The purpose of inflammation part 1

There is a need to elminate=

intruders and dead cells

Survival is dependent on our ability to=

dilute, destroy, and neutralize

Inflammation is designed to remove=

cause of injury, necrotic cells and tissues

Inflammation becomes chronic and injurious when

-the infection is severe

-when the eliciting agent resists eradication

-when directed at harmless antigens or self-antigens in autoimmune diseases

itis

inflammation of that tissue

WBC nickname

policemen

5 cardinal signs of inflammation serves an important purpose:

calor (warmth), rubor (redness), tumor (edema), dolor (pain), and Functio laesa (fatigue)

Inflammatory response depends on

adequate blood supply and leukocyte infiltration

Non-vascularized tissues

cannot mount an inflammatory response and healing impeded and not a lot of WBCs

Example of non-vascularized tissue

diabetic gangrene

Swelling

brings blood and WBCs to the damaged regions

Low usage of glucose—→

2. blood vessel damage

3. low perfusion

4. low WBCs, O2, nutrients, waste removal

5. low drainage by lymphatics

6. increased infection risk

7. necrosis

8. gangrene

9. amputation

Acute inflammation

-resolves, repairs, and regenerates

-involves collagen remodeling and removal of dead cells

-minutes to days

collagen synthesis is done by

fibroblasts

granulocytes (granules)

-eosinophils, basophils, and mast cells/mastocytes

-innate immune cells—→ neutrophil —> first responders

Chronic inflammation

-Involves vascular proliferation and fibrosis (collagen ropes)

-Lymphocytes and macrophages dominate

-days to years

-Ex: TB, bronchitis, R.A.

-fibrosis=scarring

Adaptive immune cells

lymphocytes= T cells and B cells= CTLs and NK (kill host cells)

Endothelial cells

gate keepers of our blood vessels

Endothelial cells is a type of

epithelium

Junctions between the endothelial cells

1.vessel tight in brain (Blood Brain Barrier)

2.window/fenestration (none in BBB)

3.pinocytosis (drinking fluid) sample the environments

4.Active transport (need ATP); influx and efflux

Vascular endothelial cells form

a thin layer on the interior surface of all blood vessels of the entire circulatory system

Contraction and junctional retraction of endothelial cells

-adjusts vessel diameter, regulates blood flow, and leads to gaps in blood vessels from cytoskeletal changes

-elicted by chemical mediators such as histamine, bradykinin, leukotrines, TNF, and IL

Leukotriences can exit blood vessels through the

endothelial pores formed during inflammation

Leukocytes are made by

bone marrow

Leukocytes are stained by

Hematoxylin and Eosin

thrombus=

clot

Phagocytes examples

macrophages and neutrophils

Phagocytes

engulf intruders and digest them in lysosomes

B lymphocytes

create antibodies and T cells directly killed pathogens

Granulocytes

-eosinophils and basophils

-play a role in allergic reactions and protect against parasitic infections

what type of stem cells come out of bone marrow

hematopoietic

Hematopoietic stem cells lead to

myeloid progenitor cell and lymphoid progenitor

Myeloid progenitor cell

megakaryocyte, eosinophil, basophil, erythrocytes, monocyte, neutrophil, mast cell

Neutrophil nickname

police man

Neutrophil

-multilobar nucleus

-first responders

-phagocytes

-ROS

-die out fast

Monocytes differentiate

dendritic cell (border guards) and macrophage

Erythrocytes

-RBCs

-storage

Basophils

-rarest (2%)

-histamine (Ha)

-Heparin (anti-coagulant)

Eosinophil

-allergy

-parasitic infection

Basophils and Eosinophil

ROS and elosanoids

Megakaryocyte=

platelets (janitors and cleaners)

Platelets

clots and thrombocytes

Granules store

HA, heparin, ROS, and eicosanoids, are involved in itching, pain, allergies, asthma, anaphylaxis

Fibroblasts

-construction worker

-make scar tissue

chemotaxis is the

bread crumb trail

Leukocyte trafficking

1. static blood leads to swelling, redness, heat, and margination of leukocytes

2. weak adhesion to the endothelium

3. rolling along the endothelial lining by making and breaking bonds

4. firm adhesion to endothelium and transmigration through gaps in the endothelial lining

5. extravasation and migration through the tissue towards a chemoattractant stimulus

6. the movement towards a chemoattractant stimulus= chemotaxis

chemoattractant cytokines=

chemokines

Leukocytes find the site of infection via=

chemotaxis

Selectins=

receptors found on endothelial cells

-bind oligosaccharides attracted to glycoproteins

Selectins are upregulated by=

chemical mediators

Selectins mediate=

weak adhesion involved in rolling

bonds are made and broken

rolling

Integrins are transmembrane glycoproteins that mediate=

firm adhesion

Integrins are on leukocytes=

low-affinity form

chemokines activate

integrins on leukocytes

The integrins on leukocytes—→

high affinity form

High affinity forms of integrins on leukocytes

can interact w/ ligands on endothelial cells now—> levels of endothelial ligands are raised by cytokines

____and___ through the endothelium is mediated

extravasation; migration

Extravasation and migration are mediated by

cellular adhesion molecules (PECAM-1/CD31)

CD31 is expressed on

leukocytes and endothelial cells

Leukocytes can cross basement membranes after secreting=

collagenases to destroy the matrix

Leukocytes designed to destroy pathogens and disinfect and repair injured tissue

1.leukocytes are activated by= bacterial and chemical mediators from injured tissues—→ activation

2.release even more mediators to amplify injection

3.autophagic system of digestion=leukocytes engulf and digest microbes and infected cells through

4.neutrophils release= reactive oxygen species lysosome products (proteases/cathapsins) to help break down

debris, including H2O2+ hypochlorous free radical —>apoptosis

_____ and ____ of necrotic debris to clear the battlefield and heal the tissue

Lymphatic drainage; macrophage ingestion

3 outcomes of acute inflammation

Resolution, Progression to chronic inflammation, and Fibrosis

Resolution

-Neutralization, decay, or enzymatic degradation of chemical mediators (only around when and where needed)

-Apoptosis of extravasated neutrophils

-Macrophages clear detritus lymphatics drain fluid and proteins, new blood vessels are created

Progression to chronic inflammation

-can also resolve and restore normal function

-may also lead to fibrosis

Fibrosis

-when there is major tissue destruction

-when tissues cannot regenerate (e.g. muscle vs skin)

-when abscesses form

Acute phase Injury is characterized by

vasodilation, swelling, hemostasis, vascular permeability, leukocyte chemotaxis, cellular secretion of chemical mediators, and amplification of pro-inflammatory cascades

The pro-inflammatory response to tissue injury accomplishes the following goals:

• limits catastrophic blood loss

• seals the wound surface by clot formation

• clears internal and foreign debris by phagocytosis

• heals the tissue by cell regeneration or fibroblast- mediated scar formation

The correct sequence of events in leukocyte trafficking

Margination, rolling, firm adhesion, extravasation, collagenase secretion, phagocytosis

What part of the arachidonic acid metabolic pathway does Zyfo inhibit

Lipoxygenase enzyme function

What parts of the arachidonic acid metabolic pathway does aspirin inhibit

Prostaglandin synthesis and Cyco-oxygenase enzyme activity

FGF stimulates

fibroblasts to lay down more matrix fibers

VEGF encourage

angiogenesis (blood vessel growth)