14. t lymphocytes subsets and effector functions

how can humoral immunity be transferred?

transfer antibodies from one animal to another

how can cell-mediated immunity be transferred?

transfer T cells from one animal to another

why might transfer of cell-mediated immunity be unsuccessful?

• T cell recognition is self-MHC restricted → cannot recognize peptides in new host

• transfer of cells between genetically dissimilar animals → rejection by recipient

T-cell mediated defense against intracellular and extracellular microbes

• intracellular

  • infected cell possesses antimicrobial mechanisms (phagocyte) → T cell enhances antimicrobial mechanisms

  • infected cell lacks intrinsic antimicrobial mechanisms (non-phagocytic cell; e.g. epithelial cell) → T cell kills cells that cannot kill microbes

• extracellular

  • cytokine secretion → inflammation, killing of microbes

what are the general functions of T cell-mediated immunity?

• protect against intracellular pathogens and cancer

• protect against extracellular pathogens by recruiting inflammatory cells

• responsible for graft rejection

what determines the effector functions of CD4+ T cells?

the array of cytokines (effector molecules) they produce

pleiotrophy

a single cytokine can have different effects based on the target cell

redundancy

same functions driven by multiple different cytokines

synergy

the effect of multiple cytokines working together is greater than the sum of their individual effects

antagonism

cytokines produce opposing effects

what determines the functional differentiation/polarization of CD4+ T cells?

cytokines present in the early phases of activation

type 1 immunity is associated with which type of CD4+ cell?

T_H1

what cytokine(s) does T_H1 produce?

INF-γ

what are the overall effects of type 1 immunity?

• classical macrophage activation (enhanced microbial killing)

• complement binding and opsonizing IgG antibodies

which immune cells are prominent during type 1 immunity?

monocyte/macrophages

(phagocyte-mediated defense)

what type of pathogen is primarily targeted by type 1 immunity?

intracellular (vesicular) pathogens → ex. leishmania, mycobacteria

type 2 immunity is associated with which CD4+ cell?

T_H2

what cytokine(s) does T_H2 produce?

• IL-4

• IL-13

• IL-5

what are the overall effects of type 2 immunity?

• antibody production

• mast cell degranulation (IgE)

• intestinal mucus secretion and peristalsis

• eosinophil activation (IL5 = potent eosinophil activator)

• alternative macrophage activation (enhanced fibrosis/tissue repair)

which immune cells are prominent during type 2 immunity?

• eosinophils

• mast cells

(IgE-eosinophil/mast cell-mediated defense)

what type(s) of pathogens are primarily targeted by type 2 immunity?

parasites (helminths, arthropods); also involved in allergies

type 3 immunity is associated with which CD4+ cell?

T_H17

where are T_H17 cells often found?

mucosal tissues

what cytokine(s) does T_H17 produce?

• IL-17

• IL-22

what are the overall effects of type 3 immunity?

• neutrophil recruitment

• inflammation

• increased barrier integrity

• epithelial production of antimicrobial peptides

which immune cell is prominent during type 3 immunity?

neutrophils

(inflammation and neutrophil defense)

what type(s) of pathogens are primarily targeted by type 3 immunity?

• extracellular pathogens (bacteria)

• fungi

what stimuli triggers differentiation into T_H1?

IL-12 and IFN-γ

• macrophages/dendritic cells produce IL-12

• NK cells produce IFNγ

what is the signature transcription factor of T_H1?

TBET

what stimuli triggers differentiation into T_H2?

IL-4 (IL-25, IL-33, TSLP)

• IL-4 produced by mast cells, eosinophils

• others produced by epithelium

what is the signature transcription factor of T_H2?

GATA-3

what stimuli triggers differentiation into T_H17?

fungal glycans/peptidoglycans activate macrophages and DCs to produce:

• IL-1

• IL-6

• IL-23

• TGF-β

what is the signature transcription factor of T_H17?

RORγt

how do T_H1 and T_H2 activation interact with each other?

antagonistic interaction

• T_H1 response activates macrophages

• T_H2 response suppresses macrophages