Goal: To recognize but not respond to self; to recognize and respond to non-self for a long enough period with enough intensity to result in immunomodulation

Development of B and T Cell Repertoire (How do we get the ammo?)

• both B and T cells’ specificities are conferred via RANDOM gene rearrangement
• We have a ton of different ones each with their very own specifity (10⁷-10⁸)
• We gots to have a way to know they’re ours or we’d croak from killing them all.

Control of Immune Response to Self Ags

Antigen Sequestration

• select few Ag
• Anatomical barrier protection
• Traumatic injury breaks down barrier causing an autoimmune response
• lens of eye; spermatozoa

Positive and Negative Clonal Selection – direct thymic influence

Positive selection (Ti⁺, CD4⁺, CD8⁺)

• clonal expansion and rescue

Negative Selection

• clones w/ MHC antigens come into contact w/ APC which leads to enrichment of self-MHC-restricted foreign Ag-specific T cell clones

Control of Immune Response to Foreign Antigens

Regulation by Foreign Antigen

• Requires appropriate dose, timing, and the correct nature of Ag.
• Remember protein>>carbs>lipid>nucleic acid
• Adjuvant- increases rate of response

Regulation by Ab

• feedback inhibition (IgG downregulates IgM)
• Competition- IgG and IgM have different affinities for Ag
• you can make Ab against TCR and Ab to down regulate activity of T and B cells

We can acquire tolerance to Foreign Antigens

• in utero
• specific immune unresponsivenenss

Coonditions favoring tolerance to Foreign Antigens

• age- decreases tolerance w/ the maturity; favors tolerance w/ immunosuppression
• Antigenicity- if the Ag is not as immunogenic it may be more tolerable
• Chemical form of Ag- small mw, aggregation, adjuvant
• Dosage of Ag- the smaller or the largest — the more tolerable. Intermediate dosages confer immunogenicity
• Nonmetabolizable substances- are tolerigenic

Cellular Influences in Tolerance

Accessory Cells

• necessary for immune response
• tolerance is induced when bypassed

Role of Lymphocytes

• Both B and T are susceptible to tolerance
• DURATION OF TOLERANCE IN B is SHORTER than T cells
• Status of host’s immunogenic state reflects the status of specific T cells (AIDS?)

Kinetics of T and B cell tolerance

• T cells tolerize quicker and last longer
• B cells tolerize slower and don’t last as long
• low dose Ag tolerizes only T cells
• High dose Ag tolerizes BOTH

Mechanisms of Acquired Immunologic Tolerance

T cells

• TCR is where the tolerance take place
• Remember the 1^st signal from the B cell (APC)- T cell interaction is the MHC-Ag presentation. The second signal which activates and causes proliferation of the T cells is IL-2. Well, tolerance occurs when you don’t have the second signal (no proliferation)
• can occur in pancreas and kidneys, et al.

B cells

• Occur at level of Il-4 and IL-5 signal from the T cell
• If large doses of Antigen is given, the surface Igs on the B cells will saturate (no B cell APC or T cell Helper). Therefore, no IL-4 or IL-5 will be produced which leads to a tolerance

Suppressor T cells

• CD8⁺ cells are capable of suppressing normal T cells
• infectious tolerance

Idiotype Networks can control also

• on both B and T levels
• V region of genes codes for idiotypes
• the unique configuration of the idiotype is antigenic
• therefore anti-idiotype (Ab against this idiotype) can iniate control loops (Ig on B cells & TcR on T cells)

Tolerance- characteristic of immune system

Annergy- particular cell incapable of responding

Tags: Ab, Annergy, antigen sequestration, antigenicity, antigens, B Cells, clonal selection, clones, Idiotype Networks, immune response, immunomodulation, Lymphocytes, T-cell, thymic

This entry was posted on Sunday, March 8th, 2009 at 5:39 am and is filed under Immunology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.