Innate Immunity

Immune System & Responses

• Immune Responses

  • Immune Response Definition:

  • A physiological process coordinated by the immune system to eliminate antigens (foreign molecules).

Our immune system includes two key branches:

• Innate Immunity (inborn/ specific)

  • Generalized responses exemplified by skin and specialized cells.

  • Nonspecific immunity.

• Adaptive Immunity

  • Matures over time (acquired).

  • Exhibits memory (e.g., vaccines or exposure to antigens)

• Common Features of Both Immunities:

  • Recognize diverse pathogens.

  • Eliminate identified invaders.

  • Discriminate between self and foreign antigens.

  • Demonstrate self-tolerance.

• Three Lines of Defense

  • Barrier- 1st line of defense

  • Cellular and Molecular- 2nd line of defense

  • Adaptive- 3rd line of defense

11.2 Introduction to First-Line Defenses

• First-Line Defenses aim to prevent pathogen entry.

• Subcategories of First-Line Defenses:

  • Mechanical barriers.

  • Chemical barriers.

  • Physical barriers.

Mechanical Barriers

• Rinse, flush, or trap pathogens to limit their spread into the body.

Examples:

• Tears wash debris/pathogens and microbes from the eyes.

• Urine flushes microbes out of the body.

• Saliva limits microbe adherence.

• Mucus membranes trap microbes; line all body entrances and internal organs such as the stomach, intestines, lungs, and bladder.

• Mucociliary escalator sweeps pathogens away from the lungs toward the mouth by ciliated cells.

• In the respiratory tract, mucus traps invaders and cilia sweep them away

Chemical Barriers

• Directly attack invaders or create environments that limit pathogen survival.

Examples:

• Lysozyme: Found in secretions (e.g., tears, breast milk), breaks down bacterial cell walls.

• Hydrochloric acid in the stomach limits pathogens.

• Skin is relatively dry, salty, and slightly acidic.

• Fatty acids in sweat and earwax.

• Antimicrobial peptides (AMPs): Proteins that destroy a wide spectrum of viruses, parasites, bacteria, and fungi.

• AMPs stimulate leukocytes and directly target pathogens

Physical Barriers

• Include structures that physically block pathogen entry.

Examples:

• Epithelial tissue: A main physical barrier in animals that lines every body cavity and entrance.

• Skin: One of the most important physical barriers, epidermis is made up of tightly compacted dead epithelial cells (enriched with proteins and lipids, serving as a water-resistant layer).

Second-Line Defenses & the Lymphatic System

• Second-Line Defenses activate when first-line defenses are breached.

  • microbes breach effective first-line barriers.

  • Second-line defenses consist of assorted molecular factors and leukocytes (white blood cells).

• Lymphatic System

  • Collects, circulates, and filters body fluids.

  • Interconnected with and dependent upon the immune system.

  • Lymphatic system definition: A collection of tissues and organs that collect, circulate, and filter fluid in body tissues before returning it to the blood.

  • Lymph and Lymphatic Vessels:

  • As blood is delivered to tissues, some plasma exits the capillaries and becomes interstitial fluid and seeps into the small spaces becoming interstitial fluid

  • Lymphatic capillaries take up interstitial fluid

  • Lymph travels to lymph nodes.

  • Lymph is screened for pathogens and filtered before returning to the circulatory system.

  • Primary Lymphoid Tissues: thymus and bone marrow

  • Secondary Lymphoid Tissues: lymph nodes, spleen, tonsils, MALT

Molecular Second-Line Defenses

• Cytokines

  • Signaling proteins that facilitate cell communication and coordinate immune actions.

  • Most cells in the body can make and release at least one type of cytokine.

  • Cytokine storm: A cytokine response that may lead to severe tissue damage.

• Chemokines

  • are cytokines that act as signalling proteins, attracting white blood cells to areas where needed, inducing chemotaxis.

  • Over 40 known chemokines assist in various processes such as wound healing, blood vessel formation, lymphoid tissue development, and activation of both innate and adaptive responses.

• Interferons (IFNs)

  • Signalling molecules that signal pathogen detection, (particularly viruses or tumors).

  • Stimulate nearby uninfected cells to mount defenses and interfere with viral replication.

  • Many viruses can block interferon signaling in infected cells.

Complement System

• Complement system: Consist over 30 different proteins that work together in a cascade fashion. Mostly produced by the liver and circulate in the blood in an inactive form.

• When activated, a cascade of events enhances immune defenses.

• The complement proteins can be activated by three main pathways:

  • Classical Pathway

  • Alternative Pathway

  • Lectin Pathway

Outcomes of Complement Pathways

• All three pathways lead to the same three outcomes:

  • Opsonization: Tags invaders with complement proteins, enabling efficient clearance by phagocytic cells (marks pathogens for death via phagocytosis).

  • Formation of a membrane attack complex (MAC): Causes cytolysis by creating holes in the cell membrane, leading to cell lysis.

  • Inflammation: Complement proteins C3a and C5a recruit leukocytes from blood vessels to tissue. Leukocytes release factors that promote inflammation

11.6 Inflammation & Fever

• Inflammation and Fever are key protective innate immune responses.

• Upon threat detection, tissue cells and local leukocytes release chemical mediators, converging cellular defenses on the affected site.

• Inflammation and sometimes fever are triggered as part of this response.

Inflammation

• An essential part of the innate immune defense, critical for healing.

• Occurs during tissue injury, initiating blood-clotting cascades to curb blood loss and limit pathogen spread.

• Three main goals of inflammation:

  1. Recruit immune defenses to injured tissue.

  2. Limit the spread of infectious agents.

  3. Deliver oxygen, nutrients, and chemical factors essential for tissue recovery.

• Cardinal signs of inflammation:

  • Redness.

  • Pain.

  • Localized heat (not fever).

  • Swelling.

  • Possible loss of function.

Fever

• Abnormally high systemic body temperature (pyrexia), typically at least 37.5°C (or 99.5°F).

• Pyrogens: Fever-inducing agents, such as certain bacterial toxins (e.g., endotoxin (LPS)

• trigger cytokine release.

• Cytokines signal the hypothalamus to raise the body’s baseline temperature.

• Studies concerning fever suggest:

  • It enhances the antiviral effects of interferons.

  • Increases phagocyte efficiency.

  • Enhances leukocyte production.

  • Limits the growth of certain pathogens.

  • Promotes tissue repair.

• Critical temperature thresholds:

  • A fever of 40.5°C (or 105°F) that does not decrease with treatment is life-threatening; essential cellular enzymes and proteins begin to denature.

  • Body temperature over 43°C (or 109.4°F) is fatal.