PERIO W12/13 Basic Concepts of Immunity and Inflammation; Host Immunoinflammatory Response to Biofilm

Compare and contrast Innate vs Adaptive Immunity

Innate Immunity

• Onset: Immediate, non-specific.

• Cells: Neutrophils, macrophages, dendritic cells, NK cells.

• Mechanisms: Phagocytosis, inflammation, complement system, physical barriers.

• Memory: None. Responds the same way every time.

Adaptive Immunity

• Onset: Delayed (days), antigen-specific.

• Cells: B lymphocytes (antibody production), T lymphocytes (helper, cytotoxic).

• Mechanisms: Antigen presentation, clonal expansion, antibody-mediated and cell-mediated responses.

• Memory: Yes. Faster, stronger response upon re-exposure.

Comparison

• Work together: innate provides first line + presents antigens to activate adaptive.

• Innate = broad defense; adaptive = targeted, long-lasting protection.

The body’s response to infection is called? What is it’s main purpose?

Host response → to defend the life of the host by identifying foreign substances in the body.

The immune system can become so intense that its response harms the host body while trying to protect the host. What is an example?

Rheumatic Heart disease

• Invasion of Streptococcus pyogenes (strep throat bacteria)

• Immune system acts against it by releasing cytokines

• some structures in heart tissue are similar to s.pyogenes so the immune mediators attack the cardiac tissue.

What are the functions of Polymorphonuclear leukocytes (PML)?

1. Phagocytosis

2. Release lysosomes

3. Release powerful regulatory proteins (cytokines) that signal the immune system to send additional phagocytic cells to the site of infection

PML = Neutrophil, Eosinophil, Basophils

What are the functions of Macrophages?

1. Phagocytosis

2. Release of Lysosomes

3. Release cytokines to call additional phagocytic cells to site of infection

What are the functions of B-lymphocytes and T-lymphocytes?

B-cells → production of immjunoglobulins

T-cells → amplify the immune response 

What are the functions of Immunoglobulins?

1. Neutralize bacteria or bacterial toxins

2. coat bacteria to facilitate phagocytosis

3. Activate complement system.

What are the functions of the Complement System?

1. Lysis of cell membranes of certain bacteria

2. Recruitment of additional phagocytic cells

3. Clearance of immune complexes from circulation

Leukocytes are categorized according to the presence or absence of…?

Cytoplastic granules

1. Agranulocytes → lymphocytes and monocytes/macrophages

2. Polymorphonuclear leukocytes (PML) → does not include mast cells (mononuclear)

Describe Fx of Neutrophils AKA polymorphonuclear neutrophils (PMNs) 

1. First immune cells deployed → Rapid responders providing first line of defense

2. Most abundant 

3. Can pass through capillary wall through chemotaxis 

4. Short-lived cells → die when they are engorged with bacteria 

5. contains bactericidal digestive enzymes 

Describe Fx of Eosinophils

1. Primarily combat parasitic infections

2. Collaborates with mast cells and basophils to regular allergic response

Describe Fx of Basophils

1. Primarily involved with allergic response

2. Coordinates activity against immune diseases

Describe Fx of Mast cells

1. Protects against pathogens and

2. Releases key inflammatory mediators that modulate allergic response

Which immune cell has a single irregular, kidney-shaped nucleus, lacks granules and performs phagocytosis?

Monocytes

Describe Lymphocytes. What are the 3 types?

1. B-lymphocytes (B-cell)

2. T-lymphocytes (T-cell)

3. NK-Lymphocytes (Natural Killer cell)

What are the 2 subclasses of B-cells? What are their functions?

1. Plasma B-cell → produces antibodies

2. Memory B-cell → remembers previous exposures

Describe Antibodies.

Y-shaped proteins composed of:

• FAB = fragment antigen binding region

• Fc = fragment constant → tail end that binds to immune cells and proteins of complement system.

**Antibodies are also called immunoglobulins.

What are the 5 major classes of Immunoglobulins?

Ig M, D, G, A, E, 

(my dentist gave me an exam) 

Which immunoglobulin is the only one that can pass through placental barrier? It is also the most abundant antibody.

IgG - potent activator of complement system; responds to invading pathogens.

Which is the largest antibody that has a pentamer structure and the first to respond to initial exposures to antigens in blood and lymph?

IgM

Which Immunoglobulin can pass through breast milk to the baby and is the principal defense at mucosal barriers

IgA

Which Immunoglobulin is involved with allergic response?

IgE

Which Immunoglobulin is the least abundant and least understood antibody?

IgD

How do antibodies eliminate invading agents?

Antibodies will coat the target, marking the foreign substance for immune cells to phagocytose.

• Also activates the complement system.

What are the 4 subtypes of T-cells?

1. T-helper (CD4) → regulates b-cell maturation

2. T-cytotoxic (CD8)  → directly attacks pathogens by releasing perforin (destroys plasma membrane of target cells) 

3. T-memory (Tm-lymphocyte) → remembers past exposures

4. NKT (natural killer T) → first line defense against some bacterial and viral infections; attributes of innate and adaptive immunity

How are NK-Lymphocytes different from NKT-lymphocytes?

1. NK cells are part of the INNATE immunity

2. NK-Cell mature and develop in circulation

3. NK-cell DO NOT require pre-activation.

4. NKT-cells are bridge the innate and adaptive immune system

5. NKT-cells secrete cytokines to modulate immune response

6. NKT-cells require activation.

What is the complement system?

Complement system is composed of inactive, non-nucleated proteins that patrol the body for potential invaders. 

• They directly or indirectly neutralize them upon exposure to invaders

• Work together with antibodies and phagocytes to neutralize pathogens

Fx: 

• Destruction of pathogens

• Opsonization of pathogens

• Recruitment of phagocytes

• Immune clearance 

The complement system creates a protein called ____ to destroy MO by forming pores in their cell membranes.

membrane attack complex (MAC)

What is opsionization?

opsonization = capture and destruction of bacteria by phagocytosis completed by the complement system.

**it is the most important action of the complement system.

Describe the function of immune clearance by the Complement system.

Immune clearance = removing immune complexes from circulation as an act of “house keeping”

Which immune cells are important for the control of Periodontal disease?

1. PMNs

2. Macrophages

3. B-cells

4. T-cells

What is Chemotaxis?

The process in which leukocytes migrate towards the infection site in response to bioactive compounds released by leukocytes. 

• Swarm like migration pattern of neutrophils. 

List the 5 steps of Phagocytosis.

1. Bacteria get attached to Phagocyte pseudopedia (membrane extensions)

2. bacteria get ingested forming a phagosome

3. Phagosome fuses with Lysosome

4. Lysosomal enzymes digest captured material

5. Digested products are released from the cell.

What is the purpose of Inflammation?

Increase blood flow to deliver immune defending cells to the site of infection/invasion.

1. Dilation of blood vessels

2. Increased permeability of blood capillaries

3. Leukocyte migration into tissues

Describe the symptoms of Acute inflammation.

• heat

• redness

• swelling

• pain

• loss of function

• short-lived

The acute inflammatory response process is initiated by…?

blood vessels near injured tissue

Why does chronic inflammation occur?

1. occurs when acute inflammatory response was not effective in eliminated the invading MO.

2. Immune response is defective or aggravated

What are the unique signs of chronic inflammation in comparison to acute inflammation?

Chronic inflammation:

• Classic inflammatory signs are absent

• clinically no pain

• Problem may go unnoticed by the host

• prolonged inflammation can result in varying degrees of tissue injury

What are the 4 chronic inflammation mediators?

1. IL1, IL6, IL8 (cytokine) 

2. Leukotrienes

3. Prostaglandin

4. TNF-Alpha (cytokine) 

What are the effects of IL-1 as a inflammatory biomechanical mediator?

• increased vascular permeability

• T-cell and B-cell activation

• Fever

What are the effects of IL-6 as a inflammatory biomechanical mediator?

• increased vascular permeability

• T-cell and B-cell activation

• Fever

• Increased immunoglobulin synthesis

What is the effect of IL8 as a inflammatory biomechanical mediator?

Attraction of neutrophils (PMNs) to infection site 

What is the effect of Leukotrienes as a inflammatory biomechanical mediator?

Allow leukocytes to exit the blood vessel and move into CT

What is the effect of Prostaglandin as a inflammatory biomechanical mediator?

• Causes Vasodilation (increasing permeability/increasing blood flow)

• fever and pain

• trigger osteoclasts to destroy alveolar bone

• promote overproduction of MMP enzymes (destructive)

What is the effect of TNF-alpha as a inflammatory biomechanical mediator?

• Increased vascular permeability

• Chemotaxsis

• T-cell and B-cell activation

• Fever

• Systemic effects of inflammation such as loss of appetite, increased HR.

What are some examples of disease conditions associated with chronic inflammation? (7)

1. Rheumatoid arthritis

2. Diabetes

3. Neurological disorders

4. Cardiovascular disease

5. Asthma and COPD (Chronic obstructive pulmonary disease)

6. Gingivitis

7. Periodontitis

T or F - The presence of periodontal pathogens is sufficient to cause tissue destruction seen in periodontitis.

F - Presence of periodontal pathogens alone is INSUFFICIENT to cause tissue destruction seen in periodontitis.

The host immunoinflammatory response is the direct cause of nearly all destruction seen in periodontal disease

T or F - the host’s defences are employed to save the life of the host and NOT to preserve the tooth or its supporting periodontal structures.

T

What is virulence factor?

Virulence factor is the mechanism that enable biofilm bacteria to colonize and damage tissue of periodontium. 

Examples:

• lipopolyssachride (LPS) presence on bacteria membrane

• bacterial ability to invade 

• bacterial ability to produce enzymes (acid to weaken enamel) 

Which cells are involved in host response to acute inflammation?

1. inflammatory cells

2. PMNs

3. Antigen-presenting cels

4. T and B cells

5. Gibroblasts

6. Epithelial cells

What is Catabasis?

Catabasis is the return to homeostasis after inflammatory process

What are the proinflammation mediators in periodontitis?

1. Prostaglandins

2. Thromboxane

3. Prostacyclin

4. Leukotrienes

What are pro-resolving lipid mediators?

AKA shut-down mediators 

They work to:

1. terminate PMN recruitment

2. stimulate macrophages to remove dead cells

3. Promote antibacterial activities

4. Promote tissue repair and regeneration

What are biochemical mediators? What are the 3 most important ones?

Biochemical mediators are biologically active compounds secreted by immune cells that activate the bodys inflammatory response

Most important BMs:

1. Cytokines

2. Prostaglandins

3. Matrix Metalloproteinases (MMPs)

Which biochemical mediator is capable of initiating and perpetuating irreversible tissue destruction and bone loss in chronic inflammatory diseases?

Cytokines → IL1, IL6, IL8, TNF-alpha 

Which prostaglandins types are important? Which one specifically plays a role in bone destruction in periodontitis?

Prostaglandin types: D, E, F, G, H, I

Prostaglandin E (PGEs) = bone destruction in periodontitis.

Which immune cells produce MMP (matrix metalloproteinases)? What is its function? 

• PMNs

• Macrophages, Gingival fibroblasts

• JE cells 

Fx: enzyme that acts together to break down CT matrix. 

______ balance helps maintain the integrity and health of connective tissue.

MMP-TIMP relationship

TIMP = tissue inhibitors of matrix metalloproteinases

• TIMP regulates MMP

Overproduction of MMPs result in ?

results in breaking down of the connective tissue in the periodontium.

• High MMP levels = extensive collagen destruction

Summarize the biomechanical mediators local effects in Periodontitis.

1. IL1 → stimulate osteoclast activity causing bone resorption; break down collagen matrix in periodontium

2. IL6 → stimulates bone resorption and inhibits bone formation

3. IL8 → stimulates CT destruction and bone resorption

4. TNF-alpha → stimulates bone resorption; break down collagen matrix in periodontium

5. PGE → stimulates MMP secretion and bone resorption

6. MMP enzymes → induces break down of collagen matrix in periodontium

What are the 4 Histologic stages of Periodontal Disease development?

Initial Lesion AKA Bacterial Accumulation (2–4 days)

• Acute inflammation, vasodilation, ↑ neutrophils, ↑ gingival crevicular fluid.

• Clinically: gingiva looks healthy

• Host response successful if most bacteria destroyed (gram neg) 

Early Lesion AKA Early Gingivitis (4–7 days)

• Forms “wall of cells” between biotilm and sulcus wall, releasing more cytokines

• Macrophages recruited 

• JE proliferates, SE forms epithelial ridges 

• Clinically: inflammatory changes, erythema, edema, bleeding on probing.

Established Lesion AKA Established gingivitis  (21-days after biofilm acc.)

• JE loosens attachment to root surface, being to form pocket epithelium 

• Clinically: chronic gingivitis, persistent inflammation, bleeding.

• Patient education is vital in controlling bacterial challenge 

Advanced Lesion AKA Periodontitis (no specific date) 

• Plaque biofilm grows laterally and apically along root surface 

• Irreversible tissue destruction by PGE2 (destroy alveolar bone) 

• Clinically: periodontal pocket formation, BOP, Periodontium destruction, furcation, tooth mobility 

• Chronic infection induces chronic inflammation = more damage to periodontium