophils)
    • clearing immune complexes and downregulating inflammatory responses
    • promoting wound healing via elaboration of growth factors.(primary to do so)
  • A subset, e.g. splenic red pulp macrophages and osteoclasts, become highly specialized in their location and function.
    • splenic red pulp macrophages: clear and recycle senescent red blood cells
    • osteoclasts: critical to remodeling bone throughout adult life
62
Q

What are the 1st cells to go fight bacteria?

A

neutrophils!

63
Q

Role of neutrophils (aka PMN) in defense

A
  • buy time devouring organisms (esp bacteria) waiting for healing & inflammation to begin
  • degrade organisms through activation of proteases, of other antibiotic molecules, and generation of toxic oxygen radicals
    • remove debris if sterile
    • phagocytize bacteria if nonsterile
  • die early - leftover is pus
64
Q

How do neutrophils kill?

A

carry molecular weapons called free radicals that are poisonous to bacteria. Typically, these poisons are hidden in specialized storage sacks kept separate from body tissues.

65
Q

Meaning of “band” or “left shift”

A

Immature neutrophils. Sign of bacterial infection.

66
Q

Life of a neutrophil

A

myeloid lineage. Short lived.

bands, neutrophils, recruitment & rolling….

67
Q

angry neutrophils

A

Golgi complex is making more vesicles- so electron microscopy looks denser w/black vesicles (similar to macrophages)

68
Q

abnormal neutrophil function

A

uncommon, impair ability respond to life-threatening infections

69
Q

noninfectious attraction of neutrophils

A

major role in rheumatic conditions, noninfectious stimuli e.g. complement activation & lipid inflammatory mediators

70
Q

Lymphocytes: 2 broad classes

A

T cell and B cell

71
Q

Where do lymphocytes begin and mature?

A

Begin in bone marrow

B mature in marrow

T mature in thymus

72
Q

Role of PLTs in inflammation

A

we know they stimulate blood clotting

  • In inflammation
    • shed certain molecules that directly activate inflammation inside blood vessels
    • produce variety of inflammatory mediators, e.g., GFs, adhesion molecules, cytokines

so site is stickier for other cells, signals sent

73
Q

When is platelet action unwanted in inflammation?

A

Clots - e.g., during CAD. Why we give PLT inhibitors (aspirin, heparin)

74
Q

Overview of innate immunity and inflammation

A
75
Q

3 plasma protein systems essential to effective inflammatory response

A

complement, clotting, kinin

all contain inactive enzymes (proenzymes) which are sequentially activated. Substrate of activated enzyme becomes next component in series

76
Q

3 pathways to complement activation

A

classical, lectin, alternative

77
Q

Complement Cascade Image

A
78
Q

Complement: interaction w/other components of inflammatory response

A

all of them! Team players.

79
Q

How do complement proteins get to target area

A

Quickly, freely, through bloodstream.

React directly w/antigens

80
Q

What can the complement system do when it is activated?

A
  • Trigger inflammation
  • Attract eater cells such as macrophages to the area
  • Coat intruders so that eater cells are more likely to devour them
  • Kill intruders : direct hole in chest
81
Q

What does complement need to blast holes into lipid bilayer of target membrane?

A

must develop membrane attack complex (MAC)

82
Q

Complement Cascade, another image

A
83
Q

How does the classical pathway start for the complement cascade?

A

usually started through antigen/antibody complexes through component C1 (consists of C1q, two C1r, C1s molecules)

C1q must simultaneously bind to 2 Ab molecules

84
Q

Important common point to all complement pathways

A

Get to C3 convertase - then you have a common path

85
Q

What begins the lectin pathway in the complement cascade?

A

Mannose-binding lectin (MBL) binding to oligosaccharides on certain virions/infected cells. (or 2 mannose-rich pathogen associated molecules on surface of bacterium)

Lectins bring leukocytes in during inflammation, even if no bacteria present - so complement can get started w/o Ag/Ab

86
Q

How does alternative pathway to complement cascade begin?

A

Component of complement (C3) spontaneously breaks down as a result of inflammation.

activated by many agents, e.g., gram-negative bacterial and fungal cell wall polysaccharides, which bind and stabilize C3b, which is produced by normal breakdown of C3 in blood

87
Q

Relationship between number of pathways begun and magnitude of response

A

Just one molecule of C42b can cleave up to 1000 molecules of C3 and C3b. Many C3b molecules bind to microbial surface > multiple holes in the membrane

The complement snowball

88
Q

Classical complement pathway (image)

A
89
Q

Test question: C3a and C3b - uses in and around complement cascade

A

C3b: opsonization; C3a (and C5a, to limited extent C4a): recruiter of mast cell (histamine): leaky blood vessels, attract phagocytes. (“anaphylatoxins - induce mast cell degranulation)

complement helps mediate direct destruction of enemy (cytolysis)

*carboxypeptidase inactivates C3a and C5a to stop anaphylatoxic activities

90
Q

5 processes begun by bacterial activation of complement

A

chemotaxis, degranulation of mast cells, enhancement of humoral immune responses, opsonization for phagocytes, lysis of susceptible microbes

91
Q

complement pathway: cleaving components into fragments during activation

name components & effect

A

components: 2b, 4a, Ba, C3a, C5a

smaller fragments often have biologic activities & serve as chemotactic factors and anaphylatoxins

Larger activated fragments usually converted to active enzymes (bar above names in book image) and form complexes w/additional components in the cascade

92
Q

Characteristics of MBL as part of complement cascade

A

MBL contains 2 associated enzymes, MASP-1 and MASP-2, and functions in a manner similar to C1.

93
Q

Main substance in coagulation system

A

fibrin, an insoluble protein

94
Q

Complement cascade: similar function of C1 and MBL

A

each activate complement components C4 and C2

95
Q

Role of C3b in alternative complement pathway and following steps

A

C3b produced by normal breakdown of blood. Bound and stabilized by many agents, e.g., bacterial polysaccharides.

C3b forms site of binding of factor B (fB), which is activated by factor D (fD) into Bb and the small fragment Ba. Properdin (P) helps stabilize the complex.

96
Q

C3 and C5 convertases in complement pathways

A
  • both produced by all pathways
  • enzymatically active complexes that activate C3 and C5, respectively
  • C3b produced by C3 convertase can function as an opsonin
  • C5b initiates assemblage of Membrane attach complex (MAC), which results in multiple C9 molecules forming a pore in the bacterial membrane
  • C5a is the major chemotactic factor for neutrophils
97
Q

What is C1?

A

a macromolecular complex consisting of C1q and two molecules each of C1r and C1s

begins classic complement pathway w/Ag-Ab immune complex. A conformational change in C1 results in enzymatically active molecules whose substrates are C4 and C2

98
Q

Other ways to activate classical pathway

A

e.g. heparin, DNA, RNA, C-reactive protein (increased during inflammation)

99
Q

chemotactic factor

A

biochemical substance that attracts leukocytes to the site of inflammation

C5a is the major CF for neutrophils

100
Q

Purpose of coagulation system

A
  • Prevents the spread of infection
  • Keeps microorganisms and foreign bodies at the site of greatest inflammatory cell activity
  • Forms a clot that stops bleeding
  • Provides a framework for repair and healing
101
Q

Action of coagulation system

A

Forms a fibrinous meshwork at an injured or inflamed site

102
Q

2 coagulation pathways

A
103
Q

Two ways to activate clotting

A

intrinsic & extrinsic pathways

104
Q

How is the intrinsic pathway initiated?

A

by the activation of Hageman factor (XII) into XIIa

(activated factors are enzymes and are indicated by lowercase a)

105
Q

sequential activation of the intrinsic pathway components results in the formation of a complex of ….

A

IXa, VIIIa, and X

106
Q

Extrinsic pathway is activated by

A

exposure of tissue factor (TF) during tissue damage.

TF complexes w/factor VII, which is activated (VIIa), and forms a complex with factor X (TF, VIIa, X)

107
Q

similarities between intrinsic and extrinsic pathways

A
  • dependent on calcium
  • form on phospholipid membranes that are rich in phosphatidylserine
  • have “tenase” activity (can activate factor X into Xa)
108
Q

Intrinsic/extrinsic common pathway

A

Factor X begins a common pathway in which Xa complexes w/Va and prothrombin (PT), with calcium and phospholipid membranes, to form an active prothrombinase (activates prothrombin into thrombin).

109
Q

Thrombin and fibrin

A

an enzyme that cuts high-molecular-weight fibrinogen into fibrin molecules. Fibrin polymerizes to form a clot.

fibrin is end product of coagulation cascade!

110
Q

What substances can activate the clotting system?

A

substances released during tissue injury and infection, including collagen, proteinases, kallikrein, plasmin, bacterial products such as endotoxins

111
Q

activation of extrinsic vs intrinsic pathway

A
  • Extrinsic is tissue factor pathway, activated by TF (aka tissue thromboplastin) released by damaged endothelial cells in blood vessels. Reacts w/factor VII (VIIa)
  • Intrinsic pathway - contact activation pathway. Activated when vessel wall is damaged and hageman factor (XII) in plasma contacts negatively charged subendothelial substances.
  • Factors converge at factor X
112
Q

clotting system and inflammation

A

as w/complement, fragments produced by cascade enhance the inflammatory response.

2 low molecular weight fibrinopeptides, A and B, are released from fibrinogen when fibrin is produced. Both, esp B, are chemotactic for neutrophils and increase vascular permeability by enhancing the effects of bradykinin

113
Q

Function of kinin system

A

to activate and assist inflammatory cells

  • Primary kinin is bradykinin
  • Causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis
114
Q

What activates the kinin pathway?

A

Factor XIIa from the clotting system (the hagemon factor!)

XIIa functions as an enzyme (prekallikrein activator) to convert prekallikrein intokallikrein. Enzymatically active kallikrein converts kininogen into bradykinin.

115
Q

Hageman factor

A

The mastermind! XIIa. Connects all 3 pathways

know how all three activate each other

116
Q

Kinin system & inflammation

A
  • in a sense, once you have bradykiinin, you have vasodilation, vascular permeability, pain.
  • Sometimes want these things, sometimes not. Inhibit bradykinin – prevening vasodilatation & pain
117
Q

PAMPs

A

essential polysaccharides and polynucleotides that differ little from one pathogen to another but are not found in the host.

many recognized by receptors in innate immunity

118
Q

Cellular mediators of inflammation

A

Cellular components

  • Granulocytes, platelets, monocytes, and lymphocytes

Cell surface receptors

  • Pattern recognition receptors (PRRs)‏
  • Pathogen-associated molecular patterns (PAMPs)‏
  • Toll-like receptors
  • Complement receptors
  • Scavenger receptors (nonspecific receptors)
119
Q

Mast Cells

A

Cellular bags of granules located in the loose connective tissues close to blood vessels

Skin, digestive lining, and respiratory tract

120
Q

Mast cell activation

A
  • Physical injury, chemical agents, immunologic processes, and toll-like receptors
121
Q

Mast cell chemical release

A

Two ways:
Degranulation and synthesis of lipid-derived chemical mediators
(Degranulation: release “bags” of granules on site of inflammation)

122
Q

Mast cell degranulation: what is “in the bag”?

A

Histamine & chemotactic factors

123
Q

H1 receptor

A
  • Proinflammatory
  • Present in smooth muscle cells of the bronchi
  • Why histamine plays a role in the devpt of asthma. Prevent mast cell degranulation through drugs called “mast cell stabilizers”. Brings inflammation in bronchus down. We used to think asthma was bronchospasm, but bronchospasm tied to inflammation
124
Q

H2 receptor

A
  • Anti-inflammatory
  • Present on parietal cells of the stomach mucosa
  • Induces the secretion of gastric acid
  • Some pts want you to block these – even if anti-inflammatory, b/c they have ulcers, etc. H2 blockers – not benefiting from their anti-inflammatory, but need to stop acid/ulceration. OTC dosage of H2 blockers is half “real” dosage.
125
Q

action of histamine

A
  • Vasoactive amine that causes temporary, rapid constriction of the large blood vessels and the dilation of the postcapillary venules (does both!)
  • Retraction of endothelial cells lining the capillaries
  • there are 2 histamine receptors (one pro and other antiinflammatory)
126
Q

Action of mast cell’s chemotactic factors

A
  • Chemotactic factors – named after who they attract
  • Neutrophil chemotactic factor
    • Attracts neutrophils
  • Eosinophil chemotactic factor of anaphylaxis (ECF-A)‏
    • Attracts eosinophils
127
Q

4 mediators synthesized by mast cells

A

Lipid derived

  • Leukotrienes
    • Product of arachidonic acid from mast cell membranes
    • Similar effects to histamine in later stages (used w/asthma)
  • Prostaglandins
    • Similar effects to leukotrienes; they also induce pain. PG inhibitors address pain (ibuprofen)
  • Platelet-activating factor
    • Similar effect to leukotrienes and platelet activation

Growth Factors & cytokines

128
Q

Margination (pavementing)‏

A

Adherence of leukocytes to endothelial cells

129
Q

Diapedesis

A

Emigration of cells through the endothelial junctions

130
Q

Types of phagocytes

A

monocytes & macrophages, eosinophils, NK cells, PLTs

131
Q

Monocytes and macrophages

A
  • Monocytes are produced in the bone marrow, enter the circulation, and migrate to the inflammatory site, where they develop into macrophages
  • Macrophages typically arrive at the inflammatory site 3 to 7 days after neutrophils
  • Macrophage activation results in increased size, plasma membrane area, glucose metabolism, number of lysosomes, and secretory products
132
Q

Eosinophils

A
  • Mildly phagocytic - main job is not to eat
  • Duties
    • Defense against parasites and regulation of vascular mediators
      • Eosinophils high on CBC: 1) drug allergy or 2) parasitic infection. More likely #1 in U.S., 3) lab error
133
Q

NK Cells

A

Function is to recognize and eliminate cells infected with viruses and some function in eliminating cancer cells. We’d prob have cancer more frequently & younger w/o them. As we age, NK cells lose surveillance ability

134
Q

Platelets

A

Activation results in degranulation and interaction with components of the coagulation system – need both to make a good clot

135
Q

Important cytokines

A

interleukins, interferons, TNF-alpha

136
Q

Interleukins

A
  • Produced primarily by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation
  • Many types
  • Examples
    • IL-1 is a proinflammatory cytokine
    • IL-10 is an anti-inflammatory cytokine
    • Must be able to move to inflammatory state and back out of inflammatory state
137
Q

Interferons: who do they fight and how?

A
  • Protects against viral infections
  • Produced and released by virally infected host cells in response to viral double-stranded RNA
  • Types
    • IFN-alpha and IFN-beta
      • Induce production of antiviral proteins
    • IFN-gamma
      • Increases microbiocidal activity of macrophages
  • Important in drug therapy
138
Q

TNF: who does it fight and how?

A
  • Secreted by macrophages in response to PAMP and toll-like receptor recognition (also in mast cells)
  • enhances endothelial cell adhesion molecule expression
  • Systemic effects:
    • Induces fever by acting as an endogenous pyrogen
    • Increases synthesis of inflammatory serum proteins
    • Causes muscle wasting (cachexia) and intravascular thrombosis
    • probably responsible for shock fatalities caused by gram- bacteria

some attempts to use w/septic pts

139
Q

Steps to inflammation, agents

A
140
Q

Transudative vs exudative fluid

A

3 components to r/o exudative: protein, LDH, total LDH (LDH is 2 of clinical parameters)

141
Q

Systemic manifestations of inflammation

A

fever, leukocytosis, increased plasma protein synthesis

142
Q

What causes fever?

A

Caused by exogenous and endogenous pyrogens
Act directly on the hypothalamus

143
Q

What are the plasma proteins that are increased in systemic inflammation?

A

Acute-phase reactants: C-reactive protein, fibrinogen, haptoglobin, amyloid, ceruloplasmin, etc.

144
Q

Role of plasmin in protein cascades

A
  • regulates clot formation: degrades fibrin and fibrinogen
  • can activate complement cascade through C1, C3, C5
  • can activate kinin cascade by activating Hageman factor (factor XII) and producing prekallikrein activator
145
Q

4 effects of Hageman factor (XII)

A
  1. Activation of clotting cascade through factor XI
  2. Control of clotting through conversion of plasminogen proactivator to plasminogen activator, resulting in the generation of plasmin
  3. Activation of the kinin system by activated Hageman factor (prekallikrein activator)
  4. Activation of C1 in the complement cascade
146
Q

C1-esterase inhibitor (C1-inh)

A

inhibits:

complement activation

  • through reactivity w/all 3 pathways
    • C1, MASP-2, C3b

clotting & kinin

  • e.g., kallikrein, activated hageman factor XIIa

*genetic defect w/C1-inh: hereditary angioedema

147
Q

Role of eosinophils

A

parasites or regulate vascular mediators released from mast cells.

Mast cells produce ECF-A, which attracts eosinophils to site of inflammation. There, they help control.

148
Q

Role of basophils

A

assoc w/allergies and asthma, but primary role unknown

149
Q

macrophage and T-cell

A

T-cells or cells activated by TLRs produce inflammatory cytokines which increase bacteriacidal activity of macrophages

macrophages have cell surface receptors for these cytokines

Pathophysiology (10 decks)

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