Exam 2- Lecture 2: T & B Cells Activation

What are the steps in cell-mediated immunity?

• Recognition

• Attack

• Memory

What happens in recognition?

Th & CTL both need to recognize epitopes in MHC molecules

• Th cells help CTL activation → proliferation of CTL clones

What happens in attack?

Cell-cell contact, apoptosis of target cells

What happens in memory?

• Most clones die shortly after activation

• Each encounter w/ an antigen generates a small percentage of long-lived memory T cells

What are helper T cells?

T cells which express CD4 molecule are usually helper T cells

• Respond to antigen presented in context of class II MHC molecules, which means they are responsive to antigen presented by antigen-presenting cells such as macrophages, B cell, & dendritic cells

What are cytotoxic T cells?

T cells which express CD8 molecule are usualyl cytotoxic T cells

• Respond to antigen presented in context of Class I MHC molecules, which means they can respond to antigens presented by virtually any nucleated cell

• Respond to activation developing into cytotoxic T lymphocytes, which can kill abnormal self cells

  • Could be tumor cells, or cells infected w/ a virus

What do activated T cells release?

IL-2 & upregulate IL-2 receptors

• Autocrine

• Paracrine

What is B7-CD28?

B7 molecules on antigen-presenting cells bind to CD28 molecule that is present on T lymphocytes

• After capturing an antigen, there is a rapid surface expression of B7 molecule on APC to provide 2nd signal of antigen presentation

What is costimulation?

A distinct feature of APCs

What happens w/ signal 1 & 2?

Activation

• Proliferation of antigen- specific T cells

What happens w/ signal 2 only?

No activation (inflammation)

• Clonal energy, apoptosis, ignorance (inactivated)

What happens w/ signal 1 only?

No activation

• Clonal energy, apoptosis, ignorance (Inactivation)

What does APC select?

T cells for specific antigen

• naive T cells → Clonal expansion → cells infected w/ virus

What are cytokines?

Diverse & potent chemical messengers secreted by cells of the immune system- & chief tool of T cells

What do cytokines bind to?

Specific receptors on target cells, cytokines recruit many other cells & substances to field of action

What do cytokines encourage?

Cell growth, promote cell activation, direct cellular traffic, & destroy target cells- including cancer cells

What are the main source of IL-2?

Activated CD4 helper T cells

What is IL-2 required?

Proliferation of lymphocytes

What is IL-2?

A protein that has short half-life- acts locally

What do B cells work chiefly by?

Secreting soluble substances known as antibodies

What each B cells programmed to make?

Antibodies that bind to a specific epitope

What happens when a B cell encounters its trigger antigen give rise to?

Many plasma cells, all producing antibodies w/ same specificity

What do B cells recognize?

Intact antigens via BCR

What do B cells express?

• BCR

• MHC II

• Costimulatory molecules (B7-CD80, CD86)

• IL-2 receptor (IL-2R)

• MHC I

What is activation of B cells?

• Antigen drained to lymph node from tissue or blood via lymphatic vessels

• Intact antigen captured by B cell w/ a specific BCR

What do activated B cells make?

Antigen-specific antibodies

What does a B cell use its receptor to bind to?

Intact antigen, which it proceeds to engulf & process (endocytosis)

• It then combines a fragment of antigen w/ class II MHC protein

• Combination of antigen & MHC is recognized & bound by CD4 T helper cell carrying a matching receptor (all produce exact same antibody)

• Binding activates T cell, which then releases IL-2 that transforms B cell into plasma cells

What is antibody structure known?

Immunoglobulin (Ig) (endogenous) neutralize & tag antigens for destruction

What is the antibody configuration?

• 2 identical heavy chains

• 2 identical light chains

What is the variable region (aka “Fab”)?

• Antigen binding fragment

• Recognizes a specific epitope

• Bivalent: each antibody has 2 Fabs

  • Once bound to 1 Fab, its easier to bind to the 2nd

What is the constant region?

• Constant fragment

• Also called Fc region

• Mediates killing mechanism

What is IgG (human antibody)?

Major immunoglobulin in blood is able to enter tissue spaces

• T1/2 = 21 days in blood

What is IgD (human antibody)?

Almost exclusively found inserted into membrane of B cells, where it regulates cell’s activation

What is IgE (human antibody)?

Normally present in only trace amounts, but it is responsible for symptoms of allergy (mast cell → histamine)

What is IgA (human antibody)?

A doublet- concentrates in body fluids such as tears, saliva, & secretions of respiratory & gastrointestinal tracts (highly effective)

What is IgM (human antibody)?

Star-shaped clusters

• Early response to antigens (bacteria)

What is the recognition step in humoral immunity?

B cells recognize (via BCR) an antigen & divide repeatedly

What is the attack step in humoral immunity?

Plasma cells release antibodies, which bind to antigen, render it harmless, & “tag” it for distribution by other agents

What happens w/ Fc receptors in the attack step?

Expressed on select leukocytes (neutrophils)

• Innate cells capture antibody bound antigens

What happens w/ opsonization in the attack step?

Internalization of antibody-tagged antigens

What is the memory step in humoral immunity?

Some B cells differentiate into memory cells, which provide lasting protection against future exposures to same pathogen