Vertebrates are unique among animals in having acquired immunity in addition to __. B cells and T cells, types of white blood cells called __, are critical for htis __ defense. Like all blood cells, __ originate from stem cells in the bone marrow.
__ that migrate from the bone marrow to the __, an organ int he thoracic cavity above the heart, mature into __. __ that mature in the bone marrow develop as __.
T cells (t for thymus)
_ and _ cells recognize and inactive foreign cells and molecules. Both types of cells also contribute to __, an enhanced response to a foreing molecule encountered previously. __, which can persist for many decades, is responsible for the protection we obtain against chickenpox and many other idseases from either a prior infection or vaccination. Its existence was apparent to Thucydide. He noted that individuals who had recovered fromt eh plague could safely care for those who were sick or dying "for the same man was never attacked twice-at least not fatally."
B and T
immunological memory x2
Although B and T cells function only in the __, __ and __ are not independent. At the start of an infection, signaling molecuels from phagocytic cells carrying out innate immune responses activate __,s etting the stage for the slower-developing acquired response. For ex, as macrophages and dendritic cells ingest microbes, these phagocytic cells secrete __, proteins that help recruit and activate lymphocytes.
Macrophages and dendritic ells also have direct role in pathogen recognition by B and T cells.
acquired immune system
The basic facts of __ can be summarized by:
- Each _ or _ cell has on its surface many receptor proteins that can each bind a part foreign moleucel. The receptor proteins on a single __ are all the same, but there are mils of __ in the body that differ in the foreign molecules that thier receptors recognize.
B or T
lymphocyte (s) x2
When an animal is infected, B and T cells with receptors that can recognize the microbe are activated for part roles in the immune response. In teh activation process, the B and T cells interact with fragments of microbes displayed on teh surface of cells.
- Activated __ undergo cell division, with a set of daughter cells being set aside to fight any future infections of the host by the same microbe. Some T cells assist in activating other __. Other T cells detect and kill infected host cells. Specialized B cells secrete soluble receptor proteins that attack foreign molecuels nad cells circulating in body fluids.
Any foreign molecule that is specifcally recognized by lymphocytesand elicits a response from them is called an __. Most __ are large molecules, either proteins or polysaccharides. SOme __, like toxins secreted by bacteria, are released into the extracell fludid. Many other __ protrude from the surface of pathogens or other foreign cells.
B cells and T cells recognize __ using the __ specific receptors embedded in their plasma membranes. A signel B or T lymphocyte has about 100,000 of htese __ on its surface. B cells sometimes give rise to __ that secrete a solube form of the antigen receptor. This secreted protien is called an __, __.
Antigen receptors and antibodies recognize just a small, accessible portion of an antigen that is called an __, or __. A single antigen has several different __,e ach capable of inducing a resposne from a lymphocyte that recognizes the __.
All fo the antigen receptors on a single lymphocyte are identical; that is, they recognize the same __. Each of the body's lymphocytes thus displays __ for a particular __. Consequently, each lymphocyte defends against any pathogen that produces molecuels containing that __.
Each __ for an antigen is a Y-shaped molecule consisting of four polypeptide chains: two identical __ and two idential __, with disulfide bridges linking chains together. A transmembrane region near one end of each heavy chain anchors hte receptor in the cell's plasma membrane. A short tail region at the end of the heavy chain extends into the cytoplasm.
B cell receptor
The light and heavy chains each ahave a __, where amino acid sequences vary little among the receptors present on dif B cells. The __ includes the cytoplasmic tain and transmembrane region of the heavy chain and all of the disulfide bridges. Within the two tips of the Y shape, the light and heavy chanins each have a __, so named because its amino acid sequence varies extensively from one B cell to another. Together, parts of a heavy-chain V region and a light- chain V region form an asymmetrical binding site for an antigen.
constant (C) region x2
variable (V) region
Antibodies have the same overall organization as B cell receptors, except that they lack the __ and __. As a result, antibodies are secreted rather than membrane bound, a difference associated with distinct functions.
transmembrane region and cytoplasmic tail
Each __ for an antigen consists of two different polypeptide chains, an __ and a __, linked by a disulfide bridge. Despite having two rather than four chains, __ have many features in common with B cell receptors. Near the base of the __ is a transmembrane region that anchors the molecule in the cell's plasma membrane. At the outer tip of the moleucle, the alpha and beta chain variable (V) regions form a single antigen-binding site. The remainder of the molecule is made up of te Constant (C) regions.
T cell receptor
t cell receptors x2
B cell and T celll receptors have closely related but distinct functions. Both types of receptors bind to antigens via __ bonds that stabilize the interaction between an __ and the binding surface. In this manner, B cell receptors recognize and bind to an intact antigen, whether that antigen is free or on the surface of a pathogen.
In contrast, __ receptors bind only to antigen fragments that are displayed, or __, on the surface of host cells. Each of the genes in a group called the __ produces a host cell protein that can present an antigen fragment to T cell receptors in this way. The simulltaneous interaction of an antigen fragment, an MHC molecule, and a T cell receptor is a central event in acquired immunity.
major histocompatibility complex (MHC)
Antigen recognition by T cells begins with a pathogen either infecting or being engulfed by a host cell. Once the pathogen is inside a host cell,e nzymes in the cell cleave the pathogen proteins into smaller pieces, called __ or __.
These __ then bind to an __ molecule inside the cell. Movement of teh __ molecule and bound fragment to the cell surface results in __, the display of the antigen fragment on the cell surface. If an antigen-presenting cell encounters a T cell, the receptors on the T cell can bind to the antigen fragment.
Antigen presentation by MHC protiens either activates immune responses aagainst the antigen or targets for destruction an infected cell displaying the antigen fragment. The type of cell that presents the antigen determines what?
which kind of response occurs
When a __ or __ that has engulfed a pathogen displays an antigen, it signals the immune system that an infection is under way. The immune system responds by increasing its response to taht antigen and the pathogen that produces it. When a cell that has been invaded by a pathogen displays an antigen, it signals the immune ssetm that teh cell is infected. The immune system responds by __ such cells, disrupting further spread of the infection.
To recognize the type of cell displaying an antigen, the immune system relies on two classes of MHC molecules: __ +__
Class I MHC molecules
Class II MHC molecules
__ are found on almost all cells of the body. __ bind to peptide fragments of foreign antigens synthesized within the cell. Any body cell that becomes infected or cancerous can synthesize foreign antigens and display antigen fragments by virute of its __. __ displaying bound antigen fragments are recognized by a subgroup of T cells called __. The term __ refers to their use of toxic gene products to kill infected cells.
Class I MHC molecules x4
cytotoxic T cells
_- are made by just a few cell types, mainly __, __ and __ cells. In tehse cells, __ typically bind to antigen fragment derived from foreign materials that have been internalized through __ or __.
o __, __, and __ cells are known as __ because fo their key role in displaying such internalized antigens. __ display antigens for recognition by cytotoxic T cells and __,a group of T cells that assist both B cells and cytotoxic T cells.
Class II MHC molecules
class II MHC molecules
antigen-presneting cells x2
helper T cells
Three major properties of the acquired immune system:
__, __, _
1) tremendous diversity of receptors ensures that even pathogens never before encountered will be recognized as foreign
2) this ability to recognize vast numbers of foreign molecules coexists with a lack of reactivity against the moelcuels that make up the animal's own cells nad tissues
3) the response to an antigen that has been encoueterd previously is stronger and more rapid than the initial response- a feature called immunological memory
Differneces in the amino acid sequence of the variable region account for the specificity of antigen receptors on __.
- Recall that a single B or T cell displays abouout 100,000 antigen receptors, all identical. If we randomly selected any two B cells or T cells, it is highly unlikely that they would have the same antigen receptor. Instead, the ariable regions at the tip of a particular antigen receptor would idffer in their amino acid sequence from one cell to the other. Beacause the variable regions form the antigen-binding site a particular amino acid sequence generates specificity for a certain __.
True or False:
Each person has more than 1 mil dif B cells and 10 ml different T cells,e ach with a part antigen-bidnding specificity. Yet theree are only about 20,500 protein coding genes in the human genome.
Assembling a functional light-chain gene requires rearranging the DNA. Early in B cell development, a set of enzymes collectively called __ links one V gene segment to one J gene segment. This recombination event eliminates the long sstretch of DNA between teh segments, forming a single exon that is part V and part J. Because there is only an intron between the J and C DNA segments, no further DNA rearrangement is required. Instead, the J and C segments will be joined after transcriptionby splicing out the __.
__ acts randomly, linking any one of the 40 V gene segments to any one of the 5 J gene segments. Heavy-chain genes undergo a similar rearrangement. In any given cell, only one __ gene and one __ gene are rearranged. Furthermore, the rearrangements are permanent and are passsed on to the daughter cells when the __ divides.
After both the __ and __ genes have rearranged, antigen receptors can be synthesized. THe rearranged genes are transcribed, and the transcripts are processed for __. FOllowing __, the light chain and heavy chain assemble together, forming an antigen receptor. Each pair of randomly rearranged heavy and light chanins results in a differnet antigen- binding surface. For the total population of B cells in a human body, the umber of such combos has been calculated as 1.65x 10^6. Furthermore, mutations introduced during VJ recombination add additional variation, making the number of possible antigen- binding specificities even greater.
light and heavy chain
Because antigen receptor genes are randomly rearranged, some immature __ produce receptors specific for __ on the body's own moleucles. I fthese self-reactive _ wer e not eliminated or inactivated, the immune system could not distinguish self from nonself and would attack body proteins, cells and tissues. Instead, as lymphocytes mature in the __ or __, their antigen receptors are tested for self-reactivity.
__ with receptors specific for the body's own molecules are typically either destroyed by __ or rendered nonfuncitnal, leaving only those that react to forengn molecuels. Since hte body normally lacks mature __ that can react against its own components, the immune system is said to exhibit __. Failure of self-tolerance can lead to __, such as multiple sclerosis.
Becuase hte body contains an enormous variety of antigen receptors, only a tiny fraction are specific for the __ on a given antigen. As a result, it is very rare for an antigen to encounter a lymphocyte with a receptor specific for that antigen.
- How then can the acquired immune response be so effective? The answer lies in teh changes in cell number and behavior triggered by the binding of antigen to lymphocyte.
The binding of an antigen receptor to its specific antigen initiates events that activate the lymphocyte. Activated B cells and T cells amplify the response by dividing many times, forming two types of clones: __ + __.
__, which are short-lived, attack the antigen and any pathogens producing that antigen.
__, which are long-lived but less numerous, bear receptors specific for the antigen.
effector cells and memory cells x2
The proliferation of a lymphocyte into a lone of cells in response to binding an antigen is called __.
This concept is so fundamental to understanding acquired immunity that it is worth restating: The presnetaion of an antigen to specific receptors on a lymphocyte leads to repeated rounds of cell division. The result is a clonal population of thousands of cells, all specific for that antigen.
Prior exposure to an antigen alters the speed, strength, and duration of hte immune response. The production of effector cells from a clone of lymphocytes during the first exposure to an antigen represents the __. The primary response peaks about 10 to 17 days after the initial exposure.
primary immune response
During this time, selected B cells generate antibody-secreting effector B cells, called __, and sleected T cells are activated to their effector forms, consisting of helper cells and cytotoxic cells. If an individual is exposed again to the same antigen, the response is faster (typically peaking only 2 to 7 days after exposure), of greater magnitude and more prolonged. This is the __.
- Measures of antibody concentrations in blood serum over time clearly show the difference between primary and secondary immune responses.
secondary immune response
The __ relies on the reservoir of T and B memory cells generated following initial exposure to an antigen. Because thes ecells are long-lived, they provide the basis for immunological memory that can span many decades. If and when an antigen is encountered again, memory cells specific for that antigen enable the rapid formation of large clones of effector cells and thus a greatly enhanced immune defense.
secodnary immune response
Although the processes for __, __ and __ are similar for B cells and T cells, these two classes of lymphocytes fight infection in dif. ways and in dif. settings.