Phagocytes Flashcards
Macrophage antigen presentation
- Pathogens become bound to PRRs on the cell surface (e.g., bacteria to mannose receptors)
- The pathogen is then engulfed into the cell by the process of endocytosis into a phagosome, it fuses with a lysosome to form a phagolysosome and the bacterium is completely degraded
Macrophage will load peptide fragments into MHC proteins to present to adaptive immune cells -> rare, since most macrophages are in tissues
Macrophage basics
monocyte that changes into macrophages after entering the tissue
long lifespan
Respiratory burst
- When phagosome fuses with lysosome, NADPH-dependent oxidases generate toxic oxygen radicals and H+
Hydrogen peroxide (H2O2) made from superoxide via superoxide dismutase - Accompanied by transient increase in O2 consumption known as respiratory burst
damages DNA among other things
Nitric oxide
NO
reacts with oxygen radicals to produce peroxynitrite (ONOO-)
Why doesn’t superoxide damage our cells?
- Accompanied by the synthesis of enzymes to inactivate the damaging molecules
- Superoxide dismutase converts superoxide to hydrogen peroxide
- Catalase converts H2O2 to water and O2
what is a cytokine
Small proteins/glycoproteins that mediate immune cell communication
types of cytokines
Affect the behaviour of the same cell (autocrine), local cell (paracrine), or distant cell (endocrine)
IL-1 beta
local effects: activate vascular endothelium, activates lymphocytes, local tissue destruction and increases the access of effector cells
systematic effects: fever and production of IL-6
Tumour necrosis factor alpha
LOCAL: activate vascular endothelium, increases vascular permeability, which leads to increased entry of IgG, complement and cells to tissue, increase tissue drainage to lymph nodes
systematic: - Fever
Mobilization of metabolites
IL-6
local: lymphocyte activation and increased antibody production
systematic: - Induces fever
Acute phase protein production
IL-8
chemotactic factor that recruits neutrophils, basophils and T cells to site of infection
IL-12
activate NK cells, induces differentiation of CD4 T cells into TH1 cells
Acute phase proteins
- Proteins produced by the liver and released into circulation
- In the absence of infection:
○ plasma concentration is very low
Neutrophil migration: basics
directed by cytokines
induces higher expression of adhesion molecules and stronger interactions
neutrophil binds to endothelium and squeezes in between junctions
- Neutrophil rolling adhesion: adhesion
- vascular endothelial cells transport selectin to surface after exposure to inflammatory mediators
- selectin bind to Sialyl-Lewisx (S-LEx) carbohydrate ligand on the neutrophil
- adhesion is reversible
- neutrophil rolling adhesion: tight binding
LFA-1 (neutrophil) binds to ICAM-1 (endothelial)
normal conditions: weak binding
inflammation: chemokine CXCL8 promotes conformational change to strengthen adhesion
tight binding to endothelium
- Neutrophil rolling adhesion: diapedesis
- neutrophil crosses blood vessel wall by squeezing in between cells
- proteases (such as elastase) secreted by neutrophil break down basement membrane
- rolling adhesion: migration
- Neutrophil migrates towards
centre of infection following
concentration gradient
– CXCL8/IL-8
– TNF-α
Neutrophil NET formation
neutrophil undergoes cell death where they release everything in their cell
nuclear chromatin forms fibril matrix that trap micro-organisms
triggered by reactive oxygen species promoting translocation of enzymes from granules to nucleus
