Immunology 3: Innate Immunity Flashcards
What are the 3 recognition stratergies
Detect conserved microbial structures - PAMPs
Detect metabolic consequences of cell infection or injury - DAMPs
Detect ‘missing self’
4 innate immunity defensive barriers
Anatomical (physical):
Skin - mechanical barrier, acidic environment
Mucous membranes - mucus secretions trap microorganisms, cilia (respiratory tract) expel microorganisms
Physiological:
Body temperature / fever
Low pH - acidic pH of stomach kills many ingested microorganisms
Chemical mediators - lysozyme, interferons, complement
Phagocytic: cells ingest material
Inflammatory: local vascular permeability increases
7 Cell types in innate immunity
Neutrophil: phagocytosis and killing of microbes
Eosinophil: phagocytosis, granule release, defence against parasitic infections, help B cell responses in GALT (IgA production)
Basophil: granule release, may act as APC for “type 2 immunity”
Monocyte / macrophage: phagocytosis, killing, cytokine release, act as APC
Mast cell: granule release (pro-inflammatory)
Dendritic cell: antigen capture and presentation
Natural killer cell: lysis of infected cells
Describe neutrophils
(polymorphonuclear leukocyte)
40-75% of leukocytes;
short lived cells,
circulate in blood then migrate into tissues;
first cells to be recruited to a site of tissue damage/infection
Describe macrophages
less abundant,
dispersed throughout the tissues;
signal infection by release of soluble mediators
What 3 things do neutrophils do to fight infection
Bind pathogen
Phagocytose pathogen
Kill pathogen
Describe the Movement of Neutrophils into Tissues:
Low affinity bidning to selectins at the start if the tissue
Integrin activation by chemokines - chemokine receptor on neutrophil binds to chemokine on endothelial surface and activates integrin converting it to the high-affinity state.
Stable Adhesion - Integrin binds STRONGLY to the integrin ligand and the neutrophil is immobilised
Cells migrate into tissue - the cells then follow a chemokine gradient to figure out where to go - this is chemotaxis
What is diapedesis
movement of a cell across the endothelial layer
What is opsonisation
coating of micro-organisms with proteins to facilitate phagocytosis
Opsonins act as adapter molecules which bind to the pathogen and link it to receptors present on the phagocyte.
Antibodies and Complement Proteins act as opsonins. - which then bind to phagocytes
What are the two neutrophil killing mechanisms
Oxygen-Independent Enzymes Lysozyme Hydrolytic Enzymes Antimicrobial Peptides (Defensins)
Oxygen-Dependent
What are NEUTROPHIL EXTRACELLULAR TRAPS (NETs)
When neutrophils become highly activated they release these nets that help trap extracellular bacteria and immobilise them.
This helps other cells find these trapped bacteria.
2 Function of macrophages
phagocytosis
signal infection by releasing soluble mediators (alarm cytokines).
Describe Mast cells
Not in blood-> in tissues
secrete histamine and other inflammatory mediators, including cytokines
mucosal mast cells (lung)
connective tissue mast cells (skin and peritoneal cavity, near blood vessels)
can recognise, phagocytose and kill bacteria
can be activated by complement products (anaphylatoxins)
leads to vasodilation and increased vascular permeability
Describe natural killer cells
large granulated lymphocytes: cytotoxic, lyse target cells and secrete the cytokine interferon-
5-10% peripheral blood lymphocytes
no antigen-specific receptor, but express both activating and inhibitory receptors: balance of signals
have receptors which bind to antibody-coated cells (Antibody Dependent Cell-mediated Cytotoxicity)
important in defence against tumour cells and viral infections (esp. herpes)
Describe target cell recognition in natural killer cells
Missing self recognition
target cells have MHC class I markings on the cell
these are inhibitory to NK cells
If theres a problem with the cell these markings might not be present
Induced self recognition
Target cells have stress-induced molecules on its surface if theres a problem
these activate the NK cells