Microbio Ch. 17

Immunology: Study of the mechanisms that the body uses to defend itself against disease.

Health Context: Immunology is critical to understanding health, illness, and homeostasis.
- Pathogens enter our bodies every day.
- Connection between the microbiome and immunity.
- Importance of understanding autoimmune disorders and microbiome dysbiosis.
- Recognizing immune system disorders (genetic & acquired).
- Awareness of opportunistic infections.
- Cytokine Storm: A life-threatening systemic inflammatory syndrome caused by elevated levels of cytokines.
- Vaccination and antibody therapy: Vaccines train the immune system; antibodies bind toxins, pathogens, and abnormal human cells.

The immune system consists of multiple parts or Lines of Defense: ## 1st Line of Defense: Innate Immunity
- Type: Non-specific; present at birth (built-in mechanisms)
- Function: May prevent infections from establishing.
  ## 2nd Line of Defense: Adaptive Immunity
- Type: Specific; develops as the body is exposed to antigens throughout life.

The immune system includes both innate and adaptive components:
- Innate Immunity: Nonspecific defenses.
- Adaptive Immunity: Specific immune responses, including humoral immunity (serum antibodies) and cellular immunity (antigen presenting cells, B cells, and T cells).

Mechanisms are immediate and rapid, targeting invading pathogens nonspecifically to prevent infections.
Components include physical, chemical, and cellular elements.

Physical Barriers:
- Skin and mucous membranes serve as important barriers to invasion.
- Unbroken skin is particularly effective against microbes.
- Cell junctions (tight junctions, desmosomes, gap junctions) prevent microbe passage.
- Blood-brain Barrier protects the central nervous system from microbial invasion.
Mechanical Defenses:
- Mucous membranes trap particles and microbes; contain antimicrobial substances.
- Mucociliary Escalator in the respiratory tract removes trapped particles.
- Peristalsis in intestines helps expel microbes.
- Flushing Action of urine maintains sterility in the urinary tract.
- Tears and other secretions prevent microbial colonization of the eyes.

Cytokines: Secreted by white blood cells; serve as signaling molecules.
Antimicrobial Substances:
- Lysozyme: Degrades peptidoglycan, breaking bonds between NAG and NAM.
- Lactoferrin and transferrin: Bind iron to starve microbes during growth.
- Lactoperoxidase: Produces antimicrobial compounds in bodily fluids.
- Antimicrobial Peptides (AMPs): Such as defensins and bacteriocins, that damage microbial membranes; secreted by macrophages and neutrophils.

Definition: A group of plasma proteins that participate in nonspecific defenses against invading microbes, linking innate to adaptive immunity.
Mechanism:
- Proteins circulate in blood and tissue fluids and are activated in a cascade manner.
- Activation Pathways:
- Alternative pathway: Initiated by spontaneous activation of C3b which binds to foreign invaders.
- Lectin pathway: Triggered by mannose-binding lectins (MBLs).
- Classical pathway: Requires specific antibody binding to antigen, leading to an activation cascade.
Protective Outcomes:
- Opsonization: Opsonins enhance phagocyte attachment to microbial cells.
- Inflammatory Response: C5a recruits phagocytes and increases vascular permeability.
- Chemotaxis: C5a acts as a chemoattractant for neutrophils.
- Lysis of Foreign Cells (Cytolysis): Formation of membrane attack complexes (MAC) that insert into cell membranes of pathogens, especially Gram-negative bacteria.

Process: Phagocytes assist in engulfing and digesting pathogens.
- Steps in Phagocytosis:
- Chemotaxis: Attraction to sites of infection.
- Recognition and Attachment: Direct binding or opsonization.
- Engulfment: Formation of a phagosome.
- Digestion: Fusion with lysosomes to form phagolysosomes, which release toxic ROS and enzymes for degradation.
- Exocytosis: Expulsion of debris.

Definition: An immune response triggered by tissue damage or pathogen invasion.
- May be acute (short-term, neutrophil-driven) or chronic (long-term, macrophage-driven).
Signs of Inflammation: Redness, swelling, heat, pain, and altered function.
Mechanisms:
- Vasodilation and increased vascular permeability facilitate fluid and blood cell movement into affected tissues.
- Migration of leukocytes and phagocytes to the injured site promotes clearance of pathogens and cellular debris.

Function: Signaling molecules that mediate communication between cells.
- Types:
- Chemokines: Recruit leukocytes to sites of infection.
- Interleukins (ILs): Modulate immune responses.
- Interferons (IFNs): Regulate responses to viral infections.
- Tumor necrosis factor (TNF): Participates in inflammation, promotes apoptosis.
Interferons Overview:
- Type I Interferons: (e.g., IFN-α, IFN-β) inhibit viral replication and promote apoptosis in infected cells.
- Type II Interferons: (e.g., IFN-γ) activate immune cells including macrophages.

Hematopoiesis: Formation of blood cells from hematopoietic stem cells located in bone marrow.
Categories of White Blood Cells (Leukocytes):
- Granulocytes (Neutrophils, Eosinophils, Basophils)
- Mononuclear Phagocytes (Monocytes, Macrophages, Dendritic cells)
- Lymphocytes (T cells, B cells)
Lymphocytes: Responsible for adaptive immunity.
- T Cells: Mature in the thymus, involved in recognizing specific antigens.
- B Cells: Mature in the bone marrow, produce antibodies in response to antigens.
Cytotoxic Cells: Natural killer cells target and destroy infected or abnormal cells.

Key Mediators:
- Bradykinin: Induces blood vessel dilation and fluid leakage.
- Histamine: Promotes vasodilation and increases permeability.
- Prostaglandins: Cause inflammation, pain, and fever.

Key Functions:
- Opsonization: Coating of pathogens to facilitate phagocytosis.
- Iron-binding to inhibit microbial growth.
- Activation of the complement cascade.

Understanding immune responses is critical for developing effective vaccines and therapies against infections and inflammatory diseases. The interplay between different immune cells and signaling molecules shapes the effectiveness of the overall immune response.