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Bio217 F2014 Unit 2

1

Bio217 Pathophysiology Class Notes

Professor Linda Falkow

Unit 2: Mechanisms of Defense

Chapter 5: Innate Immunity: Inflammation &

Wound Healing

Chapter 6: Adaptive Immunity

Chapter 7: Infection & Defects in Mechanisms of

Defense

Chapter 8: Stress and Disease

1

Innate Immunity:

Inflammation & Wound Healing

Chapter 5

2

Human Defense Mechanisms

First line of defense

Innate resistance (or natural immunity)

Includes natural barriers

Second line of defense

Inflammation

Third line of defense

Adaptive (acquired or specific) immunity

Inǀolǀes ͞memory"

3

First Line of Defense

Physical and mechanical barriers

Skin

Mucous Membranes - linings of the GI,

genitourinary, and respiratory tracts

Mechanical removal:

Sloughing off of cells

Coughing and sneezing

Flushing from urinary system

Vomiting

Mucus and cilia 4

First Line of Defense

Biochemical barriers

Enzymes synthesized and secreted in saliva,

tears, ear wax, sweat, and mucus

Antimicrobial peptides ( _______________)

Normal bacterial flora on the skin and in gut

5

Second Line of Defense

Inflammatory response

Caused by a variety of materials

Infection, mechanical damage, ischemia,

nutrient deprivation, temperature extremes, radiation, etc.

Local manifestations

_________, ____________, _________, ________________

Vascular response

Vasodilation (VD), blood vessels become

leaky, WBCs adhere to inner walls of vessels & migrate through the vessels 6

Bio217 F2014 Unit 2

2

Inflammation

Goals (Benefits of Inflammation)

Limit tissue damage and control the

inflammatory process

Prevent and limit infection and further damage

Initiate adaptive immune response

Initiate healing

7

Inflammation

8

Plasma Protein Systems

Protein systems

______________ system

Circulating proteins that can destroy pathogens

directly ____________ system

Forms a clot that stops bleeding

___________ system

Bradykinin - causes VD, pain, SMC contraction,

vascular permeability, and leukocyte chemotaxis 9

Cellular Mediators of Inflammation

Cellular components

- Granulocytes, monocytes, platelets, lymphocytes

Neutrophils & macrophages (mature monocytes)AE

phagocytic

Eosinophils AE kill parasites

Platelets AE clotting sequence & release mediators

Lymphocytes (NK cells) AE attack virus and cancer

infected cells 10

Mast Cells

Important activator of inflammatory response

Contain granules, located in loose CT

Skin, digestive lining, and respiratory tract

Release:

Histamine AE VC of large blood vessels & VD of venules

Leukotrienes AE SMC contraction, incr. vascular

permeability

Prostaglandins

Similar to leukotrienes; they also induce pain (affect nerves)

Platelet-activating factor (PAF)

Similar effect to leukotrienes and platelet activation 11

Mast Cell Degranulation

12

Bio217 F2014 Unit 2

3

Phagocytes

Neutrophils (PMNs)

Predominate in early inflammatory responses

arrive 6-12 hr after injury

Ingest bacteria, dead cells, and cellular debris

Cells are short lived and become component

of purulent exudate 13

Phagocytosis

14

Phagocytes

Monocytes and macrophages

Monocytes - produced in bone marrow AE

blood AE inflammatory site, where they develop into macrophages

Macrophages typically arrive at the

inflammatory site 24 hours or later after neutrophils 15

Monocytes and Macrophages

Increased cell size and lysosomal granules

16

Phagocytes

Eosinophils

Mildly phagocytic

Duties

Main defense against parasites and regulation

of vascular mediators from mast cells 17

Phagocytes

Natural killer (NK) cells

Function against cells infected with viruses

and cancer

Platelets

Activation results in degranulation

(release of serotonin) and to stop bleeding 18

Bio217 F2014 Unit 2

4

Cytokines

Most cytokines are classified as:

Interleukins (IL)

Produced by macrophages and lymphocytes

in response to a pathogen or stimulation by other products of inflammation

Interferon (INF)

Protects against viral infections

Produced and released by virally infected host

cells in response to viral double-stranded RNA 19

Cytokines

20

Local Manifestations of

Acute Inflammation

Due to vascular changes & leakage of

circulating components into the tissue Heat

Redness

Swelling

Pain 21

Exudative Fluids

Serous exudate

_________ exudate: indicates early inflammation

Fibrinous exudate

Thick, ________ exudate: indicates more advanced inflammation

Purulent exudate

____: indicates a bacterial infection

Hemorrhagic exudate

Exudate contains _________: indicates bleeding

22

Systemic Changes due to

Acute Inflammation

Fever

Caused by exogenous and endogenous

pyrogens AE act on hypothalamus

Leukocytosis

Increased numbers of circulating leukocytes

Increased plasma protein synthesis

- Produced in liver 23

Chronic Inflammation

Inflammation lasting 2 weeks or longer

Often related to an unsuccessful acute

inflammatory response 24

Bio217 F2014 Unit 2

5

Wound Healing :

Resolution and Repair

Resolution:

Restoration of damaged tissue

Repair:

Replacing destroyed tissue with scar tissue

25

Healing

Primary intention

Wounds that heal under conditions of

minimal tissue loss

Secondary intention

Wounds that require a great deal more

tissue replacement

Open wound

26

Healing by Primary Intention

27

Healing by Secondary Intention

28

Dysfunctional Wound Healing

Dysfunction during inflammatory response

due to:

Hemorrhage

Fibrous adhesion

Infection

Excess scar formation

29

Dysfunctional Wound Healing

- Keloid (scar) formation 30

Bio217 F2014 Unit 2

6

Dysfunctional Wound Healing

Wound disruption

Dehiscence

Wound pulls apart at the suture line

Excessive strain and obesity are causes

Increases risk of wound sepsis

31

Concept Check

1. Inflammation:

A. Confines and destroys injurious agents

B. Stimulates and enhances immunity

C. Promotes healing

D. All of the above

2. Which of the following is not a local

manifestation of inflammation?

A. Swelling

B. Pain

C. Heat and redness

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