C4 Phagocytes Flashcards
describe mast cells involved in released from what cell line then differentiate to what what is development influenced by what do they form
involved: allergy, asthma, hay fever. protective against bacteria & large pathogens: gut helminths
released from BM as CD24+, KIT+, CD13+ –> differentiate in tissue (skin, connective, epithelial)
form ETS: extracellular nets (made from DNA, histones, tryptase)
what happens upon activation of mast cell
become bigger & degranulates
what are mast cell deficient mice more susceptible to?
Bacterial infections
(C3b deficient mice also impaired mast cells)
(leukotriene KO mice more susceptible to bacterial infection)
what are the two types of rodent mast cells
Mucosal-type e.g. Gut mucosa - 40 day life span
Connective- tissue type - skin or peritoneal cavity >6 months
what are the types of human mast cells
What type of Th response favors production of mast cells
MCT: tryptase containing - mainly airway & small bowel submucosa
MCTC: tryptase & chymase - mainly skin & small bowel mucosa
Th2 –> IL4: promotes mast cell proliferation in presence of SCF
Th1 –> IFNy reduces mast cell number
role of SCF
stem cell factor: Acts to ↑ no. of mast cells present during an infection
(increases in intestine during bacterial infection)
Activity regulated by cytokines: IL-3, IL-4, IL-5, Il-9, IL10, GM-CSF receptors present
Th2 –> IL4: promotes mast cell proliferation in presence of SCF
Th1 –> IFNy reduces mast cell number
describe activation of mast cells
- Opsonized pathogens (antibodies: FceR1 for IgE & FcyR1 for IgG)
(complement coated: CR3aR & C5aR) - PRR (lectin binds mannosylated Mast cell R, TLR1-& & TLR9)
- Host molecules (fibrinogen/ fibronectin subfragments produced by cleavage of plasmin)
- Venom components
- Physical stimuli
- Chemical agents
describe action of mast cells
- Secrete performed mediators (e.g. histmaine, mast cell proteases (25% content))
- Direct toxicity via granules produced: TNFa directly toxic to cells/pathogen
- Phagocytosis: produce respiratory burst - via MHCI (stim Tc)
Effectors of mast cells
- histamine (potent vasodilator/ facilitates arrival of inflammatory cells/antibodies to site of infection)
- LTB4 (chemotactic to neutrophils and eosinophils)
- Tryptase (can cleave C3 to C3a and activate fibroblasts)
- Tryptase & prostaglandin D2 (induces neutrophil influx )
- Prostaglandins (bronchoconstrictors/ cell permeability)
- Stimulate macrophages (via MIP1a & MIPB & MIP2)
- TNFa - major cytokine produced (upreg adhesion molecule/ increase bronchoresponsiveness)
- IL-4 (effects differentiation of Th –> Th2, stims IgE production)
- APC - via MHCI to stim Tc
describe Eosinophils
Involved in protection against gut/lung infections
Phagocytic (not main job)
Can cause adverse effects e.g. Asthma
Can generate a respiratory burst (high levels of NAPDH oxidase)
Important in antigen presentation (have MHC-II molecules & co-stim molecules)
Make extracellular traps – explosive - mitochondial DNA
describe direct action of eosinophils & indirect action
Direct
Imp defense against gut helminths
Impt against viral infection e.g. Respiratory syncytial virus
Indirect
Tissue remodeling
Immunomulation
Defense against reinfection - memory development - present antigen
what is involved in the activation of eosinophils
- Opsonins: antibody – receptors for IgG (FcyRII) and IgA (FcyRI) and IgE (FcyRI, low)
complement: receptors for C3a, C5a, CR1 - cytokines – receptors for IL-3, IL-5, GM-CSF
- chemokine receptors
- Toll receptors – express TLR1, TLR4, TLR7, TLR9 and TLR10 (TLR7 and TLR8 may be more impt).
name the 4 types of eosinophils
- crystalloid granules: major basic protein, eosinophil peroxidase, eosinophil cationic protein, eosinophil neutrotoxin.
- Primary granules: Charco-t-Leyden crystal
- small granules
- secretory vesicles
describe Cyrtalloid granules
all contents cytotoxic
- Eosinophil basic protein - causes degranulation of mast cells & basophils (toxic to parasites)
- Major basic protein - increases membrane permeability, effects lipid cell surface bilayer
- Eosinophil cationic protein - causes formation of selective ion pores
- Eosinophil derived neurotoxin - directly toxic
- Eosinophil peroxidase - involved in bacterial killing - catalyzes peroxidation of halides - formation of acids