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