1. Specific Internal Defenses The Acquired (or Adaptive) Immune System

2. Adaptive immune response Specific internal defenses, the final line of defense, comprise the adaptive immune response, in which immune cells selectively destroy the specific invading toxin or microbe and then “remember” the invader, allowing a faster response if it reappears in the future skin, mucous membranes Nonspecific External Barriers phagocytic and natural killer cells, inflammation, fever Innate Immune Response If these barriers are penetrated, the body responds with If the innate immune response is insufficient, the body responds with cell-mediated immunity, humoral immunity Adaptive Immune Response

3. The adaptive immune system consists of three major components  Immune cells  Tissues and organs  Secreted proteins

4. Immune cells  several types of white blood cells, including macrophages and lymphocytes  Unique to the adaptive immune response are specialized white blood cells called lymphocytes  B cells and T cells are two types of lymphocytes that arise from dividing stem cells in the bone marrow and thymus

5. thymus tonsils bone marrow spleen thoracic duct lymph vessels lymph nodes valve prevents backflow lymph node chambers packed with white blood cells Tissues and organs  lymph nodes: which contain masses of macrophages and specialized white blood cells called lymphocytes  Thymus: is located beneath the breastbone, slightly above the heart, and is essential for development of T cells  Spleen: fist-sized organ located on the left side of the abdominal cavity - filters blood, exposing it to white blood cells that destroy microbes and aged red blood cells  Tonsils: are located in a ring around the pharynx Macrophages and other white blood cells in the tonsils directly destroy many invading microbes and often trigger an adaptive immune response

6. Secreted proteins  Cytokines: secreted by leukocytes,  A large number of proteins in the blood, collectively called complement, assist the immune system in killing invading microbes  Some cytokines and complement proteins are involved in both the innate and adaptive responses  For example, some cytokines stimulate innate immune responses such as inflammation, which activates fever  Antibodies: proteins produced by B cells and their offspring, help the immune system to recognize invading microbes and destroy them

7. All adaptive immune responses include the same three steps 1.Lymphocytes recognize an invading microbe and distinguish the invader from self 2.They launch an attack 3.They retain a memory of the invader that allows them to ward off future infections by the same type of microbe

8. How Does the Adaptive Immune System Recognize Invaders?  To understand how the immune system recognizes invaders and initiates a response, we must answer three related questions 1.How do lymphocytes recognize foreign cells and molecules? 2.How can lymphocytes produce specific responses to so many different types of cells and molecules? 3.How do they avoid mistaking the body’s own cells and molecules for invaders?

9. Antigens:  The adaptive immune system recognizes invaders’ complex molecules - ANTIGENS  Antigens: large, complex molecules are called, because they are “antibody generating” molecules that can provoke an immune response, including the production of antibodies  Bacteria and humans differ from one another because each contains specific, complex molecules that the other does not have  Antigens are often located on the surfaces of invading microbes  Many viral antigens become incorporated into the plasma membranes of infected body cells  Viral or bacterial antigens are also “displayed” on the plasma membranes of dendritic cells and macrophages that engulf them  Other antigens, such as toxins released by bacteria, may be toxins in the blood plasma, lymph, or other extracellular fluids

10. Antibodies  Antibodies, produced only by B cells and their offspring  Y-shaped proteins composed of two pairs of peptide chains: one pair of identical large (heavy) chains and one pair of identical small (light) chains  Both heavy and light chains consist of a constant region, which is similar in all antibodies of the same type, and a variable region that differs among individual antibodies  The light and heavy chains combine to form the two functional parts: the “arms” of the Y and the “stem” of the Y  The variable regions at the arm tips form sites that bind antigens  Each binding site has a particular size, shape, and electrical charge so that only certain molecules can fit in and bind to the antibody  The sites are so specific that each antibody can bind only a few, very similar, types of antigen molecules

11. antigen Figure 36-6 Antibody structure antigen light chain heavy chain Variable regions form antigen binding sites Constant regions are the same in all antibodies of a given type

12. Antibodies  Antibodies serve two functions in the adaptive immune response 1.Recognizing foreign antigens and triggering the response against invaders 2.Helping to destroy the invading cells or molecules that bear antigens B cell antibody antigen microbe

13. T-cell receptors  T-cell receptors are found only on the surfaces of T cells  Every T cell produces T-cell receptors that differ from those of all other T cells  Variable regions, which form highly specific binding sites for antigens, protrude from the cell surface  Both antibodies and T-cell receptors play crucial roles in helping to destroy invading microbes

14. The immune system can recognize millions of different antigens  The adaptive immune system recognizes and responds to millions of potentially harmful antigens  B and T cells randomly synthesize millions of different antibodies and T-cell receptors  At any given time, the human body contains perhaps 100 million different antibodies and even more T-cell receptors

15. The immune system distinguishes self from non-self  The body manufactures thousands of different proteins, including MHC proteins that are unique to you  These proteins can stimulate powerful immune responses in other people’s bodies: that is, they can act as antigens  This is why transplants are often rejected, unless the transplant recipient takes drugs to suppress the immune response  If the immature immune cells contact antigens that bind to their antibodies or T-cell receptors, they undergo apoptosis, or programmed cell death, in which they essentially commit cellular suicide  Therefore, the immune system distinguishes self from non-self by retaining only those immune cells that do not respond to the body’s own molecules  Not all self-reactive B and T cells are eliminated in this way  One of the functions of regulatory T cells is to prevent any remaining self-reactive lymphocytes from attacking the body and causing an autoimmune disease

16. the Adaptive Immune System Attacks Invaders  The invading microbe usually includes a handful of different antigens, each capable of binding only to a few antibodies or T-cell receptors  Your immune system contains millions of B and T cells, each bearing antibodies or T-cell receptors that differ from the antibodies or T-cell receptors of every other immune cell in your body  The benefit to having millions of unique immune cells is that almost any invader will provoke an adaptive immune response  The drawback to having very small numbers of cells that can recognize any given invader is that a handful of cells isn’t enough to kill the invaders immediately  It usually takes 1 to 2 weeks to mount a good immune response to the first exposure to an invading microbe, as the responding cells multiply and differentiate  The adaptive immune system simultaneously launches two types of attack against microbial invaders 1. Humoral immunity 2. Cell-mediated immunity

17. Humoral immunity  produced by antibodies dissolved in the blood  provided by B cells and the antibodies that they secrete into the bloodstream  When a microbe enters the body, the antibodies on a few of these B cells can bind to antigens on the invader  Antigen-antibody binding causes these B cells to multiply rapidly  The daughter cells differentiate into two cell types 1. Memory B cells, which do not release antibodies, but play an important role in future immunity to the invader that stimulated their production 2. Plasma cells, which become enlarged and packed with rough endoplasmic reticulum, which synthesizes huge quantities of antibodies  These antibodies are released into the bloodstream

18. antibodies antigens Invading antigens bind to antibodies on one B cell (dark blue) The B cell “selected” by the antigen multiplies rapidly A large clone of genetically identical B cells is produced These B cells differentiate into plasma cells and memory B cells plasma cell endoplasmic reticulum Plasma cells release antibodies into the blood memory B cell antibodies

19. Humoral immunity  Antibodies in the blood combat invading molecules or microbes in three ways 1. The circulating antibodies may bind to a foreign molecule, virus, or cell and render it harmless by a process called neutralization 2. Antibodies may coat the surface of invading molecules, viruses, or cells and make it easier for macrophages and phagocytes to destroy them 3. When antibodies bind to antigens on the surface of a microbe, the antibodies interact with complement proteins that are always present in the blood

20. Antibodies bind to antigens on a microbe and promote phagocytosis by macrophages antibody antigen microbe macrophage

21. Cell-mediated immunity  Cell-mediated immunity is produced by cytotoxic T cells, which attack virus-infected body cells and cells that have become cancerous  When a cell is infected by a virus, some pieces of viral proteins are brought to the surface of the infected cells and “displayed” on the outside of the plasma membrane  When a cytotoxic T cell with an appropriate matching T-cell receptor binds to a viral antigen, the cytotoxic T cell passes through pores, killing the infected cell  If the infected cell is killed before the virus has finished multiplying, then no new viruses are produced, and the viral infection cannot spread to other cells  Cancer cells often display unusual proteins on their surfaces that cytotoxic T cells recognize as foreign, and can be killed by the same mechanism

22. cytotoxic T cell dying cancer cell

23. Helper T cells enhance both humoral and cell-mediated immune responses  B cells and cytotoxic T cells require assistance from helper T cells  Helper T cells bear receptors that bind to antigens displayed on the surfaces of dendritic cells or macrophages that have engulfed and digested invading microbes  When its receptor binds an antigen, a helper T cell multiplies rapidly, and its daughter cells differentiate and release cytokinins that stimulate cell division and differentiation in both B cells and cytotoxic T cells

24. A summary of humoral and cell-mediated immune responses Targets invaders outside cells (e.g., viruses, bacteria, fungi, protists, and toxins) HUMORAL IMMUNITY Stimulate both humoral and cell- mediated immunity by releasing cytokines HELPER T CELLS Targets defective body cells (e.g., infected cells and cancer cells), transplants CELL-MEDIATED IMMUNITY infected cell Viral antigens presented on the surfaces of dendritic cells or macrophages, and infected cells T-cell receptors bind to viral antigens cytotoxic T cell helper T cell dendritic cell or macrophage virus viral antigen cytokines B-cell antibodies bind to viral antigens and stimulate the B cells to divide and differentiate antibody B cell Cytokines released by helper T cells stimulate B cells and cytotoxic T cells plasma cell memory B cell memory helper T cell memory cytotoxic T cell cytotoxic T cell Plasma cells secrete antibodies into the blood and interstitial fluid Memory cells confer future immunity to this specific virus but not to any other microbes Cytotoxic T cells release pore-forming proteins that destroy infected cells infected cell

25. Memory B cells and Memory T cells  After recovering from a disease, you remain immune to that particular microbe for many years, perhaps a lifetime  Some of the daughter cells of the original B cells, cytotoxic T cells, and helper T cells that responded to the original infection differentiate into memory B cells and memory T cells that survive for many years  If the body is reinvaded by the same type of microbe, the memory cells recognize the invader and mount an immune response

26. Animation: Humoral Versus Cell-Mediated Immunity

27. Adaptive Immune System Memory  Memory B cells rapidly produce a clone of plasma cells, secreting antibodies that combat this second invasion  Memory T cells produce clones of either helper T cells or cytotoxic T cells specific for the “remembered” invader  Each memory cell responds so quickly and so largely in a second infection, the body fends off the attack before the person suffers any symptoms—they have become immune  Acquired immunity confers long-lasting protection against many diseases such as smallpox, measles, mumps, and chicken pox

28. Figure 36-12 Acquired immunity first exposure interval: months or years second exposure time since exposure (weeks) 0 123 0 123 immune response (amount of antibody produced)

29. How Does Medical Care Assist the Immune Response?  The battle against disease, for most of human history, was fought by the immune response alone  Currently, the immune response has a powerful assistant  Medical treatment  Antibiotics and vaccinations are two very important medical tools

30. Antibiotics  Antibiotics slow down microbial reproduction  Antibiotics are chemicals that help to combat infection by slowing down the multiplication of bacteria, fungi, or protists  The occasional mutant microbe that is resistant to an antibiotic will pass on the genes for resistance to its offspring; resistant microbes thrive while susceptible microbes die off  Eventually, many antibiotics become ineffective in treating diseases  Antibiotics are not effective against viruses because they target metabolic processes that viruses do not possess  Drugs are now available that target different stages of the viral cycle of infection, including attachment to a host cell, replication of viral parts, assembly of new viruses within the host cell, and the release of these viruses to infect more body cells  Antiviral drugs are available to treat HIV, herpes virus (cold and genital sores), and the flu virus

31. Vaccines  A vaccine stimulates an immune response by exposing a person to antigens produced by a pathogen  Vaccines often consist of weakened or killed microbes, or some of the pathogen’s antigens, usually synthesized using genetic engineering techniques  Exposure to these antigens results in the body producing an army of memory cells that confer immunity against living microbes of the same type

32. HIV and AIDS  AIDS is caused by human immunodeficiency viruses (HIV) that undermine the immune system by infecting and destroying helper T cells, which stimulate both the cell-mediated and humoral immune responses  AIDS does not kill people directly, but AIDS victims become increasingly susceptible to other diseases as their helper T-cell populations decline  HIV enters a helper T cell and hijacks the cell’s metabolic machinery, forcing it to make more viruses, which then emerge, taking an outer coating of T-cell membrane with them  Helper T-cell levels continue to decline over time and without treatment, and eventually the immune response becomes too weak to overcome routine infections  At this time, the person is considered to have AIDS  The life expectancy for untreated AIDS victims is 1 to 2 years

33. Animation: HIV: The AIDS Virus