MCAT Biology Review

Chapter 8: The Immune System

Conclusion

The ability to fend off microbial invasion is critical to our survival. The immune system is housed in many locations in the body and involves multiple different organs and cell types. Nonspecific mechanisms, such as intact skin, mucous membranes, defensins, lysozyme, complement, interferons, natural killer cells, neutrophils, eosinophils, basophils, and monocytes/macrophages, constitute a complex first line of defense; these mechanisms comprise the innate immune system, which is capable of an immediate response but cannot target a specific pathogen or maintain immunologic memory. The adaptive immune system, comprised of B- and T-cells (lymphocytes), allows for our immune system to target individual pathogens and learn from past exposure. Thus, once we are infected with a certain strain of virus, activation of specific immunity confers long-term protection against that particular virus. We take advantage of this secondary response through immunization, and we can see the problems specificity can have when a self-antigen is labeled as foreign, leading to autoimmune disease.

If the immune system is focused on destroying pathogens, including bacteria, then it’s an interesting transition we make in the next chapter. We’re going from a “sterilization” system to one in which bacterial colonization is the norm. From oral flora to the normal gut bacteria, our ability to digest and absorb nutrients is intimately linked to symbiotic bacteria throughout the digestive tract. In the next chapter, we will explore the anatomy and physiology of the digestive system, which provides us with the raw materials to generate energy, build proteins, and carry out activities of daily living.

Concept Summary

Structure of the Immune System

·        The immune system can be divided into innate and adaptive immunity.

o   Innate immunity is composed of defenses that are always active, but that cannot target a specific invader and cannot maintain immunologic memory; also called nonspecific immunity.

o   Adaptive immunity is composed of defenses that take time to activate, but that target a specific invader and can maintain immunologic memory; also called specific immunity.

·        The immune system is dispersed in the body.

o   Immune cells come from the bone marrow.

o   The spleen and lymph nodes are sites where immune responses can be mounted, and in which B-cells are activated.

o   The thymus is the site of T-cell maturation.

o   Gut-associated lymphoid tissue (GALT) includes the tonsils and adenoids.

·        Leukocytes, or white blood cells, are involved in immune defenses.

The Innate Immune System

·        Many of the nonspecific defenses are noncellular.

o   The skin acts as a physical barrier and secretes antimicrobial compounds, like defensins.

o   Mucus on mucous membranes traps pathogens; in the respiratory system, the mucus is propelled upward by cilia and can be swallowed or expelled.

o   Tears and saliva contain lysozyme, an antibacterial compound.

o   The stomach produces acid, killing most pathogens. Colonization of the gut helps prevent overgrowth by pathogenic bacteria through competition.

o   The complement system can punch holes in the cell walls of bacteria, making them osmotically unstable.

o   Interferons are given off by virally infected cells and help prevent viral replication and dispersion to nearby cells.

·        Many of the nonspecific defenses are also cellular.

o   Macrophages ingest pathogens and present them on major histocompatibility complex (MHC) molecules. They also secrete cytokines.

o   MHC class I (MHC-I) is present in all nucleated cells and displays endogenous antigen (proteins from within the cell) to cytotoxic T-cells (CD8+ cells).

o   MHC class II (MHC-II) is present in professional antigen-presenting cells (macrophages, dendritic cells, some B-cells, and certain activated epithelial cells) and displays exogenous antigen (proteins from outside the cell) to helper T-cells (CD4+ cells).

o   Dendritic cells are antigen-presenting cells in the skin.

o   Natural killer cells attack cells not presenting MHC molecules, including virally infected cells and cancer cells.

o   Granulocytes include neutrophils, eosinophils, and basophils.

o   Neutrophils ingest bacteria, particularly opsonized bacteria (those marked with antibodies). They can follow bacteria using chemotaxis.

o   Eosinophils are used in allergic reactions and invasive parasitic infections. They release histamine, causing an inflammatory response.

o   Basophils are used in allergic reactions. Mast cells are related cells found in the skin.

The Adaptive Immune System

·        Humoral immunity is centered on antibody production by plasma cells, which are activated B-cells.

o   Antibodies target a particular antigen. They contain two heavy chains and two light chains. They have a constant region and a variable region; the tip of the variable region is the antigen-binding region.

o   When activated, the antigen-binding region undergoes hypermutation to improve the specificity of the antibody produced. Cells may be given signals to switch isotypes of antibody (IgM, IgD, IgG, IgE, IgA).

o   Circulating antibodies can opsonize pathogens (mark them for destruction), cause agglutination (clumping) into insoluble complexes that are ingested by phagocytes, or neutralize pathogens.

o   Cell-surface antibodies can activate immune cells or mediate allergic reactions.

o   Memory B-cells lie in wait for a second exposure to a pathogen and can then mount a more rapid and vigorous immune response (secondary response).

·        Cell-mediated (cytotoxic) immunity is centered on the functions of T-cells.

o   T-cells undergo maturation in the thymus through positive selection (only selecting for T-cells that can react to antigen presented on MHC) and negative selection (causing apoptosis in self-reactive T-cells). The peptide hormone thymosin promotes T-cell development.

o   Helper T-cells (Th or CD4+) respond to antigen on MHC-II and coordinate the rest of the immune system, secreting lymphokines to activate various arms of immune defense. Th1 cells secrete interferon gamma, which activates macrophages. Th2 cells activate B-cells.

o   Cytotoxic T-cells (TcCTL, or CD8+) respond to antigen on MHC-I and kill virally infected cells.

o   Suppressor (regulatory) T-cells (Treg) tone down the immune response after an infection and promote self-tolerance.

o   Memory T-cells serve a similar function to memory B-cells.

·        In autoimmune conditions, a self-antigen is recognized as foreign, and the immune system attacks normal cells.

·        In allergic reactions, nonthreatening exposures incite an inflammatory response.

·        Immunization is a method of inducing active immunity (activation of B-cells that produce antibodies to an antigen) prior to exposure to a particular pathogen.

·        Passive immunity is the transfer of antibodies to an individual.

The Lymphatic System

·        The lymphatic system is a circulatory system that consists of one-way vessels with intermittent lymph nodes.

·        The lymphatic system connects to the cardiovascular system via the thoracic duct in the posterior chest.

·        The lymphatic system equalizes fluid distribution, transports fats and fat-soluble compounds in chylomicrons, and provides sites for mounting of immune responses.

Answers to Concept Checks

·        8.1

1.    Innate immunity consists of defenses that are always active against pathogens, but that are not capable of targeting specific invaders. It takes longer to mount a response with adaptive immunity, but the response targets a specific pathogen and maintains immunologic memory of the infection to mount a faster response during subsequent infections.

2.     

Cell Type

Site of Development

Site of Maturation

Major Functions

Specific or Nonspecific?

Humoral or Cell-Mediated?

B-cell

Bone marrow

Bone marrow (but are activated in spleen or lymph nodes)

Produce antibodies

Specific

Humoral

T-cell

Bone marrow

Thymus

Coordinate immune system and directly kill infected cells

Specific

Cell-mediated

3.    Granulocytes include neutrophils, eosinophils, and basophils. Agranulocytes include B- and T-cells (lymphocytes) and monocytes (macrophages).

·        8.2

1.    Skin provides a physical barrier and secretes antimicrobial enzymes. Defensins are examples of antibacterial enzymes on the skin. Lysozyme is antimicrobial and is present in tears and saliva. Mucus is present on mucous membranes and traps incoming pathogens; in the respiratory system, cilia propel the mucus upward so it can be swallowed or expelled. Stomach acid is an antimicrobial mechanism in the digestive system. The normal gastrointestinal flora provides competition, making it hard for pathogenic bacteria to grow in the gut. Complement is a set of proteins in the blood that can create holes in bacteria.

2.    Professional antigen-presenting cells include macrophages, dendritic cells in the skin, some B-cells, and certain activated epithelial cells.

3.    MHC-I is found in all nucleated cells and presents proteins created within the cell (endogenous antigens); this can allow for detection of cells infected with intracellular pathogens (especially viruses). MHC-II is only found in antigen-presenting cells and presents proteins that result from the digestion of extracellular pathogens that have been brought in by endocytosis (exogenous antigens).

4.    Natural killer cells are activated by cells that do not present MHC (such as virally infected cells and cancer cells). Neutrophils are activated by bacteria, especially those that have been opsonized (tagged with an antibody on their surface). Eosinophils are activated by invasive parasites and allergens. Basophils and mast cells are activated by allergens.

·        8.3

1.    Plasma cells form from B-cells exposed to antigen and produce antibodies. Memory B-cells also form from B-cells exposed to antigen and lie in wait for a second exposure to a given antigen to be able to mount a rapid, robust response. Helper T-cells coordinate the immune system through lymphokines and respond to antigen bound to MHC-II. Cytotoxic T-cells directly kill virally infected cells and respond to antigen bound to MHC-I. Suppressor (regulatory) T-cells quell the immune response after a pathogen has been cleared and promote self-tolerance. Memory T-cells, like memory B-cells, lie in wait until a second exposure to a pathogen to be able to mount a rapid, robust response.

2.    Circulating antibodies can mark a pathogen for destruction by phagocytic cells (opsonization), cause agglutination of the pathogen in insoluble complexes that can be taken up by phagocytic cells, or neutralize the pathogen by preventing its ability to invade tissues.

3.    B-cells originally mature in the bone marrow and have some specificity at that point; however, antibodies that can respond to a given antigen undergo hypermutation, or rapid mutation of their antigen-binding sites. Only those B-cells that have the highest affinity for the antigen survive and proliferate, increasing the specificity for the antigen over time.

4.    Positive selection occurs when T-cells in the thymus that are able to respond to antigen presented on MHC are allowed to survive (those that do not respond undergo apoptosis). Negative selection occurs when T-cells that respond to self-antigens undergo apoptosis before leaving the thymus.

5.    Memory cells allow the immune system to carry out a much more rapid and robust secondary response.

6.    Active immunity refers to the stimulation of the immune system to produce antibodies against a pathogen. Passive immunity refers to the transfer of antibodies to prevent infection, without stimulation of the plasma cells that produce these antibodies.

·        8.4

1.    Fluid would be unable to return from the lower leg, and edema would result. This infection leads to elephantiasis, severe swelling of the limb with thickening of the skin.

2.    The thoracic duct carries lymphatic fluid into the left subclavian vein.

Shared Concepts

·        Biochemistry Chapter 3

o   Nonenzymatic Protein Function and Protein Analysis

·        Biology Chapter 1

o   The Cell

·        Biology Chapter 6

o   The Respiratory System

·        Biology Chapter 7

o   The Cardiovascular System

·        Biology Chapter 9

o   The Digestive System

·        Biology Chapter 10

o   Homeostasis