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Detailed List of Learning Concepts

Students build and control a virtual immune system to defend their human host from increasingly cunning microbes.

Each successive level introduces new immunity components and capabilities that enables students to create more complex immune responses. Learning by doing!

ImmuneQuest effectively captures the functional interactions between the immune functions that are difficult to convey in linear learning formats.

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Part 1: First Responders Innate Immunity Part 1

Macrophage Concepts

• One of the first lines of defense in the innate immune system
• Receptor mediated phagocytosis
• Recognition of microbes – Pathogen Associated Molecular Patterns (PAMPs)
• Only a finite number of pattern recognition receptors to detect PAMPs
• Macrophage activation via signaling molecules from other immune cells and PAMPs
• Destruction of ingested microbes within phagolysosomes
• Complement opsonins recognized by macrophage receptors for enhanced phagocytosis
• Activated macrophages release toxic molecules through vesicles
• Activated macrophages action also damages host tissues
• Macrophage receptors for C3a and C5a facilitate chemotaxis toward microbes

Complement Concepts

• Complement system is made up of proteins that rapidly self-assemble when activated
• Complement proteins present at high concentrations in the tissues and blood
• Alternate Pathway
  • C3 Convertase required to initiate self-assembly of the complement cascade
  • C3 reacts with any surface containing hydroxyl or amino chemical groups
• Membrane attack complexes form holes (pores) in microbes
• Opsonization increases the attachment efficiency of phagocytes
• Receptors on macrophages recognize the C3b and iC3b opsonin molecules
• MBL Pathway
  • Complement cascade activated by lectin protein bound to microbe
  • After C3 convertase, subsequent steps are identical to the alternative pathway
• Complement cascade releases peptides that signal to macrophages/immune cells

Host Tissue Concepts

• Barrier: The host's first line of defense. An epithelial layer of cells (skin and mucous membranes) the separates human tissues from outside world (including microbiome)
• Host tissues must protect their surfaces from complement
  • Decay accelerating factor prevents C3 convertases from forming on host surfaces
  • CD59 prevents final assembly of membrane attack complexes on host cells
  • Factor I inactivates the complement cascade at C3b on host cells
• Mannose-binding lectin released via bloodstream activates MBL Pathway

Microbial Concepts

• Many relatively harmless microorganisms living on the skin or mucous membranes can end up in the tissues when the barrier is damaged.
• Bacteria surfaces include prominent PAMPs such as lipopolysaccharide (LPS)
• Some bacteria with thick cell walls can resist membrane attack complexes
• Microbes with polysaccharides capsules resist phagocytosis unless opsonized
• Mannose/fucose on surface is susceptible to complement activation (MBL Pathway)
• Bacterial resistance mechanisms also includes stealth, rapid growth, capsules, and toxins
• Pathogenic microbes evolved many specific mechanisms to foil the immune system

Part 2: Reinforcements Cometh Innate Immunity Part 2

Blood Vessel Related Concepts

• Blood vessels play an important role in regulating the transport of immune cells, such as macrophages/neutrophils, or molecules, such as complement, to sites of inflammation.
• Bone marrow is the source of all circulating blood cells.
• Neutrophil recruitment requires cooperation of blood vessel endothelium, macrophages, and neutrophils in the blood.
• Activation of vessel wall endothelium: rolling/tethering, adhesion, and transmigration
• The blood replenishes complement depleted in the local environment
• Tissue macrophages can signal the blood vessel endothelium to bring in circulating monocytes that become activated macrophages

Neutrophil Concepts

• Like macrophages, they are leukocytes and professional phagocytes
• Present in high concentrations in the blood
• Recruited to enter tissue in response to infection or inflammation
• Highly aggressive and destructive cells. Significant potential for collateral host damage.
• Like macrophages, receptors for C3a and C5a facilitate chemotaxis toward microbes
• Other types of molecules neutrophils follow via chemotaxis (such as PAMPs)
• Degranulation kills microbes, damages host cells
• Like macrophages, they recognize microbes opsonized by complement
• Important to control a neutrophil's lifespan due to the massive damage it can inflict
• Neutrophil can commit suicide via an extracellular trap (NET) to kill more microbes

Macrophage Concepts

• Macrophage signal molecules activate blood vessel wall for neutrophil recruitment
• Like neutrophils, macrophages detect chemoattractant gradients of other types of molecules and follow via chemotaxis
• Clean up dead neutrophils before neutrophil toxins released into environment
• Macrophage cytokine signals can extend the lifespan of neutrophils

Microbial Concepts

• Fast growing microbes can quickly overwhelm macrophages
• Impact of bacterial cell wall (gram negative/positive) on immune response
• Innate immune response to pathogenic fungi

Universal Concepts in Part 1 and Part 2

• Cells sense there environment via receptors
• Chemotactic movement of cells to higher concentrations of chemoattractant molecules
• Cells "communicate" via signaling molecules released in the local environment
• Pattern recognition used to recognize "foreign" from "self"
• Immune response is ideally proportional to the threat to minimize host tissue damage

Immune System Concepts Covered in Parts 3 – 5Coming Soon!

Support through purchasing Part 2 and Bonus levels will allow us to build out Parts 3-5.

These parts focus on immune defenses against viruses and building the adaptive immune system. By the end of Part 5, one will have mastered how all eight immune components work as an interconnected whole to defend host tissues!

Part 3: Invasion from WithinViruses, MHC 1, Natural killer cells

• How innate immunity deals with viruses and bacteria that live inside host cells
• Recognition of self: MHC 1 (major histocompatibility complex)
• Natural Killer Cells (NKs) recognize stressed or infected cells
• NKs warn uninfected cells (gamma interferon) or kill infected cells
• How parenchyma host cells defend themselves from viruses after receiving signal
• How macrophages and NK cells work together

Part 4: Building the WeaponHumoral Immunity

• Naïve B-cells and T-cells created in the bone marrow
• VDJ recombination: antibodies (B-cells) and pattern recognition receptors (T-cells)
• Antigen presenting cells (APC); major histocompatibility complex 2 receptors (MHC 2)
• B-cell and T-cell tolerance (MHC restriction)
• B-cell activation, differentiation, and clonal expansion
• Helper T-cell activation and replication; role in APC presentation, B-cell activation
• Humoral Response: Microbial neutralization and opsonization by antibodies

Part 5: Unleashing a Full ResponseCell-mediated Immunity

• Dendritic cells serves as a coach, intel expert; potent professional APC for helper T-Cells
• Dendritic cells display both MHC 1 and MHC 2 antigen
• How helper T-cells respond differently to bacteria and viruses (th0, th1, th2 responses)
• Cell-mediated immunity and cytotoxic T-cells
• How innate and adaptive immunity work together to combat viruses
• Memory cells to protect against future attacks
• Full working virtual immune system battling nasty pathogens!

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