Effectors

Ways to get rid of pathogens

1. neutralization of pathogen /toxin

• the act of binding can inactivate or neutralize things

2. agglutination (clumping of ag)

• clumps are easier for other parts of the immune system to get rid of it

3. opsonization

• anything with ab on it will stick tight to neutrophils/macrophages when ab binds the Fc receptor makes a conformational change

4. complement activation

• has its own collection of activities lysis, inflammation

5. ab dependent cell mediated cytotoxicity

• Tc cells and NK cells will kill virally infected cells, coat the target cell with ab NK cell will kill it

6. degranulation

• one specific ab good at degrading ab and MAST cells, IgE binds to trigger the degranulation of MAST cells

Plasma cell action when it encounters a MAST cell with worm

• B cell will make IgA the only cell that can make ab

• make ab/dimeric IgA will make a J chain which binds them together

• binds Fc receptor on mucosal epithelial cells

  • PolyIg receptors will bind, go into a vesicle move from basal lateral to the other side and cleave the receptor wrap Fc receptor with portions of IgA and pop out a 2 headed monomer to protect it from proteases

• need to protect IgA from protease bc it is in the mucus not the serum anymore

Effector function IgG

• many subclasses

• some human ones are good at complement activation others are not

• all are good at binding the Fc receptors so it is good at acting as an opsonin

• good at neutralizing IgG increase binding affinity

Effector Function IgM

• good at agglutination to get swallowed and complement

• first ab produced in an immune response

• macrophages will be good at swallowing them

Effector function IgA

• in secretions, its job is to catch pathogens while they are still in the mucosa before they contact the cell (keep them from getting too close)

• anti-inflammatory doesn’t contact the mucosa or activate complement

• boundaries help maintain bacteria but don’t let them sit on the cell

Effector function IgE

• allergy and asthma

• good at dealing with parasites (anything large)

• prevalence is based on where you live in the world

• good a degranulation

• basophils or MAST cells

  • histamine holds the granules together so when broken causes inflammation

Antibiotics

• we got good at making ab

• can produce ab that binds a specific thing

• can look at targets to make them get rid of certain health conditions

  • pull things out of circulation or block certain receptors

• some ab can produce against bacterial toxins and keep it around as a drug

Fc Domains

• Ig superfamily

• signal transduction

  • ITAMS = stimulatory

  • ITIMS = inhibitory bind unbound ab and tell the B cell that they are overshooting

  • gamma

Signal transduction pathway

• all use the same pathway to get information through the cell

• but you can switch what triggers the pathway.

• we see this structure over and over

  • certain drugs can cause bad affects because the pathway has meany different triggers which can cause weird side effects

Timing of ab

• ab is not good at dealing with things already in the cell

• odd timing

  • see the target stick to it

  • cytoskeleton rearranges shifts to the problem site

  • two cells stay together then separate

  • not an instant death not punching holes in the membrane it will die internally

How CTL kills cells

• perforin polymerize into a barrel we can see holes it punches in the membrane

• cell does not explode like they normally would when they activate complement

• instead goes through apoptosis swallowed no inflammation

• These holes allow granzyme (protease) into the target cell

CTLs recognize and kill infected or tumor cells via TCR

• Perforin/granzyme pathway

  • we have a target cell and Tc

  • granules in Tc have both perforin and granzyme in them

  • perforin forms a pore the purpose is to allow granzyme access to the target cell

  • granzyme will activate caspase (the normal apoptosis pathway that all cells carry)

  • trigger the activation of a normal pathway (all cells want to go through apoptosis at some point)

  • when granzyme is release things to chop DNA into fragments, cytoskeleton pulls the membrane into vesicles makes it easier for macrophages to phagocytize and recycle

  • cytoplasms doesn’t spill into circulatory (explode)

    • if it does the trigger damaged associated molecular molecules = inflammation

• Fas pathway joins the same pathway to trigger apoptosis

  • granzyme is triggering here

  • FADD fast associated death domain molecules on the surface of cells ask if they need to undergo apoptosis

Evolution and viruses

• turn down MHC I so they cant be detected

• Tc wont see them to kill them

Sequential

• Th

  • virus has a protein encoded extracellular form

  • phagocytic cells recognizes the verions in circulation and bind to them using trigger pattern recognition molecules

  • which are turned up in the phagolysosome present in MHC II to Th cells and get Th cells specific for viral peptides to start produce IFN-gamma

• Tc

  • see ag in MHC I and response to that is to kill the cell that presented it unless it is a licensed dendritic cell

    • Dendritic cells will swallow virus and produce some of the peptides in MHC I and present co stimulatory molecules to convince Tc to not kill it but to continue to replicate it

    • make memory and effector cells

Simultaneous

• in nodes clusters of cells

• dendritic cells pull ag and drop it into the node

• Tc and Th cells then decide what to do next

Graph

• titer is a biological concentration (activity per volume)

• virus titer is how many viral plagues are we going to have

• virally specific Tc we don’t see till later

• surge of NK cells

• early IFN - alpha and beta which is good for antiviral activity they turn down protein transduction and cause the sick feeling

NK vs Tc cells

• Tc looks for ag and NK cells always looks for activated ligands but they are inhibited by inhibitory receptors that bind MHC I

• look for absence of something

• tension between killing or not

  • reason bc MHC I is the way that Tc sees viral ag and if the virus turns off MHC I it would be invisible (fail safe)

Tolerance

Has MHC I inhibitory signal to turn off NK cells and prevent it from killing the cell

Missing self

No MHC I no inhibitory signal so MK cells activation is on and will kill the cell

Balanced signals

• up regulation of stimulatory cells due to DNA damage

• stress molecules increase to get NK cells to delete them

• KIR killer inhibitory receptors get damaged cells to delete

NK cells and MHC I

• Nk cells ask for MHC I and if it has it then there is a inhibitory signal and lets the cell through

• No MHC I will stimulate NK cells and kill it

  • virally infected cells produce more stimulatory molecules to NK cells even if no MHC I if there are enough signals it will delete the cell

NKT cells

• Tc cells kill by apoptosis and triggered by fas or perforin/granzyme

• Th looks for ag on MHCII, Tc look for ag on MHC I

• NK cells no MHC I will kill the cell

• Immune system needs something the middle so NKT cell sees MHC but not I or II looks for ag on CD1

  • nonstandard MHC present ag in glyccolipid no VDJ recombination

  • main idea is that yes there is killing or not but there is also a mechanism in the seems

Innate lymphoid cells

• myeloid cells run this and lymphoid cells run specific immune system

• NK cells are not ag specific but they are lymphoid specific

• ILC 1 response (Th1)

  • IFN-gamma

  • viral

• ILC 2 response (Th2)

  • IL4,5,13

  • fungal

• ILC 3 don’t rearrange their ag receptor but they produce cytokines

  • IL17A,22

  • cells in the mucosa

• Th1 cells are long and difficult to make slow

• ILC can make many for less time and energy produce similar cytokines to support action of Th cells they create less issues with autoimmunity because they are under the control of a t cell