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
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
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
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.
