Specificity
-Highly specific to the antigen against which the third line of defense is directed
Memory
-The rapid mobilization of lymphocytes that have been programmed to recall their first engagement with the invader and rush to the attack again
Major functions of immune system markers
-Attachment to nonself or foreign antigens
-Binding to cell surface receptors that indicate self
�MHC molecules
-Receiving and transmitting chemical messages to coordinate the response
-Aiding in cellular development
Class I MHC Genes
-Markers appear on all nucleated cells
-Display unique characteristics of self
-Allow for recognition of self and the regulationof immune reactions
-Each human inherits a particular combination of class I MHC genes
Class II MHC Genes
-Code for immune regulatory markers
-Found on macrophages, dendritic cells, and B cells
-Involved in presenting antigens to T cells during cooperative immune reactions
Class III MHC Genes
Encode proteins involved with the complement system
Tissue dendritic cells
-Ingest the antigen
-Migrate to the nearest lymphoid organ
-Process and present antigen to T-lymphocytes
Antigen presenting cells
-Dendritic cells
-Macrophages
-B cells
Clone
-Proliferation of a particular lymphocyte
-Genetically identical cells, some of which are memory cells
Three main functional types of T cell
-Helper T cells
Regulatory T cells
-Cytotoxic T cells
Helper T cells
activate macrophages, assist B-cell processes, and help activate cytotoxic T cells
Regulatory T cells
control the T-cell response
Cytotoxic T cells
lead to the destruction of infected host cells and other "foreign" cells
When activated by antigen, a B cell divides, giving rise to plasma cells
-Each plasma cell has the same reactive profile
-Release antibodies into the tissue and blood
-Attach to the antigen for which they are specific and mark it for destruction or neutralization
Markers found on T cells
-Antigen-specific T-cell receptor
-CD3 markers: surround the T-cell receptor and assist in binding
-CD4 or CD8 coreceptor
CD4
binds to MHC class II molecules
CD8
found on cytotoxic T cells and binds MHC class I molecules
B cells mature in the bone marrow
-Hundreds of millions of distinct B cells develop as the result of gene modification and selection
-Circulate through the blood, "homing" to specific sites in the lymph nodes, spleen, and other tissue where they adhere to specific binding molecules
-Have
Each na�ve lymphocyte bears an antigen receptor that recognizes a unique antigen
-Stem cells become granulocytes, monocytes, or lymphocytes in the bone marrow
-Lymphocytes become either B or T cells
�B cells stay in the bone marrow
�T cells migrate to the thymus
�Each builds a unique antigen receptor
Development of B and T cells
-Both B and T cells migrate to secondary lymphoid tissues
�Some cells self-destruct if they are not used, others become activated and leave
-By the time B and T cells reach the lymphoid tissues, each one is equipped to respond to a single, unique antigen
Immunoglobulins composed of
-Two heavy (H) chains
-Two light (L) chains
-One light chain is bonded to one heavy chain
-The two heavy chains are bonded to each other with disulfide bonds
-Creates a symmetrical, Y-shaped arrangement
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
-Relatively small
-Never secreted
Immune tolerance
-Tolerance to self
-Removal of any potentially harmful clones through clonal deletion
-Some autoimmune diseases are thought to be caused by the loss of immune tolerance, the survival of "forbidden clones," or failure of other systems
Antigen (Ag)
-A substance that provokes an immune response in specific lymphocytes
-To be perceived as an antigen or immunogen, a substance must meet certain requirements in foreignness, shape, size, and accessibility
Antigenicity
Property of behaving as an antigen
Must be perceived as foreign
-Whole microbes or their parts
-Cells or substances that arise from other humans, animals, plants, and various molecules
-Molecules of complex composition
�Proteins or protein-containing compounds are more immunogenic than repetitious polymers composed of
Chemical categories of antigens
-Proteins and polypeptides
-Lipoproteins
-Glycoproteins:
-Nucleoproteins:
-Polysaccharides and lipopolysaccharides
(Characteristics of Antigens)
A substance must be large enough to catch the attention of surveillance cells to initiate an immune response
-Molecules with a MW less than 1,000 are seldom complete antigens
-MW of 1,000 -10,000 are weak antigens
-MW of 100,000 are the most immunogenic
Epitope
-A portion of the antigen molecule recognized and responded to by a lymphocyte
-The primary signal that a molecule is foreign
Haptens
-Consist only of a determinant group
-Too small by themselves to elicit an immune response
-If linked to a carrier group, the combined molecule develops immunogenicity
Alloantigens
-Proteins and other molecules of one person that are antigenic to another
-Cell surface markers 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 f
Superantigens
-Bacterial toxins
-Potent stimuli for T cells
�Activate T cells at a rate 100 times greater than ordinary antigens
�Can result in an overwhelming release of cytokines and cell death
-Toxic shock syndrome and certain autoimmune diseases are associated with
Antigens must be further acted upon and formally presented to antigen-presenting cells (APCs)
-Macrophages
-B cells
-Dendritic cells
T Helper (TH) Cells
Play a central role in regulating immune reactions to antigens
-Including B cells and other T cells
-Involved in activating macrophages
�Directly by receptor contact
�Indirectly by releasing cytokines such as interferon gamma (IFN?)
Regulatory T cells
-In the THclass
-carry CD4 markers
-Act to control the inflammatory process
-Prevent autoimmunity
-Make sure the immune response does not inappropriately target normal biota
Regulatory B cells also regulate the degree of response from T cells
-B cells become activated to become plasma cells by cytokines from activated T cells
-Already activated regulatory B cells can secrete their own cytokines to dampen the T-cell response
Cytotoxicity
The capacity of certain T cells to kill a specific target cell
Killer T cell (CD8) activation
must recognize a foreign peptide complexed with self MHC-I presented to it and mount a direct attack on a target cell
Cells targeted by TC
-Virally infected cells
-Cancer cells
-Cells from other animals and humans
Natural killer (NK) cells
-Lymphocyte related to T cells
-Lack specificity for antigens
-Circulate through spleen, blood, and lungs
-First killer cells to attack cancer cells and virus infected cells in a similar manner to TCcells
-Not considered part of specific cell
-mediated im
Basic immunoglobulin (Ig) molecule
-Four polypeptide chains connected by disulfide bonds
-Two functionally distinct fragments:
�Antigen binding fragments (FAbs): two arms of the Ig molecule
�Crystallizable fragment (Fc): the rest of the molecule
FAb fragment
-Amino terminal end consists of the variable regions of the heavy and light chains
-Special region of attachment between the FAb and Fc regions allows swiveling of the FAb fragments
Fc fragment
-Serves as an anchor
-Involved in binding to various cells and molecules of the immune system itself
Hypervariable region
-Site on the antibody where the epitope binds
-Amino acid content extremely varied
-A minimal complementary fit is necessary for the antigen to be held effectively
Principal activity of antibody
-Unite with, immobilize, call attention to, or neutralize the antigen for which it was formed
-Opsonization
-Agglutination
-Neutralization
-Antitoxin
Vaccine considerations
-Antigen selection
-Effectiveness
-Ease in administration
-Safety
-Cost
Adjuvant
-A special binding substance added to some vaccines
-Any compound that enhances immunogenicity and prolongs antigen retention at the injection site
-Precipitates the antigen and holds it in the tissues so that it will be released gradually
-Facilitates co
Relatively rare side effects
-Panencephalitis: 1 in 220,000 vaccinations from the measles vaccine
-Back-mutation to a virulent strain: polio vaccine
-Disease due to contamination with dangerous viruses or chemicals
-Neurological effects of unknown cause: pertussis and swine flu vacci
Vaccine safety
-Some people have attempted to link childhood vaccinations with the development of diabetes, autism, and asthma
-Very public debate about vaccine safety
-Difficult for parents and consumers to discriminate between good and bad information
-Scientists are
Herd immunity
-Each microorganism requires a certain density of susceptible individuals in a population (herd) to maintain the chain of transmission
-With a sufficient number of immune individuals, the microbe does not spread
-Collective immunity through mass immunizat