Killing extracellular pathogens L22 Flashcards
2) DC activate T cells
when there is a pathogen in the body, DCs take the Ag to the LN where the naive T cells are
these Naive T cells interrogate DC to see if the Ag being presented is one they recognised
Th cells - helper
coordinates immune response
amplify innate immunity
expresses CD4 and recognises extracellular Ag presented by MHC 2
secretes IFN-Y to:
activates macrophages
inflammation
activation of T and B proliferation
Regulatory T cells - Treg
turn off immune response
express CD4 and recognise extracellular Ag presented by MHC 2
CTL - cytotoxic
kill infected cells
express CD8 and recognise intracellular Ag presented by MHC 1
3) T cells activate, divide and differentiate into effector cells
first antigen recognition from APC to naive T cell, causes activation and this secretes cytokines and cytokine receptor expression (IL-2 AND IL-2R)
proliferation occurs via mitosis and then differentiation - this occurs in lymphoid organs
differentiation of T cells is in the peripheral tissues, either becoming :
- effector T cell
- memory T cell
CD4+ receptor
activation of macrophages, B cells and other cells
CD8+ receptor
killing of targeted infected cells, macrophage activation
different Th cells
subsets are specialised at dealing with different infection types so it is important can differentiate into these to specialise their immune attack
Th1
Th2
Th17
Tfh
what does Th1 do
promotes cell-mediate immunity, targeting macrophages and causing activation of macrophage
secretes IFN-Y mostly, but also IL-2 and TNF-A
targets intracellular pathogens and cancer cells
IL-12 drives naive T cells to become Th1
can play a part in autoimmunity and chronic inflammation
migrate to infection site
what does Th2 do
this promotes humour (antibody mediated) immunity
producing cytokines IL-4, IL-5, IL-13
main role is activating eosinophils (IL-5), promoting B cells to switch to IgE (IL-4) , stimulation of mast cells and basophils, alternative macrophage activation
this attacks, kills helminths
can play a role in allergies
migrate to infection site
what does Th17 do?
enhances neutrophil-mediate response
produces IL-17, IL-21, IL-22 MAINLY
causes neutrophil recruitment (IL-17) and activation, can strengthen epithelial barrier (IL-22)
attacks extracellular bacteria and fungi, especially at mucosal barriers
can play a role in autoimmunity and inflammation
migrate to infection site
what does Tfh do
helps B cells in germinal centres - antibody production and isotype switching
produces IL-21 and IFN-Y or IL-4
promotes affinity maturation and class switching, essential for long -term humour immunity and supports generation of memory of B cell
these remain at LN to activate B cells
how does Th cell subset differentiation occur?
1st need signal 1 and 2 for T cell activation and clonal expansion via IL-2
then signal 3 directs T cell effector function - subset differentiation
signal 3 and effects for T cell differentiation
signal 3 is usually given by cytokines secreted from other cells (from APC) to tell T cell the infection type - bacteria, virus , parasite etc,
so it can differentiate into a specific type best for the type of microbe infection
IL-12
drives differentiation into Th1
IL-4
drives differentiation into Th2
TGF-Band IL-6/IL-23
drives differentiation into Th17
IL-6 and IL-21
drives differentiation into Tfh
TGF-B and IL-2
drives differentiation into Treg
activated and naive B cells
activate B cells are known as plasma cells and secreted antibody is their effector molecule
naive cells do not produce Ab until activated, membrane bound antibody is the B cell antigen receptor
naive B cells
haven’t encountered antigens yet
express IgM and IgD on their surface
circulate in blood and lymph
awaiting activation by antigen and T cell help
Plasma B cells - effector B cells - activated
differentiated into antibody secreting cells
secrete large amounts of antibodies
short lived in circulation but long lived in bone marrow
memory B cells
formed after activation and class switching
long lived and quick responders to repeat infections
express class -switched BCRS
IgM
pentamer
first antibody made
strong complement activation
good at agglutination
fast responder
found on naive b cells
IgG
monomer
most abundant in blood
neutralisation
opsonisation - phagocytosis aid
crosses placenta
protects foetus
main antibody after vaccination
IgA
dimer with secretory component
mucosal protection
neutralisation of pathogens without inflammation
passed to baby via breast milk
mucosal barrier antibody
IgE
monomer
binds to mast cells and basophils
triggers histamine release
defense against parasites
key for allergies
IgD
monomer
possible in role in b cell activation
not much known
co expressed with IgM on naive b cels
complement system 3 main functions
opsonisation to enhance phagocytosis
stimulating inflammation by recruiting and activating immune cells
lysising microbes and cells
complement mediated opsonisation
binding of C3b to microbe
recognition of bound C3b by phagocyte C3b receptor CR1
phagocytosis and killing of microbe
complement mediated inflammation
C3a, C4a, C5a released during complement activation
act locally similar to inflammatory cytokines to recruit cells to infection site and activate cells like neutrophils, lymphocytes and macrophages
complement mediated cytolysis
membrane attack complex MAC forms in membrane of bacteria to cause water to rush in, ions rush out and burst microbe
can also kill host/foregin cells
steps of phagocytosis
1) phagocyte detects microbe via PRR, complement protein of Ab and then extends pseudopodia to engulf microbe
2) membrane invaginated forming an inside out vesicle called phagosome
3) phagosome fuses with lysosome to form a phagolysosome and this enzyme degrades microbe
4) chemical in phagolyosome active and digest microbe
vacuolar ATPases -phagosome killing mechanisms
these pump H+ ions into phagosome to acidify the environment
lowers ph to activate enzymes and inhibit pathogen survival
ROS - respiratory burst - phagosome killing mechanisms
phagocyte oxidase converts O2 to superoxide to form H2O2 or OH radicals, this is toxic to bacteria and viruses
bleach bomb - phagosome killing mechanisms
MPO use H202 + CL- to form HOCL which is a potent microbicidal oxidant to kill bacteria by oxidising proteins lipids and DNA
proteolytic enzymes - phagosome killing mechanisms
neutrophils = elastase, cathepsins
macrophages = lysosomal hydrolase
these degrade bacterial proteins, cell walls and nucleic acids to destruct microbial components
nitric oxide and RNS - phagosome killing mechanisms
macrophages produce NO via iNOS to react with superoxide to form ONOO-, damages microbial DNA, proteins and membranes
nutrient deprivation - phagosome killing mechanisms
lactoferrin binds iron to limit avaliablty to pathogen
scavenger proteins remove other essential nutrients
starves microbes of key elements
antimicrobial peptides - defensives - phagosome killing mechanisms
insert into bacterial membranes to form pores to cause direct microbial lysis
antibodies make phagocytosis more efficient
Ab bind to microbe with high specificity and affinity
phagocyte binds to Ab via Fc receptor (FcR)
this is more efficient detection system than PRRS
the binding of the Ab to FcR activates phagocyte for phagocytosis
neutrophil extracellular Traps NETS
neutrophil dies via NETosis
nucleus swells and burst to extrude DNA like net
the DNA has anti-microbial molecules attached like defenesins and proteases which trap and kill bacteria fungi, viruses = forming pus
neutralisation of microbes and molecules via Ab
- antibodies prevent penetration of microbe through epithelial barrier
- antibody blocks binding of microbe and infection of cells
- antibody blocks binding of toxins to cellular receptors
granulocytes
these are pressure effect molecules in granules in cytoplasm that are ready to fire out when activated
include mast cells, basophils, eosinophil, neutrophils
Antibody dependent cell mediated cytotoxicity
ADCC
antibodies bind to target cell or microbe
Fc portion of Ab binds to FcR on innate cell
cel is activated if multiple FcR-Ab interactions occur
cells firs out its granules at target
destructive process and can cause lots of damage to healthy tissue
mast cell degranulation
weep response - cause liquid to flow from tissue into lumen to push things away from gut wall
sweep response - release histamines to cause muscle contractions and push microbes out with faeces - this is what causes wheezing
cytokines production - amplifies inflammatory response
