Chapter 12 - Adaptive Cells Part 2

T cells and B cells

Coordinate the adaptive immune response against foreign antigens

T- and B- Lymphocytes

• The most important adaptive immunity leukocytes (white blood cells) are lymphocytes

• T cells (killer/CD8+ and helper/CD4+)

  • Initially produced in the bone marrow

  • Immature T cells migrate to the thymus

  • Undergo maturation

• B cells

  • Produced and mature in the bone marrow

Antigen Receptors

T cell receptors (TCRs) and B cell receptors (BCRs) are antigen recognition receptors

B and T cells: what do they recognize?

• B cells and T cells have:

  • 1,000s of receptors on their surface

  • Each receptor on a cell recognizes the same epitope

• Despite “one epitope type recognized per lymphocyte” rule…

  • Antigen recognition capacity is essentially unlimited because the body makes a vast number of T and B cells

Stage 1 – Antigen Presentation

• Dendritic cells and certain other white blood cells act as antigen-presenting cells (APCs)

• APCs show antigen to T cells

• B cells do not require APCs to show them antigens; instead they can directly interact with an antigen

Stage 1: APCs use MHC I or II to present antigens to T cells

• There are two main classes of MHCs important for antigen presentation: MHC I and MHC II

  • MHC I – found on the surface of all cells (including phagocytic cells) except red blood cells

  • MHC II – only on antigen-presenting cells (APCs)

    • Macrophages, B cells, dendritic cells

Stage 1: APCs use MHC I or II to present antigens to T cells

• Having two classes of MHCs makes sense if we consider that antigens can exist in two locations:

  • Either inside a host cell (intracellular antigen)

    • Viral proteins inside an infected host cell

    • Intracellular bacterium or protist

    • Abnormal proteins made by cancer cells

• Outside of a host cell (extracellular antigens)

  • Extracellular bacteria, parasitic worms, and various fungi

MHC I: Presenting Intracellular Antigens to T Cytotoxic Cells

All nucleated cells have the capacity to present intracellular antigens in the context of MHC I

MHC II: Presenting Extracellular Antigens to T Helper Cells

Only antigen-presenting cells (the professional phagocytes) have the capacity to present extracellular antigens in the context of MHC II

MCH I vs MCH II

• MCH I

  • location: on all body cells except red blood cells; serves as the body’s uniform

  • interact: CD8 on T cytotoxic cells

  • antigens presented: Intracellular antigens

• MCH II

  • location: Only on antigen-presenting cells (APCs); main APCs are dendritic cells

  • CD4 on T helper cells

  • Extracellular antigens

Stage 2: T cells are activated by antigen-presenting cells in lymphatic tissues

• T cells require two signals for full activation:

  • Primary activation signal – TCR interacting with the MHC–antigen complex

  • Secondary activation signal involves co-stimulatory proteins on the surface of the APC binding to co-stimulatory proteins on the T cell’s surface

    • B7 (CD80/86) protein on the APC’s cell surface binding with CD28 on the surface of T cells

Stage 3 – Lymphocyte Proliferation and Differentiation (adaptive response)

• Activated T cells undergo multiple rounds of cell division to proliferate (clonal expansion). Clones will recognize the same epitope

• Effector cells – engage in the response against the antigen

• Memory cells – remain in lymphatic tissues to serve as a rapid recognition of the antigen if it’s encountered again later

Stage 3: Activated T cells undergo proliferation and differentiation

• The types of cytokines released influence what T helper cell subclasses develop

• TH1 cell response

  • Leads to the cellular response

  • Cytokines activate T cytotoxic cells & macrophages

• TH2 cell response

  • Leads to the humoral response

  • Cytokines promote B cell maturation

CD4+ T cells (T helper cells) also form a regulatory subset

• T helper 1 (TH1) cells

  • Activate cytotoxic T cells, macrophages, and natural killer cells to destroy intracellular pathogens

• T helper 2 (TH2) cells

  • Stimulate B cells to make antibodies

• T regulatory (Treg) cells

  • Control functions of other white blood cells (e.g., dendritic cells, mast cells, B and T cells)

T Cytotoxic Cells (TC)

• Cytotoxic T cells

  • Directly destroy cells that are virus infected, damaged, foreign/transplanted, or cancerous

  • CD8+ T cells

• Cytotoxic T cells can be referred to as

  • Killer T cells

  • CD8+ T cells

  • Cytotoxic T lymphocytes

  • CD8 cells

  • Tc cells

Cytotoxic T Cell Direct Interferons Elimination

• When the TCR of a patrolling T cytotoxic cell binds to an MHC I–antigen complex:

  • Releases perforins

  • Forms pores in the target cell

  • Releases granzymes

  • Enter through the pore

  • Breakdown host cell proteins

  • Induce apoptosis

Stage 4 – Antigen Elimination and Memory

• Cellular and humoral responses collaborate to eliminate the antigen against which they were activated

• Once the threat passes, effector cells die off

• Memory cells endure for years in lymphatic tissues

Humoral Immunity Remember:

• Both the cellular and humoral branches can be described as going through four general stages:

  • Stage 1: antigen presentation

  • Stage 2: lymphocyte activation

  • Stage 3: lymphocyte proliferation and differentiation

  • Stage 4: antigen elimination and memory

Stage 1: B cells are antigen-presenting cells (Humoral Immunity)

• B cells have two different paths to activation:

• T-independent antigens bind to B cells and instigate a direct activation cascade ~ Polysaccharides

• T-dependent antigens require T helper cells (especially TH2 cells) for full activation ~ Proteins

Stage 2: B cells are activated by T-dependent antigens (Humoral Immunity)

• Activation pathway is a two-signal mechanism:

  • First signal is the binding of the antigen to the B cell receptor (BCR)

• Co-stimulatory proteins interact

  • CD40 on the B cell & CD40L on the T cell

Stage 3: Activated B cells proliferate and differentiate into plasma cells & memory cells

• If the B cell interacts with a T-dependent antigen, then a T helper cell is needed to advance to proliferation.

• If the B cell interacts with a T-independant antigen, then the B cell can proliferate without further interactions.

Stage 4: Antibodies help eliminate antigens

• Activated complement proteins lead to cytolysis, inflammation, and opsonization

• Antibodies directly neutralize antigens to prevent them from interacting with target host cells

• Antibodies increase phagocytosis by:

  • Precipitation

  • Agglutination

  • Opsonization

Antibody Structure and Isotypes

• The tips of the molecule are the antigen-binding sites

• An antibody’s single-unit, monomeric structure consists of:

  • 2 heavy chains

  • 2 light chains

  • Held together by covalent bonds

• Fc portion: determines complement activation, phagocytosis, half-life

• A given plasma cell makes antibodies that all recognize the same epitope

• A given B cell can’t change what epitope it recognizes but it can undergo isotype switching

  • Alters what class of antibody is made

  • 5 antibody isotypes: IgG, IgA, IgM, IgE, IgD

Immunoglobulin G (IgG)

• Constitutes 85% of antibody in human blood (most abundant)

• Found in all bodily fluids

• Half-life of about 21 days in circulation

• Detecting IgG to a particular antigen indicates the patient has been exposed to that antigen

• Monomer

• Crosses the placenta, activates complement, neutralizes antigens and is a powerful opsonin

Immunoglobulin A (IgA)

• Accounts for up to 15% of total antibodies

• Half-life of about 6 days

• Prevalent in mucous (e.g., mucous membranes of the gut, respiratory tract, and urogenital tract)

• Found in secretions (e.g., tears, saliva, sweat, and milk)

• Exists as a monomer or as a dimer

• Neutralizing and opsonization capabilities

Immunoglobulin M (IgM)

• Mainly in blood

• Accounts for up to 10% of total antibodies

• Half-life of about 10 days

• Made early in infection upon a primary antigen exposure

• Exists as either a monomer or pentamer

• Functions in agglutination, precipitation, and complement activation (not a strong opsonin)

• always formed first

Immunoglobulin E (IgE)

• Present in very low concentrations

• Found mostly in lungs, skin, and mucous membranes

• Monomer with a half-life of only 2 days

• Functions to fight parasites and mediate allergic responses

• Causes mast cells and basophils to release allergy mediators (e.g., histamine, leukotriene)

Memory cells allow for fast, amplified response upon re-exposure to an antigen

• Effector cells die off once the threat subsides, but memory cells are long-lived

• Memory cells reside in lymphoid tissues and provide immunological memory

• Our memory cells allow for a rapid reactivation of the cellular and humoral adaptive response if the same antigen is encountered again later