Immunology exam 3: Cytokines, Tdth, Tctl
What are chemotactic cytokines?
Call Tdth cells to come to site of infection
What is cytokine chemotactic factor?
Calls for WBC to come to site of infection
What does a Tdth cell do?
Delayed hypersensitivity. Defense against intracellular bacteria
What is MIF?
Antichemotactic agent that prevents macrophages from leaving area
Where does the effector phase occur?
At the site of infection
What occurs in the sensitization phase?
1. APC ingests M. tuberculosis 2. Presents Ag to Th cell 3. APC produces IL-1 4. IL-1 causes Th to produce IL-2 and express IL-2 receptors 5. IL-2 acts on same Th cell 6. IL-2 casues Tdth proliferation for current infection 7. IL-2 causes Th proliferation for future infection
What are the functions of cytokines?
1. Cell Activation 2. Cell Proliferation 3. Protein Synthesis 4. Class Switching
51Cr release assay...
1. Inject mouse with xeno/allogenic cells 2. Produces primary IR 3. Spleen sample containing B cells, Th, Tctl, macrophages 4. Column affinity separation- macrophages stick to column, B cells bind to AB 5. Left with Th and Tctl 6. 51Cr inside cells 7. Target cell killed, 51Cr released 8. Compare to detergent release (100%)
What occurs in the effector phase?
1. Tdth binds Ag 2. Tdth releases cytokines: cytokine chemotactic factor, macrophage arming factor, BM factor 3. Macrophages release cytokines: chemotactic factor, MIF
What occurs in Tctl defense?
1. Tumor cell sheds TAA (exogenous) 2. TAA taken up by APC 3. APC produces IL-1 4. IL-1 acts on Th 5. Th produces IL-2 6. IL-2 autocrine, and acts on Tctl 7. Tctl kills tumor cells
CD4 + CD8 + Macrophages...
100% killing
Just CD8 (Tctl)...
30% killing
What is cytokines' molecular weight?
30K MW
Just CD4 (Th)...
5% killing
How do you measure Tctl activity?
51Cr release assay
CD4 + CD8...
90% killing
What does paracrine mean?
Cytokine acts on a nearby cell, short distance
What does autocrine mean?
Cytokine acts on the same cell
What does a Tctl cell do?
Cytotoxic reactions
Example of Tdth function?
Defense against mycobacteria tuberculosis
What is macrophage arming factor?
Excites macrophages, promotes killer type cells, which increase phagocytosis
What does IL-1 do?
First product from Ag bridge. Causes Th to produce IL-2 and express IL-2 receptors
Acute infection?
Infiltration of neutrophils, 12-18 hrs.
What produces cytokines?
Lymphocytes, macrophages
What are other names for cytokines?
Lymphokine, Monokine, Interleukin
What cells are needed to kill tumor cells?
Macrophages, CD4, CD8
Chronic infection?
Monocytes turn to macrophages, 24-48 hrs.
Cytokines are redundant...
Multiple cytokines produce the same function
How does the TB skin test work?
PPD (antigent) injected into arm, acts as a "site of infection" and Tdth and macrophages cause inflammation = positive
How do Tctl cells kill tumor cells?
Perforin
What do B-cells do?
Produce antibody. Defense against exogenous antigens such as bacteria
What is the sensitization phase of Tdth response?
Production of "soldiers" for current and future use (infection)
What does IL-2 do?
Promotes Th proliferation. Tdth proliferation for current infection, and Th proliferation for future infections
What is BM factor?
Promotes bone marrow to produce more monocytes, which increases macrophages
What is perforin?
Released by Tctl, acts like complement on target cell, lysis
What are cytokines?
Substances from cells
What is a perfect example of Tdth defense?
TB Skin Test
MHC Class I
Tctl, CD8, endogenous peptide, any cell
Example of redundant?
Th cell produces IL-2, IL-4, IL-5, which all promote B-cell proliferation
Example of antagonism?
Th cell produces IL-4 which promotes B-cell proliferation. Macrophage releases INF which cancels out IL-4 effects
Example of pleiotropic?
Th cell produces IL-4, which promotes B- cell, thymocyte, and mast cell proliferation
Example of synergism?
Th cell produces Il-4 and Il-5, which work together to cause a greater effect on B-cell proliferation
MHC Class II
Th, CD4, exogenous peptide, APC
Cytokines are pleiotropic...
They have multiple functions.
What do cytokines bind to?
They have specific receptors and only bind to their corresponding receptor
Cytokines are antagonistic...
They reduce the effect that each cytokine promote individually
Cytokines are synergistic...
They work together to produce an effect greater than the sum of two cytokines
Example of Tctl function?
Tumor cell destruction
What is the sneak through theory?
Tumor cells that almost look like normal cells (have a weak TAA), sneak past immune system. TAA is less antigenic, which means less of an immune response
Are cytokines soluble?
Yes, they are soluble proteins
