Antigen Processing and Presentaion - T cell Activation

What does adaptive immunity activation rely on?

Antigen-presenting cells to process antigens and present them to T cells

How are antigens presented to T cells?

Via peptides on MHC molecules

What MHC class is used to display cytosolic pathogens?

MHC class I

What MHC class is used to display extracellular pathogens?

MHC class II

How are bacterial toxins captured and presented?

Receptor mediated endocytosis

What cells are professional antigen presenting cells?

Macrophages, B lymphocytes, and dendritic cells

What is the main function of macrophages?

Trap and destroy pathogens using phagosomes

What T cells do macrophages interact with?

Effector and memory T cells

Macrophage interactions with T cells are what?

Short, they cannot engage in prolonged interactions

What T cells do B cells present antigens to?

Helper T cells

Which cell is the most important full time professional antigen processing cell?

Dendritic cells

Why are dendritic cells the most important professional antigen presenting cells?

They're the only cell with the ability to activate naive T cells

Why are naive T cells hard to activate?

They require an extended period of time in contact

What cells are the only ones able to activate naive T cells and why?

Dendritic cells

They are the only ones with appropriate cell surface molecules that allow extended contact needed for activation W

Where are dendritic cells derived from?

Bone marrow

Where are dendritic cells found?

In most tissues and blood

Reside under epithelial surfaces

What happens when a dendritic cell is activated?

It develops dendrites to increase surface area

What are dendrites?

Long thin cytoplasmic processes on activated dendritic cells

What are dendrites important for?

Increasing surface area to increase efficiency in trapping and presenting antigens to many T cells

When are dendritic cells mature?

When pattern recognition receptors (PRRs) are engaged

What are mature dendritic cells best at?

Processing internalized antigen and presenting antigens to naive T cells

What are immature dendritic cells good at?

Capturing antigens

Where are dendritic cells located ?

In the periphery

Where do mature dendritic cells present antigens to T cells?

In lymph nodes

What can dendritic cells produce to activate various T cell subsets?

Cytokines

The cytokines dendritic cells produce are based on what?

Binding to PAMPs and alarmins

What type of cell do dendritic cells act as?

Sentinel cells

How do dendritic cells act as sentinel cells?

By monitoring the environment for harmful particles and initiating an immune response

What are the classical dendritic cells?

Langerhans cells

Interdigitating dendritic cells

Thymic dendritic cells

Follicular dendritic cells

Where are classical dendritic cells found?

All over the body

What are Langerhans cells?

Immature dendritic cells in the skin

What are Langerhans cellls the origin of?

Histiocytomas

What are histiocytomas?

A benign proliferation of histiocytes that appear as a red, round, raised, hairless lesion

Spontaneously regresses in 3-6 months

What are interdigitating dendritic cells?

Mature dendritic cells that interact with T cells in the paracortex of the lymph node

What are thymic dendritic cells?

Dendritic cells that present self-antigens to thymocytes in the thymus

What are thymic dendritic cells important for?

Negative selection of T cells in the thymus

What are follicular dendritic cells?

Dendritic cells in the follicles of lymph nodes that provide survival signals to naive B cells and present antigens to effector B cells

What are follicular dendritic cells important for?

Affinity maturation of B cells

What are plasmacytoid dendritic cells?

Dendritic cells derived from plasma cells that are found in blood, bone marrow, and lymphoid organs

What are plasmacytoid dendritic cells essential for?

Anti-viral responses

Activate natural killer cells

What happens as dendritic cells mature?

Increase surface expression of MHC

Upregulate co-stimulatory molecules for T cell activation

Secrete cytokines needed for T cell proliferation and differentiation

How are cytosolic antigens processed and presented?

Ubiquitin targets tags viral proteins for proteasome targeting

Proteasome cleaves proteins into peptides

TAP transports peptides into the endoplasmic reticulum, where they're attached to MHC class I

MHC class I molecules are expressed on the cell surface

How are vesicular/exogenous antigens processed and presented?

The antigen is phagocytosed and partially digested

The antigenic peptide replaces the invariant chain on MHC class II

MHC class II molecule is expressed on the membrane

What is an invariant chain?

A protein that prevents peptides from binding to MHC class II molecules in the endoplasmic reticulum

What type of adaptive immunity is activated by MHC class I?

Cell-mediated immunity

What type of adaptive immunity is activated by MHC class II?

Humoral immunity

What cytokines mediate dendritic cell migration to lymph nodes?

CCL19, CCL21, and CXCL12

What receptors on dendritic cells respond to CCL19 and CCl21?

CCR7

What receptors on dendritic cells respond to CXCL12?

CXCR4

How long does T cell activation take after binding to a dendritic cell?

12-24 hours

What three signals are needed for T cell activation?

Antigen specific signal

Co stimulatory signal

Cytokines

What determines what MHC class a T cell can bind to?

T cell receptor co-recptors (CD4 and CD8)

T cell co-receptor CD4 can bind to which MHC class?

MHC class II

T cell co-receptor CD8 can bind to which MHC class?

MHC class I

What is the CD3 complex?

A complex found in T cells that assists in signal transduction

What is the first signal in T cell activation?

Engagement of T cell receptor with MHC:peptide complex

What is the second signal required for T cell activation?

Co-stimulatory signals

What T cell receptors are involved in co-stimulator signals during activat?

CD154 (CD40L), binds to CD40

CD28, binds to CD80/CD86

CTLA-4, binds CD80/86 after 2-3 days

What happens during the co-stimulatory signal during T cell activation?

CD40L binds to CD40 on dendritic cells

Dendritic cells release cytokines to upregulate T cell receptor CD28

CD28 binds to CD80/CD86 on dendritic cells

What does CD28 binding to CD80/CD86 during T cell activation do?

Enhances cytokine expression and survival genes in T cell

Upregulates CTLA-4 expression

What does CTLA-4 do?

Binds to CD80/CD86 on denritic cells after 2-3 days to stop activation

What is peripheral tolerance?

Prevention of activation of T cells to help minimize chances of autoimmunity

What is the immunological synapse?

Region of contact between T cell and antigen presenting cell

What are supramolecular activation clusters?

Concentric rings of molecular complexes in the immunological synapse

What does the central supramolecular activation cluster contain?

MHC and TCR molecules needed for the first signal in T cell activation

CD28 and CD80/86 needed for the second signal in T cell activation

What is in the peripheral supramolecular activation cluster?

Adhesion molecules ICAM-1 and LFA-1 to stabilize the interaction between the T cell and antigen presenting cell

What happens to the supramolecular activation center after T cell activation is completed?

It's endocytosed and degraded, terminating cell interactions

What is the third singal needed for T cell activation?

Cytokines to induce proliferation and differentiation

What does IL-2 do in T cell activation?

Signals proliferation/clonal expansion

What does a high affinity IL-2 receptor require?

Alpha chain

What happens to the IL-2 receptor during T cell activation?

Alpha chains are produced and high affinity receptors are upregulated

What cytokine causes differentiation of T cells into Th1 cells?

IL-12

Absence of what cytokine casuses T cell differentiation into Th2 and Th17 cells?

IL-12

What influences the cytokines released by dendritic cells?

PAMPs and DAMPs

What happens if the co-stimulatory signal is missing during T cell activation?

T cells becomes anergic and can't become activated in the future

What happens when there's no specific peptide:MHC complex but there is a co-stimulatory signal during T cell activation?

Naive T cell doesn't resond at all

What are follicular dendritic cells important for?

Affinity maturation of B cells

What are follicular dendritic cells important for?

What are follicular dendritic cells important for?