Ch 14 Basic Concepts of Immunity and Inflammation

We are surrounded by millions of microorganisms! Our hands are covered by up to _ million microorganisms

2

We survive by developing a protective defense system that is very effective at….

recognizing and fighting disease-causing microorganisms

Immune System’s Two Subdivisions:

1. innate immune system

2. adaptive immune system

Innate Immune System:

• present at birth

• not antigen specific

• always present

• does not improve with repeated exposures to infectious agents

Adaptive Immune System:

• develops throughout life

• antigen specific

• there is a lag time between infection and response

• develops a memory, which may provide lifelong immunity to reinfection by the organism

Immune Response:

defends us by identifying foreign substances in the body and developing a defense against them

Host Response:

The way an individual’s body responds to infection, attack, or invasion

Host Response: The body responds by…

Sending certain cells to the infection site.

• Producing biochemical substances to counteract foreign invaders

Loss of Immune Function Can Lead to _________ or Even _____

Illness, death

Examples of loss of immune function:

HIV/AIDS

• HIV disables a specific group of immune cells. (CD4 white blood cells)

HIV+ individuals often develop life-threatening infections from microorganisms that:

rarely cause infections in persons with healthy immune systems.

Overzealous Immune System:

The immune system can become so intense in its response that it begins to harm the body it is trying to protect

ex. autoimmune diseases

An overzealous response occurs in __________.

periodontitis

Immunodeficiency:

The immune system fails to respond adequately

Immunocompromised:

A person suffering from immunodeficiency.

Autoimmune response:

• The opposite condition.

• An overactive immune system attacks healthy cells as though they are foreign bodies and destroys them by mistake.

Common Autoimmune Disorders:

There are more than 80 known autoimmune disorders.

• Rheumatoid arthritis

• Psoriatic arthritis

• Diabetes

• Lupus

• Multiple sclerosis

• Addison’s disease

• Celiac disease

• Graves disease

• Hashimoto thyroiditis

• Myasthenia gravis

• Crohn’s disease

(AKA Inflammatory bowel disease)

In addition to many diseases and disorders, the immune system can also be weakened by:

• smoking.

• poor nutrition.

• excess alcohol

What happens when a person is immunocompromised?

• They are more likely to get sick.

• Their symptoms tend to be more severe.

• They tend to stay sick longer.

Components that play an important role in combating periodontal disease:

• Cellular defenders (phagocytes, lymphocytes)

• Complement system

Leukocytes:

• White blood cells that capture microorganisms on their own.

• PMNs (Neutrophils) (short life-span)

• Monocytes/Macrophages (long-life span)

Lymphocytes:

• Small white blood cells that reorganize and control invaders.

• B-lymphocytes (B-cells)

• T-lymphocytes (T-cells)

Phagocytosis:

The process by which leukocytes engulf and digest microorganisms

Polymorphonuclear Leukocytes (PMNs):

• Also called neutrophils.

• Rapid responders, provide the 1st line of defense.

• Capture and destroy bacterial invaders.

• Short-lived (~ 5 days) cells that die when they become engorged with bacteria.

PMNs are attracted to bacteria by a process called ______

chemotaxis

PNS contain ______

• strong bactericidal and digestive enzymes

lysosomes

Periodontal pathogens are most effectively destroyed by ____

PMNs

Monocytes/Macrophages:

• Called monocytes when in the bloodstream.

• Called macrophages when in the tissues.

• Slower to arrive at the infection site than the PMNs.

• Surround and destroy bacteria.

• Long-living cells seen in chronic inflammation.

Lymphocytes are small ______ that help defend the body and originate in the bone marrow

leukocytes

Two main types of Lymphocytes:

• B-lymphcytes (B-cells)

• T-lymphocytes (T-cells)

B-Lymphocytes (B-Cells):

Once activated, makes millions of antibodies and pours them into the bloodstream. (Their primary function.)

Can differentiate into 2 types of B-cells

• Plasma B-cells

• Memory B-cells

Antibodies:

Y-shaped proteins

• One end of the Y binds to the outside of the B-cell.

• The other end of the Y binds to a microorganism and helps to kill it.

• Coat bacteria to aid in phagocytosis

• Neutralize bacteria toxins to prevent the host cells from being destroyed.

Antibodies are known collectively as ________

immunoglobulins

Five major classes of immunoglobulins are:

1. Immunoglobulin M (IgM)

2. Immunoglobulin D (IgD)

3. Immunoglobulin G (IgG)

4. Immunoglobulin A (IgA)

5. Immunoglobulin E (IgE)

T-Lymphocytes (T-Cells) main function is to….

intensify the response of other immune cells (macrophages, B-lymphocytes) to the bacterial invasion

T-cells produce substances called ________ that further stimulate the immune response

cytokines

Cytokine:

A general name for any protein that is secreted by cells and

affects the behavior of nearby cells.

Complement System:

A complex series of proteins circulating in the blood that work to

• facilitate phagocytosis of bacteria.

• kill bacteria directly by forming pores in bacterial cell membranes.

• antibodies activate

Complement System (CS):

Provides a second layer of defense in case pathogens are able to avoid contact with immune cells

Functions of Complement System:

• Destruction of pathogens.

• Opsonization of pathogens.

• Recruitment of phagocytes.

• Immune clearance.

Functions: Destruction of Pathogens

• Components of complement can destroy certain

microorganisms forming pores in their cell membranes.

• For this task, the complement system creates a protein called the membrane attack complex.

• This protein punctures cell membranes of certain bacteria, known as “lysis.”

Opsonization of pathogens:

• The complement system facilitates the capture and

destruction of bacteria/pathogens by phagocytes.

• Opsonization is the MOST IMPORTANT ACTION of the

complement system.

• Complement components coat the surface of bacteria,

allowing the phagocytes to recognize, engulf, and destroy

bacteria.

Recruitment of Phagocytes:

The complement system recruits additional phagocytic cells to the site of an infection

Immune Clearance:

The complement system acts as a “housekeeper” for the body by removing immune complexes from circulation

Activities of the Complement System(Recruitment/activation)

1. Proteins are small red triangles.

2. Poke holes in the bacteria to kill it (lysis)

3. Opsonization- phagocyte eats the bacteria to get rid of it

4. Initiates more phagocytes to come into the area of infection

5. The phagocytes clear out the immune complexes from circulation.

Leukocyte Migration to the Tissues":

• Near the infection site, leukocytes push their way between the endothelial cells and enter the connective tissue.

• This process is called transendothelial migration.

Chemotaxis is the process whereby leukocytes:

• enter the connective tissues.

• are attracted to the site of the infection in response to biochemical compounds released by the invading bacteria

Phagocytosis:

The process by which leukocytes (AKA neutrophils) surround and digest microorganisms

Inflammatory Biochemical Mediators:

Biologically active compounds secreted by cells that activate the

body’s inflammatory response

Mediators of importance in periodontitis include:

• Cytokines – cell signalers

• Prostaglandins (fatty acid in the blood)

• Matrix metalloproteinases (enzymes that can break down protein)

Cytokines=

cell signalers

Leukocytes secrete _______ that play a major role in regulating the behavior of immune cells

cytokines

Chemokines:

a subgroup of cytokines—cause additional immune cells to be attracted to the site of an infection/injury.

• Best known for their ability to stimulate the migration of cells.

Two Stages of Inflammation:

• Acute inflammation

• Chronic inflammation

Acute Inflammation:

• Short-term process that protects and heals the body.

• Increase of plasma and leukocytes from the blood into the injured tissues

Five Classic Signs of Acute Inflammation:

• Heat: Increase in temperature due to increased blood at the site.

• Redness: Increased blood in the area

• Swelling: Accumulation of fluid (plasma and leukocytes) at the site.

• Pain: Pressure from edema and excess fluid.

• Loss of function: Result of edema and pain.

The Acute Inflammatory Response:

• Blood vessels near the infected site become more permeable.

• PMNs are the first cells to arrive at the site.

• PMNs release cytokines.

• The liver produces C-reactive proteins (CRP).

• If the body succeeds in eliminating all the microbes, healing takes place and inflammation ceases. C-Reactive Proteins elevated in periodontitis

Chronic Inflammation:

• Long-term inflammatory response that continues for more than a few weeks.

• A pathologic condition that can destroy healthy tissue and cause more damage than the original problem.

• Classic warning signs seen in acute inflammation usually are absent in chronic inflammation.

• Frequently there is no pain.

• The problem may go unnoticed by the host.

Why Does Chronic Inflammation Occur?

• The body is unable to rid itself of the invading organisms.

• The invading microorganisms are persistent and stimulate an

exaggerated immune response.

• The inflammatory response can become so intense that it does

permanent damage to the body tissues.

The Chronic Inflammatory Process:

• Characterized by an accumulation of macrophages.

• Macrophages engulf and digest microorganisms.

• Leukocytes release several inflammatory mediators that

perpetuate the inflammatory response.

• Tissue damage is a key factor in chronic inflammation.

Examples of Chronic Inflammation:

• Rheumatoid arthritis

• Diabetes (Types 1 & 2)

• Asthma

• Periodontal diseases

• Ulcerative colitis

• Crohn’s disease

• Lupus

• Fibromyalgia

• Autoimmune diseases

Remission:

Signs and symptoms of chronic inflammation may partially or

completely disappear during periods of remission

Exacerbation:

Signs and symptoms recur during active periods.

Biochemical mediators:

• Biologically active compounds.

• Secreted by cells that activate the body’s inflammatory response

Important biochemical mediators include

IL-1, IL-6, IL-8

• Responsible for activating PMNs, T-cells, B-cells and C-reactive

proteins. (The immune response team.)

Leukotrienes:

• Inflammatory chemicals the body releases after contact with an allergen.

• Cause tightening of airway muscles.

• Cause excess mucus and fluid.

Prostaglandins:

• Hormones created during a chemical reaction at the site of the injury.

TNF-α:

• Triggers the production of several immune system molecules, including IL-1 and IL-6.

• IL-1 and IL-6 are involved in destroying cartilage and bone.