Week 10 Microbiology- Adaptive Immune Response

Immature Lymphocytes

lack fully developed antigen-specific receptors

Naïve lymphocytes

has never encountered antigen

Immature Lymphocytes

lack fully developed antigen-specific receptors

Naïve lymphocytes

has never encountered antigen

Activated lymphocyte

received specific signals, proliferates, and produces effector and memory lymphocytes

Effector lymphocyte

short lived, primary response

Memory lymphocyte

secondary response

B cell receptor (BCR)

specific to antibody the cell is programmed to make

• Y-shaped like an antibody

• binding triggers the response

• membrane-bound version of a B-cell’s specific antibody

  • Binding antigen triggers response

  • Usually needs confirmation from T cell

  • binds to an antigen

    • the antigen is internalized and degraded into peptide fragments

    • Fragments are delivered to MHC class II molecules for inspection by T_H cells:

    • antigen presentation

T cell receptors ( TCR)

does not recognize free antigen

• Two polypeptide chains—like one arm of a BCR

• must be presented on the surface of another cell in its major histocompatibility complex (MHC)

• Binding initiates activation

If bound to a fragment,

• activates B cells with cytokines

• initiates clonal expansion

• If T_H cells do not recognize peptides, B cells may become anergic

• does NOT interact with free antigen

  • Only interacts with antigen with antigen presented by another cell

  • Antigen is held in major histo-compatibility complex (MHC)

Lymphatic system

A collection of tissues and organs

• Brings B cells and T cells into contact with antigens

• Here lymphocytes encounter the appropriate antigen

Lymphatic vessels (lymphatics)

Fluid leaves body’s circulatory system, not all fluid returns to capillaries; enters lymphatics instead

• Contains antigens from tissues

• Lymph empties into circulatory system

Primary lymphatics

Bone marrow and thymus

Sites where lymphocytes contact antigens

• lymph nodes

• spleen

• tonsils

Peyer’s patches

allow sampling of intestinal contents via specialized M cells & dendritic cells

mucosa-associated lymphoid tissue (MALT)

prevents microbial invasion via mucous membranes

skin-associated lymphoid tissue (SALT)

lymphoid tissues under the skin

Adaptive immunity

Most effective means to eliminate invader

• It takes a week or more to build

• Body relies on innate immunity during this time

Adaptive immunity memory

strong response to re-exposure

• B and T memory cells

Adaptive immunity specificity

• Vaccination relies on these abilities

• Targets and eliminate specific pathogens

Humoral immunity

• eliminate extracellular antigens

  • Bacteria, toxins, viruses in bloodstream, tissue fluids

  • Uses antibodies

Cell-mediated immunity (CMI)

• deals with antigens residing within a host cell

  • virus infected cell

B lymphocytes (B cells)

• Develop in bone marrow

• Proliferate, in response to extracellular antigens

• Differentiate into plasma cells that produce antibodies

Antibodies protect

• by binding to antigen, preventing attachment to cell

• Indirectly by tagging antigen for elimination

Antigen

Antibody generator

• A molecule that reacts specifically with an antibody, a B-cell receptor, or a T-cell receptor

Immunogen

An antigen that elicits immune response. small molecules aren’t usually this.

T-dependent antigens

B cell requires help from T_H cell to be activated

T-independent antigens

activate B cells without T_H cell help;

include lipopolysaccharide (LPS) and molecules with repeating subunits such as carbohydrates

Strong antigen

proteins

Weak antigen

lipids

Epitopes

Small regions of the antigen that are recognized by antibodies

• regions of macromolecules

Antibodies

immunoglobulins

• Y-shaped protein with two parts

Variable region

at ends of Fab regions; give them specificity

• Antigen-binding site attaches to specific epitope

• Fit precise but reversible: numerous non-covalent bonds

Constant region

includes Fc and part of two Fab regions

• Allows immune system to recognize otherwise diverse antibody molecules

• Consists of two heavy chains and light chains

• Disulfide bonds join heavy, light chains and two halves

Neutralization

prevents toxins, viruses from binding to cells

Opsonization

enhancement of phagocytosis

Aggregation

Two arms of antigen bind separate antigens

Immobilization and prevention of adherence

binding to bacterial flagella or pili interferes

Complement system activation

classical pathway of antibodies

IgM structure & function

Pentameter

1st antibody class produced in primary response. Binding leads to activation of complement

IgG structure & function

Monomer

Most abundant class in tissues and blood

binding activates complement

IgA structure & function

Dimer

Most abundant class produced, secreted in saliva, tears, and mucous

IgD structure & function

Monomer

Involved in development and maturation of antibody response

IgE structure & function

Monomer

Binds via the Fc region to mast cells and basophils involved in allergic reactions

Anergic

tolerance to the antigen

Primary response

• Needs 10-14 days for substantial antibody accumulation

• B cells differentiate to form plasma cells that

  • generate antibodies

  • Plasma cells die after a few days

• Activated B cells continue proliferating in presence of antigen, so antibody titer steadily increases

Secondary response

Vaccination exploits this

• Additional exposure to antigen is significantly faster, & more effective than primary

  • Pathogens usually eliminated before causing harm

Memory B cells

When activated, some quickly become plasma cells and produce antibodies.

Responsible for Secondary response

T-Independent Antigens

Can activate B cells without the aid of T_H cells

• Molecules with numerous identical evenly spaced epitopes are bound by clusters of B-cell receptors

  • Leads to activation

  • Lipopolysaccharides (LPS)

T cell response

Cell mediated immunity

• Play a different role than B cells

• Do not produce antibodies

• Effector T cells directly interact with targets cells

• Cause changes in target cells

T cells

Mature in the thymus

T_C & T_H

Cytotoxic T cells

Helper T cells

• help eliminate antigens, different surface proteins

• Both have multiple surface copies of T-cell receptor (TCR)

• Must be activated before they can multiply

T_R

regulatory T cells

• Have TCR, but role is to prevent immune system from mounting a response against “self” molecules

Dendritic cells

responsible for T-cell activation

• Once activated, the T cell proliferates, differentiates

• reside in peripheral tissues

• gather materials via phagocytosis, pinocytosis

• Sample material between epithelial cells of mucosal barriers and in the respiratory tract and lumen of the intestine

Effector T_C cells

respond to intracellular antigens, induce cell to undergo apoptosis

• Can form memory cells

Effector T_H cells

help humoral and cell-mediated immunity

• activates B cells, macrophages; produce cytokines to direct and support T cells

• Can form memory cells

Major histo-compatibility complex (MHC)

Molecules on surface of the presenting cell

MHC class I

present endogenous antigens, produced by all nucleated cells

endogenous antigens

made within the cell

MHC class II

present exogenous antigens, produced by antigen-presenting cells, dendritic cells, B cells, macrophages. can produce co-stimulatory molecules

Exogenous antigens

antigens taken up by the cell

Toll-like receptors (TLR)

• If pathogens detected, cell takes up more material

• Travels to secondary lymphoid organs;

• Produces co-stimulatory molecules signaling danger

• Presents antigens on both MHC class I and class II— activates T_c and T_h cells

T_C (CD8) Cells

Cells present internal proteins (endogenous antigens) on MHC class I:

• binding by T_C indicates recognition of pathogen or cancer

• T_C induces apoptosis: by secreting granzymes, proteases, cytotoxins (perforin)

T_H (CD4) Cells

Recognize exogenous antigens presented on MHC class II from antigen-presenting cells (APCs)

Antigen presenting cells

• Naive B cell binds to antigen and takes it up by endocytosis

• The T_H cell delivers cytokines when it encounters the MHC class II

• The cytokines activate the B cell to proliferate

Hapten

A molecules too small to elicit a response unless bound to a protein (penicillin causing allergic reaction)

Natural Killer (NK) cells

Induce apoptosis in antibody-bound “self” cells

• recognize host cells with foreign proteins in membrane bound by antibodies

• Have F_C receptors for IgG molecules

• cells bind to the antibodies, deliver perforin- and protease-containing granules to cell, causing apoptosis

• recognize host cells lacking MHC class I

Antibody dependent cellular cytotoxicity (ADCC)

An immune mechanism where effector cells (e.g., natural killer (NK) cells, macrophages) recognize and kill target cells that are coated with antibodies