Overcoming Host Defence Flashcards
Ability to overcome host D relates to
Virulence
Challenge and infective dose
Host response efficacy
Specific pathogen mechanisms of overcoming host D
Mechanisms of overcoming host d
Rapid repl Low immunogenicity Phagocytosis inhibition IC survival Concealment Antige variation EC products
Rapid replication
Avoid and or overwhelm spec imm resp.
Can allow ‘out running’ of host D or provide too much to deal with
Low imunogenicity mechs
Low antigenicity
Tolerance
Low antigenicity
Expr poorly react antig allow avoidance of inflam opson and spec imm resp
Eg some capsules and LPS O antig fail to act complem or be recog as foreign by phagocytes
Eg Hyaluronic acid capsule strep equi
Low antigenicity hyaluronan eg
Anionic non sulph GAG distrib through CT epi and neural tissue. Major skin comp and cartilage comp
Thick capsule or slime layer made of polysacch (eg hyaluronic acid) expr during infection eg pasteurella multocida
Some bact produce hyaluronidase to break down host hyaluronic acid
Low antigenicity sialic acid eg
Prod by G-ve bact incl E.Coli, neisseria and klebsiella
Neisseria (important cause of sepsis and meningitis) have homopolymeric sialic acid capsule
Grp C caps: alpha 2-9 sialic acid unique bact struct (good vacc)
Grp B caps: alpha 2-8 sialic acid similar ti human so essentially non immunogenic
Tolerance
Imm system doesnt attack antigen
Natural/self tolerance (no imm resp against self antigs)
Acquired/induced tolerance (ext antig tolerance created by imm syst manip eg pregnancy)
Acquired Tolerance cause
De sensitisation of imm cells by spec antigs
Prenatal infection can cause tolerance and persistance
High persistant Ag dose can also cause
Host genetic factors influence dev of tolerance
Phagicytosis inhib
Anti-opsonic act
Inflam inhib
Chemotaxis inhib
Phagocyte killing
Anti opsonic activity: cell surface components
LPS of some G-ve have v long O chain that bind and act complem at remote site to OM so Comp pro can’t insert and cause lysis
M pro of pyogenic strep bind factor H therefore block complem cascade
Pro A of staph a bind Fc region on IgG and present Ab in wrong orientation for Fc recog by phagocytes
Anti opsonic activity: EC components
Staph a prod staphylokinase that act plasminogen to plasmin that degrades compl and IgG
Strep and mycoplasmas prod IgA proteases
Pseudomonas and strep prod EC enz that digest and inact compl
Inflam inhib
Some bact (mycobact infected macrophage) prod anti inflam cytokines eg IL6 - inhib T cell act and strong imm suppressive cytok IL10 and TGF beta
IL10 role in inflam inhib
Inhib macro act and production of reactive O and N intermediates, supress inflam cytok pros abd down reg MHC c2
Chemotaxis inhib
Staph a produce CHIPS that binds transmem rec on phagocytes and blocks recog of chemotactic molecules
Phagocytic killing: apoptosis induction
Salmonella control PCD to facilitate lifestyle, involve SpI1 pathogenicity island involvement
Phagocytic killing: leukocidin production
M haemolytica leukotoxin (resp pasteurellosis in cattle, 1/2wk stress, pleuritis, fibrinous bronchopneumonia)
Leukotix inpairs phagocytosis, red lymphocyte prolif, lyse platelets, cause cytotox lung dam
IC survival and growth
Some prevent phagosome lysosome fusion, escape from phagosome or res to intra phagolysosomal killing
IC survival and growth mycobac Tb eg
Bact CW components released from phagosome - modify lysosomal mem and inhib fusion
IC survival and growth chlamydia eg
Element of bact wall appears to modify phagosome mem
IC survival and growth salmonella typhi eg
pH in phagosome after engulfment induce bact gene products essential for macro survival
IC survival and growth listeria mono
Several molecules for early phagosome lysis to ensure release into cytoplasm incl hemolysin, 2 types of PLC
In cytoplasm induces its own movement via host cell actin polym and form of microfil within a comet like tail
Concealment
Host molecule acquisition
IC location
Host molecule acquisition staph and strep eg
Bind IgG mon-spec via Fc dom, also fibronectin some staph deposit fibrin in surf
Host molecule acquisition mycoplasma eg also what is mycoplasma and its structure
Acquire host cell mem comp, no CW so no peptidoglycan layer so sens to lysis byt res to antibact affecting CW
Pleomorphic org, small stain poorly, only stain with Giesma
Cause chronic resp tract disease
IC location
Can cause target absence for imm resp, spec mech conferring entry to host cell. Infect professional and non professional phagocytes
Also immuno priveleged sites/poorly accessible to imm resp eg kidney tubules, salivary gland, mammary gland
IC location egs
RBC: trypanosomes
Macro: brucella listeria mycobact
Cause of antigenic variation
Mutation
Genomic rearrangement
Regulatory resp
Gene acquisition/loss
When antigens change
During infection course
Can exist in nature as multiple antigenic types (steotypes/vars)
Phase variation/ antigenic shift
Imm evasion technique switch surf antigens to evade adaptive imm resp (eg salmonella switch flagellin pro type) so flagella struct changes
Therefore imm resp against old type of flagellin cause high affinity Ab, TCR, BCR to be useless
Antigenic drift
Imm selected pro variants with aa alteration cause new epitope to arise not recog by existing Ab.
Cause multiple antig types so variant strain exist
Based on flagellar, CW, capsular, etc antigens cause diff serotypes
EC products
Secreted antigs
EX toxins
Moduluns
Secreted antigs
Bind opsonins and prev interact with intact microorg eg staph teichoic acid
EC toxins
Affect phagocytes - inhibit phagocytosis, chemotaxis, destroy phagocytes
Eg streptolysin O, staph alpha tox
Can be toxic to other cell types too
Modulins
Induce and modulate host response via cytokines eg LPS
