Immunity to Microbes Flashcards
take home points
- only those organisms who successfully evade the immune response are successful pathogens
- primary adaptive immune response to bacteria is an antibody response. local is IgA and serum is IgG
- in most cases the microorganism is actually destroyed in a phagocytic cell
- only infected host cells are killed by CD8 cells
- specific immunity acts to enhance the uptake of microorganisms by phagocytic cells or to enhance the activity of phagocytic cells
innate immunity
-numerous non-specific barriers to infection exist that limit the entry of, or in the aid of rapid clearance of microoganisms:
skin
pH barriers
flushing
lysozyme
phagocytes (with general receptors for bacteria-TLR)
-complement via alternate pathway (classical needs Ig)
virulence factors
- ability to survive the acid environment of the stomach as demonstrated by Salmonella typhosa
- production of spreading factors
- production of toxins that inhibit or kill immune cells
- the presence of an antiphagocytic capsule such as S pneumonia
- proteins like staph aureus protein A which binds and blocks the opsonizing action of IgG
- other antiphagocytic factors like M protein
- some bacteria are not flushed from the resp tract or the digestive tract due to their ability to attach to the epithelium
primary immune defense against bacteria
-antibody
antibody
- prevent attachment to epithelium, mediated by secreted IgA
- trigger complement leading to increased opsonization or lysis
- bind to antiphagocytic M proteins or capsules, preventing the antiphagocytic activity and acting as an opsonin
- opsonized bacteria are not only taken up better but are also killed faster than are non-opsonized bacteria
- neutralize toxins
- neutralize spreading factors such as tissue damaging enzymes
facultative intracellular parasites
- ability to survive within the phagosome
- survive digestive enzymes of the phagolysosome or preventing the fusion of lysosomes with phagosomes
- examples are M TB and listeria monocytogenes
activated macrophages
- kill microorganisms much more efficiently
- result of specific T cell response
- TH1 helper repsonse
- sometimes need CD8 cells to kill infected macrophage to release the stowed bacteria for activated macrophages to eat it
immunity to listeria
- developed strain that will kill mice at high dose
- low dose will induce immunity
- these mice will be immune to the high dose of listeria
- phagocytosed by macrophages but not killed
- antibody increases the rate of phagocytosis but not the killing
- macrophages from the site of infection are able to kill-they are activated macrophages
listeria cont
- activated macrophages can kill many intracellular parasites (non-specific killing)
- long term immunity is specific
- immunity can be transferred from one animal to another will cells not serum
- CELL MEDIATED
- the cells that transfer specific immunity are CD4+ T cells
cell mediated immunity
- specific immunity is a function of T cells
- non specific killing is a function of activated macrophages
- only live bacteria induced CMI, both live and dead produced antibody
- mechanism of antigen presentation is important in what response occurs
- TH1- cell TH2- antibody increases
two types of helper T cells
- TH1 stimulate CMI
- TH2 stimulate antibody production
- the way the dendritic cells present can influence response
- TH1 cells go to infected site to activate macrophages
- TH2 cells go the lymphoid tissues to activate B cells
TH1
- IL2, IFN gamma
- macrophage activation
- production of opsonizing antibodies
- GM-CSF
- TNF alpha
TH2
- IL 4,5, 10, 13
- general activation of B cells to make antobodies
IFN gamma and CD40 ligand
- kills intravesicular bacteria
- activates macrophages
Fas Ligand/LT
-kills chronically infected macrophages, releasing bacteria to be destroyed by healthy macrophages
IL2
-induces T cell proliferation
IL3 and GM CSF
-induces macrophage differentiation in the bone marrow
TNF a and LT
-activated endothelium to induce macrophage adhesion and exit from BV at site of infection
CXCL2
-causes macrophages to accumulate at site of infection
immune mechanisms involved in the clearance of parasites
- T cell response is important in clearance and control
- cytotoxic T cells are involved in limited manner-rarely kill parasites but may kill cells infected with the parasites
- T cells activate macrophages that kill many different parasites
- T cell dependent granulomata formation-interaction b/n activated macrophages that accumulate and release fibroblast growth factors-parasite walled off
- T cells produce factors that causes the infiltration and increased production of eosinophils-can kill worms
- T cells and B cells produce specific antibodies to parasite antigens
- parasites have escape mechanisms
IgG and IgM
- able to kill some blood borne parasites-plasmodium
- complement mediated
antibodies and parasites
- neutralize some parasites by blocking receptor specific uptake into cells
- act as opsonin enhancing Fc and C3b mediated phagocytosis
- IgE-helminths-mast cells kill worms
- cellular toxicity from antibody can kill some organisms-macrophages, neutrophils, eosinophils and mast cells
inaccessibility
- parasites can hide inside the hosts cells
- exist only in gut
- form cysts
avoidance of recognition
- vary cell surface antigen expression
- pick up host antigen
immunosuppresion
-t spiralis and leishmania can suppress host
immunity to viruses
- T cell mediated immunity important
- antibody prevents infection
- CTLs kill infected targets
- NK cells stimulated by T cells
- activated macrophages can kill infected cells
antibody and virus
- neutralizes virus
- binding of antibody to a portion of virus required for absorption, penetration, uncoating or replication
- steric hindrance
- localized IgA important to resp, GU, GU tracts
- in resp IgA is prime of antiviral
- may also lyse virions
- alone or with complement can increase rate of clearance by increasing rate of uptake by phagocytes
- can prevent but not likely to kill
CTLs and virus
- not always virus strain specific
- can immune against several strains of A with just one shot
- uses MHC class I
interferons
- alert other cells to protect themselves
- IFN a and b induce resistance to viral replication in all cells
- increase MHC class I expression and antigen presentation in all cells
- activate NK cells to kill virus infected cells