Lecture 5 - Innate Immunity (Basics, Phagocytosis, and Migration) Flashcards
How can pathogens enter the body?
Pathogens can enter the body through mucosal surfaces (mouth/respiratory tract, gastrointestinal tract, reproductive tract) and external epithelial surfaces (external surface, wounds/abrasians, insect bites).
True or False?:
Saliva, hair, mucus, and tears all contribute to adaptive immunity.
False
Saliva, hair, mucus, and tears all contribute to innate immunity.
What provides the first barrier against infection?
Epithelial surfaces like skin, gut epithelium, and, and respiratory eptithelium provide the first barrier against infection.
What cells are involved in innate immunity?
Neutrophils & Other Granulocytes, Monocytes & Macrophages, Dendritic Cells, and Natural Killer & Innate Lymphoid Cells
Enzymes, anti-microbial peptides, and complement are all involved with which type of immunity?
Innate Immunity
True or False?:
Infectious agents must overcome innate host defenses to establish a focus of infection.
True
What is phagocytosis?
Phagocytosis is the internalization of pathogens or their components upon their binding to receptors on the cell surface of phagocytes.
Which types of cells is phagocytosis mediated by?
Phagocytosis is mediated by phagocytes – macrophages, granulocytes (neutrophils), and immature DCs.
Which of the following does phagocytosis not lead to?
- Removal and Killing of Pathogens.
- Clearing of Debris
- Complete Stop of the Immune Response
- Generation of Antigenic Peptides for Presentation to T-Cells
Complete Stop of the Immune Response
True or False?:
Macrophages have phagocytic receptors that bind microbes and their components.
True
What are the four steps of phagocytosis?
- Bacterium becomes attached to membrane evaginations called pseudopodia.
- Bacterium is ingested, forming phagosome.
- Phagosome fuses with lysosome.
- Bacterium is killed and then digested by lysosomal enzymes.
How are phagolysosomes able to kill microbes?
Phagolysosomes contain products (reactive oxygen species, enzymes, antimicrobial peptides) and an environment (acidification) that can kill microbes.
What does phagocytosis ligand binding trigger?
Phagocytosis ligand binding triggers signaling that results in a cellular change.
How are phagocytes “turned on”? What does this lead to?
Phagocytes are turned on by phagocytosis. It leads to the digestion of pathogen.
How does the phagosome contribute to adaptive immunity?
The phagosome contributes to adaptive immunity through its role in antigen degradation, antigen processing, antigen presentation (MHCII), and antigen presentation via cytosol (MHCI).
What are microglia?
Microglia are CNS-residents responsible for establishing proper neuronal connections. They play a role in brain development, learning, and memory. They are often considered to be the “macrophages of the brain”.
What is multiple sclerosis?
Multiple sclerosis is a complex inflammatory disease characterized by myelin breakdown. It leads to lots of toxic debris in brain lesion microenvironments.
True or False?:
Microglia and peripheral infiltrates of macrophages participate in debris clean-up in MS. Various animal models show that this is required for CNS repair.
True
The picture below is from research published by Lou et al. in 2016. They used a laser to injure mouse CNS tissue with normal microglia (left) and microglia with receptors knocked out (right). What are the results and conclusions of their research?
Results: In the wildtype microglia tissue, pseduopodia are extended into the region where the damage was inflicted. This does not occur in the receptor KO microglia tissue.
Conclusions: Microglia’s role in CNS damage repair is dependent upon receptors expressed by microglia.
What experimental set-up is used to measure phagocytosis?
To measure phagocytosis, a substrate is dyed with a pH-sensitive fluorophone that only fluoresces under low pH conditions (like those in a phagolysosome). You feed the substrate to macrophages or microglia and measure the fluorescence
What are the four steps of recruitment of leukocytes to sites of infection?
- Cytokines produced by macrophages cause dilation of local small blood vessels.
- Leukocytes move to periphery of blood vessel as a result of increased expression of adhesion molecules by endothelium.
- Leukocytes extravasate at site of infection.
- Blood cloting occurs in microvessels.
Which types of cells are recruited to sites of infection?
Monocytes and Neutrophils
What do monocytes bind to to allow them to migrate into surrounding tissues?
Adhesion Molecules
What are the three main classes of adhesion molecules?
Selectins, Integrins, and the Immunoglobulin Superfamily
What do selectins do?
Selectins bind carbohydrates and initiate leukocyte-endothelial interaction.
What do integrins do?
Integrins strongly bind to cell-adhesion molecules and extracellular matrix molecules.
What do leukocytes roll along?
Vascular Endothelium
What are the four steps to leukocyte migration into tissues?
- Rolling Adhesion
- Tight Binding
- Diapedesis
- Migration
Which non tissue-resident cell is recruited to the site of infection to ingest and kill microgranisms via phagocytosis?
Neutrophils
What is pus the result of?
Pus is the result of dead and dying neutrophils.
What can neutrophils produce?
Neutrophils can produce an extracellular matrix called a NET (neutrophil extracellular trap) to trap microorganisms.
