Effect of long term antibiotic treatment on commensal bacteria in gut

1. kill resident commensal bacteria
2. Clostridium can grow and produce toxins that cause mucosal injury
3. neutrophils and RBCs go to gut between injured epithelial cells

• toxins (mostly by E.C. pathogens)
  • exotoxins (secreted toxins)- released by bacteria and bind to host cell receptors
  • endotoxins - released when organism dies or are expressed on cell surface pathogens (ex: LPS in gram neg. bacteria)
• cytopathic killing (mostly by I.C. pathogens)

• immune response itself (usually seen in chronic infections)
• non-immune mechanisms

• innate
  • phagocytic cells
  • complement
  • antimicrobial peptides
• adaptive- Ab

• neutralization (prevent bacterial adherance)
• opsonization
• complement activation
• ADCC (could also be mediated by eosinophils)

• crosslinking of FcεR on eosinophils with IgE bound to the surface of pathogen
• causes degranulation

Function of B1 cells. Mechansim of action of B1 cells. Location

• function- react to T-independent Ag's
• mechanism of action
  • secrete IgM and IgA
  • rapidly mobilize Ab secretion
• location- tissue where exposure to pathogen is high

• thin peptidoglycan layer
  • with layer of LPS
    • side chains called O antigens/side chains

• their LPS has low endotoxin activity due to molecular mimicry
  • express LPS O Ag's that are structurally similar to blood group Ag's on human cells (example of immune ignorance)

• gram negative bacteria
• Structural
  • usually noninvasive free living in mucus layer and can attach to apical cells
• Effect- no symptoms unless stomach wall breached

• MRSA
• skin abscesses
• food poisoining (produce toxins in gut called enterotoxins)
• pneumonia
• toxic shock syndrome (TSS)

• some toxins are superAg's
• they will cause a massive systemic inflammation leading to TSS
• it is a way to evade immunity because the response is large, but nonspecific, therefore uneffective

• superAg
• Protein A- on surface of S. aureus, binds to Fc portion of IgG, preventing interaction of Fc with FcR on phagocytic cells
• alter plasma membrane charge (against AMP)

• enter via breach of skin
• produce toxins that kill cells by inducing pores

• gram positive
• group A streptococcus

• STSS (systemic inflammation induced)
• necrotizing fasciitis (invades CT)

• express superAg's
• produce exotoxins that lyse cells
  • steptolysin O induce neutrophils to self destruct

• antigenic variation (84 serotypes that differ in their capsular polysacc.)
• PPV- vaccine contains carbohydrates from multiple serotypes

• extreme form of antigenic variation
  • makes IgM and IgG Ab's against variant specific surface glycoprotien (VSG) coat
  • under immune pressure, VSG switch to stay a step ahead of immune system

• induces Th2 response (release IL-4) that cause Ab responses (especially IgE) and eosinophilia
• ADCC can be induced against worms coated with IgE

• large size
• sheds outer coat removing adhered cytotoxic Ab's and cells
• excretion and secretion of immunomodulatory products
  • induce IL-10 and TGFβ causing hyporesponsiveness
• coat outer surface with host proteins
  • absorbs some of host components to give them the appearance of self (ex: MHC's, RBC Ag's)

• innate- phagocytes
• adaptive- Th1 cells

• Th1 cells activate macrophages to induce more potent respiratory burst

How does immune system attach Leishmania major?

• Th1 release IFN γ, leading to confering resistance
• since this infection of self mediating, once your immune system responds, it usually never comes back due to memory Th1 cells formed
• ex: Lishmanization program (inject with with promastigotes)

Mechanism of evasion of Mycobacterium tuberculosis

• evolved a mechanism to prevent phagosomes from fusing with lysosomes
• ·         when macrophages come, it infects these macrophages

• ·         leads to formation of a granuloma that walls off the area of infection

• eventually granuloma becomes liquefied and burst sending virus into circulation

• innate- NK cells
• adaptive
  • Ab
  • CTL cells

viruses

• protein coat
• nucleic acid

• uses host cell machinery to produce their components
• viral components must self assemble

Ab's most influential in fighting influenza

IgG

IgA

CD8 T cells

Immune evasion mechanism of viruses

• block host Ag presentation pathway
• antigenic variation: shift and drift
• latency/hiding in sactuary sites
• killing immune cells

• different subtypes based on distinct combinations of surface glycoproteins
  • hemagglutanin (HA)- 16 variants
  • neuroaminidase (NA)- 9 variants

• drift
  • cause- pt mutation in HA epitope
  • leads to seasonal epidemics
  • effect- only mild disease due to immune cross-presentation
• shift
  • cause- large changes in HA epitope due to reassortment of RNA segments between viruses of animal and human genome
  • leads to pandemics
  • effect- severe, substantial morbidity

• infects CD4 T cells (bind using CXCR4) and macrophages (bind via CCR5) and kills them
• this cause loss of immune response and opportunitistic infections
• kills immune cells

• direct viral lysis
• induce apoptosis
• activation of CTL to kill

• chemokine receptors and ligands
• HLA gene variants