Failures of host immunity/allergy, autoimmunity, cancer

mast cells needed.

direct activator -> FCeR1 - binds to FC part of IgE

IgE activates mast cells and then produces histamine

B-cells

when IL4 is produces(?)

TH2 cells

due to AG presenting cells which produce IL2

bc of the NKcells which produce IFNy and early IL4 which comes into play with allergies

Activation of NK1.1+ subset of CD4T cells -> Naive T cells are primed and develop into Th2 cells in the presence of IL-4 -> activated TH2 cells secrete IL4, inducing isotype switching of IgE

more IL 4 in last step, which activates cell with the ligand interaction

in presence of IL4 mainy IgE is produced

IgE binds to epislon receptor 1 and binds mast cells which then produce histamine and other stuff

1. degranulation - histamine, proteoglycans, proteases, TNF

2. lipid mediators - prostaglandins, leukotrienes

3. cytokine transcription - inflammatory, immunoregulatory

FCeRI with ß, a, y,y, regions

IgE secreted by plasms cells bind to a high-affinity FCR - FCeR1, on mast cells -> activated mast cells provide contact and secreted signals to B cells to stimulate IgE production

Features of inhaled allergens that may promote the priming of TH2 cells that drive IgE responses

protein - only proteins induce Tcell response -> have to be proteins bc there need to be MHCII presentation and only peptides are presented

enzymatically active - allergens are often proteases - house dust -> acting as danger signals increasing signal

low dose - favors activation of IL-4-production CD4T cells - like pollen, favor TH2 responses bc if high -> strong immune response. low dose - IL4 production

low molecular weight - allergen can diffuse out of particle into mucus - pollen particle -> protein needs to diffuse out

high solubility - allergen can be readily eluted from particle - the longer lasting

contains peptides that bind host MHCII - required for T cell priming -> bc of binding/recognition of MHCII

1. active elimination of immune cells - HIV, active elimination, crucial for macrophage activation

2. suppression of adaptive immune responses - malaria, measles (interferes with DC interactiin)

3. induction of a “wrong” immune respone (TH1 wrigth, TH2 wrong e.g.) - not suppression but modulation (Lepra, Leishmania, SARS)

4. polyclonal lymphocyte activation by superantigens - cant be sustained, Eppstein barr virus, staphylococcus - TSST1 - lethal infection

5. Antigen variation - influenza, AG shift and drift, HIV, SARS, Trypanosoma brucei

• induction of apoptosis

  • HIV (CD4+ Tcells), BVD (bovine virus diarrhoea), ND (newcastle disease), Shigella flexneri (macrophages)

• Consequences of CD4+ T cell depletion

  • Reduced CD8+ Tcell responses - bc IFNy is needed

  • weak AB responses - CD4 tcell leads to increasing

  • decreased NK cell activity (no TH1-derived IFNy)

• Induction of necrosis

  • staphylococcus aureus

  • truperella pygogenes (Pyolysin)

    
    

  leads to disturbance, proliferation and/or elimination

• virus encode for cytokine receptor homolog:

  • e.g. viral receptor homologs IFNy, TNF-a, IL-1. IL18

  • receptor homolog acts as competitive inhibitor of cytokine binding to the host cell cytokine receptor

  • if protein is homologous - binds to cytokine “catches” it out of the circulation

• virus encodes for cytokine homolog

  • e.g. viral homolog for IL10 -> down regulation of immune response similar for leishmania

  • inhibits macrophage activation

  • inhibits activation of DCs

  • inhibits TH1 responses

  • everything what can be attaked -> target of IL10

Tcell -> polyclonal activation; cytokine production; Apoptosis; anergy -> bc of overwhelming

APC (Macrophages, Bcells, DCs) -> cytokine production; proliferation; apoptosis -> double directed action mainly on cell but on part also on APC

VSG - variant surface glycoproteins. each VSG gene causes immune response

ca 1000VSG genes are encoded in the trypanosoma genome - only one expressed at a time, only 1 duplicated

pathogen - just swimming in the fluids - blood

excessiable for complement and AG/AB - for humoral immune response

trypanosomes transmitted via CC fly

onces in CNS - symptomes of sleeping disease , therefor treating in the very beginning - periodic syptomes bc of VSG genes activated one after another

AG variation as long as the immune response needs

around 1000x doable variations, but after certain month invasion of CNS

one varian each week e.g.