Host Defenses - Innate Immunity Flashcards
Compare and contrast innate immunity and adaptive immunity.
Innate immunity:
- Constitutive
- Nonspecific
- Does not target a specific pathogen
- Pattern recognition
- Exists prior to exposure to a microbe/microbial product
- Provides the first line of defense
Adaptive immunity:
- Induced
- Acquired
- Specific
- Targets a specific antigen
- Develops only after exposure, including vaccine
- Is “remembered” by the host
- Is strengthened progressively after multiple encounters
List the components of the innate immune system.
- Physical, chemical, and biological barriers
- Phagocytes
- The complement system
- Inflammation
List the components of the adaptive immune system.
- Antibody-mediated (humoral) immunity
- Cell-mediated immunity
Explain why the innate defense system is regarded as the first line of defense
- Barriers prevent pathogens from entering the body
- Non-specific but rapid response
Describe the structure of the skin and explain why intact skin is an effective barrier to bacterial invasion.
- Composed of layers of closely packed cells
- Antimicrobial peptides (AMPs)
- Acidic sebum (fatty acids)
Describe at least one physical factor and one chemical/molecular factor that prevents microbes from entering the body through the digestive system.
- Physical: mucus membrane
- Chemical/molecular: acid in stomach
Describe at least one physical factor and one chemical/molecular factor that prevents microbes from entering the body through the respiratory tract.
- Physical: mucus membrane
- Chemical/molecular: antimicrobial peptides
Describe at least one physical factor and one chemical/molecular factor that prevents microbes from entering the body through the urogenital tract.
- Physical: flow of urine
- Chemical/molecular: antimicrobial peptides
Define mucus and explain how mucus contributes to the defense of mucus membranes against bacterial colonization.
- A secretion of mucous membrane that provides a slippery coating that prevent drying of the
epithelium - Traps and removes particles
- Keeps bacteria away from the epithelium
Reading assignment: Describe how the normal human skin microbiota protects the skin.
Commensal bacteria produce antimicrobial peptides
Define phagocyte.
Cells that ingest microorganisms or particular matters
Define phagocytosis.
Ingestion of bacteria or other material by phagocytes
Define intracellular phagocytic killing.
Process by which phagocytes kill the bacteria/pathogen they ingested (intracellular or extracellular)
Define extracellular phagocytic killing.
When cells release antimicrobial substances to kill pathogens without engulfing them
Explain how neutrophils, monocytes, or macrophages contribute to host defense against bacterial infection.
- Neutrophils: phagocytosis, NETs, release ROS
- Monocytes and macrophages: detect invading pathogens, secrete proinflammatory cytokines, and initiate innate and adaptive immune responses
Explain why neutropenic patients are susceptible to bacterial infection.
Because they do not have enough neutrophils to kill organisms that cause infection
Describe the events that occur during phagocytosis and intracellular phagocytic killing.
- Chemotaxis and adherence of microbe to phagocyte
- Ingestion of microbe by phagocyte
- Formation of a phagosome
- Fusion of the phagosome with a lysosome to form a phagolysosome (lysosomal granules)
- Digestion of ingested microbe by digestive enzymes
- Formation of residual body containing indigestible material
- Discharge of waste material
- In the case of macrophages, presentation of antigens
Propose at least two strategies bacteria may utilize for evasion of phagocyte-mediated defenses.
- Evade binding
- Prevent fusion
- Escape into cytoplasm
Define pathogen-assisted molecular pattern (PAMP) and give an example.
Microbial conserved structures recognized by the innate defense system
- Ex. O-antigen
Define pattern recognition receptor (PRR) and give an example.
Receptors specific for microbial molecules that are not present in the host
- Ex. MBL, CRP, SAP
Explain the significance of PRRs in the innate immune response to bacterial infection.
They recognize pathogens and trigger the immune response
Define phagosome.
Membrane-bound vesicle produced by a phagocytic event, usually containing an ingested particle
Define phagolysosome.
Membrane-bound vesicle formed by the fusion of a phagosome and its contents with a lysosome
Describe oxygen-dependent phagocytic killing mechanisms.
Intracellular killing due to exposure to reactive forms of oxygen, for
example, H2O2, superoxide ions
Describe oxygen-independent phagocytic killing mechanisms.
Intracellular killing mediated by intracellular enzymes or antimicrobial
peptides, for example, defensins
Describe the composition of neutrophil extracellular traps (NETs) and the function of DNA in the antibacterial activity of NETs.
- Composition
- Chromatin
- Granule proteins- Elastase
- Cathepsin G
- Myeloperoxidase
- Lactoferrin
- Gelatinase
- Chromatin
- Function of DNA
- Trapping bacteria
- Increasing local concentration of antimicrobial molecules
Explain why activation of phagocytes by bacterial infection can contribute to tissue damage.
Because both oxygen-dependent and oxygen-independent methods of killing are also toxic to host cells (no specificity for bacteria)
List the components of the complement system (Table 6.5 and Fig. 6.3)
- Classical pathway
- C1q, C1r, C1s, C4, C2, C3 (also part of lectin and alternative) - Lectin pathway
- MBL, MASP-1, MASP-2 - Alternative pathway
- Factor B, Factor D, properdin - MAC
- C5, C6, C7, C8, C9 - Complement receptors
- Complement receptor type 1-4, complement receptor of Ig family, C3a receptor, C5a receptor
Use Fig. 6.3 to list the steps that lead to the activation of the complement system via the alternative pathway.
- Activating surface (non-self surface)
- Binding of C3b and factors B/D
- Formation of C3 convertase
- Cleaves C3 –> C3a and C3b
- Deposition of C3b - Formation of C5 convertase
- Cleaves C5 –> C5a and C5b - Formation of MAC
- Activation of C5, C6-C9
Use Fig. 6.3 to list the steps that lead to the activation of the complement system via the classical pathway.
- Sequential binding and activation of C2 and C4
- Formation of C3 convertase
- Cleaves C3 –> C3a and C3b - Formation of C5 convertase
- Cleaves C5 –> C5a and C5b - Formation of MAC
- Activation of C5, C6-C9
Explain why complement activation through the classical pathway is more specific than through the alternative pathway.
Because the classical pathway requires antibodies that are specific for a bacterium (antigen)
Describe similarities and differences between these two activation mechanisms.
Similarities
- Formation of C3 convertase and products
- Formation of C5 convertase and products
- Formation of MAC
Differences
- Initiation
Propose at least two strategies bacteria may utilize for evasion of complement activation.
- Change cell surface
- Degrade C3b
- Change antigens
Define the role of C3 convertase and the role of C5 convertase in complement activation.
- C3 convertase: cleaves C3 into C3a (anaphylotoxin) and C3b (opsonin); allows the continuation of complement cascade, with assembly of MAC
- C5 convertase: cleaves C5 into C5a (anaphylotoxin) and C5b; allows the continuation of complement cascade, with assemble of MAC
Define opsonin.
- Slides: Molecule that coats the surface of a target for phagocytosis
- Textbook: Antibody or other host proteins that binds to microbial surfaces and mediates the uptake
and killing of the microbe by phagocytic cells
Define opsonization.
- Slides: Deposition of opsonins
- Textbook: Attachment of antibodies or other host proteins to microbial surfaces that mediates the
uptake and killing of the microbe by phagocytic cells
Define opsonophagocytosis.
Opsonin-promoted phagocytosis
Explain how complement opsonization facilitates phagocytosis of bacteria.
Opsonization increases the adherence of microbes to phagocytic cells
Explain how C3a and C5a contribute to inflammation.
C3a and C5a induce degranulation in mast cells and basophils, resulting in release of mediators eg. histamine) that induce contraction of smooth muscle and increased vascular permeability
Define the membrane attack complex and its antibacterial function.
- End product of the complement system which assembles the
late complement components into a pore-like structure that inserts into membrane and kills targeted
microorganisms or cells - Function: Lyses cells by poking holes in the cell membrane
Reading assignment: Explain whether S. pneumoniae strain D39 is able to activate the mouse complement system in the absence of the classical pathway (Fig. 1).
Yes, S. pneumoniae strain D39 is able to activate the mouse complement system in the absence of the classical pathway (Fig. 1E is CP deficient but AP sufficient)
Reading assignment: Interpret the data shown in Fig. 3 on the role of the complement system in mouse resistance to S. pneumoniae.
Mice that were deficient in any part of their complement system had a faster drop in population than wild-type mice.
Define cytokines and chemokines and give two examples.
- Cytokines: small proteins released by immune cells that regulate the immune response (ex. TNF-α, IL-1, IL-6)
- Chemokines: cytokines that act as chemoattractants for migration of leukocytes to sites of
inflammation (ex. IL-8 in CXCL family, CCL family)
Describe the process of acute inflammation.
- Heat: increased blood flow
2 & 3. Redness and swelling: accumulation of fluids from the blood in the extravascular space - Pain: nerve damage, irritation by toxins, or the pressure of swelling
- Loss of function: e.g. pain or severe swelling that interferes with mobility
Define vasodilation.
Dilation of blood vessels (decreases blood pressure)
Define margination.
Adhesion of phagocytes to endothelium
Define diapedesis.
Passage of blood cells through capillary walls (into tissue)
Describe the role of inflammation in host defense against bacterial infection.
- To destroy, remove, or confine a tissue damaging agent
- To repair tissue damage
Explain why inflammation can be an important aspect of bacterial pathogenesis.
Inflammation can actually cause damage to host tissue (fluid loss because of increase permeability, damage to host blood vessels, decreased blood pressure)
