Innate Immunity Flashcards
First line of defense in innate immunity
- Anatomical
- Skin
- Mucous membranes
- Mechanical
- Cilia in respiratory tract
- Tight jxns between cells
- Tears
- Physiological
- Lysozymes
- Fatty acids on skin
- Low pH/digestive enzymes in the gut
- Antibacterial peptides
Second line of defense in innate immunity
- Phagocytosis - neutrophils (PMNs), monocytes, macrophages
- Immune surveillance - natural killer cells’ cytotoxic activity
Neutrophils (PMNs) are short-lived and fast-acting.
Function
- Phagocytosis releases hydrolytic enzymes responsible for other processes that effect acute inflammation
- Also involved in the complement system
- Releases cytokines for cell-cell communication
- Neutrophil extracellular traps (NETs): neutrophil vomits out its own DNA (suicide), which sticks to bacteria and traps them from moving
Overview of innate immuner response when there is a barrier breach of skin
- Bacteria enter through the breach
- Cytokines recruit neutrophils to the site of invasion
- Neutrophils create redness, heat, swelling
Recall from acute inflammation:
How do neutrophils and other leukocytes leave the bloodstream and enter the intersitial space?
- Cytokines at the site of injury signal endothelial cells to present selectins –> margination
- Selectins weakly bind to leukocytes –> rolling
- Adhesion to the postcapillary venule (veins thinner than arteries)
- TNF and IL-1 upregulate CAMs
- C5a and LTB4 upregulate integrins (interacts w CAMs)
- Transmigration across the endothelium
- Chemotaxis - leukocytes move toward chemical attractants
- Neutrophils are attracted by bacterial products, IL-8, C5a, and LTB4
Macrophages are long-lived mononuclear phagocytes. Like neutrophils, they undergo diapedesis to leave the blood.
No recognition of self vs non-self, only uses ___
toll-like receptors
Describe the process of macrophage phagocytosis
- Opsonins (IgG & C3b) target microbe for phagocytosis
- Pseudopods extend to ingest the microbe
- Phagosome is formed and merged with lysosomes –> phagolysosome
- Digestion by enzymes
- Discharge residual bodies containing indigestible materials (waste), which flows through nodes to interact w lymphocytes
Naural killer cells
Large, granular lymphocytes that are involved in cytotoxicity against virus-infected cells and tumor cells.
How do NK cells know which cells to kill?
They recognize cells that lack MHC-1. However, overproduction of a stimulatory ligand can also cause an NK cell to kill it, even in the presence of MHC-1 (normally inhibits NK cell)
Many viruses and tumors downregulate ___ to
MHC-1
to protect from killing by cytotoxic T cells, but then NK cells recognize this loss of MHC, and kill these cells
___ are a pattern recognition receptor (PRR) on immune cells that allow recognition of pathogen-specific molecules called PAMPs.
It is the main way that the innate immune system identifies foreign vs self
Toll-like receptor
Dendritic cells recognize __ through TLRs, then travel to the lymph nodes ot recruit the ___
Recognize PAMPs through TLRs –> travel to lymph nodes to recruit the adaptive immune response
This is why vaccines contain PAMPs - they want to stimulate the innate immune response, then the adaptive immune repsonse
TLR4
recognizes LPS (lipopolysaccharides), a component of gram-negative bacteria cell walls
present on macrophages, dendritic cells, mast cells, and eosinophils
Complement system
Serum enzymes (“complements antibody activity”) that…
- Recruitment of inflammatory cells
- Opsonization of pathogens for phagocytosis
- Perforation of pathogen cell membranes
Complement system consist sof classical, alternative, and lectin pathways. What are they and what is the order in wihch they occur?
Alternative > lectin > classical
- Alternative: pathogen surfaces activate complement; continuously activated in a low level
- Lectin: mannose-binding lectin binds to pathogen surface (low yield)
- Classical: C-reactive protein or antibody binds to a specific antigen on pathogen surface -> activate complement
Complement proteins C1-9 are activate din numerical order, but the system converges on ___, which will __
Converge on C3, which sticks to the surface of bacteria
FUNCTIONS OF CYTOKINES
o T cell activation
o B cell activation
o Hematopoiesis
o Toxicity
o Antiviral defense: Interferons (esp IFN-a & IFN-B)
o Inflammation: Pro-inflammatory cytokines, IL1, IL6, TNF-a
