16: Adaptive Immunity

T cell positive selection

Is it useful; can it recognize an MHC molecule

T cell negative selection

Is it dangerous; does it recognize self proteins

How does the thymus mediate negative selection

The AIRE gene that allows it to express any self protein

Naive T cells

Single positive T cells that make it out of the thymus

Naive T cell function

Recognition of foreign antigens presented by APCs

First antibody class produced by the adaptive immunity in response to an infection

IgM

Most common antibody class in the blood/serum

IgG

Induction phase of infection

Recognition of foreign Ag and recruitment of the adaptive immune system by the innate immune system

Effector phase of infection

2 phase period: first, rapid multiplication, then mass apoptosis of most immune cells to prevent overreaction

Memory phase of infection

Infection is handled, and memory cells are left behind to defend against subsequent infections

Why is there a lag time before the adaptive immune system kicks in

It has to be activated by the innate immune system

T_H cell activation summary

CD4 T cell binds to MHC II → LFA-1 and ICAM-1 bind → IL-2 secreted → proliferation → other cytokines direct differentiation

Cytokine that directs T_H1 differentiation

IFN-γ

Cytokine that directs T_H2 differentiation

IL-4

Cytokine that directs T_H17 differentiation

Il-6, IL-23, TGF-β

Cytokine that directs T_reg differentiation

TGF-β and IL-10

Most significant cytokine that T_H1 produces

IFN-γ

What major cells do T_H1 help activate

Macrophages→ M1 (also activated by IFN-γ!)

What other T_H cell can activate macrophages

T_H2 (M2→ alternative pathway of activation)

Most significant cytokine that T_H2 produces

Il-4, IL-5, and IL-13

What major cells do T_H 2 help activate

Mast cells and eosinophils

What other T_H cell does T_H2 work with

T_fH (follicular helper)

What does T_fH stimulate

Production of IgE

Most significant cytokine that T_H17 produces

Il-17 and IL-22

What major cells do T_H17 help activate

Neutrophils

Why are T_H17 cells implicated in numerous inflammatory diseases

Il-17 is responsible for immune recruitment, and too much can lead to chronic inflammation

T_FH cell location

Lymph nodes

T_FH cell function

Helps B cells activate

T_reg cell function

Controls immune response and prevents autoimmune/food responses

Types of T_reg cells

Natural and induced T_reg cells

Natural T_reg cell

Thymically derived, come from T cells that fail negative selection and are recoded to stop the immune response against their antigen

Induced T_reg cell

From Naive cells activated by cytokines from DCs, prevents inflammatory immune response to normal microflora

Key molecules for T_reg cell function

• CTLA-4 (protein)

• CD25 (receptor)

CTLA-4 function

Competes for B7 binding and can completely remove it, blocking co-stimulatory activation

CD25 function

Alternate receptor for IL-2, and binds with WAY higher affinity, getting in the way of the proliferation signal