 Thymus independent antigen

- Ex: polysaccharide capsule + LPS (gram -)

- T cells not no (no CD40 ligand)= NO ISOTYPE SWITCH
-NO MEMORY

Bcell development and selection

 PRO- B: The cytoplasmic μ is the heavy chain waiting for the light chain to be made
 Negative selection in the Immature B cell when only surface IgM
- clonal deletion of those that bind to tight
 Activated Blast is when ANTIGEN BINDS and causes proliferation in the GERMINAL
CENTER
-here somatic hypermutation
-isotype switching
 The plasma cell is a dead end ( make Ig and then die in two weeks)
 Memory cells when activated 2nd  directly to memory cell transform
T cells development and selection
 Everything before thymus DOUBLE NEGETIVE (NO CD4 OR CD8)
 Cortex DOUBLE POSITIVE
 Medulla commit to CD4 or CD8
 Postive and negative selection in Cortex
-Positive: select those bind MHC ( done by epithelial cell)
-Negative: remove bind to tight to self

Major histocompatibility complex (MHC)/ HLA

 HLA are on chromosome 6
 CoDominant expression (mom and dads)
 - B2 microglobulin isn’t encoded with HLA but needed for function
 MHC II have INVARIANT CHAIN so MHC II don’t bind self
MHC I MHC II
HLA- A, B, C “ grade 1 ABC” HLA- DR, DP, DQ “ Dr DePide likes DQ”
Alpha chain + B2 microglobulin Alpha + Beta
“ alpha and beta present to T “alpha and
beta”
On all NUCLEATED On APC cell
-not on RBC
CD 8 + T cell CD 4+
Endogenous pathogen Exogenous pathogen
 the antigen degraded by proteasome
 tranposrt into ER by TAP
 combine with MHC 1 in ER
 to golgi  cell membrane
 phagocytosis of antigen
 phagosome+ lysosome fuse + degrade
antigen
 MHC II made in ER sent via vesicle to
lysosome
 Lysosome degrade INVARIANT CHAIN,
So antigen can bind

Acute Inflammation
1) cytokines increase selectins adhesion on endothelial cells
2) ROLLING : PMN bind E-Selectin on endothelial cells
3) ADHESION: the Integrin binds to ICAM on endothelial
-LAD : if CD18 missing, part of integrin
4) pseudopods sent in and extravagation into tissue following chemokine gradient
 Chemokines for PMN : IL-8, C5a, LTB4

* APC picks up the antigen and then goes to the lymph node or spleen in order to activate T
cells (B cells activate here too)

Antigen Presentation In 2nd lymph tissue INTERACTIONS

 T cells bind to MHC on APC (the CD4 or CD8 stabilize it)
 CD3 send the intracellular signal
 CO-stimulatory signal : CD28 ( T) = B7 (APC)
-without this causes ANERGY
-CTLA-4/ CD152 compete with CD28 for B7 to turn off T cell
- Superantigen : binds to the outside of TCR and causes it to join MHC II, leading to activation of
MANY T CELLS  HIGH CYTOKINE  EXCESSIVE pro inflammation causing multiple organ failure

T cell types
 THo gets diff signals and transforms to diff cells ( CD4+)
TH1 IL-12 from macrophage activate NK to secrete IFN-gamma= TH1
-Cell mediated response
-marcophages (IFN-gamma)
- CD8+ CTL ( IL-2)
-makes IL-2, IFN-gamma, TNF-β
-IFN-gamma inhibits TH2
TH2 IL4 causes TH2 to be made
- Humoral response (antibodies)
- Produces IL4,5,6,10,13,TGF- β
-IL-10 and IL-4 inhibit TH1
Treg - Made when TGF-beta ( antinflammatory)
 - Make il-10 to turn off TH1 cells
- CD25 surface marker, and FOXP3 transcription factor
T17 - Made when TGF-beta + IL-6
- Pro-inflammation when makes IL-17
 CD8+ T/ cytotoxic T cells :
- Tumor cell, viral, transplanted tissue bc HLA don’t match

Clincial : Leprosy
 Mycobacterium leprae is intra macrophage pathogen therefore antibodies don’t work
 Tuberculoid: Th1 response good, forms granuloma to wall off infection + recover
 Lepromatous : TH2 response bad, antibodies don’t fix issue and further turn down TH1.
HYPERgammaglobulinemia

Humoral Immunity
 Need T cells for isotype switching
-CD40 ligand (T) = CD40 B
- W/o CD40 L= X-linked Hyper- IgM Syndrome

Papain Pepsin
- cut above hinge -cut below hinge
-3 fragments
-2Fab + 1FC - 2 fragments
-1F(ab)2 + 1 FC
-agglutinate +
precipitate

 The J chain keeps antibodies together ( IgM and IgA)

 IgM always first made even in allergic rxn ( 1st exposure)
 IgA has secretory component that protected it form degradation in the lumen
 ADCC: Antiody dependant cell- mediated cytotoxicity
-IgG for NK cells
-IgE for Eosinophils in parasite infection

Compliment
 Made in Liver
 C3a, 4a, 5a anaphylatoxins (bind to mast cell and basophil to degranulation)
 C5a chemotactic for PMN
 C3b Opsin
 MAC 5 9 * essential for Neisseria infection ( meningitis and gonorrhea)
 Alternative (activated by pathogen) vs Classic IgM and IgG