Extra cellular bacteria mediate tissue distraction in what 2 ways?
- Induce inflammation
2. Release of toxins
the goals of host immune responses to extracellular bacteria:
Neutralize toxins and kill bacteria
Innate responses to extra cellular bacteria
- Phagocytosis via neutrophils, monocytes, and macrophages
2. Peptidoglycan and LPS can trigger alternative complement pathways to lyse or opsonize bacteria
Adaptive immunity towards extracellular bacteria
-Activated Tcell produce interferon gamma to activate macrophages and initiate B cell mediated humoral immunity.
- humoral immmnity: igG opsonizes bacteria. Toxin specific antibodies neutralize toxins
IgM and IgG activate complement pathway to Lyse Microbes
Immunity evasion by extracellular bacteria is achieved by what 2 mechanisms?
- Polysaccharide capsules resist phagocytosis and inhibit complement activation via alternative pathway
- genetic variation attempt to keep one step ahead of antigen specific antibodies
Deleterious effects of immune system responses to extracellular bacteria
- Septic shock: gram negative bacteria promote macrophage production of TNF and IL-1
- superantigens bind tightly to MHC class II proteins and the variable region of the TCR on tcells Causing them to be activated and release a large amount of cytokines such as TNF-alpha = shock-like presentation. Eg. Staph enterotoxins causing toxic shock syndrome
- Disease causing Ab’s can be made in response to strep. Eg rheumatic fever
Method for eradicating intercellular bacteria (innate)
NK cells are activated by IL-2 that is produced by macrophages. NK cells produce interferon gamma which in turn activate macrophages to high levels making them more efficient killers or intracellular microbes.
Adaptive immunity to intracellular bacteria…
- mediated by “delayed-type hypersensitivity reaction” where T-cells become activated to release interferon gamma then macrophages eliminate the microbes
- cytotoxic T cells are generated. Class I mhc activation occurred is bacteria if the microbe escapes a phagosome or protein antigens bend up in the cell cytosol.
How mycobacterium evades immune system:
Prevents fusion of the phagosome and lysosomes, also scavenges for reactive oxygen intermediates to prevent bacterial killing
How listeria evades he immune system
Disrupts phagosome and escapes into the cytosol
Deletriuus effects of the immune response towards intracellular bacteria
-granuloma formation, esp. in lungs
Innate response to viruses
- stimulation of interferon alpha and beta production by infected cell hosts
Aka type 1 interferon: acts to inhibit viral replication in surrounding host cells - NK cells lyse infected cells ( activity increased by interferon 1) also viruses down regulate mhc 1 molecules. The absence of mhc 1 allows more NK activity
Adaptive immunity to viruses
- the presence of antibody is most helpful before the virus invades a cell. This prevents binding of the virus to host, opsonization, and activate complement.
- CTC are most important during established viral infections; they can lyse cells before the virus completes replication process. They also recognize particles presented on mhc class I
Viral evasion of immunity
- point mutations
- reassortment of genomes
- Eg HIV has an error probe reverse transcriptase point mutations . Influenza does antigen alterations and rearrangements
- prevention of MHC I presentation so the cell won’t be killed by CTC’s
- hiv kills CD4 + Tcells
Deleterious impacts of viral immune response
-CTC’s may Cause pathological lesions instead of solely targeting the virally infected cells. Hep B - liver attack
-viruses may have homologous proteins to humans –> cross reactivity with normal
Host tissues
Immunity to fungi innate
Neutrophils are the principle mediator- phagocytosis of fungus, lysosomal degradation and reactive O2
-neutropenia causes fungal susceptibility
Fungus: adaptive immunity
Cell Mediated and humoral
Th1 Mediated response
Elimination by CTC or granuloma formation
Humoral - unknown
Innate immunity to parasites
- macrophages phagocytosis only works for protozoans, sometimes
- alternative complex pathway- initiated by helminths (often there is resistance)
Also there is resistances to granule contents of neutrophils and macrophages
Additive immunity to protozoan
- eg. Leishmania lives in macrophages and generates CD4 + activation generate th1 response. CD4+ tcells secret interferon gamma. = meaner and more efficient macrophages
Question : intracellular protozoan cause a CD4 reaction.. why?
What are grabulomas?
??
Adaptive immunity: schistosoma
- th1 mediated response that causes granulomas
Adaptive immunity: plasmodium
Malaria
Induces th1 response in the form of CTC’s
Ab’s are not effective against this parasite as the CTC
Adaptive immunity: helminths
Helminths elicits lots of igE used by eosinophils in an ADCC attack as an example of th2 response
How parasite avoid immunity
- protective shields/hideouts in GI lumen
- coating with host proteins (ABO or MHC)
- outer surface does not activate complement
- repair after MAC
- extracellular enzymes that cleave Abs
- continuously change surface antigen
- she’s their antigens after being bound by an ab
- resistance to immune effector mechanisms
