Inflammation, Fever
& Complement
Explore the body's innate defense mechanisms: how inflammation isolates threats, fever accelerates healing, and the complement system destroys pathogens.
Anatomy & Physiology
What Is Innate Immunity?
Your body has two major lines of defense. The innate immune system is your rapid, non-specific first responder: it activates within minutes to hours and does not require previous exposure to a pathogen.
Inflammation
Localised response that recruits immune cells and isolates damaged tissue
Fever
Systemic rise in body temperature that inhibits pathogen growth
Complement
Cascade of plasma proteins that lyse pathogens and tag them for destruction
The Inflammatory Response
Cardinal Signs of Inflammation
Redness (Rubor)
Increased blood flow to the injured area via vasodilation
Heat (Calor)
Warm blood from the body core reaches the tissue surface
Swelling (Tumor)
Increased capillary permeability allows fluid to leak into tissue
Pain (Dolor)
Prostaglandins and bradykinin stimulate nerve endings
Key Chemical Mediators
1
Histamine: Released by mast cells; causes vasodilation and increased capillary permeability within seconds.
2
Prostaglandins: Lipid compounds that amplify inflammation, cause pain, and help trigger fever.
3
Cytokines (IL-1, TNF): Signalling proteins that recruit leukocytes and can act systemically to induce fever.
4
Kinins (Bradykinin): Peptides that increase permeability and stimulate pain receptors.
How Fever Works
Why Fever Helps
1
Inhibits pathogen reproduction: Most bacteria and viruses replicate optimally near \( 37^\circ\text{C} \); elevated temperatures slow their growth.
2
Increases metabolic rate: Immune cells become more active: phagocytosis, antibody production, and T-cell proliferation all accelerate.
3
Enhances iron sequestration: The liver and spleen absorb iron, depriving bacteria of a nutrient they need to multiply.
4
Triggers heat-shock proteins: These molecular chaperones protect host cells and flag infected cells for destruction.
The Complement System
The complement system consists of over 30 plasma proteins (primarily synthesized by the liver) that circulate in an inactive form. When activated, they trigger a proteolytic cascade that amplifies the immune response exponentially.
Three Outcomes of Complement
Inflammation
C3a and C5a (anaphylatoxins) trigger mast cell degranulation, attracting neutrophils and increasing vascular permeability.
Opsonisation
C3b coats pathogen surfaces, acting as a molecular "flag" that macrophages recognise and engulf far more efficiently.
Cytolysis (MAC)
C5b through C9 assemble the Membrane Attack Complex, a pore that punctures the pathogen's membrane, causing lysis.
Local vs Systemic Defenses
| Feature | Inflammation | Fever | Complement |
|---|---|---|---|
| Scope | Local | Systemic | Both |
| Speed | Minutes | Hours | Seconds-Minutes |
| Trigger | Tissue damage/infection | Pyrogens (IL-1, IL-6) | Pathogen surface / antibodies |
| Key mediators | Histamine, prostaglandins | PGE2 in hypothalamus | C3, C5, MAC (\( \text{C5b-C9} \)) |
| Primary outcome | Recruit immune cells | Inhibit pathogen growth | Lyse / opsonise pathogens |
Inflammation: Step by Step
1
Injury or infection: Damaged cells and resident macrophages release histamine, prostaglandins, and cytokines.
2
Vasodilation & increased permeability: Arterioles widen and capillary walls become leaky, producing redness, heat, and swelling.
3
Leukocyte migration (diapedesis): Neutrophils squeeze between endothelial cells and follow chemical gradients (chemotaxis) to the site.
4
Phagocytosis & cleanup: Neutrophils and macrophages engulf debris and pathogens; pus may form from dead cells.
5
Tissue repair: Anti-inflammatory signals dominate; fibroblasts rebuild connective tissue and new capillaries form.
Example: Splinter in Your Finger
You get a wooden splinter under your skin. Within minutes, the area turns red, swells, and throbs. What is happening at the cellular level?
1
Mast cells degranulate: The physical damage triggers local mast cells to release histamine, causing immediate vasodilation.
2
Fluid leaks out: Plasma proteins and clotting factors seep into the tissue, causing swelling (edema).
3
Neutrophils arrive: Within an hour, neutrophils migrate to the splinter and begin phagocytosing bacteria introduced by the wood.
Example: Complement vs Bacteria
E. coli bacteria enter a wound. The alternative complement pathway activates immediately. Trace the cascade:
Example: Fever in Action
A patient with a bacterial lung infection presents with a temperature of \( 39.2^\circ\text{C} \) and chills. Explain the physiological chain of events.
1
Macrophages in the lungs phagocytose bacteria and release endogenous pyrogens (IL-1, IL-6, \( \text{TNF-}\alpha \)) into the blood.
2
Pyrogens reach the hypothalamus and stimulate production of prostaglandin E2 (PGE2), raising the thermoregulatory set point.
3
The body "thinks" it is too cold: shivering and vasoconstriction generate and conserve heat until the new set point is reached.
4
At \( 39.2^\circ\text{C} \), bacterial enzymes slow down, immune cell activity increases, and iron is sequestered: the infection is fought more effectively.
Common Mistakes
✕ Confusing Local & Systemic
Inflammation is primarily local; fever is systemic. They often co-occur, but they are distinct mechanisms with different triggers.
✕ Fever = Always Bad
Moderate fever is a beneficial defense. Only extreme fever (\( > 41.5^\circ\text{C} \)) is dangerous. Do not equate "fever" with "disease."
✕ Complement = Adaptive
The complement system is part of innate immunity, even though the classical pathway uses antibodies. Its proteins are always present in plasma.
Summary at a Glance
| Mechanism | Key Players | Primary Function |
|---|---|---|
| Inflammation | Histamine, prostaglandins, neutrophils | Contain damage, recruit immune cells, initiate repair |
| Fever | IL-1, IL-6, PGE2, hypothalamus | Raise body temp to inhibit pathogens and boost immunity |
| Complement | C3, C5, MAC (\( \text{C5b-C9} \)) | Opsonise, inflame, and directly lyse pathogens |
Question 1 of 5
Which chemical mediator is primarily responsible for the immediate vasodilation during an inflammatory response?
Histamine is released by mast cells within seconds of tissue injury and causes rapid vasodilation and increased capillary permeability. Prostaglandins amplify the response but are not the immediate trigger.
Question 2 of 5
The hypothalamus raises the body's temperature set point in response to which molecule?
PGE2 is produced in the hypothalamus in response to circulating pyrogens (IL-1, IL-6). It directly raises the thermoregulatory set point, triggering the shivering and vasoconstriction that produce fever.
Question 3 of 5
Which complement component acts as an opsonin, coating pathogen surfaces to enhance phagocytosis?
C3b binds directly to pathogen surfaces and is recognised by complement receptors on macrophages, dramatically increasing phagocytosis efficiency. C3a and C5a are anaphylatoxins (inflammatory signals), while C9 is part of the MAC pore.
Question 4 of 5
A patient has chills and a temperature of \( 39^\circ\text{C} \). Why does the patient shiver even though their temperature is above normal?
When pyrogens raise the hypothalamic set point (e.g., to \( 39.5^\circ\text{C} \)), the body perceives its current temperature (e.g., \( 38^\circ\text{C} \)) as too cold. Shivering is the body's attempt to generate heat and reach the new, higher set point.
Question 5 of 5
The Membrane Attack Complex (MAC) destroys pathogens by:
The MAC (composed of C5b, C6, C7, C8, and multiple C9 molecules) assembles into a transmembrane pore that allows ions and water to flood into the pathogen, causing osmotic lysis. Opsonisation is performed by C3b, not the MAC.