Innate Immunity Flashcards
2 broad roles of the innate immune system
- First line of defense that slows the growth of infectious diseases until adaptive immune responses develop
- Means of directing adaptive immunity
Innate vs. Adaptive Immunity: Response time
Minutes/hours vs. Days
Innate vs. Adaptive Immunity: Specificity
Innate immunity is specific for molecules and molecular patterns associated with pathogens and molecules produced by dead/dying cells
Adaptive immunity is highly specific and can discriminate between very minor differences in molecular structure
Innate vs. Adaptive Immunity: Diversity
Innate immunity has a limited # of conserved germ-line encoded receptors
Adaptive has highly diverse receptors arising from genetic recombination
Innate vs. Adaptive Immunity: Memory responses
Innate immunity has some (observed in certain organisms and human NK cells)
Adaptive has persistent memory
Innate vs. Adaptive Immunity: Self/nonself discrimination
Innate is perfect
Adaptive is good but has some occasional failures that result in autoimmune diseases
Innate vs. Adaptive Immunity: soluble components of blood
Innate: many antimicrobial peptides, proteins, and other mediator like cytokines
Adaptive: antibodies and cytokines
Innate vs. Adaptive Immunity: major cell types
Innate: Phagocytes (neutrophils, macrophages, monocytes) NK cells, other leukocytes, epithelial and endothelial cells
Adaptive: T cells, B cells, and antigen presenting cells
what are 4 barriers that are important in the innate immune defense?
- Anatomical barriers
- Physiologic barriers
- Soluble factor-based and chemical barriers
- Phagocytic and other cellular barriers
What are 3 components of physiologic and chemical barriers?
- Acid pH
- of lactic acid and fatty acids in sweat and sebaceous glands prevents microbe growth
- of the stomach kills most ingested microorganisms - Body temperature (fever response) can inhibit the growth of certain microbes
What is the structure of antimicrobial peptides?
Short cationic peptides (29-35 AA) with an amphipathic structure
- negatively charged portions tend to be buried in the protein while the positive parts are exposed
What are defensins and what produces them?
One of the most important antimicrobial peptides; made by intestinal paneth cells, epithelial cells, neutrophils, and macrophages
Can kill bacteria very efficiently
-can precent DNA and RNA synthesis by binding to negatively charged structures in the pathogen
What are antimicrobial peptides active against?
Bacteria, fungi, and enveloped viruses
What is the mode of action for antimicrobial peptides?
Bind to negatively charged microbial structures and membranes
What are the mechanisms of killing of antimicrobial peptides?
Disruption of microbial membrane integrity, inhibition of DNA, RNA, and or protein synthesis
Lysozyme location
Mucosal/glandular secretions like tears and saliva
Antimicrobial activities of lysozyme
Cleaves the glycosidic bonds of peptidoglycan in bacteria leading to lysis
Lactoferrin location
Mucosal and glandular secretions
-milk, intestine mucus, nasal + respiratory + urogenital tracts
Lactoferrin antimicrobial action
Binds and sequesters all free iron which limits the growth of bacteria and fungi as well as disrupts microbial membranes and limits the infectivity of some viruses
Defensins (alpha and beta) location
Skin, mucosal epithelia
Defensins antimicrobial activities
Disrupt membrane of bacteria, fungi, protozoan parasites, and viruses
Additional intracellular toxic effects
Kill cells and disable viruses
What are 5 examples of ways to penetrate the epithelial barrier and what are example pathogens that make use of this route
- via the airways (Streptococcus pneumoniae)
- via the gastrointestinal tract (E. coli
- via the genitourinary tract (Human Immunodeficiency Virus)
- via cuts in the skin (Staphylococcus aureus)
- via mosquito bites (West Nile Virus)
What are 3 elements that are activated after the penetration of epithelial barriers?
- Soluble innate immune recognition elements
- Phagocytic and other cells
- Cellular receptors present on innate immune cels that function as sentinel cells in tissues
what are small proteins that cause bacteria to aggregate (enhancing phagocytosis) as well as causing cell wall disruption?
Collectins
What are the 3 major types of interferons?
- Alpha-interferon produced by leukocytes
- Beta-interferon produced primarily by fibroblasts
- Gamma-interferon produced by T cells and NK cells
- not directly induced by viruses