The Specific Immune Response Specific Defense: The Specific Immune Response

Third Line of Defense Is called specific immunity The body’s ability to recognize and defend itself against distinct invaders and their products Is a “smart” system whose “memory’ allows it to respond rapidly to a second encounter with a pathogen

Elements of Specific Immunity Is acquired over time Antigens trigger specific immune responses Various cells, tissues, and organs are part of specific immunity Includes B and T lymphocytes

Antigens Molecules that trigger a specific immune response Include components of bacterial cell walls, capsules, pili, and flagella, as well as proteins of viruses, fungi, and protozoa Food and dust can also contain antigenic particles Enter the body by various methods Through breaks in the skin and mucous membranes Direct injection, as with a bite or needle Through organ transplants and skin grafts

Types of Antigens

Properties of antigens Antigens are recognized by the 3-dimensional shapes of their antigenic determinants (epitopes). Large molecular masses (5,000-100,000). Chemical nature Complexity Incomplete antigens (haptens)

Lymphatic System Screens the tissues of the body for foreign antigens Composed of lymphatic vessels and lymphatic cells

Lymphatic Vessels Form a one-way system that conducts lymph from local tissues and returns it to the circulatory system Lymph is a liquid with similar composition to blood plasma that arises from fluid leaked from blood vessels into surrounding tissues

Lymphoid Cells Develop from stem cells in the red bone marrow Includes lymphocytes, the smallest of the leukocytes

Lymph Nodes Houses leukocytes that recognize and attack foreign antigens present in the lymph Concentrated in the cervical (neck), inguinal (groin), axillary (armpit), and abdominal regions Receives lymph from afferent lymphatic vessels and drains lymph into efferent lymphatic vessels

Other Lymphoid Tissues and Organs Spleen Similar in structure and function to the lymph nodes Filters bacteria, viruses, toxins, and other foreign matter from the blood Tonsils and mucosa-associated lymphoid tissue (MALT) Physically trap foreign particles and microbes MALT includes the appendix, lymphoid tissue of the respiratory tract, and Peyer’s patches in the wall of the small intestine

B Lymphocytes Arise and mature in the red bone marrow Found primarily in the spleen, lymph nodes, red bone marrow, and Peyer’s patches Small percentage of B cells circulate in the blood Major function is the secretion of antibodies

Antibodies Also called immunoglobulins (Ig) & make up 20% of plasma proteins. Soluble, proteinaceous molecules that react specifically with the antigen that stimulated their production. Secreted by plasma cells, which are B cells actively fighting exogenous antigen Considered part of the humoral immune response since bodily fluids such as lymph and blood were once called humors Antibody mediated immunity is important mainly in toxin-induced disorders against capsulated bacteria in the prevention of some viral infections.

Antibody Function Antigen-binding sites are complementary to antigenic determinants (epitopes), they are hypervariable regions within the variable domains of heavy and light chains Due to the close match can form strong, noncovalent interactions Hydrogen bonds and other attractions (van der Waals, electrostatic) may also be involved

Antibody Function Function in several ways Activation of complement Stimulation of inflammation Agglutination Neutralization Opsonization

Classes of Antibodies A single type of antibody is not sufficient for the multiple types of invaders to the body The class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed 5 different classes of antibodies

Immunoglobulin classes Depends upon the class of the heavy chain γ chain in IgG µ chain in IgM  chain in IgA ε chain in IgE δ chain in IgD

Immunoglobulin classes IgG is divalent. It crosses the placenta. 80% in serum. 2ry immune response. It is agglutinating, fixes complement, neutralizing. IgM is a pentamer. 6% in serum. 1ry immune response. IgA is dimer in secretions (milk, saliva, tears, respiratory & intestinal secretions) , monomer in serum (13%) IgE bound to the surface of basophils and mast cells, <1% Increases in anaphylactic reactions and helminth infections. IgD bound to the surface of some cells, <1%.

Characteristics of the Five Classes of IGs

Characteristics of the Five Classes of Immunoglobulins Structure ( Molecular Weight In Daltons) Name function(s) Location(s) percentage in serum IgG Complement activation, agglutination Monomer (180,000) serum, intercellular fluid 85 opsonization, and neutralization; crosses placenta to protect fetus IgM Complement activation, agglutination, Pentamer (900,000) serum 5-10 and neutralization IgA Agglutination and neutralization Monomer (150,000) External secretions, 5 Dimer (300,000) including milk IgE Triggers release of histamines Monomer (200,000) Serum, <1 from basophil mast cells mast cell surfaces IgD Unknown Monomer (180,000) B cell surface (as receptors) <1

B Cell Receptor (BCR) Is an antibody that remains associated with the cytoplasmic membrane Each B lymphocyte has multiple copies of a single type of BCR (105) Antigen binding site is identical to that of the secreted antibody for that particular cell The randomly generated antibody variable region determines the BCR (it is not formed in response to antigens)

B Cell Receptor (BCR) Each BCR is complementary to only one antigenic determinant The BCRs on all of an individual’s B cells are capable of recognizing millions (107-108) of different antigenic determinants

T Lymphocytes Produced in the red bone marrow and mature in the thymus Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches Part of the cell-mediated immune response because they act directly against various antigens Endogenous invaders Many of the body’s cells that harbor intracellular pathogens Abnormal body cells such as cancer cells that produce abnormal cell surface proteins

T Lymphocytes 3 types Cytotoxic T cells 2 types of helper T cells

Cytotoxic T cells (TC Cells) Distinguished by the CD8 cell-surface glycoprotein Directly kill certain cells Cells infected with viruses and other intracellular pathogens Abnormal cells, such as cancer cells

Helper T Cells (TH Cells) Distinguished by the CD4 cell-surface glycoprotein Function to “help” regulate the activities of B cells and cytotoxic T cells during an immune response Secrete various soluble protein messengers, called cytokines, that determine which immune response will be activated

Helper T Cells (TH Cells) 2 types Type 1 helper T cell (TH1) Assist cytotoxic T cells Express CD26 and a cytokine receptor named CCR5 Type 2 helper T cell (TH2) Assist B cells Have cytokine receptors CCR3 and CCR4

Cytokines Soluble regulatory proteins that act as intercellular signals when released from certain body cells Immune system cytokines signal among various leukocytes The complex web of signals among all the cell types of the immune system is referred to as the cytokine network

Cytokines of the Immune System Interleukins (ILs)- signal among leukocytes (IL-1 produced by macrophages and activates various cells eg T & B cells) (IL-2 produced by T helpers and stimulate growth of T cells) Interferons (IFNs)- antiviral proteins that may act as cytokines (especially gamma) Growth factors- proteins that stimulate stem cells to divide, maintaining an adequate supply of leukocytes Tumor necrosis factors (TNFs)- Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation (cachectin) Chemokines- signal leukocytes to go to a site of inflammation or infection and stimulate other leukocytes

Lymphocyte Editing by Clonal Deletion Vital that immune responses not be directed against autoantigens Body “edits” lymphocytes to eliminate any self-reactive cells

Major Histocompatibility Complex (MHC) Group of antigens first identified in graft patients Important in determining the compatibility of tissues in successful grafting Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals Function to hold and position antigenic determinants for presentation to T cells

Major Histocompatibility Complex (MHC) Antigens bind in the antigen-binding groove of MHC molecules 2 classes of MHC proteins MHC class I (A, B, C) MHC class II (Dp, Dq, Dr)

Antigen Processing T-independent antigen Large antigen molecules with readily accessible, repeating antigenic determinants B cells can bind these directly without being processed Stimulates B cells to differentiate into a plasma cell and produce antibodies

Antigen Processing T-dependent antigens Smaller antigens with less accessible antigenic determinants B cells require involvement from helper T cells to target these antigens Helper T cells are assisted by leukocytes that process the antigen to make the antigenic determinants more accessible Processing is different based on whether the antigen is exogenous or endogenous

Processing of Exogenous Antigens APC internalizes the invading pathogen and enzymatically digests it into smaller antigenic fragments which are contained within a phagolysosome Phagolysosome fuses with a vesicle containing MHC II molecules Each fragment binds to the antigen-binding groove of a complementary MHC II molecule The fused vesicle then inserts the MHCII-antigen complex into the cytoplasmic membrane so the antigen is presented on the outside of the cell

Processing of Endogenous Antigens The intracellular pathogens are also digested into smaller antigenic determinants Each fragment binds to a MHC I molecule located in the endoplasmic reticulum membrane The membrane is packaged into a vesicle by a Golgi body which is inserted into the cytoplasmic membrane so the antigen is displayed on the cell’s surface

Humoral Immune Response Body mounts humoral immune responses against exogenous pathogens Components of a humoral immune response B cell activation and clonal selection Memory B cells and the establishment of immunological memory

Plasma Cells Make up the majority of cells produced during B cell proliferation Each plasma cell secretes only antibody molecules complementary to the specific antigenic determinant Are short-lived cells that die within a few days of activation, though their antibodies and progeny can persist

Memory B Cells Cells produced by B cell proliferation that do not secrete antibodies Cells that have BCRs complementary to the specific antigenic determinant that triggered their production Long-lived cells that divide only a few times and then persist in the lymphoid tissue Are available to initiate antibody production if the same antigen is encountered again

Cell-Mediated Immune Response Responds to intracellular pathogens and abnormal body cells The most common intracellular pathogens are viruses but the response is also effective against intracellular bacteria Triggered when antigenic determinants of the pathogen are displayed on the host cell’s surface

The perforin-granzyme cytotoxic pathway Tc cells have vesicles containing cytotoxins (perforins & granzymes) Upon attachment of Tc cell to a target, the vesicles release the cytotoxins Perforins aggregate into a tubular structure in the infected cell membrane forming a channel Granzymes move through this channel into target cells and activate apoptotic enzymes Tc disengages and moves on to another infected cell.

The CD95 cytotoxic pathway CD95 is present on cell membrane of most body cells Its receptor CD95L is present on activated Tc CD95L from activated Tc binds to CD95 on target cell, this activates enzymes that trigger apoptosis

T Cell Regulation Careful regulation of cell-mediated immune response to prevent T cells from responding to autoantigens T cells require additional signals from an antigen presenting cell Interaction of the T cell and antigen presenting cell at an immunological synapse stimulates the T cell to respond to the antigen

Acquired Immunity Specific immunity acquired during an individuals life 2 types Naturally acquired- immune response against antigens encountered in daily life Artificially acquired- response to antigens introduced via a vaccine Further distinguished as either active or passive Active- active response to antigens via humoral or cell-mediated responses Passive- passively receive antibodies from another individual

A Comparison of the Types of Acquired Immunity