Innate Immunity II Flashcards
What are hematopoietic stem cells? What do they give rise to?
Self-renewing Stem cells in bone marrow that give rise to myeloid progenitor (phagocytes) and lymphoid progenitor (lymphocytes)
What type of innate immune cells have do myeloid progenitor origin?
- neutrophils
-monocytes (differentiated to macrophages) - dendritic cells
What type of type of innate immune cells have lymphoid progenitor origin?
Natural killer cells
What is the role of myeloid origin innate immune cells?
Kills extra cellular pathogens via PHAGOCYTOSIS
What is the role of lymphoid origin innate immune cells?
Kill intracellular viruses via APOPTOSIS
What is the process of phagocytosis?
- bacterium binds to PRRs on membrane evaginations called pseudopodia
- bacterium is ingested, forming phagosome (innocuous)
- phagosome fuses with lysosome (drops pH) to make phagolysosome
- bacterium is killed and then digested by low pH-activated lysosomal enzymes
- digestion products are released from cell
Why does phagocytosis occur in a vesicle?
control/contain toxins from lysosome so they don’t damage the cell
What are the phagolysosome antimicrobial properties?
- low pH from lysosome
- NADPH oxidizes making reactive oxygen species
- myeloperoxidase (MPO) can transform H2O2 into hypochlorous acid
- lactoferrin captures Fe2+ that is essential for bacterial growth (nutritional immunity)
- denensins form pores on pathogen membrane
- Lysozyme degrades peptidoglycan (gram + bacteria)
What is nutritional immunity?
host actively sequesters essential nutrients to reduce pathogen growth (usually trace metals that are cofactors for metabolic enzymes like Fe, Zn, Mn)
What is Hypoferremia?
too much nutritional immunity of Fe causing low blood iron
What are types of phagocytes>
- neutrophils
-monocytes/macrophages - dendritic cells
What are neutrophils?
abundant blood circulating leukocytes and have a like span of a few days (replicate quickly)
How do neutrophils act?
exit blood and rapidly enter infected tissues in large numbers in response to inflammatory molecules. neutrophils are the main component of pus and can be used as a measure of infection
What are neutrophils mechanisms?
- activation stimuli
- neutrophils “eject” its chromatin which are decorated with antimicrobial proteins (from granules)
- chromatin “net” ensures extracellular pathogens
- antimicrobial proteins intoxicate microbes
this process is called NETosis (neutrophil Extracellular Traps)
What is neutropenia? What are the consequences and how can it be treated?
abnormally low levels of neutrophils
- patients highly susceptible to deadly infections with a wide range of pathogens
- can lead to neutropenic sepsis (septic shock)
- treatment: frequent blood transfusion of plasma (WBC component)
- frequent bc neutrophils have short life span
What are macrophages? What do they do?
- professional phagocytes
- remove pathogens and damaged host cells
- differentiate from monocytes that circulate in the blood and enter tissues
- also have a role in adaptive immunity
- longer life span (months/years)
What are resident macrophages?
immune surveillance for a region and has specialized functions depending on location in tissues
- phagocytosis
- antigen presentation
- immune suppression
What are dendritic cells? immature vs mature
immature: circulate in blood and reside in lymphoid organs and peripheral tissues and perform phagocytosis
mature: adaptive immunity role by activating T cells via antigen presentation
What are natural killer cells? What do they do?
cytotoxic proteins (perforin & granzyme) containing cells that circulate in blood and kills virus infected and cancer cells
migrate cell-to-cell contact area to relate granules (p+g) and cause cell death in target cells
What is perforin?
forms a pore in the cell membrane which helps deliver granzymes into the target cell
What is granzyme?
turns of caspase which triggers apoptosis and triggers degradation of viral nucleic acid to prevent viral replication
What is the sequence of responses after a viral infection?
- Cytokine release
- wave of NK cells
- T-cell mediated killing of infected cells
(control viral replication)
What occurs in NK cell deficiency?
frequent herpesvirus infections
How do cells “sense” the presence of pathogens?
patter recognition through signal transduction
