The immune response Flashcards
A pathogen has to (4)
- Colonise host tissues
- Avoid host defence
mechanisms - Grow within host tissues
- Cause damage to the
host
Colonisation is
microorganisms that are carried normally by the host, cause no harm and produce no overt symptoms (commensal)
Infection is
the invasion of a host organism’s bodily tissues by disease causing organisms. This can result in
disease
Innate immunity is
NON SPECIFIC, IMMEDIATE response, NO IMMUNOLOGICAL MEMORY
humoral: enzymes, cytokines
(cellular: phagocytes, NKCs, pattern receptors)(inflammation, complement system)
Adaptive immunity is
SPECIFIC to ANTIGEN, exposure-response LAG, IMMUNOLOGICAL MEMORY
(humoral: antibodies, cytokines)
(cellular: B cells, T cells)
(antigen processing and presentation)
Most immune cells are circulatory except
- Alveolar macrophages (fixed macrophages and dendritic cells have protrusions to bring pathogens in)
- M cells (microfold cells in the gut, don’t have as many villi as surrounding gut cells - key mediators in pulling in pathogens through the epithelial layer (through phagocytosis, endocytosis, transcytosis) and feed to macrophages in the tissues or bloodstream)
The professional phagocytes are:
monocytes macrophages neutrophils tissue dendritic cells mast cells
A professional phagocyte takes up
endocytosis and destroyed within a phagolysosome
Steps of killing in the phagolysosome
- bacteria are engulfed
- taken up into a phagosome
- ph lowers in the phagosome
- in professional phagocytes, phagosome fuses with the lysosome
- release of cell products and presentation on phagocyte surface
What is opsonisation?
the process by which the pathogen is marked for ingestion and eliminated by the phagocytes
Phagocytes are the interplay between
the innate and adaptive immune system
c3b complement
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes, and apoptotic cells for phagocytosis
- antibodies recognise structures on the surface of a bacteria
- macrophages have an FC receptor
- part of an antibody is called the FC chain
- if a macrophage has an FC receptor it will pick up a bacteria and coat it with antibody
- coating of a bacteria is called opsonisation
- c3b is a protein involved in the complement cascade (extra reading?) C3b has a thioester bond which makes it really reactive so it will react with amine and hydoxyl groups on the surface of the bacteria and bind to the bacteria covalently
- macrophages have a c3b receptor, stronger interaction and macrophages more likely to take up the pathogen
- if the pathogen has been subjected to antibodies (FC) and C3B uptake is a lot stronger
Professional phagocytes produce
ROS
in the lumen of the phagolysosome, but they can also be secreted by macrophages
ROS’s stem from the production of superoxide anion
(O2•− ) by NADPH oxidase.
The O2•− is rapidly
transformed to numerous other reactive oxygen species
(ROS),mainly H2O2, OH•, and HOCl.
Known as the ‘respiratory burst’.
Macrophages acidify the phagosomal lumen by
recruiting V-ATPase (H+ pump)
NRAMP
antimicrobial peptide produced by phagocytes
natural resistance associated macrophage protein (strips divalent magnesium from bacteria so they can’t grow)
antimicrobial peptides are delivered to the phagosome by
granular organelles in neutrophils and by fusion with the lysosome in macrophages
Lactoferrin is an antimicrobial peptide produced by the host that
strips iron: makes iron unavailable to bacteria
defensins and cathelocidins are antimicrobial peptides that bind to
the membrane causing cellular destruction
the Lysosome breaks down
sugar chains in peptidoglycan
cytokines are produced by phagocytes to
activate other phagocytes and recruit monocytes
PAMPS (pathogen associated molecular patterns) are recognised by TLRs
DAMPS recognise host cell damage
PAMPS
Lipopolysaccharides, DNA, cell surface proteins etc are all PAMPs which are recognised by TLRs
NODS recognise
peptidoglycan
TLRs
a class of proteins, are single, membrane-spanning, non-catalytic receptors usually expressed on macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes
chemokines
chemotactic and chemokinetic for leukocytes: stimulate cell migration and attract phagocytic cells and lymphocytes. Central role in inflammatory response.
hematopoetins
stimulate and regulate growth and differentiation processes involved in blood cell formation (hematopoeisis)
interleukins
produced by lymphocytes and monocytes, regulates the growth and differentiation of other cells, particularly lymphocytes and hematopoeic stem cells
TNFs
cytotoxic to tumour cells, promote inflammation, fever and shock (and some apoptosis)
Following destruction of an ingested microbe, what happens?
Phagocytes as APC’s – recognition by CD8+ and CD4+ T cells
CD4 = Th
CD8 = Tk
CD4+ T cells recognise
antigen presented by MHC II molecules on phagocytes
CD8+ T cells recognise
antigen presented by MHC I molecules
beta2 microglobulin is a key part of the presentation of antigen to CD8 t cells. The proteosome chops up foreign cell products from the CYTOSOL, send them to the ER to be sent to MHCI (NOT FROM THE PHAGOSOME)
