microbiology chapter 13

adaptive immunity

acquired only after an immunizing event such as an infection or vaccination

- B and T lymphocytes undergo a selective process that prepares them for reacting only to one specific antigen or immunogen

Immunocompetence

the ability of the body to react with countless foreign substances

Antigens

molecules that can be seen and identified by the immune system

• Usually protein or polysaccharide molecules on or inside cells and viruses

• Any exposed or released protein or polysaccharide is potentially an antigen, even those on our own cells:

- Our own antigens usually do not evoke a response from our own immune system

Immunogens

antigens that are able to trigger an immune response.

Specificity

antibodies produced against the chickenpox virus will not function against the measles virus

memory

lymphocytes are programmed to "recall" their first engagement with the invader and rush to the attack once again

Stages of immunologic development & interaction

1. Lymphocyte development and clonal deletion

2. Presentation of antigen and clonal selection

3. Challenge of B and T lymphocytes by antigens

4. T-lymphocyte response: cell-mediated immunity; and B-lymphocyte response: production and activities of antibodies

Lymphocyte Development

• All lymphocytes arise from the same basic stem cell type

• B cells mature in specialized bone marrow sites

• T cells mature in the thymus

• Both cell types migrate to separate areas of lymphoid organs

• B and T cells constantly recirculate through the circulatory system and lymphatics, migrating into and out of the lymphoid organs

When pathogens carrying antigens cross the first line of defense:

• Resident phagocytes migrate to the site

• Tissue macrophages ingest the pathogen and initiate an inflammatory response

• Dendritic cells ingest the antigen and migrate to the nearest lymphoid organ, where they process and present antigen to T and B lymphocytes

• B cells often require the assistance of specific T cells called T helper cells

All cells have a variety of different markers on their surfaces for:

• Detection

• Recognition

• Cell communication

These markers play an important role in activating different components of immunity

Major Histocompatibility Complex (MHC)

one set of genes that codes for human cell markers or receptors:

• Gives rise to a series of glycoproteins found on all cells except red blood cells

• Also called the human leukocyte antigen (HLA) system

• These markers play a vital role in recognition of self by the immune system and in rejection of foreign tissue

Class I genes

code for markers that appear on all nucleated cells. They display unique characteristics of self and allow for the recognition of self molecules and the regulation of immune reactions

Class II genes

also code for immune markers. These markers are found on macrophages, dendritic cells, and B cells and are involved in presenting antigens to T cells during cooperative immune reactions

Class III genes

encode proteins involved with the complement system, among others

CD molecules

"cluster of differentiation":

a naming scheme for these cell surface markers

• Over 400 CD molecules have been named

• Many are involved in the immune response

Lymphocyte Receptors

Major role is to accept or grasp antigens in some form

B cells have receptors that bind antigens

T cells have receptors that bind antigens that have been processed and complexed with MHC molecules on the presenting cell surface

How T cells respond to antigen

T cells secrete cytokines to help destroy pathogens, but they do not produce antibodies

Helper T cells

activate macrophages, assist B-cell processes, and help activate cytotoxic T cells

Regulatory T cells

control the T-cell response by secreting anti-inflammatory cytokines or preventing proliferation

Cytotoxic T cells

lead to the destruction of infected host cells and other "foreign" cells

How B Cells Respond to Antigen

When activated, B cells divide and give rise to

plasma cells

Plasma cells release antibodies into the tissue

and the blood

Antibodies attach to the antigen for which

they are specific, and the antigen is marked for

destruction or neutralization

Specific Events in T-Cell Development

• Maturation of T cells and development of their receptors is directed by the thymus gland and its hormones

• CD3 receptors: surround the T-cell receptor and assist in binding

• CD4 coreceptors found on T helper cells: accessory receptor proteins that help the T-cell receptor bind to MHC class II molecules

• CD8 coreceptors: found on cytotoxic T cells and helps bind MHC class I molecules

Specific Events in B-Cell Development

•Develop in the bone marrow

•Naïve lymphocytes circulate in the blood, "homing" to specific sites in the lymph nodes, spleen, and other lymphoid tissue, where they adhere to specific binding molecules and come into contact with antigens throughout life

Building Immunologic Diversity

-By the time B and T cells reach lymphoid tissues, each one is equipped to respond to a single unique antigen

-Diversity is generated by rearrangement of gene segments that code for antigen receptors on T and B cells

--Every possible recombination occurs, leading to a huge assortment of lymphocytes

--It is estimated that each human produces antibodies with 10 trillion different specificities

Immunoglobulin (Ig)

• Large glycoprotein molecules that serve as the antigen receptors of B cells

• Serve as antibodies when secreted

Antigen-binding sites

pockets in the ends of the forks of the molecules that can be highly variable in shape to fit a wide range of antigens

Variable (V) regions

areas of extreme versatility from one clone to another

Immunoglobulin structure

-Antigen binding sites: pockets in the ends of the forks of the molecules that can be highly variable in shape to fit a wide range of antigens

-Variable regions: areas of extreme versatility from one clone to another

-Light chains, heavy chains, constant regions: amino content does not vary greatly from one antibody to another

T cell receptors

Belong to the same protein family as the B-cell receptor.

-Similar to the B cell receptor

-Formed by genetic modification

-Has variable and constant regions

-Inserted into the membrane

- have an antigen binding site

differ from B cell receptors in that they are:

-Relatively small

-Never secreted

Clonal selection

the mechanism by which the exactly correct B or T cell is activated by any incoming antigen

- Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the tissues

• Each genetically distinct lymphocyte expresses only a single specificity and can react to that chemical epitope

Clonal deletion

One potentially problematic outcome of random genetic assortment is the development of clones of lymphocytes able to react to self:

• Can lead to severe damage

process by which any such clones are destroyed during development

Stage II: Presentation of Antigens—Entrance of Antigens

To be perceived as an antigen or immunogen, a substance must meet certain requirements in foreignness, shape, size, and accessibility

Foreignness is met by whole microbes or their parts, cells or substances from other humans, animals and plants.

characteristics of good immunogens (provoking a strong response) are

• their chemical composition

• their context, meaning what types of cytokines are present

• their size

- In general, large antigens are better than small antigens, but size alone is not sufficient for antigenicity

Haptens

small foreign molecules that are too small by themselves to elicit an immune response

• If this incomplete molecule is linked to a larger carrier molecule, the combination develops immunogenicity

• The carrier group contributes to the size of the complex and enhances the proper spatial orientation of the determinative group

• The hapten serves as the epitope

examples of haptens

Drugs, metals, and ordinarily innocuous household, industrial, and environmental chemicals.

- Many haptens develop antigenicity in the body by combining with large carrier molecules such as serum proteins

Alloantigens

cell surface markers and molecules that occur in some members of the same species but not in others

• The basis for an individual's blood group and major histocompatibility profile

• Responsible for incompatibilities that can occur in blood transfusion or organ grafting

Superantigens

bacterial toxins that are potent stimuli for T cells

• Activate T cells at a rate 100 times greater than ordinary antigens

• The result can be an overwhelming release of cytokines and cell death

• Toxic shock syndrome and certain autoimmune diseases are associated with superantigens

antigen-presenting cells (APCs)

n most immune reactions, the antigen must be formally presented to lymphocytes by ___

examples:

• Macrophages

• B cells

• Dendritic cells

- After processing is complete, the antigen is bound to the MHC receptor and moved to the surface of the APC so it will be readily accessible to T lymphocytes

Antigen processing and presentation

Most antigens must be presented first to T cells, even though they will eventually activate both the T-cell and B-cell systems

T-cell-independent antigens: antigens that can trigger B cells directly without APCs or T helper cells

stage III and IV: t-cell response

• T-cell reactions are the most complex and diverse in the immune system and involve several subsets of T cells

• Actions of T cells are dictated by the APCs that activate them

• T cells are 'restricted': they require some type of MHC(self) recognition before they can be activated

• All T cells produce cytokines with a spectrum of biological effects

• End result of T-cell stimulation is the mobilization of other T cells, B cells, and phagocytes

T helper cells

Many types of T helper cells all bear the CD4 marker and are critical in regulating immune reactions to antigens

Also involved in activating macrophages:

• Directly by receptor contact

• Indirectly by releasing cytokines such as interferon gamma (IFNγ)

Cytotoxic T cells

Target cells that TC cells can destroy include:

• Virally infected cells: recognize these because of telltale virus peptides expressed on their surface

• Cancer cells: TC constantly survey the tissues and immediately attack any abnormal cells they encounter • Cells from other animals and humans: the most important factor in graft rejection

Products of B Lymphocytes

Symmetrical Y-shaped arrangement

The two arms of the 'Y' are the antigen-binding fragments(Fabs):

• The end of each Fab fragment folds into a groove that can each accommodate an epitope

Hypervariable region

the site on the antibody where the epitope binds

amino acid content of this region is extremely varied

• Specificity of antigen binding sites for antigens is very similar to enzymes and substrates

• Specificity on the two Fab sites is identical, so an Ig molecule can bind epitope on the same cell or on two separate cells, and link them

Functions of the Fc Fragment

Fc end can bind to receptors on the membranes of cells, such as macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes

Effect of Fc binding depends on the cell's role:

•Opsonization: attachment of antibody to foreign cells and viruses is followed by binding of the Fc end to phagocytes

•Fc end of IgE binds to basophils and mast cells, causing release of allergic mediators such as histamine

Isotypes

structural and functional classes of immunoglobulins

Two forms of IgA

- Monomer that circulates in small amounts in the blood

- Dimer that is a significant component of mucous and serous secretions of the salivary glands, intestine, nasal membranes, breast, lung, and genitourinary tract

- Dimer is two monomers held together by a "J" chain and a secretory piece is added to facilitate transport of IgA across membranes

IgA

coats the surface of mucous membranes

• Suspended in saliva, tears, colostrum, and mucus

• Provides adaptive immunity against enteric, respiratory, and genitourinary pathogens

Colostrum

earliest secretion of breast milk; high in IgA that coats the gastrointestinal tract of a nursing infant

Titer

levels of antibodies in the serum over time

Primary response

the first exposure to an antigen thesystem undergoes

Secondary response

When the immune system is exposed again to the same immunogen within weeks, months, or even years

natural immunity

any immunity that is acquired through the normal biological experiences of an individual

artificial immunity

protection from infection obtained through medical procedures such as vaccines and immune serum

active immunity

• Occurs when an individual receives immune stimulus that activates B and T cells to produce immune substances such as antibodies

• Creates memory that renders the person ready for quick action upon reexposure to the same antigen

• Requires several days to develop

• Lasts for a relatively long time

• Can be stimulated by natural or artificial means

passive immunity

• Occurs when an individual receives antibodies from another human or animal

• Recipient is protected for a short period of time, even though they have not had prior exposure to the antigen

• Lack of memory for the original antigen

• Lack of antibody production against the disease

• Immediate onset of protection

• Short-term effectiveness

• Can be natural or artificial in origin

basic principles behind vaccination

- Stimulate a primary response and a memory response

- Prime the immune system for future exposure to a virulent pathogen

- If the pathogen enters the body, the response will be immediate, powerful, and sustained

Most vaccines are administered via the routes:

subcutaneous, intramuscular, intradermal

Adjuvants

Special binding substance required by some vaccines:

• Enhances immunogenicity

• Prolongs antigen retention at the injection site

• Precipitates the antigen and holds it in the tissues so that it will be released gradually

• Facilitates contact with antigen-presenting cells and lymphocytes

• Helps involve the innate immune system as well