55. Control of Immune Processes. Immune Tolerance and Types

Question 1

Immunogen

Answer 1

Substance initiating immune response

Question 2

Antigen

Answer 2

Substance that react w/ Ab

Question 3

Immunogenicity

Answer 3

Ability to produce an immune response

Question 4

Network theory

Answer 4

Involves B cells (Ab), T cells that reg production of Ab and non-specific accessory cells (A cells)

Immune system = interacting network of lymphocytes and Ab molecules w/ variable (V) regions.

• “recognizers” of the immune system (lymphocytes and Ab) recognize foreign particle + eachother to interact
• Ab can recog almost unlimited number of different substances & such recognition inc the recog parts of the Abs themselves producing anti-antibodies.
• Ab’s V regions bind not only to things that are foreign t but also to other V regions within the system.
• -> network, with the components connected to each other by V-V interactions.

Question 5

Ways of controlling immune response

Answer 5

Regulation via antibody

• soluble Ab compete w/ BCR for Ag > negatively reg activation of additional B cells.
• Immunocomplexes with IgG are also negative regulators. > bind to the surface of B cells and inhibit their activation via agglomerating BCR with inhibiting Fc receptor

Regulation via antigen
Main reg of immune response. Its presence in body starts the immune response and once the antigen is gone the response ends. Antigens are also important for affinity maturation of B cells

Regulation via cytokines and intercellular synapse

• Cytokines - influence can be inhibit by endocytosis of receptors able to bind them or by inhibitors binding directly to the receptor instead.
• Intercellular synapse - immune response wont be activated without proper communication between cells. Moreover, effector cells need costimulation in order to be actually activated and to avoid anergy.

Negative regulation (supression) via T lymphocytes

• via Th1 cells and Th2 cells (mutual negative regulation via cytokines)
• Th2 cells > IL 4 and IL- 10 > suppress Th1 induced immune response.
• T reg - suppressing autoreactive cytotoxic T cells.

Neuroendocrine regulation

Question 6

hapten-carrier effect

Answer 6

Hapten - not immunogenic but can bind to antibodies of the appropriate specificity [recog by BCR], can be immunogenic when coupled with a carrier [recog by Th cells]

Th and B cells cooperate by interacting [class II self-MHC restricted]

B cell

• Express both (Ig) and class II MHC on cell surface
• Can producing Ab of same specificity as that of its surface Ig
• Capable of functioning as an APC

Hapten recog by BCR > Carrier processed and presented on class II MHC to Th cell > Activated Th cell produces cytokines > Cytokines enable B cell to be activated to produce anti-hapten antibodies

Question 7

Cytokines

Answer 7

Non Ab proteins acting as mediators between cells

• Monokines - mononuclear phagocytes
• Lymphokines - activated T cells esp Th
• IL

Properties

• produced by cells of natural and specific immunity
• Mediate immune response
• secretion is brief and limited (not stored pre-formed and made as req)
• pleiotropic (produced by many differeny cells and can act on many diff cells)
• redundant - have similar actions
• can influence synth of tother cytokines ( cascades, ehance/suppress production, +/- reg of immune response)
• influence on other cytokines - antag, add, synergistic
• bind to R w/ high affiniy
• autocrine, paracrine, endocrine
• cell response is slow

Question 8

Cytokines of Natural Immunity

Answer 8

TNFa

• produced by activated macrophages
• mediate acute inflamm in response to gram - bacteria, recruit neutrophils, macrophages, act on hypothalamus > fever, promote APP

IL-1

• from activated macrophages, sim effects to TNFa
• promote tissue remodelling and repair
• promote anti viral state of cell
• stim fibroblasts > . fibrogenesis and ECM

Chemokines - produced by diff leukocytes and tissue cells and recruit leuk to infection site

INFa +b (type 1 IF)
- IFNa from macrophages, IFNb from many cells
- inhib viral replication
Increase MHC 1 expression and activate NK

IL-12
- from activated macrophages and dendritic clls
stim IFNy productions
Th > th1
enhance cytolytic t og Tcytotoxic and NK

IL-10
Produced b activated macrophages and Th2
- inhib cytokine production and inhib MHC class ii express and costim molecules on macrophages

Question 9

Cytokines of Specific immunity

Answer 9

IL-2 - from Th0 and Th1 cells
T cell growth factor

Il-4 - from Th2, CD4+ T, and mast cells

• B cell GF, TH2 CD4 GF
• Promote IgE class switching and IgG synth
• inhib Th1 CD4+

IL- 5 - Th2 and mast cells

• Stim B cell growth, Ig secretion
• growth and differentiation factor for eosinophils + activate mature eosinophils
• Il-4 and 5 work topgether (opsonise helminth w/ IgE)

IL-10 - Th2, macrophages
-inhib Th1 production and macrophage fct > inhib IFNy

INF-y - from Th1
- activate NK and macrophages, T cell, endohelial cells
inhib Th2CD4+
- Induce MHC II expression