Adaptive Immunity

B cells & T cells

major classes of effector cells

drivers of adaptive immune response

B cells

produce antibodies (secreted proteins)

humoral response

recognize epitopes of soluble or particulate Ag’s

antibodies (AB)

respond to specific antigens (Ag)

not general response

requires specific receptors and ligands

T cells

kills cells directly (direct attachment)

cell-mediated response

secretory pathway

protein enters rough ER

transported to golgi via vesicle to undergo chemical modifications

vesicle leaves gogli & fuses w PM

secretory pathway biological result

proteins are secreted into ECM or membrane bound proteins are installed in membrane

CD4/T helper cell

interacts w other parts of immune system to initiate different kinds of responses

recognize peptides bound to self-MHC proteins

recognize MHC-2

APC’s

Ag presenting cells that trigger immune maturation

collect Ag’s & display them

dendritic cells, B cells, macrophages

CD8/cytotoxic T cells

activated by APCs

trigger apoptosis intrinsically & extrinsically to kill messenger

recognize MHC-1 on all nucleated cells

MHC 1 & 2

determine Ag sources by displaying Ags on their surface

signals immune response

MHC class 1

displays endogenous (w/in the cell (cytoplasm)) Ags

includes intracellular bacteria, viral components, & mutant proteins that release proteins in cytoplasm of cell

MHC class 2

display exogenous Ags

endocytosed from external source

endogenous pathway (MHC-1)

endogenous Ag degraded by proteasome

peptide transported to RER via TAP

MHC captures peptide & MHC-peptide is transported from RER to golgi to PM to be displayed

exogenous pathway

MHC-2 bind invariant chain to prevent binding of Ag

MHC complex moves through golgi to endocytic pathway compartments

invariant chain is degraded & leaves CLIP fragment

Ag is taken up, degraded by endosomes, & routed to endocytic pathway compartments

CLIP is exchanged for Ag peptide & transported to PM to be displayed

invarient chains

block Ag binding site

endosome fuses to Ag vesicle & triggers differentiation into lysosome

lysosome

endosome + Ag vesicle

matures MHC-2

CD8 activation

activated by APC’s

APC binds to target cell via MHC-1 and specific CD8/TCR

binding activates clonal expansion of naive T cell into mature memory and cytotoxic cells

naive T cell

not seen Ag yet

not mature

memory T cells

Ag reserve

mature T cells

intrinsic pathway of CD8

vesicles exocytose perforin & granzyme from APC

perforin creates channel (pores) in PM of target cells to allow granzyme to pass through

granzyme activates caspase (final protein that kills cell) & causes iCAD to be cleaved

cleaved iCAD activates CAD to cleave DNA between nucleosomes to induce apoptosis

extrinsic pathway of CD8

APC w/ FAS ligand binds to receptor on target cell

binding activates caspases through auto-inhibition to cause apoptosis

Why aren’t APCs like the dendritic cell here being killed by the CD8+ T-cell, despite participating in the same interaction as the infected cell?

Naïve T-cells don’t express granzyme/perforin yet

Naïve cells in lymph tissue, migrate away upon activation (APCs stay in lymph)

APCs express anti-apoptotic genes and proteases to defend against granzyme

B cell activation (T cell independent)

B cell binds to unique binding site on pathogenic bacterial cell for unique Ag

binding causes activation of B cell & secretion of soluble AB’s

B cell activation (T cell dependent)

BCR (B cell receptor) binds Ag

internalizes & presents on MHC-2

helper T cells (CD4) binds to MHC & activates B cell for clonal expansion

AB-Ag interactions

agglutination

opsonization

neutralization

AB-dependent cytotoxicity

complement activation

agglutination

cross link multiple Ag’s by AB binding to make removal of pathogenic cell easier

reduced number of infectious units to be dealt with

opsonization

improves efficiency of phagocytosis

coats Ag w/ AB to enhance phagocytosis

neutralization

AB destroys non-cellular components

AB binds & forms shell to neutralize & prevent reaction (immune system cannot attack cell)

AB dependent cytotoxicity

tales T cells & localizes CD8 cells to target

AB’s attached to target cell cause destruction w other immune cells

activation of complement

causes inflammation & cell lysis via MAC complex

T cell tolerance

tolerance = recognizing right thing

T cells migrate from BM to thymus & select for functional but non-self reactive T cells

functional T cell = unique TCR that binds to MHC & isnt self reactive

undergoes positive & negative selection

positive selection

survival of T cells that weakly interact with MHC-1

apoptosis of T cells with no interaction to MHC-1

negative selection

apoptosis of T cells with strong interaction of MHC-1 or self Ag

if T cell responds to self Ag, it needs to be removed

can lead to autoimmunity

Why would an immune system want T-cells that interact at all with self MHC I molecules? Why not destroy all T-cells with any interaction to self?

Functional T-cells must be able to recognize MHC I receptor AND foreign antigen. T-cell recognizing only the antigen would fail to induce response.

Important to distinguish MHC I vs MHC II so you are killing infected cells, not another part of the immune system.

Brief recognition of MHC I/self-antigens —> tonic signaling to maintain

survival signaling in T-cells