Innate Immunity Flashcards
What is immunology?
The study of the multi-layered “host defence” system that protects us against pathogens
Innate vs adaptive: speed
Innate system is much faster than the adaptive
Three layers of immunity
Intrinsic barriers, innate and adaptive
Intrinsic barriers
Pre-formed barriers to PREVENT invasion
Innate immunity
- Non-specific
- Fast
- Fixed/constant (no ability to learn from prior exposure)
Adaptive immunity
- Very specific
- Slow
- Improves throughout response (ability to learn)
Intrinsic barriers (x4)
- Mechanical
- Chemical
- Physiological
- Microbiological
Mechanical barriers
- Expulsive force (coughing/sneezing/defecation etc.)
- Ciliary beating (respiratory tract)
- Tight junctions in the epithelium (prevents pathogens from entering)
Chemical barriers
- Low pH barriers (stomach, vagina, sebaceous fatty acids - denatures pathogens)
- Proteolytic enzymes (breaks down proteins; lysozyme and pepsin found in tears + gut)
Physiological barriers
- Temperature regulation (fever)
Microbiological barriers
- Commensal flora compete with pathogens; found in the GI tract, pathogens can only take control if they outcompete the flora, competes for nutrients and adhesion spots
What are zymogens?
- Zymogen is the complement protein precursor - free floating in blood + tissues, made in the liver
- Activated in 3 different ways; antibody-antigen binding, lectin-mannose binding and by pathogens
3 pathways for zymogen activation
- Classical pathway (antibody-antigen binding): zymogens get cleaved into their active form
- Lectin-mannose binding: lectin from the human body binds to mannose sugar found on the pathogen surfaces
- Alternative pathway: some pathogens themselves naturally have enzymes on their surface that cleave + activate zymogens
What happens when zymogen is activated?
- Inflammation: small fragments of complement proteins act on BVs to cause inflammation –> BV dilation and permeabilization occurs; proteins + cells are released into the tissue to defend the body
- Membrane attack complex formation: large fractions of complement proteins polymerize to form barrel-shaped structures aka membrane attack complexes
- Pores are formed in the bacterial cell wall by the membrane attack complex
- Bacteria are under a lot of pressure (human defence mechanisms get in & bacterial material out)
- Opsonization aka tagging: phagocytes will envelope opsonized pathogens (CPs are on the pathogen surface) –> they get digested in a way so they are no longer hazardous
Resident phagocytes
Phagocytic cells
- Macrophages: found in healthy tissues, takes big bites of pathogens to engulf
- Bacteria binds to macrophage receptors & macrophage engulfs + digests the bound bacteria
- Dendritic cells: found in healthy tissues, does macropinocytosis; takes samples of pathogens and so the lymph nodes knows to turn on the adaptive immune system
- Neutrophils: recruited later and also does macropinocytosis
- Phagosome fuses with lysosome to create a phagolysosome; digests pathogens
Inflammation activation
- Pattern recognition receptors (PRRs): found on human cells to recognize pathogens
- Toll-like receptors: example of PRRs that recognize pattern-associated molecular patterns (PAMPs) on pathogens –> initiates inflammation
- Releases cytokines: allows for communication
- Releases chemokines: brings in other cells to help signalling
Inflammation activation
- Pattern recognition receptors (PRRs): found on human cells to recognize pathogens
- Toll-like receptors: example of PRRs that recognize pattern-associated molecular patterns (PAMPs) on pathogens –> initiates inflammation
- Releases cytokines: allows for communication
- Releases chemokines: brings in other cells to help signalling
- Vasodilation + increased permeability allows for fluid/protein/inflammatory cells to blood –> tissue
- After inflammation, buffy coat is larger (more WBCs)
- Signs of inflammation: redness + swelling + heat + pain
Innate immune cells
- Macrophages
- Neutrophils
- Dendritic cells
- Natural killer cells
- Mast cells
- Eosinophils
- Basophils
Macrophages
- Tissue resident “sentinel cells” –> senses + monitors presence of pathogens
- Differentiate from monocytes which travel in the blood –> tissues and then stay there
- Phagocytose bacteria + dead cells
- Produce cytokines; causes inflammatory response
- More are recruited to sites of infection when needed
Neutrophils
- Found in the body in high quantities
- Migrate to tissues during inflammation
- Recruited by chemokines; including IL-8
- Contain toxic granules that can kill invaders
- This must be regulated to prevent immunopathology
- Short-lived, replenished by bone marrow
Dendritic cells
- Antigen-presenting cells found mostly in tissue
- Differentiate from blood-borne monocytes –> tissue
- Bridge the gap between innate & adaptive immunity by ACTIVATING T & B cells in the lymph nodes and spleen
- Come from the same lineage as adaptive immune cells, but are a part of the innate response
Mast cells
- Important in allergic reactions: release histamine
- Help battle parasite infections (macrophages are too small for this)
Eosinophils
- Parasite infection + protection of mucosal surfaces (GI tract, lungs + genital tract)
Basophils
- Also important in allergic reactions: release histamine
- Release heparin to reduce blood clotting
Innate response for extracellular bacteria
- Phagocytosed by macrophages
- Release cytokines + chemokines to attach more monocytes & neutrophils
- Positive feedback loop
Innate response for intracellular viruses
- Infected cells (often epithelium) produce anti-viral cytokines (interferons)
- Change in temperature (fever)
- Recruitment of NK cells
- Infected cells are killed
- Phagocytes clean up released virus & dead cell material
Lymphatic system
- Drain the tissues of the body
- Return fluid, proteins & cells to the blood via the thoracic duct
- Bring together the components of the immune system
- Lymphoid tissues
- Lymph nodes
Lymphoid tissues
Primary lymphoid tissues: where cells develop and are educated
- Bone marrow: all immune cells are born here, B cells are also educated here
- Thymus: T cells are educated here
Secondary lymphoid tissues: where immune components are brought together to mount a response
- Lymph nodes (found in places where you’re likely to run into pathogens)
- GALT/MALT: gut/mucus
- BALT: bronchus; protects respiratory tract