Innate immune response Flashcards
What are the proportions of leucocytes in the blood?
Less than 1% 60- neutrophils 25- B and T lymphocytes 5- monocytes rest (5) eosinophils and basophils
What is complement activation?
Series of soluble proteins in the blood
C1 to C9
Acellular, circulate in inactive state
What are the pathways of activation of complements?
Classical
Mannose-binding lectin
Alternative
What is the classical pathway of complement activation?
Only occurs when there are antibodies specific to foreign antigen present (adaptive)
Antibody complexes bound by complement component C1q
Activate subsequent complement components
What is mannose-binding lectin pathway of complement activation?
Activation through mannose-binding lection binding mannose/ similar carbohydrates on bacteria- PRR like
Mannose not present on surface of host cells
What is alternative pathway of complement activation?
Complement component C3
Spontaneously activates and binds to nearby membranes
Host cells have control proteins on surface to prevent further complement activation/ bacteria do not- activate
Activates other C3s
What are the effects of complement activation?
Membrane Attack Complex/ complement lysis
Anaphylatoxins
Opsonisation
What is complement lysis?
Membrane Attack Complex (MAC) inserted into bacterial membrane
Barrel-like structure (C6-C9)- lesions
Water in, ions out- osmotic imbalance, swell and burst
Any cell marked
What are anaphylatoxins?
Toxins that cause anaphylaxis
Leaky blood vessels/ increase vascular permeability- oedema= recruitment of immune cells, activation of mast cells (histamine)
Small bits of complement that disperse
What is opsonisation?
Bind to surface of bacteria
Phagocytes have complement receptors which bind to membrane bound complement
Encourage phagocytosis and killing
Name the innate immune cells that are phagocytes
Neutrophil, dendritic cell, macrophage
Name the innate immune cells that are involved in allergic and anti parasite responses
Eosinophil, basophil, mast cell, Natural Killer cell (kills virally infected/ sick cells)
Describe neutrophils
Killers, recruited rapidly to scene (30-80% WBC), very short lived as so toxic, chief constituent of pus
Describe macrophages
Good killers if activated, reside in tissue, involved in tissue healing/ clearance of dead cells/ metabolism
Describe dendritic cells
Poor at killing, rare, reside in tissue, initiates adaptive response- messenger to T cells
What is extravasation?
Neutrophils transported from circulation to site of inflammation
Describe the process of extravasation
Endothelium of blood vessels altered by inflammatory cytokines
neutrophils roll along endothelium, firmly adheres, exits between endothelial cells (diapedesis)
Follows chemokine gradient to site of inflammation
Describe the process of phagocytosis
Phagocyte engulfs pathogen- phagosome formed
Lysosome fuse with phagosome- phagolysosome
Matures when more lysosomes fuse
Nitric oxide, oxygen radicals, proteases
Neutrophils make HOCl- bleach
How are macrophages activated?
Danger signalling/ cytokines IFN gamma (interferon)
IFN gamma from NK cells, activated macrophages, helper T cells- makes more oxygen radicals
What are NETs?
Neutrophil Extracellular Traps
Extrude DNA, traps pathogens= netosis (vs apoptosis and necrosis
Extracellular fungal infections
Describe antigen presentation
Dendritic cells in periphery sense danger, take up antigens, mature/ high density of PRR
Upregulate different chemokine receptors
Migrate to lymphatics, drained into lymph node, present antigens to T cells
Describe the structure of a lymph node
Afferent and efferent lymphatics
Blood supply- high endothelial venule
B cell follicle surrounded by T cell area in segments
Why is antigen presentation so complicated?
So we don’t generate immune responses against harmless things (allergy/IBD) or your own tissues (autoimmunity)
How are antigens recognised?
B cell receptor BcR recognises soluble antigen in native form
T cell receptor TcR have antigens presented to it on Major Histocompatibility Complex MHC molecules on another cell
Antigens hydrolysed by dendritic proteases, loaded onto MHC molecules and presented on cell surface
