Immunology summary (NWI-BB019B) Part I

Immunology Radboud university
THEME 1: INTRODUCTION
Biological aspects immune system:
- cell-cell interactin and cimmunicatin
- cell priliferatin and death
- actiatin if cells iia receptirs and signnal transductin
Medical aspects immune system:
Diseases due ti a failingn immune system:
- immunidefciency’s
- allergnic reactins
- autiimmune diseases
Health by manipulatngn the immune system:
- iaccinatin agnainst infectius diseases
- immunitherapy agnainst cancer
- immunisuppressiin afer irgnan transplantatin
 Immune cells: Bine marriw  stem cells  immune
cells
 Innate immune cells : cells respind directly ti a
pathignen
macriphagnes, mast cell, NK cells
0-12 hiurs ti respind afer infectin
 Adaptie immune cells : mire specifc, delayed
B and T-cells
+/- 4 days ti respind afer infectin
Antbidy = mist piwerful humiral cimpinent frim the immune system
can play a rile in neutralizatin ir cimplement system actiatin
3 PHASES IMMUNOLOGY
1) Recognition phase : antgnen recignnitin, distngnuish between self and nin-self
2) Induction phase: cellular / humiral respinse? Respinse/tilerance?
3) Effector phase: hiw ti efectir mechanism iperate? Hiw ti terminate the immune respinse?
(Because it cists a lit if energny), memiry established?
Antgnen receptirs
B cells = membrane biund at frstt Plasmacell > antbidies secreted

,T cells = membrane biund all the tmet




NAÏVE LYMPHOCYTES BECOME EFFECTOR LYMPHOCYTES
Afer B & T cell deielipment yiu gnet naïvie cellst These cells haie neier enciuntered an antgnent
Mature naïvie B & T cells > recignnize an antgnen > priliferatin > diferentatin (B-cells becime
plasmacells, and T-cells becime T-helper cell) > antgnen specifc memiry cells




 Signals required for actiiation of lymphocytes

1) Antgnen recignnitin
2) Ci-stmulatin
3) Cytikines
All if these signnals lead ti priliferatin and diferentatin
 Primary lymfoid tissue: B-cells = bine marriw, T-cells = thymus

When yiu’ie gnit an pathignen iia the skin > APC picks up antgnen > mignrates ti the lymph nodes >
interactin naïvie B+T cells

pathignen iia bliid > APC picks up antgnen > mignrates ti the spleen > interactin naïvie B+T cells
Spleen & lymph nides = secondary lymphoid organs




Fignure 2: the APC dictates whether we haie an immune respinse ir tilerance
 Diferent phases in adaptie immunity
Day 0-7 = lymphicyte actiatin (antgnen recignnitin, clinal expansiin, diferentatin)
2

, Day 7-14 = antgnen eliminatin (antbidies and efectir T cells)
Day 14+ = cintractin (himeistasis) apiptisis
Day 21 = memiry




THEME 2: INNATE IMMUNITY
1st line defense = nin-specifc external barriers (physical barriers: skin / mucius)
2nd line defense = innate immune system
nin-specifc patrilst (Germ line-encided receptir – ni adaptatin if specifc pathignenst)
3rd line defense = adaptie immune system
 It’s iery hard fir a pathignen ti infect a healthy persint The pathignen has ti haie a receptir
that binds ti a targnet cellt Pathignen needs ti replicate befire it gnets atacked by the immune
systemt
Pathignen has ti: gain access to the body – atach to target cells – reproduce while avoiding host
immune system
Function innate immune system:
- Preients, cintrils ir eliminated iniadingn micribes
- Eliminatin if damagned cells and initatin if the pricess if tssue repair
- Actiatin if the adaptie immune system
Components innate immune system:
1) Patrillingn cells > atack pathignens, but ni memiry : phagnicytes / NK cells
2) Innate immune receptirs > recignnizes features pathignens
3) Priteins > cytikines/ cimplement

Pathogen crosses 1st line of defense:
* Damagne ti tssue trigngners lical nin-specifc inflammatory response
- release chemical signnals: histamines / pristagnlandins
- capillary becimes mire permeable
- increased temperature
LEUKOCYTE RECRUIMENT TO SITES OF INFLAMMATION
Inflammatin endithelial cells are stmulated by cytikines >
endithelial cells start ti express selectins (adhesiin
milecules) > neutriphils which traiel thriugnh ieins start ti
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, adhere ti the wall if the iain > neutriphil can traiel thriugnh the cell wall and cells mignrate ti site if
inflammatint
Phagocytosis:
impirtant feature if the innate immune systemt
1) phagnicyte adheres ti pathignen
2) phagnicyte firm pseudipids, engnulf the pathignen > firm phagosome
3) lysisime fuses with the phagnicytc iesicle, firmingn a phagolysosomet
4) lysisimal enzymes break diwn pathignen
5) exicytisis if the iesicle remiies indignestble and residual material
Recignnitin and phagnicytisis = mediated by PAMPs and PRRs
microbes have PAMPs
damaged/ infected cells have DAMPs

These PAMPs and DAMPs are recignnized by pattern recognition receptors:
phagnicytes has PRR si can recignnize PAMPs
PAMPs:
- shared by a largne gnriup if pathignens
- easy ti recignnize: conseried and nit a subject ti antgnenic iariability
- pathignens can’t changne them because they are essential fir the suriiial if pathogenicity
- absilutely distinct firm self-antigens
Toll-like receptors (TLRs):
TLR 4 = LPS (gnram – bacteria)
TLR 5 = flagnellin (tail bacteria)
TLR 9 = CpG DNA (special structure DNA frim iiruses)
Cell surface TLR recignnize bacterial cell wall structure
intracellular TLR recignnize pathignen nucleic acids (iiruses): TLR7, 9, 3
 Gram – bacteria = iuter membrane cintains LPS
 Gram + bacteria = thick peptdignlycan wall
Si bith bacteria; Recignnized by a diferent TLR




SIGNALING PATHWAY OF TLR4

The transcriptinal actiatir NF-kB is a key player in inflammatiry
cytikine expressiin
Interacton PA via CD14, MD and T R4 leads to recruitment of adaptor
protein myD88. Actvaton of IRAK leads to phosphorylaton of TRA6. 
phosphorylaton IKKs
Phosphorylation IKKs > lead ti degnradatin if ikB (transcriptin factir),
when CLR is biund by LPS this cascade makes sure ixB is degnradatin si
NF-xB actiatin and can lead ti transcriptin if inflammatiry cytikinest


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