Host Defense Mechanisms

Understanding host defense involves various immune responses, which are categorized into several components: formed elements in the blood, phagocytosis, inflammation, fever, and antimicrobial substances.

1. Formed Elements in the Blood

• Definition: Cells and cell fragments suspended in plasma.

  • Components:

  • Erythrocytes (RBC):

    • Contain hemoglobin, a protein that binds to O$_2$ for oxygen transport.

  • Leukocytes (WBC):

    • Involved in immune function.

  • Thrombocytes (Platelets):

    • Fragments derived from megakaryocytes, involved in blood clotting upon injury.

• Production:

  • Formed in red bone marrow from stem cells via the process of hematopoiesis.

2. Leukocyte Classification

• Granulocytes: Leukocytes with visible granules in cytoplasm, observable under a light microscope.

  • Types:

  • Basophils:

    • Release histamine granules, involved in allergic responses, responsible for allergy symptoms.

  • Eosinophils:

    • Toxic against parasites and worms.

  • Neutrophils:

    • Phagocytic cells; work during early stages of infection.

    • First responders at the site of injury.

• Agranulocytes: Leukocytes lacking visible granules in cytoplasm.

  • Types:

  • Monocytes:

    • Travel in blood and mature into macrophages in tissues, acting as phagocytic cells.

    • Precursors that detect tissue injury and migrate to those sites.

  • Lymphocytes:

    • Include T cells and B cells (both important for adaptive immunity) and NK (natural killer) cells for direct cytotoxicity.

2.1 Differential White Blood Cell Count

• Definition: The relative abundance of each type of white blood cell per 100 white blood cells in a normal state.

• Hierarchy (from least to most common):

  • Neutrophils

  • Lymphocytes

  • Monocytes

  • Eosinophils

  • Basophils

  • Mnemonic: Never Let Monkey Eat Bananas

3. Phagocytosis

• Definition: The process of ingestion (engulfing) of microbes or substances by a phagocyte.

• Phagocytes: Non-specific, innate host cells capable of phagocytosis.

  • Examples:

  • Neutrophils (first responders—found in blood)

  • Macrophages (from monocytes and found in tissues)

  • Dendritic cells (located in skin)

• Mechanisms/Phases of Phagocytosis:

  1. Chemotaxis:

  • Pathogens release chemical signals (cytokines) detected by phagocytes who move towards them.

  1. Adherence:

  • Binding of phagocyte to the pathogen surface.

  1. Ingestion:

  • Pathogen undergoes endocytosis, forming a phagosome, merges with lysosome forming a phagolysosome.

  1. Digestion:

  • The pathogen is broken down within the phagolysosome.

• Microbial Evasion of Phagocytosis:

  • Mechanisms of Evasion:

  • Capsule:

    • Some pathogens, like Streptococcus pneumoniae, have capsules making them too large to be engulfed.

  • Leukocidins:

    • Toxins such as those from Staphylococcus that kill phagocytes by forming pores.

  • Mycolic Acid:

    • A component in the cell wall that inhibits lysosomal enzymes; pathogens such as Mycobacterium can multiply inside phagocytes, evading the immune response.

4. Inflammation

• Purpose: The goal of inflammation is to eliminate pathogens and facilitate tissue healing, assisted by neutrophils and macrophages.

• Causes: Often a response to infections.

• Signs and Symptoms:

  • Pain: Resulting from cytokines released by leukocytes damaging nerve endings.

  • Redness (Erythema): Due to increased blood flow to the affected area to transport leukocytes to injury sites.

  • Immobility: Local loss of function arises from tissue damage.

  • Swelling (Edema): Accumulation of fluid outside of blood vessels (ex: lymph fluid).

  • Heat: Increase in blood flow to the affected region.

• Process of Inflammation:

  1. Tissue or cells are damaged due to infection.

  2. Damaged cells release chemicals such as cytokines.

  3. Cytokines attract phagocytes (neutrophils and monocytes/macrophages) to the site of injury.

  4. Phagocytes migrate through blood vessels to the injury site.

  5. Phagocytosis of pathogens begins.

  6. Tissue repair ensues.

5. Fever

• Definition: An increase in body temperature in response to pathogen-induced toxins (often from bacterial infections), aimed at eliminating pathogens.

• Mechanism:

  • Toxins induce the release of cytokines from phagocytes.

  • Cytokines bind to receptors in the hypothalamus, raising the body temperature set point.

  • Consequently, the person experiences chills as their body temperature rises.

  • Once the new set point is reached, a high body temperature (fever) occurs.

  • As pathogens are cleared, toxins and cytokines are eliminated, resetting the body thermostat and causing the decline of fever (called a “crisis”).

• Consequences of Fever:

  • Increases metabolic rate (catabolism resulting in more ATP production).

  • Enhances immune responses by promoting phagocyte activity.

6. Antimicrobial Substances

• Overview: Host cells release substances that destroy pathogens.

• Examples:

  1. Complement System:

     • Involves proteins in blood, enhancing the immune response in pathogen destruction.

     • Activation:

     • Occurs in a cascade; an active protein activates another inactive complement protein.

     • Forms:

     • Exist as inactive or active complement proteins.

     • Outcomes of Complement Activation:

     1. Opsonization:

        • Coating the surface of pathogens to promote phagocyte attachment (similar to a 'donut shop example').

     2. Inflammation:

        • Complement proteins bind mast cells provoking histamine release, leading to increased vascular permeability.

     3. Cytolysis:

        • Complement proteins form a membrane attack complex (MAC) creating holes in pathogen membranes, causing cell lysis.

     • Microbial Evasion of Complement:

     • Capsule production, inhibition of MAC assembly, and inactivation/destruction of complement proteins by bacterial enzymes.

  2. Interferons (IFNs):

     • Produced by animal cells during viral infection, they interfere with viral replication.

     • Function: Protect uninfected neighboring cells by signaling them to enhance antiviral defenses, acting as an alert system.

     • Mechanism of Action:

     1. A virus infects an animal host cell.

     2. The infected cell produces and releases IFNs.

     3. IFNs bind to nearby, uninfected cells, prompting them to produce anti-viral proteins (AVPs).

     4. AVPs then wait to counteract any new viruses attempting to infect those neighboring cells.