Immunology 3 - Innate Immunity Flashcards
Recall the physical barriers used by the immune system in host defence
Physical:
- Skin (mechical with an acidic envitonment).
- Mucous membranes (trap microorganisms, cilia expel them)
Recall the chemical barriers used by the immune system in host defence
- Physiological
- Body temperature, low pH, chemical medicators (eg. lysozyme and compliment)
- Phagocytic
- Inflammatory
List the different cell types in the innate immune system and summarise their roles
- Neutrophil: phagocytosis 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
How do neutrophils move into tissues?
Diapedesis and chemotaxis
- Rolling along the vessel wall
- Integrin activation by chemokines
- Forms a stable adhesion
- Migration through the endothelium (chemotaxis)
What is opsonisation?
- Coating of microorganisms with proteins to aid phagocytosis.
- Opsonins may bind to antigens and be bound to phagocytes
Describe the process of a neutrophil binding to an opsonin.
- Antibody binds to receptors on the bacterial cell surface.
- Complement binds to the bacterial surface
- Receptors on the neutrophil bind to both the compliment and the antibody
What are the oxygen dependent neutrophil killing mechanisms?
- respiratory burst:
- superoxide anion
- hydrogen peroxide
- singlet oxygen
- hydroxyl radical
- reactive nitrogen intermediates
- nitric oxide
What are the oxygen-independent neutrohil killing mechanisms?
- enzymes
- lysozyme
- hydrolytic enzymes
- antimicrobial peptides (defensins)
What are neutrophil extracellular traps?
- Activated neutrophils release granule proteins and chromatin to form extracellular fibres
- This forms a NET that traps the pathogens.
How can you distinguish visually between monocytes in the blood and macrophages in the tissue?
Monocytes are smaller with fewer organelles and a smaller nucleus
Describe the process of macrophage function
- The macrophage has receptors for many bacterial constituents
- Bacteria bind to macrophages and cytokines are released to warn other cells
- Macrophages then engulf the bacteria and digest them
What is the role of mast cells?
- To secrete histamine and other inflammatory mediators such as cytokines.
- Can recognise and phagocytose bacteria
- Result in vasodilation and increased vascular permeability
- Can be activated by complement products (anaphylatoxins)
Describe how you can distinguish between a resting mast cell and an activated mast cell.
Resting mast cells have many granules, whereas activated mastcells release those granules so appear lighter except for the nucleus.
What is the role and of natural killer cells?
- Large granulated lymphocytes: cytotoxic, lyse target cells and secrete the cytokine interferon
- 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)
How does natural killer cell target recognition occur?
- Have self receptors which are inhibitor, and when they bind to the target cell the process of cell killing is inhibited
- They have activating receptors which bind to stress induced molecules and lyse the target cell
What is recognition of affected cells by natural killer cells called?
Missing self/induced self recognition
What are cytokines?
- Small secreted proteins
- Used in cell-to-cell communication
- Generally act locally
- They have biological effects at very low concentrations
- Short-lived
List the types of cytokines
- Interleukins (IL-x): between leukocytes
- Interferons (IFN): anti-viral effects
- Chemokines
- Growth factors proliferation and differentiation of cells
- Cytotoxic tumor necrosis factor (TNF)
What are the three modes of action of cytokines?
- Autocrine action is on the cell that released the cytokine
- Paracrine action is on a nearby cell
- Endocrine action has a distant target cell, requiring circulation
What are dendritic cells?
- Network of cells located at likely sites of infection
- Recognise microbial patterns¬ secrete cytokines
- Capture pathogens, and migrate to local lymph node to present antigens to adaptive immune system (important APC)
What is the complement system?
- Compliment the activity of specific antibody in lysing bacteria
- Complex series of proteins and glycoproteins produced by the liver
- Triggered enzyme cascade system
- Rapid, highly amplified response
What are the three complement activation pathways?
- Classical (antigen/antibody complex)
- Lectin (mannan binding lectin C reactive protein - lectins bind to bacterial carbohydrates)
- Alternative pathway (recognises bacterial surfaces)
What is the final common pathway in complement activation?
C3b (opsonin - causes mast cells to degranulate and release histamine) to form membrane attack complex.
How is the complement system controlled?
- Lability of components
- Dilution of components in biological fluids
- Specific regulatory proteins (circulating/membrane bound)
What are the functions of the complement system?
- Lysis of target cells
- Opsonisation to aid phagocytosis
- Activate the inflammatory response
- Clearance immune complexes by phagocytosis
What is an acute-phase response to the innate immune system?
- Fever, increased white blood cell production, and protein production
- Induced by cytokines
