Antigens, lymphocytes and antigen presentation

An antigen is the molecule recognized, often a protein or glycoprotein on a microbe or cell. Antibodies are the proteins that bind antigens.

• Correct: Any molecule a lymphocyte receptor protein or antibody binds specifically:
• A protein released by lymphocytes to kill microbes:
• A white blood cell that engulfs microbes:

The thymus and red bone marrow are the primary lymphoid organs. The spleen and tonsils are secondary organs, where mature lymphocytes meet antigens.

• Spleen:
• Correct: Thymus:
• Palatine tonsil:

The membrane flows around the bacterium and closes it into a vesicle, which fuses with lysosomes that digest it.

• By exocytosis:
• Correct: By phagocytosis into a vesicle that fuses with lysosomes:
• By diffusion through its membrane:

A large protein has many epitopes on its surface. Each is recognized by different lymphocytes, so the one protein selects many clones at once: a polyclonal response.

• The protein changed shape to fit each clone: The antigen does not reshape itself or the antigen receptors. Receptors are made at random in advance, and the antigen selects those that already fit.
• One clone switched its antigen receptor to a new shape many times over: Each lymphocyte and its clone carry one receptor specificity. Many clones, not one changing clone, explain the variety.
• The protein was contaminated with other proteins: Nothing suggests contamination. Even a pure protein carries many epitopes.
• Correct: Each clone recognizes a different epitope on the protein: Correct. Many epitopes on one antigen select many clones.

Proteins made inside a cell, including viral ones, are chopped into peptides in the cytosol, loaded onto MHC class I in the endoplasmic reticulum and shown on the surface. Nearly every nucleated cell, liver cells included, does this, so T cells of the killing kind can spot the infected cell.

• The liver cell releases free viral proteins that T cells bind: T cell receptors do not bind free antigen. They bind only peptides held on MHC proteins.
• The liver cell displays viral peptides on MHC class II: MHC class II is found on antigen-presenting cells and displays material taken in from outside, not proteins made in an ordinary liver cell's cytosol.
• Correct: The liver cell displays viral peptides on MHC class I: Correct. Class I shows what a cell makes inside itself.
• Complement coats the liver cell so T cells can grip it: T cells do not recognize complement. Their antigen receptors bind peptide on MHC.

The dendritic cell captures the bacteria, processes them into peptides in lysosome-fused vesicles, loads the peptides onto class II, and carries them through the lymph to the node's paracortex, where the rare naive T cell with a matching antigen receptor finds them.

• Correct order: 1. A dendritic cell in the skin engulfs the bacteria after its pattern recognition receptors detect them 2. The vesicle holding the bacteria fuses with lysosomes, and bacterial proteins are cut into peptides 3. The peptides are loaded onto MHC class II and carried to the cell surface 4. The dendritic cell travels through afferent lymphatic vessels to a lymph node in the armpit 5. In the paracortex, a naive T cell whose receptor fits a displayed peptide binds it

T cells recognize peptides only when held on self MHC. An antigen receptor that cannot bind self MHC at all could never recognize anything, so the thymocyte gets no survival signal and dies of neglect. This is positive selection.

• It is kept, because it cannot attack self: Being unable to attack self is not enough; the cell must also be able to use self MHC. Without that, it is useless and is not kept.
• It leaves as a naive T cell and waits for a matching microbe: It never leaves. Only thymocytes that pass both positive and negative selection are released.
• It becomes a memory cell without further testing: Memory cells form only after a mature lymphocyte meets its antigen and expands. A thymocyte has not.
• Correct: It dies, because it could never recognize any antigen: Correct. Failing positive selection means death by apoptosis.

Receptors are made at random before any antigen is met, and they do not change to fit a new antigen. The antigen selects the cells that already fit. That is the core idea of clonal selection.

• Each maturing lymphocyte builds its antigen receptor genes from randomly chosen pieces of DNA: This step is right. Random joining of gene pieces makes each lymphocyte's receptor unique.
• Correct: When the virus arrives, lymphocytes reshape their antigen receptors to fit its epitopes: This is the error. The antigen selects existing receptors; it does not reshape them.
• Dendritic cells carry viral peptides to the lymph nodes: This step is right. Dendritic cells present viral peptides in the lymph node paracortex.
• The rare naive lymphocytes whose receptors already fit are selected: This step is right. This is clonal selection.
• Selected lymphocytes divide into clones of identical cells: This step is right. This is clonal expansion.

A naive T cell needs two signals: its antigen receptor binding peptide on MHC, and a confirming signal from a dendritic cell that has detected danger. Binding without the second signal makes it unresponsive for a long time. This clonal anergy is part of peripheral tolerance.

• The T cell switches on and attacks the thyroid: Switching on needs the second signal, which a resting dendritic cell does not give. Attack would require tolerance to fail.
• The dendritic cell is killed by NK cells: The dendritic cell displays normal MHC class I and shows no stress proteins, so NK cells leave it alone.
• The T cell travels back to the thymus to be tested a second time: Mature T cells do not return to the thymus to be retested. Tolerance out in the body is peripheral tolerance.
• Correct: The T cell stops responding for a long time (clonal anergy): Correct. Binding without a confirming signal causes anergy.

Her first infection left memory B and T cells: far more numerous than the original naive cells, long-lived, and quick to switch on. When the virus returned, they responded within a day or two and cleared it before she felt ill.

• Her innate immunity has become specific to the virus: Innate immunity recognizes patterns shared by groups of microbes and does not become specific to one virus.
• Antibodies from age 5 are still circulating unchanged: The antibody molecules made at age 5 were broken down within weeks. Any antibody in her blood now is newly made by cells left from that first response, and her memory cells add a fast, strong new response.
• Her MHC proteins no longer bind the virus: Her MHC proteins are inherited and do not change. Losing the ability to present the virus would make her more vulnerable, not less.
• Correct: Memory cells respond before the virus can spread: Correct. Immunological memory rests on memory cells.

B cell receptors, membrane-bound antibodies, bind epitopes on intact antigens free in fluid. T cells can recognize the venom only after an antigen-presenting cell has processed it and displayed its peptides on MHC.

• T cells: T cell receptors bind only peptides held on MHC proteins, not free proteins in plasma.
• Thymocytes: Thymocytes are immature T cells in the thymus; they do not respond to antigens in the plasma.
• Correct: B cells: Correct. B cells bind intact, free antigen directly.
• NK cells: NK cells carry no antigen receptor. They check other cells for stress proteins and missing MHC class I.