Adaptive Immunity
A. Recognizing foreigners: Antigens,
epitopes & haptens
- There are two basic types of immune responses
- Humoral immune response: Antibodies
- Cell-mediated immune response: MHC
- Specific immunity recognizes foreign material
- Antigens:
epitopes & haptens
- PAMPs
- Antigen presenting cells process foreign material:
- MHC-I: presentation of internally derived antigens
(all nucleated cells, incl. DC, Mɸ, B-cell)
- MHC-II: presentation of externally derived antigens
(professional APC: DC, Mɸ, B-cell)
- Immune system cells have receptors for foreign material:
- Toll-like receptors (TLR): peptidoglycan, teichoic acid, LPS, flagellin, ssRNA,
dsRNA, DNA, zymosan
- T-cell receptors
- Genetic recombination generates ~ 1015 TCR combinations
- TCR links to CD3 complex to activate cellular growth &
differentiation
- CD-4 and CD-8 are co-receptors for the
TCR
- Immunoglobulins
- Specific immune responses must be activated
- B-cells: Antigen, TH, cytokines, PAMPS,
C3d
-
T-cells: antigen/MHC presentation; coreceptors; cytokines; PAMPs
may enhance activation
- TCR/CD-4 & MHC-II/antigen
- TCR/CD-8 & MHC-I/antigen
- CD28 & B7
- IL-1, 2, 4, 6, 10, 12
- NK cells: cytokines, abnormal MHC-I, IgG
- Dendritic cells: PAMPS, cytokines
- Macrophages (Mɸ): IFN-y; PAMPs
- NKT cells: TCR & CD-1
- γ/δ T-cells: γ/δ TCR & microbial metabolites
B. Humoral Immunity
- B-cell diversity
- 10 trillion B cells, 100 million different antibodies
- Gene splicing
- B-cell differentiation
- Naive B-cells (IgD, IgM)
- B-cell
activation
- T-cell independent
- T-independent antigens: peptidoglycan, capsules, flagellin
- C3d, LPS & cytokines also activate
- Produces an IgM response
- No memory cells formed
-
T-cell dependent
- T-dependent antigens: proteins
- Helper T-cells (TH1, TH2, TH3)
- MHC-II &
TCR/CD-4
- B7 /
CD28 and/or CD40 /
CD40L
- Cytokines
- Clonal selection
- Class switching
- TH2: switch to IgG, IgA, IgE via IL 4, IL5, IL6
- TH1: switch to IgG via interferon-γ
- TH3: promotes IgA production via IL5 & TGF-β
- Plasma cells
and memory cells
- Primary Immune response: primarily IgM
- Secondary Immune response: primarily IgG
- Role of cytokines
- IL-1: activator
- IL-4, IL-5, IL-6, IFN-g: differentiators
- Types of antibodies
- IgA - secreted
- IgD -
membrane-bound
- IgE
- allergic response; binds to mast cells, basophils
- IgG - major secreted plasma Ig; opsonin, complement activation,
placental transfer
- IgM
- pentameric; first responder; plasma; activates complement
- Effects of
antibodies
- Neutralization
- Opsonization
- Fc receptors - IgG
- IgE receptors (eosinophils)
- Complement activation
- Classical pathway
- Ag|Ab complex + C1 --> C2 + C4 --> C3
- C5a attracts neutrophils
- C3b enhances opsonization
B. Cell-mediated Immunity
- Antigen-presenting cells
- Macrophages (MHC-I
& MHC-2): secrete IL-1 & IL-6
- Dendritic cells (MHC-I, MHC-2, CD-1 glycolipid receptor)
- iDCs determine type of response: TH1 or TH2
- TH1 activated by IL-2, IL-12 (macrophage)
- TH2 activated by IL-4, absence of IL-12/IFN-γ
- Activation requires co-stimulatory signal (B7/CD28) & cytokines
- Absence of co-stimulation leads to apoptosis or anergy
- B-cells (MHC-II): to TH2 cells
- Virus-infected cells, tumor cells, transplant tissue (MHC-1)
- T-lymphocytes
- Helper
T-cells
- TH1: activates local, inflammatory responses
- TC and NK cells activated via IL-2
- B-cell production of IgG & IgM (IL-2, IFN-γ)
- Macrophage activation (IFN-γ)
- Inhibition of TH2 responses via IFN-γ
- TH2: activates later, systemic antibody responses
- stimulates B-cells via IL-4 & 5; class switching
- inhibits TH1 response via IL-10
- TH17: Promotes inflammation even in presence of TGF-b
- inhibits TH1 and TH2 via TGF-β
- produces TNF-a, IL-17 (neutrophil activation)
- Treg: suppress the immune response
- Suppress TH1 and TH2 via TGF-β and IL-10
- Promote memory cell formation
- Cytotoxic T-cells
- TCR/antigen
- CD8 (MHC-1 receptor)
- CD28 (coreceptor) /
B7
- requires IL-2 for activation
- Natural Killer cells
- CD16 (Fc receptor for IgG): destroy Ig-coated cells
- MHC-1 receptor (inhibits activity); if inhibitory signal absent,
NK destroys cell
- activated by IFN α & β, TNF-α, IL-12, IL-2 a.o.
- T-cell
activation
-
MHC-1: CD8+ TC cells
- MHC-2: CD4+ TH cells
- Cytokines
- Macrophages: IL-1
- Th cells - IL-2
-
T-cell responses
- CD95/Fas (apoptosis) pathway: NK, Tc, TH1
- Perforins & Granzymes: NK, Tc
- IFN-g & TNF-a
- T-cell
dependent humoral response
- T-cell independent humoral response
- Cell-mediated
immune response
Links and references
- http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/t4cell/mhctwo.html
- http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=imm.section.1722
-
https://www.researchgate.net/figure/Schematic-presentation-of-B-cell-T-cell-activation-in-the-interfollicular-or-T-cell-zone_fig3_320226448