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IMMUNOLOGY INTRO
1. Innate (non-specific) Immunity: structural, cellular, and molecular components. Present at birth and do not change in response to exposure to antigens
2. Adaptive (Acquired, specific) Immunity: T-Cells and B-Cells. w/help from MHC components. Change in response to exposure to antigens
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Cells of the immune system (slide 3)
Hematopoetic Stem Cells: Found inbone marrow. Gives rise to myeloid and lymphoid lineage.
*Separate lineages for neutrophils, macrophages, and lymphocytes
- Neutrophils: Derived from myoblast
- Macrophages: Derived from monoblast
- Lymphocytes: Derived from lymphoid stem cells
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Innate Structural Immunity (Slide 4)
Outer Skin (Epidermis layers): Dead physical barrier, salty, dry, and acidic. Contiuously sloughed off
Dermal Cells: Secrete dermicidins (40 AA long peptides)
Sweat Glands: Secrete dermicidins. Secrete lysosymes which can kill both Gram pos. and neg. bacteria
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Innate Structural Immunity Cont. (Slide 5)
Mucous Membrane: Cells lining region of body directly exposed to environment. Continuously flush microbes thru production of mucous and cilia movement
Mucous cells secrete antibacterial enzymes and lactoperoxidase
Lactoperoxidase: Secrete hypthiocyanite
Most mucosal systems sequester iron (lacto- and gastroferrin), which is a limiting nutrient in the growth of microbes.
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Innate Structural Immunity Cont. (Slide 6)
Digestive System: Saliva (Lysozyme). Microbes are killed in the stomach by acids. Stomach produces gastroferrin
Bile and pancreatic secretions in intestines inhibit growth of microbes
Urine, tears and paneth cells of intestines contain/make lysozymes
Lysozyme: Cleave between the NAG and NAM on the cell walls of microbes
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Monocyte-Macrophage System (Slide 7)
Cells from monoblast that circulate thru blood and lymph systems. May penetrate surrounding tissues and differentiate based on tissues.
All Macrophage-like cells contain receptors (Patern Recognition Receptors) that recognize and bind to Pathogen-associated molecular patterns (PAMPs)
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How phagocytes recognize pathogens: Toll-like receptors (TLRs) (Slide 8)
Most PRR's are found on neutrophils and macrophage-like cells (Both types are phagocytes)
TLRs, a type of PRR, bind to specific PAMPs from bacterial and eukaryotic pathogens triggering immune system's master gene regulator, NFkB
TLRs recognize bacterial LPS, CpG from lysed DNA, flagella, zymosan, and mannans from yeast
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How phagocytes recognize pathogens: Other Receptors (Slide 9)
Other receptors include LPS receptors, lipoteichoic acid and peptidoglycan receptors
All receptors trigger phagocytosis of pathogen
Receptors for Opsonins: Immune system cover pathogen with opsonins including igG or igM antibodies or C3b protein enducing phagocytosis
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How Phagocytes Kill Pathogens (Slide 10)
Bound pathogens are internalized in a phagosome that fuses with lysozome to create phagolysosome
Phagolysosome contain enzymes that form ROIs and RNIs (Reactive Oxygen and Nitrogen Intermediates) and digestive enzymes
Digested debris is released by ALL phagocyic cells, but ONLY macrophages carryout antigen presentation
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Lysosomal enzymes in phagocytic cells (Slide 11)
Very high levels of ROIs are made w/in phagolysosome that then kill ingested microbes
NADPH oxidase produces high levels of O2-
NO synthase makes NO from Arg
NO + O2- --> ONO2- (extremely reactive RNI)
Myeloperoxidase generates HOCl (Bleach)
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Lysosomal enzymes in phagocytic cells (Slide 12)
Neutrophils (PMNs) are very short-lived because they self destruct even w/out an infection
PMNs are very abundant
Macrophages use same lysozomal enzymes, but survive to activate rest of immune system, therefore not as efficient in killing microbes
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Chemical mediators in the circulation (Slide 13)
- Antimicrobial Cationic Peptides: Made by a variety of host and work by binding to and damaging bacterial CMs or other cell structures
- 1. Cathelicidin: Contain no Cysteine
- 2. Defensin; Contain lrg amnts of ARG and CYS
- 3. Histatin: Contain HIS
Bacteriocidin (Colicins)
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