IMMUNOLOGY INFLAMMATION

Inflammation is designed to remove

cause of injury

necrotic cells/tissues

Inflammation becomes chronic when

infection is severe

eliciting agent resists eradication

when autoimmune

five cardinal signs of inflammation

warmth

redness

swelling (edema)

pain
loss of function

Acute inflammation

lasts minutes to days

collagen remodeling, removal of dead cells

neutrophil dominates

Chronic inflammation

increase vascular proliferation

increase fibrosis

lymphocytes & macrophages dominate

lasts days to years

fibrosis

scarring

most leukocytes found in blood are produced in the

bone marrow

Eosinophil

allergies

parasitic infection

Basophil

stores histamine

stores heparin

Erythrocytes

Red blood cell

Monocyte

can differentiate into

dendritic cells and

macrophages

Neutrophils

first responders

ROS

“bleach”

Fibroblasts

construction workers

make scar tissue

Leukocyte trafficking

1. Margination

2. weak adhesion

3. rolling

4. firm adhesion

5. extravasation

   1. chemotaxis

Selectins

receptors found on endothelial cells

bind to oligosaccharides

upregulated by chemical mediators

mediate weak adhesion

involved in rolling

Integrins

glycoprotein

expressed on leukocytes

low affinity form initially

activated by chemokines

mediate firm adhesion

Angio genesis

vessel creation

Arachidonic acid

polyunsaturated fatty acid

found in cell membranes

made from phospholipids

made by phospholipase A2 (PLA2)

Eicosanoids

important chemical mediator

only synthesized as needed

COX 1

always on

found in gastric mucosa

makes prostaglandins

protect against acid induced damage

COX 2

inducible

activated by inflammatory stimuli??

Apoptosis

programmed cell death

decrease in size (atrophy)

apoptotic blebs form

engulfed by phagocyte

Necrosis

Accidental cell death

membrane damaged

cell swells

bursts open

leaks lysosomal contents

acids in matrix

induces inflammation

Phosphatidyl serine

phospholipid

usually on the inner leaflet of healthy cells

swapped to the outer leaflet

marks apoptotic bodies for removal by phagoytes

P 53

pro death protein

activates: Bax, Bak

Bax/Bak

pro death proteins

inside the mitochondria

dimerize

allow cytochrome C to escape the mitochondria and get into the cytosol

Cytochrome C

in the mitochrondria

when it escapes the mitochondria, it goes to cytosol where it activates the caspase cascade

Bcl 2 / Bcl XL

pro life proteins

inhibit BAX/BAK

executioner caspases

break down the cytoskeleton

activate endonucleases to cut up the DNA

Macro autophagy

debris engulfed by isolation membrane

isolation membrane fuses with lysosome

debris degraded by acid/enzymes

Micro autophagy

lysosome folds in on itself to engulf the debris

debris degraded by the lysosome

Chaperone mediated autophagy

protein is guided by a chaperone into a transporter

transporter delivers the protein directly to lysosome

only works on proteins

Characteristics of chemical mediators

produced locally at injury

concentration dependent effects

short lived

regulated by negative feedback

may have redundant functions

what does histamine do?

causes endothelial cell contraction and retraction

causes arteriolar dilation (redness)

Benadryl

antagonizes histaminergic effects

inhibits cardinal signs of inflammation

macrophages release

proteases

free radicals

eicosanoids

cytokines

growth factors

metaplasia

change in mature tissue type

barrett’s esophagus

chronic acid reflux

stratified squamous changes to simple columnar

smoker’s lung

pseudo stratified columnar epithelium changes to stratified squamous

ciliary clearance of debris lost

mucus secretion lost

neoplasia

new growth

can be malignant or benign

Anaplasia

rapidly growing tumors

less differentiated

hallmark of malignancy

Dysplasia

loss of normal tissue structure

can still revert to normal tissue structure

can predate cancer

Proto oncogenes

normal genes

when mutated, they cause cancer

VEGF

protein

helps body grow new blood vessels

COPD

not curable, but treatable

productive cough, present for at least 3 months/year

for 2 years

what governs resistance in the lungs?

diameter of the airways

pulmonary compliance (elasticity)

surface tension of alveoli

alveolus

sac at the end of airways

surfactant in lungs?

prevents alveolar collapse

Emphysema

destruction of alveolar lining/respiratory membrane

initial symptoms of COPD

shortness of breath

coughing/wheezing

weight loss

reduced FEV1

FEV1

forced expiratory volume in 1.0 seconds

how much air can you forcibly breath out in 1 second?

vital capacity

the deepest possible breath

FEV1 is usually

75 - 85% of vital capacity

chronic bronchitis

Goblet cell hyperplasia

goblet cell hypertrophy

wbc in airways

scarring thickens the airways

cilia become immobilized, reduce in numbers

Elastase

degrade elastic fiber in connective tissue

degrades collagen

inhibited by alpha 1 AT

Asthma

reversible

NOT curable

IS treatable

symptoms of asthma

coughing

wheezing

chest tightness

shortness of breath

Three main characteristics of asthma

airflow obstruction

airway hyperresponsiveness

inflammation of the bronchi

asthma is intiated by

typer 2 helper T cells