L2 Introduction to immunology Flashcards
Innate immunity
Cannot be seen: Complement Toll-like receptors Cytokines Chemokines
Can be seen:
Phagocytes-neutrophils and macrophages
Phagocytosis
Inflammation
Complement
Present in the serum
-Sensitizers or helpers
-20 serum proteins
-Many are “pro-enzymes/zymogens” which are inactive unless they are cleaved by which are activated.
-3 major effects:
Lysis-MAC (membrane attack complex)
Chemoattraction-C5a, ability to attract via conc.gradient
Opsonisation-C3b, marks something, coating a bacteria with complementary proteins, for phagocytosis.
3 Pathways of Complement acivation
Classic: started by antibody (antigen complexes)
Lectin: sugars that are present on bacterias, which are unique can activate complement
Alternative: Microbial surfaces
All 3 pathways end up with the same process
Toll-like receptors (TLR)
Think of toll-gates.
Receptors that allow immune system to detect pathogens
Both intra and extracellular pathogens.
Present on leukocytes and mucosal lining cells
Recognise PAMPS - pathogens associated molecular patterns, similar/same across bacteria.
12-15 members, usually 12 in humans.
Homo-hetero dimers, can be the same or different pairs.This determines the response
Groups:
Extracellular: 1,2,4,5,6,11
Intracellular:3,7,8,9 (viruses, need the cell to survive)
Downstream effects produce cell activation and cytokine activation
Cytokines
Cyto-cell, Kinos-movement
Diverse group of small proteins
Act at really low concentrations (pg,ng,ug range)
They are redundant relative to the immune system, if one is taken away, the immune system will replace as they have a lot of overlapping activities.
Growth, differentiation and activation.
Synergise with one another - cytokine 1 and 2 will not give an additive advantages but multiplicative, as their pathways overlap.
IL1, TNF, IL10
Inter-leuken cytokines
IL1 and TNF are for activation, IL10 for deactivation
Chemokines
Chemotactic cytokines
Major role: drag cells to particular place, 100 members
Creates gradients in tissues to allow inflammatory response.
2 Large families: CXC (2 cystine, 1 amino acid) and CC
2 additional types: C and/or CX3C
Receptors - 7 TMD, G-protein couples GPCR
2 Major receptor families CXCR and CCR
Most chemokines interact with multiple receptors and most receptors respond to multiples chemikines
Subset specificity.
Chemokines structures
C, CC,CXC,CX3C
Macrophages
Like TLR cells
Their main role as scavengers, they eat and clear bacteria and dead cells.
Made from monocytes, to tissues and become macrophages.
Killing is nitrogen related
Last for weeks
Express TLR
Phagocyte - Neutrophil
Distinctive
Short half life, with high turnover (high activity)
Multi-lobed nucleus
They have multiple granules involved in digestion (1’,2’,3’)
Killing mechanism is Oxygen related (ROS), NADPH oxidase to reduce oxygen radicals. This is the main difference to MACROPHAGES
Express TLR
Nuclear Extracellular Trap (NETs), they burst and secrete sticky, digestive material to attack foreign bodies
Neutrophil apoptosis
Programmed cell death
This is NOT NECROSIS, their membrane remains intact!!
They express molecules in their surface which signals macrophages to process dead cells.
This ultimately prevents tissue injury
Phagocytosis
Cell eating
Pathogen bind to phagocytic surface (receptor)
Internalised and sealed
cutting of cell membrane, cell membrane is left inside with the bacteria
Phagocytic receptors
Complementary receptors
Antibodies bind by the Fc region/receptor.
Sugar receptors
Phagosome maturation
Once phagosome is produced, the environment is further made destructive.
pH is more extreme, low hydrolytic activity.
inflammation
(redness, swelling, heat and pain, loss of function)
This is what is seen when innate immunity occurs.
Blood vessel (endothelial cells): Bacteria is dragged by chemokines, activated by integrins, they transmigrate from epithelial cells to tissue spaces
Acute inflammation
Look at diagram, represents time lapse of the process.
