2. Innate Immunity Flashcards
What is innate immunity?
Immunity which is not intrinsically affected by prior contract with infectious agents
- “non-specific” antimicrobial systems
- localized
- ready to go; all the components needed are already there, they just need to be expressed (this also means how you respond today is likely how you’ll respond in a few months)
What are 3 representative mechanisms of innate immunity?
- Phagocytosis
- Complement cascades
- Neutrophil NET formation
What are 3 different ways to group immune system responses?
- Innate vs. adaptive
- Humoral vs. cell-mediated
- Local vs. systemic
What are the 7 key steps in the phagocytic process?
- Chemotaxis
- Adherence: receptor binding and recognition
- Receptor activation: cross-linking and overcoming threshold of activation
- Induction of phagocytic signaling cascades
- Pseudopod formation and internalization
- Initiation of intracellular degradative mechanisms, killing responses, and release of pro-inflammatory mediators
- Digestion and release of degradation products
Evolution of phagocytosis
- What was it originally developed for?
- Driver for immune roles?
- Originally developed not for immune protection, but for control of normal cellular turnover. This dates back to multicellular bacterial biofilms. It is only over millions of years of evolution that tis has developed into a key innate antimicrobial mechanisms
- Driver for immune roles: intracellular growth of internalized microorganisms had to be controlled to prevent overwhelming of host. Pathogen innate immune recognition also needed to develop
- Highly conserved over millions of years of evolution because of its contributions to host defenses and maintenance of homeostasis
What cells display phagocytosis?
Professional phagocytes: monocytes, macrophages, immature dendritic cells, neutrophils
- different phagocytes have applied phagocytosis to different fxn
What is the major difference between professional and nonprofessional phagocytes?
Phagocytic efficiency and capacity differs due to an array of phagocytic receptors that increase particle range and phagocytic rate
What are 3 survival strategies used by intracellular pathogens?
- Prevent fusion of lysosomes to the phagosome
- Escape from phagosome before fusion of lysosomes
- “Tough-it-out” within the phagolysosome
Phagocytosis vs. Endocytosis vs. Pinocytosis
Phagocytosis: Internalization of particles that are bigger than 1 micron in diameter
- Receptor-mediated
- eg. bacteria, apoptotic cells
- Involved in immunity
Endocytosis: Internalization of particles smaller than 1 micron in diameter
- Receptor-mediated
- eg. viruses, small immune complexes
- Involved in down-regulation of surface receptors, nutrient uptake and synaptic vesicle recycling
Pinocytosis: “cell drinking” - Non-receptor mediate (non-specific)
- Involved in the uptake of fluid and soluble molecules from extracellular environment
What are the 2 types of phagocytic receptors?
- Direct recognition (eg. scavenger or mannose receptors)
- Indirect recognition (eg. antibodies, complement, focolins and collectins)
*Phagocytes contain many receptors. A number of them are involved in innate immunity (eg. TLRs). Only a fraction of them are phagocytic receptors.
Affinity
Strength of a noncovalent binding interaction; the higher the affinity the higher likelihood 2 partners will exist in a complex
Avidity
Increased “apparent” affinity of a molecule for its ligand due to the presence of multiple binding sites on both partners
Phagolysosome formation
- Once target is bound and the activation signals have been provided the phagosome must be taken into the cell
- Requires actin rearrangements, myosin interaction with actin (stimulates entry), and dynamin (helps contract and pinch off the membrane
- ## Phagosome fuses with primary, secondary granules, and lysosomes forming a destructive phagolysosome
What are reactive oxygen and nitrogen species used for?
To kill internalized microorganisms (don’t want the pathogen to survive in the phagocyte)
- highly corrosive and very toxic
Reactive oxygen intermediates (ROI) = “one punch”
- produced in the phagolysosome by NADPH oxidase (premade components) quite rapidly
- bc they are premade, they are limiting
Reactive nitrogen intermediates (RNI) = “two punch”
- produced in the cytoplasm and then diffuses into the phagosome to react with internalized microbes
- slower and long-lasting
What drives a pro- vs anti-inflammatory cellular program during phagocytosis?
- Phagocyte + Pathogen = Pro-inflammatory
- Phagocyte + Apoptotic body = Anti-inflammatory
