Inflammation & Immunity

Leukocytes

(5-10,000 normal range)

infection

(medicine) the invasion of the body by pathogenic microorganisms and their multiplication which can lead to tissue damage and disease

Two Stages of Acute Inflammation

Vascular Phase Vasoconstriction -> vasodilation Increased vascular permeability change in capillary oncotic pressure Stagnation of blood flow and clotting Cellular Phase Margination (pavementing) Adherence of leukocytes to endothelial cells Diapedesis Emigration of cells through the endothelial junctions Chemotaxis Phagocytosis

Cellular Phase

WBCs and RBCs migrate to area; Neutrophils first; within 90 minute (mature neutrophils: segs-PMN?) 1. marginization (adhesion of WBC's to walls of blood vessels. Transfers fluid from intravascular to extravascular space). Chemotaxis occurs with WBC arriving at site of injury 2. Diapedis ( Monocytes/macrophages next: within 5 hours; Macrophages call in B&T lymphocytes - specific immune response (more of a reaction next time). Debris are disposed via phagocytosis

Skin sloughing off, vomiting, saliva, earwax, mucous membranes, acidic environment in the stomach, GI tract inhibition of colonization of abnormal flora, vaginal flora

What are some defense barriers that are in the first line of defense?

1. Helper t-Cell (C4). Signal the B-cells to secrete antibodies 2.Supressor Cells (C8). The opposite of Helper cells. Decrease effects of T cell stimulation. 3.Cytotoxic T-Cells that kill virus infected cells

What are the 3 types of T-cells?

1. a phagocytic cell first comes in contact with the foreign object and send cytoplasmic extensions around it. 2. the extensions approach one another and then 3. fuse to trap the material within a vesicle. 4. lysosomes fuse with the vesicle, 5-6. activating digestive enzymes that gradually break down the structure of the phagocytized material. 7. undissolved reside is the ejected from the cell by exocytosis. ok so what this means is the cell that is going to phagocytize a foreign object sends small arms to go around the object. then it pulls it inside itself and forms a vesicle around it. lysosomes then come to the vesicle and go inside also. this activates digestive enzymes to break down the foreign object. what is left is then pushed out of the cell that did the phagocytizing. that process is called exocytosis.

What are the five stages of phagocytosis?

leukocytes

What are the major players in inflammation?

1. Natural Barriers 2. Nonspecific Response * Inflammatory Response * NK cells 3. Acquired Immunity * Humoral * Cell mediated

What are the three lines of defense the body depends on?

Neutrophils and macrophages

What are the two most important phagocytic cells in the body?

Humoral Immunity (b-cells) either plasma cells (produce specific antibodies based on antigens w/complexes)-phagocytized by macrophages. memory cells (recognize antibodies and help with further exposes by remembering antigen. Each cell only good for 1 thing). Cell-Mediated Immunity (t-cells) "Head-Honchos" in lymphoid organs (spleen, lymph nodes). Coordinate activity. Respond to single foreign invader. Communicate and control other cell response. They wear proteins on their surface. Particularly good at detecting viruses

What are the two types of acquired immunity?

The accumulate and leave a coating of fibrin on an inflammed area, stopping the loss of blood.

What do platletes do?

Very Short Term. No offered protection for re-exposure

What do we mean when we talk about Non-specific inflammatory response?

This person has an overwhelming infection. All old neutrophils are used up and immature neutrophils cannot phagocytize or mature fast enough.

What does "a shift to the left" mean?

A long-term, chronic infection. Monocytes become macrophages which are immediate inflammatory responders. A high number of monocytes indicates an extreme infection.

What does a patient with a high count of monocytes in their blood work mean?

Natural Barriers. This includes hair, the skin, and secretions. This features provide a physical obstacle for pathogens to deal with.

What does the body's first line of defense consist of?

*Phagocytes- Remove debris and pathogens. *Extracellular Killing- Destroy abnormal cells *Inflammatory Response- Blood flow increased, attracts phagocytes, capillary permeability increased, temperature increased, initiates complementary sytem. *Fever- Mobilizes defenses, accelerates repairs, inhibits pathogens. *Interferons- Increase resistance of cells to infection, slow the spread of disease. *Complement System- (attacks and breaks down cell walls, attracts phagocytes, stimulates inflammation).

What does the body's second line of defense consist of?

Exudate (serous, hemorrhagic, fibrinous, and purulent) forms from the piling up of cellular debris. This typically doesn't indicate infection, it is just a natural course of debris disposal.

What happens to the debris resulting from phagocytosis?

Non-specific effector cell. A substance found in the blood that can coat any cell and signals (ding-ding-ding) cell for destruction (phagocytosis via luekocytes) Can also poke holes in cells as well as opsonization

What is complement?

1. To provide protection (mechanical, biological,etc.)

What is the purpose of our body to provide immunity?

1.Inflammation (Immediate protection against injury or invading organisms). Includes non-specific mechanisms. 2.Antibody Mediated Immunity (Slower response). Requires prior sensitization to offending cells. Produces antibodies 3.Cell Mediated Immunity (Coordinated immune effort).

What types of immunity protection does the human body employ?

Margination

When Phagocytes adhere themselves to capillary walls and perform diapedisis, walking through capillary and tissues to get to site of infection.

Diapedis

When white blood cells leave circulation and enter tissue, become very elongated and slip between walls of the blood vessels

They just naturally float around the blood stream. Capable of killing enemies without any assistance. Key since they target cancer, tumor, and infected cells. They also protect against infectious microbes (viruses, bacteria, parasites, & fungi)

Why are Natural Killer Cells so important?

As vascularization occurs, blood flow increases as WBC's enter injured tissues. This causes redness to be visible when paired with heat and swelling.

Why does redness occur during inflammation?

When part of the body is injured, chemicals are released that act on our smallest blood vessels, called the capillaries. These chemicals cause the capillaries to vasodilate, or widen, and thus leads to both an increase in blood flow and a leakage of fluid into the injured area. It also allows infection-fighting cells to enter the injury site. Swelling occurs as a result of this fluid leakage into the surrounding tissues. Although the inflammatory process is beneficial in terms of helping the body to heal, sometimes localized swelling is a less helpful side-effect, so it is often treated by the use of ice, heat, compression, elevation and non-steroidal or steroidal anti-inflammatory medications.

Why does swelling occur during inflammation?

Pyrogenbs and cytokines activate hypothalamus, raising body temperature. Stablizes immune system and increases its function.Body can heal faster. It helps inhibit pathogens

Why does the sensation of heat occur during inflammation?

When part of the body is injured, chemicals are released that act on our smallest blood vessels, called the capillaries. These chemicals cause the capillaries to vasodilate, or widen, and thus leads to both an increase in blood flow and a leakage of fluid into the injured area. It also allows infection-fighting cells to enter the injury site. Swelling occurs as a result of this fluid leakage into the surrounding tissues. Although the inflammatory process is beneficial in terms of helping the body to heal, sometimes localized swelling is a less helpful side-effect, so it is often treated by the use of ice, heat, compression, elevation and non-steroidal or steroidal anti-inflammatory medications.

Why does the sensation of pain occur during inflammation?

Granuloma

a tumor composed of granulation tissue resulting from injury or inflammation or infection

mast cells

a vertebrate body cell that produces histamine and other molecules that trigger the inflammatory response. (blood flow signals)

Cytosis

abnormally large grouping of cells. In defense these cell engulf debris and pathogens (phagocytosis).

Chemotaxis

attraction to chemicals from damaged tissues, complement proteins, or microbial products

myeloid stem cells

begin their development in red bone marrow and give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils, and basophils

Fibroblasts

connective tissue cells that produce fibrous components of extracellular matrix like collagen and elastin

Chronic inflammation

inflammation of prolonged duration or slow progress marked histologically by an infiltration of mononuclear cells (lymphocytes, macrophages, plasma cells) often with proliferation of fibroblasts and fibrosis

Acute Inflammatory Response

omplete elimination of pathogen mainly by neutrophils with little tissue damage. The cell is injured, which causes mast cell degranulation, activation of the three plasma proteins, and the release of subcellular components of the damaged cell, which results in vasodilation, vascular permeability, cellular infiltration, thrombosis, and stimulation of nerve endings

erythemia

redness of the skin; may be caused by capillary congestion, inflammation, heat, sunlight or cold temp or embarrassment

Vascular Phase

-cut of vessels causes local construction of the vessel to reduce blood loss [vascular spasm] -endothelial cells release chemical factors and hormones

Band neutrophils

-immature neutrophil -neutrophil released from bone marrow before mature -has horseshoe nucleus w/o segmentation -indicates increased demand for neutrophils beyond what bone marrow can supply in mature neutrophils -bands cannot defend the body

Stages of inflammation

1. neutrophils respond first 2. Macrophages (mature monocytes). Immediate responders replace neutrophils (don't die out). Aquired immunity. Self-recognizing. 3. Basophils (cause manifestation of imflamation). Granulocytes that have chemicals,(heparin, histmine) 4. Eosinophils-parasites. Contain enzymes that breakdown vasoactive substances from other leukocytes (increase during allergic reactions). 5. Mast cells 6. Cytokines

Complement System

2nd line of defense A group of about 30 blood proteins that may amplify the inflammatory response, enhance phagocytosis, or directly lyse pathogens (punch holes in them). The complement directly lyses pathogens. The complement system is activated in the cascade initiated by surface antigens on microorganisms or by antigen-antibody complexes.

Monocyte

2nd line of defense A relatively large phagocytic white blood cell that circulates in the bloodstream and has a single ovoid nucleus. Once these cells migrate into the tissues from the blood, they become macrophages. They phagocytize large particles/debris.

Interferons

2nd line of defense Cell-mediated immunity (Viruses) Cytokines that help cells to resist viral infection. Interferon-α (IFN-α) and interferon-β (IFN-β) are produced by leukocytes and fibroblasts respectively, as well as by other cells, whereas interferon-γ (IFN-γ) is a product of CD4 THelper1 cells, CD8 (suppressors) T cells, and NK cells (no activation required). IFN-γ acts principally to activate macrophages.

Natural Killer Cells

2nd line of defense Large, granular, cytotoxic lymphocytes that circulate in the blood. NK cells are important in innate immunity to viruses and other intracellular pathogens and also kill certain tumor cells. They are the cytotoxic cells in antibody-dependent cell-mediated cytotoxicity (ADCC).

Extracellular Killing

2nd line of defense fight microbes without ingesting them, eosinophils and NK lymphocytes kill pathogen without phagocytizing them

Inflammatory Response

2nd line of defense tissue damage causes release of histamines- which cause blood vessel dialation (makes them leaky) ->increases wbc # and allows the wbc into damaged area->macrophages and neutrocils undergo phagocytosis and platelets clump

Fever

2nd line of defense An abnormally high body temperature that occurs during infection and inflammation (cytokine production) which intensifies the effects of interferons, inhibits growth of microbes, and speeds up body reactions that aid repair

Eosinophil

2nd line of defense-Extracellular Killer A type of white blood cell with low phagocytic activity that is thought to reduce some allergies and play a role in defense against parasitic worms by releasing enzymes toxic to these invaders.

Neutrophils

2nd line of defense-Phagocytes. (1 of 2) 55-75% of WBC. The most abundant type of white blood cell. Neutrophils are phagocytic and tend to self-destruct as they destroy foreign invaders, limiting their life span to a few days. Only mature neutrophils can phagocytize (seg, ploymorphic). Non-specific immunity defense.

Macrophages

2nd line of defense-Phagocytes. (1 of 2) Found within the lymph nodes, they are phagocytes that destroy bacteria, cancer cells, and other foreign matter in the lymphatic stream.

Phagocytes

2nd line of defense. Neutrophils, Eosinophil, Monocytes and Macrophages. These are Leukocytes that are Chemotactic. They marginate, then eat away the pus and other foreign particles.

Granuloma

A collection of inflammatory cells commonly surrounded by fibrotic tissue that represents a chronic inflammatory response to infectious or noninfectious agents

Inflammation

A general term for the local accumulation of fluid, plasma proteins, and white blood cells that is initiated by physical injury, infection, or a local immune response. This is also known as an inflammatory response. The cells that invade tissues undergoing inflammatory responses are often called inflammatory cells or an inflammatory infiltrate.

Complement

Able to destroy foreign invaders at first sight. Marks invaders for destruction OR Kills them by poking holes in cell membrane. Opsonization

Immunity

the body's capacity for identifying, destroying, and disposing of disease-causing agents.

Acquired Immunity

Antibody mediated and cell-mediated immunity. Developed through injections of antigens which build the body's immune system, it can be acquired by overcoming the disease naturally.

Humoral Immunity

B-cells produce by lymphoid stem cells. Wait to be called to action. They are sensitized to a specific foreign antigen and produce an antibody. First, b cells must be introduced to antigens. Secondly, they have to recognize invaders. Helped by T cells and macrophages. Once sensitizedspecific immunity produced by B cells that produce antibodies that circulate in body fluids

lymphoid stem cells

Begins in the bone marrow but mature in lymphoid tissue. Give rise to lymphocytes, lymphoid stem cells develop into B and t lymphocytes

Purulent Exudate

Discharge resulting from infection; also called pus. Can be yellow, brown or green. Occurs with severe inflammation accompanied by infection. Process of pus formation is called suppuration.

Up to 30 days and they can be transferred to other people. Hepatits A for passive immunity injected.

How long do antibodies circulate?

Plasma cells

Immunoglobulins (IGM) made first in response to a pathogen (chickenpox IGG-long term protection IGE-parasites IGA-protect against portal of entry (nodes to prevent chickenpox)

Fibrinous Exudate

In more severe or advanced inflammation, the exudate may be thick or clotted, such as in the lungs of individuals with pneumonia.

Hemorrhagic Exudate

Indicates bleeding. aka Sanguineous Exudate. This has a large component of RBC's (erythrocytes) because of capillary damage. This is usually present with severe inflammation. Color is bright red verses dark red. This reflects whether the bleeding is fresh or old.

Cellular components of inflammation

Leukocytes, neutrophils (1st responders),

Macrophages

Mature monocytes that live in tissues (fixed) or wander. They are immediate inflammatory response. Replace neutrophils

Chemotaxins

Messaging molecules that attract phagocytes to a site of infection. C5a, leukotriene B4, chemokines, bacterial lipids & proteins

Serous Exudate

Occurs early on in inflammation. (blister) inflammatory material composed of serum (clear portion of blood) derived from the blood and serous membranes of the body such as the peritoneum, pleura, pericardium, and meninges; watery in appearance and has few cells

Human Leukocyte antigens

unique universal product code for each person, present on nearly all body surfaces, not just leukocytes. Determine the tissue type of a person

Phagocytosis

Process by which a cell ingests and disposes of foreign material. Neutrophils & Macrophages most efficient at phagocytosis Key Words Chemotaxins-Messaging molecules that attract phagocytes to a site of infection. C5a, leukotriene B4, chemokines, bacterial lipids & proteins Opsonins-Proteins that coat pathogens so phagocytes recognize and ingest them. These could be antibodies, acute phase proteins, and complement proteins.

cytokines

Proteins that are secreted that signal other cells to induce or inhibit the inflammatory process. Interleukins Interferons chemicals released by T helper cells that stimulate B cells

Opsonins

Proteins that coat pathogens so phagocytes recognize and ingest them. These could be antibodies, acute phase proteins, and complement proteins.

Fever High WBC count Fatique Body Aches

Systemic Manifestations of inflammation

Opsonization

The coating of the surface of a pathogen or other particle with any molecule that makes it more readily ingested by phagocytes. Antibody and complement opsonize extracellular bacteria for phagocytosis by neutrophils and macrophages because the phagocytic cells carry receptors for these molecules.

Antibody mediated immunity

The production of antibodies by B cells in response to an antigen. Also called humoral immunity. Consists of B cells that transform into plasma cells which secrete specific proteins directed against extracellular pathogens