Human Body's First Line of Defense: Physical, Chemical, and Cellular Barriers

1) Physical Barriers Against Infection

Physical barriers are crucial in preventing microbes from reaching susceptible tissues.

Cellular Contributions to Physical Barriers

At the cellular level, tightly joined cells form barriers, preventing invaders from penetrating deeper tissues.

Microbial Evasion of Physical Barriers

Pathogens may use enzymes like proteases to damage physical barriers and gain entry.

2) Layers of Human Skin

Human skin has three layers:

1. Epidermis: Outer layer containing keratin (prevents microbial entry).

2. Dermis: Middle layer with hair follicles, sweat glands, nerves, and blood vessels.

3. Hypodermis: Inner layer with fatty tissue, blood, and lymph vessels.

Significance of Keratin, Fatty Acids, and Skin Shedding

• Keratin: Tough, protective protein against microbes.
• Fatty acids: Create a dry, salty, acidic environment hostile to microbes.
• Shedding: Removes dead cells and attached microbes.

3) Mucous Membranes

Location: Found in the respiratory, gastrointestinal, urinary, and reproductive tracts.

Protection by Mucous Membranes

Protection: Mucus traps pathogens, and cilia propel microbes away (mucociliary escalator).

Mucociliary Escalator Function

The mucociliary escalator is a physical removal system where mucus and cilia work together to clear pathogens.

4) Endothelia

Endothelia are epithelial cells lining blood vessels, lymphatic vessels, and other tissues.

Endothelial Protection

Endothelia (e.g., blood-brain barrier) protect sensitive areas like the brain and spinal cord from pathogens.

5) Mechanical Defenses

Mechanical defenses physically remove pathogens:

• Coughing
• Sneezing
• Washing of tears and saliva
• Urination
• Defecation
• Skin shedding

6) Resident Microbiota Protection

Resident microbiota prevent pathogen attachment and proliferation by competing for binding sites and nutrients.

Antibiotic Disruption of Microbiota

Eliminating normal microbiota with antibiotics increases susceptibility to infections.

7) Chemical and Enzymatic Mediators

(a) Skin (Dermis): Fatty acids, sweat, and enzymes (like lysozyme) kill microbes.

(b) Digestive, Urinary, Respiratory, and Reproductive Systems: Enzymes, acidic pH, mucus, and antimicrobial substances protect against pathogens.

(c) Eyes and Ears: Tears and earwax contain enzymes and antimicrobial peptides.

Environmental Factors and Susceptibility

Low humidity and reduced skin oil increase skin vulnerability to infections.

8) Antimicrobial Peptides (AMPs)

AMPs are small proteins that damage microorganisms by disrupting membranes, interfering with metabolism, etc.

AMP Mechanisms of Action

AMPs disrupt cell membranes, interfere with cell wall synthesis, inhibit protein synthesis, and induce DNA damage.

AMPs as Nonspecific Defenses

AMPs are considered nonspecific defenses due to their broad-spectrum antimicrobial properties.

9) Plasma Proteins in Innate Immunity

Plasma proteins involved in innate immunity include:

• Complement proteins
• Clotting factors
• Antibodies

Complement System

The complement system is a group of proteins that destroy pathogens, promote inflammation, and enhance phagocytosis.

Complement Proteins in Innate Immunity

Complement proteins are part of innate immunity because they act nonspecifically against pathogens.

Opsonization

Opsonization: Coating pathogens with proteins to enhance phagocytosis.

10) Phagocytes

Phagocytes are white blood cells that engulf and destroy pathogens.

Phagocytes in Innate Immunity

Phagocytes are critical in innate immunity as they remove pathogens.

Extravasation (Diapedesis)

Extravasation: Phagocytes move from blood vessels into tissues to fight infection.

11) Pathogen-Associated Molecular Patterns (PAMPs)

PAMPs are molecules on pathogens recognized as foreign by the immune system.

Pattern Recognition Receptors (PRRs)

PRRs on phagocytes bind to PAMPs, triggering immune responses.

12) Stages of Phagocytosis

Phagocytosis stages:

1. Recognition & Attachment of the pathogen.
2. Engulfment of the pathogen into a phagosome.
3. Fusion with lysosome to form a phagolysosome.
4. Digestion of the pathogen.
5. Exocytosis of waste material.

Phagosome vs. Lysosome

Phagosome: Vesicle containing the ingested pathogen.

Lysosome: Contains digestive enzymes to break down the pathogen.

13) Signs of Inflammation and Fever

Five signs of inflammation:

1. Redness (increased blood flow)
2. Heat (increased blood flow)
3. Swelling (fluid accumulation)
4. Pain (tissue damage or pressure)
5. Loss of function (swelling or pain)

Advantages and Risks of Inflammation

Inflammation helps fight infection but can cause tissue damage if chronic.

Acute vs. Chronic Inflammation

Acute: Short-term, beneficial response.

Chronic: Long-term, potentially harmful.

Granuloma

Granuloma: A chronic inflammation where tissue isolates the pathogen (e.g., tuberculosis).