Inflammation (1)

When a condition ends with "itis", ___________________ is at the heart of the disease.

Inflammation

Inflammation can be _________________ (immune response) or ________________________ (inflammatory response).

Specific

Nonspecific

We have three types of defence mechanisms:

1.

2.

3.

Natural barriers

Inflammation

Immunity

Our first line of defence, ___________________ ______________, include the epithelial layer of the skin and the mucous membranes lining the gastrointestinal, genitourinary and respiratory tracts.

Natural barriers

Physical barriers may be _______________________ (ex, coughing) or ______________________ (ex. mucous).

Mechanical

Chemical

Our second line of defence is _____________________.

Inflammation

Our third line of defence is _______________________, which is acquired, specific and adaptive. After first exposure to a pathogen our _________________ system develops antibodies which match antigens found on the pathogen.

Immune

immune

________________ response in inflammation comes from the blood/plasma and involves complement factors. This response in immunity involves the formation of antibodies.

Humoral

The _____________ response in inflammation refers to a cell derived process.

Cellular

Cells involved in inflammation include __________________ and _________________, and in the immune response we talk about lymphocytes.

Neutrophils

Macrophages

Goals of inflammation?

- Movement of cells to the site of injury

- Delivery of nutrients and blood cells to get rid of offender

- Dilution, confinement and elimination

- Stimulation of immune system

- Promote healing and new tissue generation

What are the three major events that occur with inflammation?

- increase in metabolic rate

- vasodilation

- increase capillary permeability

Why do we have an increase in metabolic rate with inflammation?

- Cells step up their daily routines when called upon to fight infection

- Increase cell production

- Increase in oxygen and glucose consumption

- Increase heat production and waste production

What purpose does vasodilation serve during the inflammatory response?

- Increases blood flow to carry nec. cells to target site, including neutrophils

- Carry glucose and nec. components to site

What purpose does increased capilliary permeability serve during inflammation?

- Cells are better able to access site of injury

- Things needed for cellular repair can leave the blood and enter the tissues such as proteins and nutrients

Microbes, immune reactions, trauma, burns, tissue necrosis, genetic or immune defects, radiation, chemical agents, temperature extremes, oxygen deprivation and physical agents can all cause _______________________.

Inflammation

_____________ inflammation occurs quickly and early. It does not last long and is self limiting. It is a _______________________ process.

Acute

Nonspecific

Acute inflammation can lead to two options:

1.

2.

Healing

Chronic inflammation

Biochemical mediators released from mast cells, dying cells and plasma proteins trigger the production of _____________________ molecules on the surface of many cells, which cause the cells to stick to the ___________________-.

Adhesion

Endothelium

________________ cells line the walls of the blood vessels and are usually really close together to stop traffic out of the blood vessel.

Endothelial

Production of anti___________ and anti_______________agents - to stop blood clots

Production of vaso_____________ and vaso______________ to regulate flow

Regulation of _____________ extravasation via adhesion molecules

Regulating immune cell _________________ through secretion of colony stimulating factors

Participating in the repair process via ________________ and formation of an extra cellular matrix

These are all processes performed by ____________________ cells

platlet

thrombotic

constrictors

dilators

leukocyte

proliferation

angiogenesis

Endothelial

_________________, or thrombocytes, circulate until activated by cell debris such as platelet stimulating factor, collagen, and thrombin. When activated they produce ___________________ mediators which increase vascular ___________________, _________________, and ____________ and proteolytic properties of the endothelium. - they make the endothelium more sticky and make the spaces between the cells bigger so things can go through

Platelets

Inflammatory

Permeability

Chemotaxis

Adhesive

____________________ are granulocytes, which have lysosomal granules in the cytoplasm and are considered phagocytic leukocytes.

Neutrophils

Neutrophils are attracted to the site of injury early in the inflammatory response by _____________________ factors.

Chemotactic

Neutrophils have many ________________ on their surface which are each designed to recognize certain types of bacterial glycoproteins, microbes, cytokines and chemokines.

Receptors

In the presence of inflammation, neutrophils are release from the ________________ _____________________.

Bone Marrow

Neutrophils are short lived and _________________________ of cell division. When they die they release _______________________ chemotactic factor.

Incapable

Macrophage

When the bone marrow can't keep up with severe inflammation it releases immature neutrophils called ________________. The presence of these cells in a CBC tells us?

Bands

Tells us the bone marrow is overworked and the body is trying vigilantly to keep up with the inflammatory process

_____________________ are leukocytes derived from bone marrow, similar to neutrophils, but contain _____________ and ____________ lysosomes.

Monocytes

larger

less

____________________ exit the blood stream and take up residence in the ____________________.

Monocytes

Tissues

Monocytes are the less mature form of the _____________________.

Macrophage

Macrophages are named in response to their _______________ ____________________. They arrive at the site of inflammation BEFORE/LATER than Neutrophils.

Tissue Location

LATER - Macrophages are sluggish and eventually replace neutrophils

Macrophages are typically associated with ___________ inflammation

chronic

Macrophages produce potent ________________ mediators like prostaglandins, leukotrienes, platelet activating factor, inflammatory cytokines and growth factor. They eat more material than _____________________.

Vasoactive

Neutrophils

Macrophages are responsive to lymphokines from ________________ cells which enhance their ability. They work with the immune system by presenting digested ___________________ to lymphocytes.

T

Antigens - they also stimulate growth and differentiation of granulocytes and monocytes in the bone marrow

_________________ are granulocytes with many lysosomes. They are present in hypersensitivity and ________________ responses.

Eosinophils

Allergic

Eosinophils have bio mediators of inflammation and _______________ vasoactive molecules, controlling vascular effects of _____________ and serotonin.

DEGRADE

histamine

Basophils produce lipid mediators and ____________________ to induce the inflammatory response. They play a role in ________________ response.

Cytokines

Allergic

Basophils bind to __________ which triggers the release of ___________ and vasoactive agents.

IgE

histamine

____________ cells are considered the most important activators of inflammation by performing _____________ and ___________________ of mediators.

Mast

Degranulation

Synthesis

Mast cells are located in _____________________ tissue, close to a blood vessel and prevelant along the mucosa of lung, Gi tract and dermis.

Connective

Mast cells are derived from ______________________ stem cells, same as basophils. They don't mature until they leave ____________ and settle in tissues.

Hemipoetic

Ciculation

Mast cells are filled with pre formed _________________. They produce ____________ mediators and _________________ that mediate the inflammatory response.

Granules

Lipid

Cytokines

When activated ____________ cells release histamine, serotonin, chemotactic factors, enzymes, proteoglycans, proteases, and cytokines such as TNF-a and IL-6 immediately.

Mast

Mast cells __________ lipid mediators from membrane precursors such as ________________________ and platelet activating factor.

Synthesize

Prostaglandins

________________ and _______________ (leukotrienes) synthesis by monocytes and macrophages is stimulated by mast cells.

Cytokines

chemokines

Mast cells bind to immune globulin ______ which triggers release of ____________ and vasoactive substances from _________________. Big in the ___________________ response.

IgE

Histamine

Basophils

Allergy

Mast cells release __________________ chemotactic factor A (ECF-A) which attracts __________ to the site of inflammation.

Eosinophil

Eosinophils

There are 3 plasma protein systems which are in the inflammatory response. These are?

Usually short lived/rapidly deactivated.

Complement

Clotting

Kinin

Plasma derived mediators of inflammation are made in the ___________.

Liver

Enzymes that are inactive are called _____________.

Proenzyme

The _________________ systems includes 20 different proteins, c1 through c9, and makes up _____% of total circulating proteins.

Complement

10

Complement system components can directly ______________ pathogens OR can work with _____________ response components to do this.

Destroy

Inflammatory

_____________ are activated which forms a cascade - this plays a role in immunity and inflammation.

Proenzymes

Complement fragments cause

1.

2.

3.

Vasodilation

Increased vascular permeability

Enhancing activity of phagocytes

______ and ______ activation result in formation of opsonins, chemotactic factors, and anaphylatoxins.

C3 and C5

_____________ tag bacteria for destruction.

Opsonins

____________ factors draw inflammatory mediators to site of injury.

Chemotactic

_______________ cause degranulation of mast cells = increase inflammatory response.

Anaphylatoxins

___________ and ___________are the most potent complement system factor. _________ has chemotactic AND anaphylotoxic properties.

C3a

C3b

C5a

Complement component ____ causes vasodilation/increased permeability and smooth muscle relaxation. ________ acts as an anaphylatoxin.

c2b

c4a

Endpoint of complement cascade is? it is formed of C___ and C____

Formation of MAC - membrane attack complex

C5 and C9

What does MAC do?

Creates holes in pathogens - cell explodes

There are 3 pathways the component system can be activated. What are these called?

Classical pathway

Lectin pathway

Alternative pathway

How is the classical pathway activated?

By antibodies bound to antigen

Requires two Ab-Ag complexes to start

The _______________ pathway is activated by bacterial carbs, but doesn't require antibodies.

Lectin

The _____________________ pathway is activated by gram negative bacteria and fungal cell wall polysaccharides (endotoxins). Begins with ______ activation which merges with the classic pathway at C5. - No antibodies required.

Alternative

C3b

What are the four major effects of the complement system?

- opsonization

- leukocyte chemotaxis

- anaphylatoxins (mast cell degranulation)

- Cell lysis (MAC)

The plasma protein system that is activated by tissue destruction and infection is the __________________ system.

Clotting

The clotting system has two pathways that converge where X becomes Xa. What are they?

Intrinsic

Extrinsic

What is the primary goal of the clotting system?

To produce a fibrous clot - this traps the offending agent, holds it at site of inflammation to prevent bleeding and provide healing framework

The clotting system two most important factors that tie clotting to inflammation are ________ and _____________.

10a

Thrombin

Plasmin in the clotting system acts on the complement system by increasing ______ and _______, therefore increasing mast cell degranulation.

C3a

C5a

During fibrin production, _____________________ releases chemotactic factors that have 3 effects. What are they?

Fibrinogen

1. Attract neutrophils to site of injury

2. Increase vascular permeability

3. Increase effect of bradykinin

In the intrinsic pathway of the clotting system, _________ is activated from X11 (Hageman factor)

X11a

Kinin

Both the _______________ and the _______________ system are initiated by activation of X11 (Hageman) factor which becomes either X11a factor (Clotting system) or Prekellekrein activator (Kinin system).

Clotting

Kinin

____________________ activate kininogens into bradykinin. Kininogens are located in the tissues and bodyfluids. Bradykinin is a ________________ peptide.

Kallekreins.

Vasoactive

The ______________ systems ultimate function is to produce bradykinin, which does these 3 main things?

Kinin

Increase vascular permeability

Increase vasodilation

Pain

Bradykinins actions are similair to ___________________ but are shorter lived. They are eventually degraded by __________________ and are more important in the LATER phase of inflammation.

Histamine

Kinases

Hageman factor Interacts with all of the systems. Name the four ways it does this.

1. Conversion of C1 - activation of the complement system

2. Hageman becomes X11A which activates the intrinsic pathway of the clotting system by converting prothrombin to thrombin

3. Hageman becomes Prekallekrein Activating Factor which begins the Kinin system.

4. Hageman factor impacts the conversion of Plasminogen to Plasmin which then acts to activate C3 to C3A and C3B in the complement system

We have controls in place to keep inflammation and the plasma protein systems in check. Therefor this is a _________ limiting reaction.

Self

There are a lot of circulating __________________ that deactivate components of the plasma protein systems. This is how we maintain _________________ and homeostasis.

Enzymes

Balance

____________ derived mediators are synthesized in the liver.

Plasma

Cell derived mediators can be synthesized before hand (preformed) or may be ___________ synthesized in response to need.

Newly

Cell derived mediators are held within intracellular _______________________ waiting for secretion.

Granules

Platelets, neutrophils, macrohpages, monocytes, smooth muscle, endothelial cells, mast cells, fibroblasts and most epithelial cells are major sources of __________ derived _________________.

Cell

Mediators

Most cell derived mediators are ___________ lived.

Short

___________________ is released in response to trauma and immune reactions involving IgE.

Histamine

____________ is found in well perfused connective tissue, platelets, basophils and mast cell granules.

Histamine

Histamine binds to _______ receptors on endothelial cells causing ____________________.

H1

Vasodilation

Histamine increases ____________________ ____________________ and stimulates adherence of _______________ to the endothelium.

Vascular permeability

Leukocytes

Histamine causes _____________ muscle contraction of the brionchioles - this makes it difficult to breathe.

Smooth

Antihistamine (H1 Receptor _______________) meds compete with histamine for binding.

Antagonists

____________________ is released by mast cells, basophils, and platelets. It causes smooth muscle _______________, vasodilation and increased vascular permeability.

Serotonin

Contraction

_______________ are membrane enclosed sacs with powerful enzymes.

Lysozomes

Arachidonic metabolites are __________ ______________ found in phospholipids of cell membranes. Released from ____________ cells.

Fatty Acids

Mast

Arachidonic metabolites lead to production of inflammatory mediators like ________________________ and ___________________________.

Prostaglandins

Leuokotrienes

_____________________ induce inflammation and enhance the effects of histamine. They promote vaso____________________ and bronchoconstriction, increase chemotaxis and cause ______________ through direct action on the nerves/fever.

Prostaglandins

Dilation

Pain

_________________ and ASA inhibit prostaglandin synthesis.

NSAIDS

Thromboxane A2 is produced by __________________ at the site of injury. It produces broncho___________________, vaso_______________, and ________________ aggregation.

Platelets

Constriction

Dilation

Platelet