CD8 T cells

Adaptive immune system

Should be capable of attacking everything

Viruses

Evolved ways to evade the immune system

Chronically Stimulated T cells

Lose function and can’t clear virus, this is called exhaustion or tolerance. The t cells becomes non-functional or dysfunctional

CD8 T cells kill via

Contact, through lytic granules and Fas;FasL that induces apoptosis in target cells

Activated CD8 T cells traffic to

Various location, this establishes memory population throughout the body

CD8 T cells don’t function well when

Cancers and chronic infections grow out/persist

ADCC

Stands for Antibody Dependent Cell Cytolysis, mediated by neutrophils, NK cells, eosinophils, and macrophages. They use antibody to clear infection. Causes lytic enzymes (granzymes) and TNFalpha to be released. This is not opsonization—no phagocytosis

Fc receptor (FcR)

Binds the Fc region of antibodies attached to target cells because of specific antigen-antibody recognition. this part is antigen specific, the action of the cell with FcR is not

Ab specific for cancer antigen induce

ADCC of tumor cells

AB specific for Cd20 used to kill

Leukemias, lymphomas, B cells in certain autoimmune diseases like arthritis

NK cells

Stands for natural killers cells, not the same as NKT. Have no memory formation, kill target cells (kind of) specifically but not through antigen-specific receptors on the NK cell (Do not have TCR or BCR). Can kill/lyse target cells through the same mechanism as activated CD8 T cells. It is an Innate immune cell and acts to condition environment and adaptive immunity by secretion of IL-12, IFN-γ

2 ways NK cells recognize target cells

1. Either through cells recognize Ab coated cells through ligation of Ab Fc portion through FcR on NK cells, will bind the Fc portion of IgG

2. Can sense the amount of MHC l on a target cell. If MHC l is down regulated then the NK cell will not get inhibition signal. If there is no inhibition signal, the NK cell will lyse target cell

NK cell activity

1. A target cell can give 2 different.opposite signals to an NK cell

2. One signal is activating one signal is inhibitory

3. Typically the inhibitory signal is mediated by engagement of MHC l on target cell

4. If a negative signal is lacking, then the activating signal wins. therefore, ligation of the activation receptor killing of target cell

5. Ligands on target cell are molecules associated with stress altered self — low MHC

Effector CD8 T cells and NK cells kill in 2 common ways

1. Granzyme and perforin pathway; CTL and NK cells produce these perforin (pore forming). Granzyme (proteases, induces DNA fragmentation both found in cytoplasmic granules in activated T cells (not naive) and resting cells. Quicker

2. Fas; FasL pathway —> Fas ligand on activated T cell, NK cells Fas on target cell. Slower

Events leading to target cell death

1. conjugate formation — receptor/ligand recognition and signaling

2. Membrane attack

3. CTL disassociation

4. Target cell destruction by apoptosis

Receptors other than antigen receptors also associate with

ITAM-containing chains that deliver activating signals

Activating and inhibitory receptors of NK cell can

Belong to the same structural family

Activating receptors

ITAMs

Inhibitory receptors

ITIMs