1 Chapter 21: Immune System. 2 INTRODUCTION The immune system protects against assaults on the body –External assaults include microorganisms: protozoans,

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Chapter 21:

Immune System

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INTRODUCTION

• The immune system protects against assaults on the body– External assaults include microorganisms:

protozoans, bacteria, and viruses– Internal assaults: abnormal cells reproduce

and form tumors that may become cancerous and spread

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ORGANIZATION OF THE IMMUNE SYSTEM

• The immune system is continually at work patrolling and protecting the body

• Identification of cells and other particles– Antigens are unique molecules that mark cells– Self-markers: molecules on the surface of cells that are

unique to an individual, thus identifying the cell as “self” to the immune system

– Non–self-markers: molecules on the surface of foreign or abnormal cells or particles that identify the particle as “non-self” to the immune system

– Self-tolerance: the ability of the immune system to attack abnormal or foreign cells but spare normal cells

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ORGANIZATION OF THE IMMUNE SYSTEM (cont.)

• Two major categories of immune mechanisms: (Figure 21-1; Table 21-1)

1. Innate immunity – In place before the person has been exposed to the harmful

substance– provides a general, nonspecific defense against anything

that is not “self”– Epithelial barrier cells, phagocytes (neutrophils,

macrophages, dendritic cells), and natural killer (NK) cells2. Adaptive immunity

- acts as a specific defense against specific threatening agents - T and B lymphocytes

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ORGANIZATION OF THE IMMUNE SYSTEM (cont.)

• Cytokines: any of several kinds of chemicals released by cells to promote innate and adaptive immune responses (e.g., interleukin, interferon, leukotriene)

• Other chemicals (e.g., complement, other enzymes, histamine) also play regulatory roles in immunity

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INNATE IMMUNITY

• Species resistance: genetic characteristics of an organism or species that defend against pathogens (Table 21-2)– Ex. The human species is resistant against disease

factors that spread easily among plants

• Mechanical and chemical barriers: first line of defense (Figure 21-2)– Internal environment of the body is protected by a barrier

composed of the skin and mucous membranes– Skin and mucous membranes provide additional immune

mechanisms: sebum, mucus, enzymes, and hydrochloric acid in the stomach

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INNATE IMMUNITY (cont.)

• Inflammation and fever: second line of defense (Figure 21-3)– Inflammatory response: tissue damage elicits responses to

counteract injury and promote normalcy• Tissue damage causes release of Inflammation

mediators (histamine, kinins, prostaglandins, ILK, mast cells)

• Chemotactic factors: substances that attract white blood cells to the area in a process called chemotaxis

• Produce the characteristic signs of inflammation: heat, redness, pain, and swelling

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INNATE IMMUNITY (cont.)

– Fever: abnormally high temperature triggered by inflammation mediators

• Triggered in systemic inflammatory response syndrome and events such as viral infections, tumors, allergies

• Pyrogen molecules are released from damaged tissues and promote prostaglandin (PG) production; PGs then reset the hypothalamic “thermostat” to a higher temperature

• aspirin and other COX inhibitors interfere with PG production

• Fever is believed to increase immune function and inhibit pathogens

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INNATE IMMUNITY (cont.)• Phagocytosis: ingestion and destruction of

microorganisms or other small particles by phagocytes

Phagocytosis in Adaptive Immunity

– Phagocyte become antigen-presenting cells (APC):• phagocytes ingest foreign particles• isolate protein segments (peptides)and

display them as antigens on their surface• triggers an immune response when

recognized by a specific (adaptive) immune cell

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INNATE IMMUNITY (cont.)

– Neutrophil: most numerous phagocyte; usually first to arrive at site of injury; migrates out of bloodstream during diapedesis; forms pus

– Phagocytes (Table 21-3)• Macrophage: large phagocytic monocytes, APC’s• Dendritic cell: type of phagocytic APC’s with long

branches or extensions, found in areas exposed to environment

• 10-15% of all cells in any organ are phagocytic cells

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INNATE IMMUNITY (cont.)

• Natural killer (NK) cells: lymphocytes that kill tumor cells and cells infected by viruses (Figure 21-9)– 2 receptors, killer activating and killer inhibiting receptors– Killer activating receptor binds to the cell– target cell is killed if killer-inhibiting receptor on NK cell does

not bind to a proper major histocompatibility complex (MHC) surface protein

– Method of killing cells: triggers apoptosis that progresses to lysing cells by damaging plasma membranes

• Interferon: protein synthesized and released into circulation by certain cells if invaded by viruses to signal other nearby cells to enter a protective antiviral state

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INNATE IMMUNITY (cont.)

• Complement: group of enzymes that produce a cascade of reactions resulting in a variety of immune responses (Figure 21-10)– Lyse cells when activated by either adaptive or innate

mechanisms– Opsonization: mark cells for destruction by phagocytes – Promotes inflammatory response

• Toll-like receptors: pattern recognition receptors in the membranes of host cells; when triggered, stimulate many different kinds of innate immune responses

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OVERVIEW OF ADAPTIVE IMMUNITY

• Adaptive immunity is part of the third line of defense • Attacks specific agents• 2 types of lymphocytes: B lymphocytes (B cells) and T

lymphocytes (T cells)– B cells do not attack antigens themselves, but produce antibodies;

antibody mediated or humoral immunity– T cells attack pathogens directly; cell mediated or cellular immunity

• Subsets of lymphocytes are defined by the CD surface markers that the cells carry (e.g., CD4 and CD8 cells)

• Activation of lymphocytes requires two stimuli: a specific antigen and activating chemicals (Figure 21-14)

• Lymphocytes flow through the bloodstream, become distributed in tissues, and return to the bloodstream in a continuous recirculation

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B CELLS AND ANTIBODY-MEDIATED IMMUNITY

• B cells develop in two stages – Pre–B cells have gone through the first phase of

development after an infant is a few months old; now known as naïve B cells

– The second stage occurs in lymph nodes and spleen—a naive B cell is activated when it binds to its specific antigen

– The B cell undergoes stages of rapid mitosis which produces 2 types of cells:

1. effector B or plasma cells -secrete antibodies

2. memory B cells - able to respond if come in contact with the same

antigen - produce more plasma and memory cells

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B CELLS AND ANTIBODY-MEDIATED IMMUNITY

• Antibodies: proteins (immunoglobulins) secreted by activated B cell (Figure 21-16)

• Structure of antibody molecules: an antibody molecule consists of two heavy and two light polypeptide chains; each molecule has two antigen-binding sites and two complement-binding sites (Figure 21-17)

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B CELLS AND ANTIBODY-MEDIATED IMMUNITY (cont.)

• Diversity of antibodies: infants are born with different clones of B cells in bone marrow, lymph nodes, and spleen; cells of the clone synthesize a specific antibody with a sequence of amino acids in its variable region that differs from the sequence synthesized by other clones

• Five classes of antibodies: immunoglobulins M, G, A, E, and D (Figure 21-18)– IgM: antibody that naive B cells synthesize and insert into their own plasma

membranes; the predominant class produced after initial contact with an antigen

– IgG: makes up 75% of antibodies in the blood; predominant antibody of the secondary antibody response; can cross the placenta to impart natural passive immunity

– IgA: major class of antibody in mucous membranes, in saliva and tears– IgE: small amount; produces harmful effects such as allergies– IgD: small amount in blood; precise function unknown

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B CELLS AND ANTIBODY-MEDIATED IMMUNITY (cont.)

• Antibody molecules produce antibody-mediated immunity (humoral immunity) within plasma

• Antibodies determine self from nonself by binding to antigens(Figure 21-19)– Antigen-antibody complex that may have several

effects (Figure 21-20)• Transforms toxins into harmless substances• Agglutinates antigens to be phagocytized• Alters shape of the antibody to expose complement

binding sites

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B CELLS AND ANTIBODY-MEDIATED IMMUNITY (cont.)

• Complement: a component of blood plasma consisting of several protein compounds– Complement binds to the exposed site on the

antibody– A cascade of enzyme activation occurs– Membrane attack complexes (MAC) form

• Drills a hole in the invader’s plasma membrane• Water rushes in causing the cell to burst =

cytolysis– Complement cascade can also initiate

vasodilation and chemotaxis to injured area

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B CELLS AND ANTIBODY-MEDIATED IMMUNITY (cont.)

• Primary and secondary responses (Figure 21-23)– Primary response: initial encounter with a specific

antigen triggers the formation and release of specific antibodies that reaches its peak in a few days

– Secondary response: a later encounter with the same antigen triggers a much quicker response; B memory cells rapidly divide, producing more plasma cells and thus more antibodies

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T CELLS AND CELL-MEDIATED IMMUNITY

• T cells: lymphocytes that go through the thymus gland before migrating to the lymph nodes and spleen– Pre–T cells develop into thymocytes while in the thymus– Thymocytes stream into the blood and are carried to the T cell–dependent

zones in the spleen and the lymph nodes• Activation of T cells

– T cells display antigen receptors on their surface membranes that are similar to antibodies

– A T cell is activated when an antigen (presented by an APC) binds to its receptors causing it to become activated

– T cells divide repeatedly to form:1. Effector T cells or cytotoxic T cells

-contact killing of the target cell-can only bind if antigen is presented by an APC; releases chemical messengers (cytokines) into inflammed tissue

2. Memory T cells-produce more active T cells

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T CELLS AND CELL-MEDIATED IMMUNITY (cont.)

• Functions of T cells– Cytotoxic T cells: T cells release lymphotoxin to kill

cells (Figure 21-26)– Helper T cells: regulate the function of B cells, T

cells, phagocytes, and other leukocytes (Figure 21-27)

– Suppressor T cells: regulatory T cells that suppress lymphocyte function, thus regulating immunity and promoting self-tolerance

– T cells function to produce cell-mediated immunity and help regulate adaptive immunity in general

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TYPES OF ADAPTIVE IMMUNITY

• Adaptive immunity can be further classified according to the way in which it develops– Natural immunity results from nondeliberate

exposure to antigens (cross recognition)– Artificial immunity results from deliberate

exposure to antigens, called immunization

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TYPES OF ADAPTIVE IMMUNITY (cont.)

• Natural and artificial immunity may be active or passive– Active immunity: when immune system responds

to a harmful agent regardless of whether it is natural or artificial; lasts longer than passive

– Passive immunity: immunity developed in another individual is transferred to an individual who was not previously immune; temporary but provides immediate protection

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SUMMARY OF ADAPTIVE IMMUNITY

• Adaptive immunity is specific immunity targeting specific antigens

• Adaptive immunity involves two classes of lymphocyte: B cells and T cells (Figure 21-27)– B cells: antibody-mediated (humoral) immunity– T cells: cell-mediated (cellular) immunity

• Adaptive immunity occurs in a series of stages (Figure 21-28)– Recognition of antigen– Activation of lymphocytes– Effector phase (immune attack)– Decline of antigen causes lymphocyte death (homeostatic balance)– Memory cells remain for later response if needed

• B cells and T cells work together in a coordinated system of adaptive immunity (Figure 21-29)

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Vaccinations

– Hx– http://videos.howstuffworks.com/science-chan

nel/30004-100-greatest-discoveries-the-beginning-of-vaccinations-video.htm

– Physiology – Pros and Cons