Is called specific immunity The body ’ s ability to recognize and defend itself against distinct invaders and their products Is a “ smart ” system whose.

Is called specific immunityThe 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

Third Line of Defense

Is acquired over time

Antigens trigger specific immune responses

Various cells, tissues, and organs are part of specific immunity

Includes B and T lymphocytes

Elements of Specific Immunity

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 methodsThrough breaks in the skin and mucous membranes

Direct injection, as with a bite or needle

Through organ transplants and skin grafts

Antigens

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)

Screens the tissues of the body for foreign antigens

Composed of lymphatic vessels and lymphatic cells

Lymphatic System

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

Lymphatic Vessels

Develop from stem cells in the red bone marrow

Includes lymphocytes, the smallest of the leukocytes

Lymphoid Cells

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

Lymph Nodes

SpleenSimilar 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

Other Lymphoid Tissues and Organs

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

B Lymphocytes

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 antigenConsidered part of the humoral immune response since bodily fluids such as lymph and blood were once called humorsAntibody mediated immunity is important mainly

in toxin-induced disorders against capsulated bacteria in the prevention of some viral infections.

Antibodies

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 waysActivation of complement

Stimulation of inflammation

Agglutination

Neutralization

Opsonization

Antibody Function

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

Classes of Antibodies

Immunoglobulin classes

Depends upon the class of the heavy chainγ chain in IgG

µ chain in IgM

chain in IgA

ε chain in IgE

δ chain in IgD

Immunoglobulin classesIgG 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.

It is agglutinating, fixes complement, neutralizing.

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 neutralizationIgA 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

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

B Cell Receptor (BCR)

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 typesCytotoxic T cells

2 types of helper T cells

T Lymphocytes

Distinguished by the CD8 cell-surface glycoprotein

Directly kill certain cellsCells infected with viruses and other intracellular pathogens

Abnormal cells, such as cancer cells

Cytotoxic T cells (TC 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 typesType 1 helper T cell (TH

1)

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

Helper T Cells (TH Cells)

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

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

Cytokines of the Immune System

Vital that immune responses not be directed against autoantigens

Body “edits” lymphocytes to eliminate any self-reactive cells

Lymphocyte Editing by Clonal Deletion

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 proteinsMHC class I (A, B, C)

MHC class II (Dp, Dq, Dr)

Major Histocompatibility Complex (MHC)

T-independent antigenLarge antigen molecules with readily accessible, repeating antigenic determinants

B cells can bind these directly without being processedStimulates B cells to differentiate into a plasma cell and produce antibodies

Antigen Processing

T-dependent antigensSmaller 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

Antigen Processing

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 Exogenous 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

Processing of Endogenous Antigens

Body mounts humoral immune responses against exogenous pathogens

Components of a humoral immune responseB cell activation and clonal selection

Memory B cells and the establishment of immunological memory

Humoral Immune Response

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

Plasma 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

Memory B Cells

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

Cell-Mediated Immune Response

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

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

T Cell Regulation

Specific immunity acquired during an individuals life

2 typesNaturally acquired- immune response against antigens encountered in daily life

Artificially acquired- response to antigens introduced via a vaccine

Further distinguished as either active or passiveActive- active response to antigens via humoral or cell-mediated responses

Passive- passively receive antibodies from another individual

Acquired Immunity

A Comparison of the Types of Acquired Immunity