UWorld Q 962, Please Explain the Explanation

[DeeJay2728]

If the polyribosyl-ribitol-phosphate (PRP) capsule of H. influenzae is immunogenic (antibodies to PRP facilitate complement-dependent phagocytosis and killing through opsonization), then why does it need to be conjugated?
I thought the purpose of conjugating, was to MAKE IT immunogenic (that way you can mount an immune response).

Thanks in advance!!

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[Halothane27]

If I understand correctly. Since H. influ is an encapsulated organism, it will follow a thymus-independent pathway. For the complement pathway to be activated for opsonization, we need IgG (and C3b). Without conjugation we would just be mounting a IgM response and nothing specific towards the capsule, and also no antibodies will be made hence no memory. The capsule by itself is not protective. The conjugation increases the immune systems ability to recognize the organism the next time it encounters it.

 

[SBR249]

T-dependent immune activation requires a protein antigen. PRP is not a protein antigen so it must be conjugated to a protein to make it a good vaccine.

 

[DeeJay2728]

The complement sys can be activated with IgM (Classical Pathway)... But you're right, thank you!! When I saw Immunogenic, Antibody, Complement, and Opsonization, I don't know why I automatically thought IgG.
Even though, all that stuff can be done with just IgM... there's no memory (no Cell Mediated Immunity) and no IgG. Right?

Is it bc the lymphocytes of CMI only recognize protein? And the capsule of H. influenzae is only polysaccharide?

 

[Halothane27]

You are right for complement activation its IgM and IgG. But for opzinzation its c3b and IgG.
Like SBR249 mentioned and you are also right.. its the polysacchride that's the issue. Protein is recognized but polysac is not.
Not sure if it would help clear things, you could refer to section in immuno of FA.. think it should be right under the Ig isotypes.

 

[DeeJay2728]

But, if IgM can activate complement (C3b) than it's an opsonin. Phagocytes have receptors for C3b, it doesn't matter who started the pathway... Is this right?

 

[DeeJay2728]

Complement activation is considered innate... Opsinization by phagocytes works great via IgM. I think the problem is when the phagocytes (APC's) process what they've eaten. If the Antigen is not protein, they can't make the "bridge" btwn the Innate and CMI... no class switching, no memory.
Please correct me where I'm wrong

 

[thehundredthone]

Complement activation is considered innate... Opsinization by phagocytes works great via IgM. I think the problem is when the phagocytes (APC's) process what they've eaten. If the Antigen is not protein, they can't make the "bridge" btwn the Innate and CMI... no class switching, no memory.
Please correct me where I'm wrong

You're right. Although the PRP capsule can be opsonized and taken care of, the goal of the vaccine is to provide long term sustained immunity in young children (usually under 2 years of age), who typically do not generate adequate immune responses to polysaccharide antigens. By conjugating these antigens to a protein, T cell immunity is generated which greatly augments the response to these antigens through creation of memory cells, and equally importantly, allowing a booster effect.

Polysaccharide vaccines typically do not generate mucosal, and thus herd immunity, which is another reason for preferring conjugated vaccines for such diseases. They do, however generate specific IgM antibodies because they can stimulate B cells independent of T cells (and B cells can recognize unprocessed antigens). They don't have a booster effect and in some cases may reduce the antibody response.

http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf

 

[DeeJay2728]

Thanks to all!! I didn't realize that this question would help me to iron out 80% of Immunology!!