Micro Chapter 15

IgG

80-85% of total serum, half-life: 21 days, most abundant class in the blood + tissue fluids, provides longest-term protection because of its long half-life, Transported across the placenta, providing protection to a developing fetus, Long half-life extends the protection through the first several months after birth, Provides direct protection by neutralizing viruses + toxins, immobilizing motile organisms, preventing microbes from adhering to cell surfaces, and cross-linking antigens, Binding of IgG to antigen facilitates phagocytosis, leads to activation of the complement system (classical pathway) and allows antibody dependent cellular cytotoxicity weight: 146,000

IgE

<0.01% of total serum, half-life: 2 days, binds via the Fc region to mast cells and basophils. This bound IgE allows those cells to detect parasites + other antigens + respond by releasing their granule contents. Involved in many allergic reactions

Major Histocompatibility Complex (MHC) molecules

Cell surface molecules that present antigen to T cells, Both are somewhat like an elongated bun + hold the peptide lengthwise. When a T cell recognizes an antigen, it is actually recognizing both the peptide and MHC molecule simultaneously.

Describe how the vast diversity of antigen specificities can be generated for antibodies and T cell receptors

Gene rearrangement, Imprecise joining, combinational associations

Cell-Mediated Immunity

Involves T cells, mature in the thymus. Cytotoxic T cells and Helper T cells, both have TCR, TCR does not recognize free antigen, must be presented by one of the body's own cells. Regulatory T cells- help prevent the immune system from mounting a response against "self" molecules. Dendritic cells responsible for T cell activation, Tc cells respond to intracellular antigens (antigens within a host cell), when they find it, they induce the "self" cell that harbors it to undergo apoptosis

How do Major Histocompatibility Complex I and II molecules on APCs help control the nature of the immune response?

MHC class I molecules present endogenous antigens. MHC class II molecules present exogenous antigens. All nucleated cells produce MHC class I molecules, but only specialized cells, APCs, make MHC class II molecules. Cytotoxic T cells recognize antigen present on MHC class I molecules, Helper T cells recognize antigen present on MHC class II molecules

Mechanism that ensures that B and T cells which can potentially attack self are eliminated

Negative selection

Biological Roles of antibodies

Neutralization, Opsonization, Complement system activation, Immobilization, and prevention of adherence, cross-linking, and antibody dependent cellular cytotoxicity (ADCC)

Opsonization

Phagocytic cells have receptors for the Fc region of IgG molecules, making it easier for the phagocyte to engulf antibody coated antigens

Helper T cells CD marker antigen recognition potential target cells effector function source of antigen recognized by effector cell

Th, CD marker CD4, antigen recognition-peptides presented on MHC class II molecules, Potential target cells- B cells, macrophages, Effector Function- activates target cell, Source of antigen recognized by effector cell- Exogenous (produced outside the target cell)

Class Switching

all B cells are initially programmed to differentiate into plasma cells that secrete other antibody classes. B cells in the lymph nodes most commonly switch to IgG production. B cells in the mucosa-associated lymphoid tissues generally switch to IgA production, producing mucosal immunity. After class switching, some B cells become memory B cells

Complement System Activation

antigen-antibody complexes can trigger the classical pathway of complement system activation, When multiple molecules of certain antibody classes are bound to a cell surface, a specific component system protein attaches to their Fc regions, initiating the cascade

Clonal selection theory

as lymphocytes mature in the primary lymphoid organs, a population of cells able to recognize a functionally limitless variety of antigens is generated, each individual cell recognizes + responds to only one epitope. Thus, if a person's immune system can make antibodies to billions of different epitopes, that person must have billions of different B cells each interaction with a single epitope. the process of generating the diversity in antigen recognition is random + does not require previous exposure to an epitope

Imprecise Joining

as the various segments are joined during gene rearrangement, nucleotides are often deleted or added between the sections.

Immobilization and prevention of adherence

binding of antibodies to flagella interferes with a microbes ability to move, binding pili prevents it form attaching to surfaces, These capabilities are often necessary for a pathogen to infect a host

Lymphatic vessels

carry lymph, a fluid that forms as a result of the body's circulatory system. The lymph- which also contains white blood cells and antigens that have entered the tissues-travels via the lymphatics to the lymph nodes, where proteins, cells and other materials are removed. The lymph then empties back into the blood circulatory system at a large vein behind the left collar bone. Inflammatory response causes more fluid to enter the tissues at the site of inflammation, this causes a corresponding increase in the antigen-containing fluids that enter lymphatic vessels

Lymphoid System

collection of tissues + organs that bring the population of B cells and T cells into contact with antigens, Each lymphocyte recognizes only one or a few different antigens, In order for the body to mount an effective response, the appropriate lymphocyte must encounter the given antigen

Antigenic epitope

discrete regions of the molecule that the adaptive immune system recognizes, some are stretches of 10 or so amino acids, others are 3-D shapes like a region that sticks out in a molecule. A bacterial cell usually has a diverse assortment of macromolecules on its surface, each with a number of distinct epitopes, so the entire cell has a multitude of different epitopes

IgA

10-13% of total serum, half-life: 6 days. Most abundant class produced but the majority if it is secreted into mucus, tears, and saliva, producing mucosal immunity. Also found in breast milk, protecting the intestinal tract of breast-fed infants. Protects mucous membranes by neutralizing viruses and toxins, immobilizing motile organisms, + preventing attachment of microbes to mast cells. Looks like two antibodies hooked together, weight: 390,000

IgM half-life characteristics shape, weight

5-13% of total serum, half-life: 10 days, first antibody class produced during the primary response, Principle class produced in response to T-independent antigens, Provides direct protection by neutralizing viruses + toxins, immobilizing motile organisms, preventing microbes from adhering to cell surfaces, and cross-linking antigens, Binding of IgM to antigen leads to activation of the complement system (classical pathway) Pentamer, weight 970,000

how does a T cell bind antigens

A T cell partly degrades (processes) the antigen and then displays (presents) individual peptides of the antigen's proteins, The peptides form the antigen are cradled in the grooves of proteins, major histocompatibility complex (MHC) molecules, on the surface of the presenting cell

Secondary response

when the same antigen is encountered later in life, there is a stronger antigen-specific immune response

5 classes of anitbodies

IgM, IgG, IgA, IgD, and IgE

Antigen

Molecule that reacts specifically with either an antibody or an antigen receptor on a lymphocyte

How does a B-cell get "help" so it can efficiently produce antibodies against a particular antigen

Naive B cells that bind the antigen present the peptide fragments to Th cells. Once activated, those B cells multiply, generating a population of cells that recognize the antigen, As some of the activated B cells continue dividing, others differentiate to form antibody-secreting plasma cells. Result is a slow but steady increase in the titer (concentration) of antibody molecules. Affinity Maturation + Class switching

Cytotoxic T cell CD marker antigen recognition potential target cells effector function source of antigen recognized by effector cell

Tc, CD marker- CD8, Antigen recognition- peptides presented on MHC class I molecules, Potential target cells- all nucleated cells, Effector Function: induces target cell to undergo apoptosis, Source of antigen recognized by Effector cell- Endogenous (produced within the target cell)

Gene rearrangement

a B cell expresses 3 gene segments, one each from DNA regions called V (variable), D (diversity), and J (joining), to form an ensemble that encodes a nearly unique variable region of the heavy chain of an antibody, A human hematopoietic stem cell has about 40 different V segments, 25 different D segments, and 6 different J segments in the DNA that encodes the variable region of the DNA

Plasma cells

effector B cells, Effector B cells are descendants of activated lymphocytes, armed with the ability to produce specific cytokines or other protective substances

Humoral immunity

B lymphocytes or cells responsible, develop in bone marrow. In response to extracellular antigens, B cells may be triggered to proliferate + then differentiate into plasma cells, which function as factories that produce antibodies (bind to antigens). Stem functions as "red flag", tagging antigen bound by antibodies + enlisting other immune system components to eliminate the molecule. B cell receptor (BCR) when a naive B cell encounters an antigen that its BCR binds, the cell is triggered to multiply. B cell activated by Th cell

MALT

Mucosa associated lymphoid tissue, play a critical role in mucosal immunity, the immune response that prevents microbes from invading the body via the mucous membranes

24. How do Natural Killer Cells perform the function known as ADCC?

NK cells induce apoptosis in antibody-bound "self" cells. Process called Antibody-dependent cellular cytotoxicity, allows them to destroy host cells that have viral or other foreign proteins inserted into their membrane. NK cells can do this because they have Fc receptors for IgG molecules on their surface, Fc receptors bind the "red flag" portion of antibody molecules. The NK cell attaches to the antibodies + then delivers perforin and protease-containing granules directly to the cell, initiating apoptosis, NK cells also recognize + destroy stressed host cells that do not have MHC class I molecules on their surface, The NK cells recognize the lack of MHC class I molecules on cells, along with certain molecules that indicate the cells are under stress, and induce the infected cells to undergo apoptosis

Neutralization

a toxin or virus coated with antibodies cannot attach to cells and is said to be neutralized

Affinity Maturation

form of natural selection among proliferating B cells, as activated B cells multiply, spontaneous mutations commonly occur in certain regions of the antibody genes, Some of these result in slight changes in the antigen-binding site of the antibody. B cells that bind antigen for the longest duration are more likely to proliferate

TCR

has 2 polypeptide chains ( a set of either alpha and beta or gamma and delta), each with a variable + a constant region. Does not interact with free antigen, the antigen must be "presented" by another host cell

Primary Lymphoid organs

include the bone marrow and thymus, B cells and T cells originate in bone marrow but only B cells mature there, immature T cells migrate to the Thymus and mature there, Once mature, the lymphocytes gather in the secondary lymphoid organs waiting to encounter antigen

Constant region

includes the entire Fc region, as well as part of the two Fab regions. The consistent nature of this region allows other components of the immune system to recognize the otherwise diverse antibody molecules. Five general types of constant regions + these correspond to the major classes of immunoglobin (Ig) molecules- IgM, IgG, IgA, IgD, ad IgE

Memory B cells

long-lived descendants of activated lymphocytes, they can quickly become activated when an antigen is encountered again, responsible for the speed + effectiveness of the secondary response

Adaptive immune system

matures throughout life, protection provided by the response is adaptive immunity, Memory- a stronger response to re-exoposure, Molecular specificity- response that protects an individual from one disease does not prevent a different disease. Tolerance- the ability to ignore any given molecule, self vs non-self recognition, Extraordinary complex, antigens, antibodies, lymphocytes (primary participants in the adaptive immune responses)

Antigen-Presenting Cell

only specialized cell types (dendritic, B cells, and macrophages) make MHC class II molecules, referred to as antigen-presenting cells. MHC class II molecules present exogenous antigens (antigens taken up by a cell). Dendritic cells: en route to the secondary lymphoid organs, the dendritic cells mature into a form that presents antigen to naive T cells. Dendritic cells that detected pathogens produce surface proteins called co-stimulatory molecules. Naive T cells that recognize antigen presented by dendritic cells displaying co-stimulatory molecules can become activated

Variable region

portion at the ends of the Fab regions, it accounts for the antigen-binding specificity. Part of this region is the antigen-binding site, the portion that attaches to a specific epitope. The fit needs to be very precise, because the interaction depends on numerous non-covalent bonds to keep the molecule together. The antigen-antibody interaction is reversible, and the molecules can separate, leaving both antigen and antibody unchanged

Combinational associations

refers to specific groupings of light chains + heavy chains that make up the antibody molecule, both types of chains independently acquire diversity through gene rearrangement + imprecise joining. Additional diversity is then introduced when these 2 chains creates the antigen-binding site

Secondary Lymphoid organs

sites where lymphocytes gather to contact the various antigens. Ex. lymph nodes, spleen, tonsils, adenoids, and appendix. They are situated at strategic positions in the body so that immune responses can be initiated almost anywhere. Purpose: capture antigens and bring them into contact with lymphocytes

Primary responses

the first response to a particular antigen

Cross linking

the two arms of an antibody can bind separate but identical antigen molecules, linking them. The overall effect is that large antigen-antibody complexes form, creating big "mouthfuls" of antigens for phagocytic cells to engulf. Antibody dependent cellular cytotoxicity: when multiple IgG molecules bind to a virally infected cell or a tumor cell, that cell becomes a target for destruction by natural killer (NK) cells. The NK cell attached to the Fc regions of IgG and once attached, kills the target cell by delivering compounds directly to it

Immunogen

used when referring specifically to an antigen that elicits an immune response in a given sitiaution