CH. 21 IMMUNE SYSTEM

MHC Restrictions CD8 cells

(which become cytotoxic T cells) are activated by antigen fragments on class I MHC proteins. All cells, except RBCs, possess class I MHC protein (including antigen presenting cells). Once activated, cytotoxic T cells look for this same antigen presented on class I MHC proteins on any cell in the body.

MHC Restrictions CD4 cells

(which become helper T cells) are only bind to antigen presented to them by APCs, since only APCs possess class II MHC proteins.

Antibodies, also called ____________________________

Immunoglobulins (Igs)

________________ are cells and chemicals that act as the _____________

Innate internal defenses second line of defense

The way your body recognizes cells that belong to you versus those that do not is from a series of glycoproteins that line the cell's surface called _______________

MHC proteins

Are NK cells phagocytic?

NO

Antigen-Presenting Cells (APCs)

Naïve T cells can only be activated by antigens that are presented to them on MHC proteins by antigen-presenting cells.

In humoral immunity, antibodies are produced that target extracellular antigens Maturation of ___________________

T Cells and B Cells

Adaptive immunity involves T and B lymphocytes, also known as _______________

T and B cells

Second Line of Defense 3. Inflammation:

Tissue Response to Injury

Your immune system can recognize at least a _______________________. Thanks to genetic recombination, each T or B cell comes equipped with a unique set of ________________________

billion different epitopes gene segments that codes for its unique antigen receptor

Antigens are substances that trigger the___________________

body's adaptive defenses

Inflammation Finally, clotting proteins enter to establish a ________ around the damaged area. Over time, the clot is ___________ and replaced by __________

fibrin "patch" broken down scar tissue

MHC proteins These are coded by genes of the major histocompatibility complex (MHC). Millions of combinations of these genes are possible, resulting in everyone's MHC code being ______________

genetically unique

Antibodies are secreted by plasma cells. Antibodies belong to a group of _____________________ (glycoproteins are large proteins with small carbohydrate groups attached) called _____________, and for this reason are also known as ______________.

glycoproteins globulins immunoglobulins

Inflammation When a tissue becomes injured, basophils and mast cells in the connective tissue release

histamine, which dilates blood vessels (this draws in more monocytes / neutrophils / macrophages [a process called positive chemotaxis - the cells are following a chemical gradient]), and increases vessel permeability allowing plasma to leak into the tissue, causing localized edema (swelling).

Second Line of Defense 4. Antimicrobial Proteins: 1. 2.

i) Interferon & ii) Complement Proteins

Inflammation is the body's way of isolating a source of infection and keeping it from spreading elsewhere. Inflammation produces: 1. 2. 3. 4.

i) swelling ii) redness iii) heat iv) pain

Inflammation a. vasodilation and increased permeability of blood vessels:

increased blood flow brings more antibodies and clotting factors into the injured area and also helps remove microbial toxins and dead cells more quickly.

Immunogenicity is the ability to Reactivity is the ability of

provoke an immune response: stimulating the production of antibodies, T cells, or both. the antigen to react specifically with the antibodies or T cells it provoked.

Inflammation The mast cell release and accompanying inflammation stimulates local nerves, causing

sensations of pain

There are two kinds of immunity:

1. innate: nonspecific defense: cells in your body that will attack anything it considers pathogenic. These are defenses you are born with and represent your body's first and second line of defenses (described further below). 2. adaptive: a disease-specific defense. Cells in your body - T and B lymphocytes - adapt to attack a very specific type of microbe. Adaptive immunity is your body's third line of defense.

Inflammation There are three basic stages:

Acute -swelling stage. Sub-acute - regenerative stage. Chronic - scar tissue maturation and remodelling stage.

Antigen

substance that triggers an immune response

Inflammation Increased blood flow to the area brings about both redness and heat:

the heat raises the local body temperature, which increases the rates of enzymatic reactions for fighting pathogens.

_______________ and _______________ immune responses can work together to eliminate a particular _____________________.

Cell-mediated and antibody-mediated antigen from the body

Some macrophages are called free macrophages because __________________________________________ the liver): those are called ______________

they migrate throughout the body, while others remain loyal to a particular tissue fixed macrophages

Natural killer cells check to make sure each cell has "identity flags" - ____________________________________________

they will attack cells that lack class I MHC proteins and cells that are coated with antibodies

All microphages have the ability to move, even if considered ______

"fixed"

Complement proteins begin as inactive proteins - numbered ___________ - with a capital letter "C" to indicate they are inactive. ________________________________________________________________________________________________

C1 through C9 When activated, they are split by enzymes into two fragments - indicated by lowercase letters a and b. Hence, inactive complement protein C3 is split into activated fragments C3a and C3b. Activation of these proteins brings about a cascade sequence of reactions that amplifies their numbers and their effects on the pathogen, enhancing phagocytosis, cytolysis (water rushes into the cell, causing it to expand and burst), and inflammation.

Dendritic cells are APCs that possess both class I and class II MHCs, and so can present to and activate both _________________. APCs can display endogenous antigen in addition to exogenous antigen.

CD4 and CD8 T cells

NK cells kill in a manner similar to _________________ but NK cells are considered part of the_____________ whereas TC cells are part of the ____________

Cytotoxic T cells (TC or CD8 cells, see below) innate immune system adaptive immune system

Typically, just a small part of an antigen molecule triggers the immune response: these parts are called ____________________________

Epitopes Most antigens have many epitopes, each of which induces production of a specific antibody or activates a specific T cell

The toxin in poison ivy, poison oak, poison sumac, - urushiol (also found in the skin of mangoes) - is an example of a _______________, or incomplete (or "partial" antigen):

Hapten a substance that stimulates an immune response but only when attached to a larger carrier molecule. In the case of urushiol, once it is absorbed into the skin, it combines with a body protein called quinone. Similarly, the reason a hospital clinic always asks if you are allergic to penicillin is because penicillin may combine with body proteins to form a hapten that then causes an allergic reaction

Incomplete antigens are also called _________

Haptens By themselves, they are harmless, but when they combine with the body's own proteins, the adaptive immune system may recognize the combination as foreign and mount an attack. Substances that can cause allergic reactions, such as poison ivy, animal dandruff, cosmetics, etc., are considered haptens: they have reactivity but not immunogenicity unless they attach to protein carriers in the body.

There are five classes of immunoglobulins: _______________________________________. B cells will switch from making one class of Ig to another during an immune response.

IgM, IgA, IgD, IgG, and IgE (it forms the acronym MADGE)

Second Line of Defense: ___________

Internal Defenses 1. Phagocytes 2. Natural killer (NK) cells 3. Inflammation 4. Antimicrobial Proteins: i) Interferon & ii) Complement Proteins 5. Fever

Activation and Clonal Selection of Helper T Cells

Most T cells that display CD4 proteins, when activated, turn into helper T cells.

Activation and Clonal Selection of Cytotoxic T Cells

Most T cells that display CD8 proteins, when activated, turn into cytotoxic T (Tc) cells. These cells recognize antigen fragments combined with MHC-I molecules on the surface of body cells infected by microbes, some tumor cells, and cells of a tissue transplant.

Second Line of Defense 1. Phagocytes

Pathogens that pass through the skin and mucous membranes (i.e., the first line of defense), will encounter macrophages (derived from monocytes) and neutrophils (the most abundant white blood cell) in the connective tissue. These cells, part of the second line of defense, engulf microbes and the digest them with lysosomal enzymes, a process called phagocytosis

First Line of Defense:

Skin, Mucous Membranes, and their secretions

Mobile phagocytes move through capillary walls by ________________, a process known as _______________

squeezing between endothelial cells diapedesis or emigration

1. Antigen binding via T-cell receptors and CD4 or CD proteins

T cells bind to antigen via T-cell receptors (TCRs): these bind to specific foreign antigen fragments that are presented in antigen-MHC complexes of APCs. There are millions of different T cells in the body, each has its own unique TCR that can recognize a specific antigen. T cells also have other proteins on their surface - e.g., CD4 or CD8 - that help with the binding of the T cell to the MHC complex, and so are called coreceptors. Antigen recognition by a TCR with CD4 or CD8 proteins is the first step, or first signal in the T cells activation.

Activation and Differentiation of T Cells

T cells can only be activated by APCs. Activation of T cells is a 2-step process, analogous to i) starting a car and ii) putting it into gear in order to make the car go.

________________ can only bind antigens that are presented to them on MHC proteins of other cells (discussed below).

T lymphocytes

First Line of Defense: 1. Skin

the epithelial cells that make up the epidermis are linked together by tight junctions (desmosomes), protecting the underlying tissues. Skin secretions (sweat, sebum) a

Toll-like receptors (TLRs):

these are receptors found on the plasma membranes of macrophages, dendritic cells, epithelial cells, and others, that are designed to recognize particular features specific to microbes. Once a receptor recognizes such a feature, an immune response kicks in. These receptors are part of the innate immune system.

5 stages of phagocytosis

a. Chemotaxis: the movement of an organism toward a chemical stimulus. In this case, the phagocytes are attracted to chemicals emitted by invading microbes, white blood cells, damaged tissue, etc. b. Adherence (binding): the phagocyte attaches to the microbe by sending out cytoplasmic extensions to pull bacteria back toward it. Some bacteria counter this by developing a slippery, external capsule, to which the phagocyte cannot adhere. In this case, another immune system cell (antimicrobial proteins) will shower the bacteria with complement proteins (a process called opsonization, discussed below) to which the phagocyte can bind. c. Ingestion: the phagocyte engulfs the microbe, surrounding it in a sac called a phagosome. d. Digestion: lysosomes within the cell fuse with the phagosome to form a phagolysosome, releasing digestive enzymes (lysozymes) that break down the microbial cell wall. e. Killing: the digestive enzymes kill the microbes. Residual material is exoctyosed

Second Line of Defense 5. Fever

an abnormally elevated body temperature in response to an invading infection, that occurs because the hypothalamic thermostat is reset (you don't sweat until after the fever is over). An increase in body temperature slows bacterial growth and also greatly accelerates enzymatic reactions for tissue defenses. Fever occurs when macrophages encounter pathogens and release pyrogens in response. Pyrogens act on the hypothalamus and help raise the body's temperature above normal levels.

During antigen processing, antigen is broken down by an antigen-presenting cell (APC) and fragments of the antigen are inserted into MHC complex of the cell's plasma membrane, a process called ________________. If a T cell recognizes the antigen-MHC complex as foreign, an immune response takes place.

antigen presentation

Antigenic determinants, or epitopes are the part of the

antigen to which antibody binds.It is the part of the antigen that is recognized by the immune system.

Antibody molecules are T- or Y-shaped, and each arm serves as an _______________________________. When an antibody molecule binds to its corresponding antigen molecule, the combined structure forms an ______________________. Antibodies do not bind to the entire antigen surface; rather, they bind to specific portions of its exposed surface: regions called _______________________, or _____________. Antibodies do not destroy antigens - they bind and inactivate them, forming an antigen-antibody complex, which tags the antigen for destruction by other components of the immune system

antigen-binding site: the part of the antibody that recognizes and attaches to a particular antigen antigen-antibody complex antigenic determinant sites epitopes

First Line of Defense: 2. Mucous membrane

are the epithelial layers that line all body cavities that open to the exterior world (respiratory, reproductive, gastrointestinal, etc.). In addition, the epithelial cells of the upper respiratory tract contain cilia to sweep inhaled dust and microbes back up toward the throat.

How do NK Cells attack?

attack the target cell by adhering to it and then releasing digesting proteins such as perforins that create holes in the pathogen's cell membrane, allowing extracellular fluid to rush in, causing the cell to burst: a process called cytolysis

Whether in the thymus (T cells) or in the bone marrow (B cells) - both cell types develop immunocompetence: the ability to ____________________________. In doing so, they create receptors on their membranes that recognize specific foreign antigen, called ____________________. A single cell can have over 100,000 receptors on it.

carry out adaptive immune responses antigen receptors

When a specific antigen invades a tissue, there are usually many copies of that antigen, and they usually outnumber the specific B cells with the correct antigen receptors that respond to that antigen. But once the correct lymphocytes are found, they are activated and undergo _______________

clonal selection

This means the lymphocytes proliferates (divides via mitosis) and differentiates (i.e., it forms a more specialized cell) in response to that antigen. The result is a population of thousands of identical cells, called ____________, all of which can recognize the foreign antigen. Clonal selection occurs in

clones secondary lymphatic organs and tissues (e.g. tonsils, which swell, resulting in a sore throat, due to lymphocytes participating in an immune response).

Interferon is a type of ___________

cytokine: a chemical messenger that allows cells to coordinate their actions. In this sense, cytokines are similar to hormones, but whereas hormones are restricted to endocrine cells, most cells can produce cytokines, and in larger amounts.

Pathogens

disease causing agents

During the secondary immune response, memory B cells are ________________________________________________________________________________________________________________________________________.

exposed to the same antigen a second time (sometime in the future) and this time divide very quickly, differentiating into plasma cells that secrete antibodies in large quantities

Tc cells check class I MHC proteins of all cells to see if there are __________________ on there (the presence of foreign antigen will stimulate a Tc attack).

foreign antigens

NK cells may release a protein-digesting enzyme called

granzyme that causes the target cell to undergo apoptosis. The microbes hiding inside are then released and destroyed by

Interferons (IFNs) are proteins released by

virus-infected lymphocytes, macrophages, and fibroblasts. The interferon proteins travel and bind to the membrane of nearby healthy cells. Once bound, the healthy cell produces anti-viral proteins in its cytoplasm. If viruses later enter these healthy cells, the anti-viral proteins prevent ("interfere with" - hence the name) viruses from replicating, halting the progress of the disease. Interferons have an indirect role in fighting cancer.

4. Antimicrobial Proteins: a. Interferon:

viruses, those sneaky microbes, replicate inside cells, thus escaping detection from circulating antibodies

Immunity

your body's ability to fend off diseases

Adaptive immunity and - to a lesser degree - innate immunity are overseen by the__________

lymphatic system

The steps for how exogenous agents are processed are listed below:

1. APCs ingest the exogenous antigen via phagocytosis or endocytosis. 2. Within the cell, the antigen is digested into smaller peptide fragments. These fragments binds with an MHCII molecule within the cell. 3. The antigen-MHC-II complex undergoes exocytosis and is inserted onto the plasma membrane. 4. The APC then migrates to lymphatic tissue to present the antigen to helper T or naïve CD4 cells, as if to say, "Look what I found!"

Skin and mucous membranes produce a variety of protective chemicals: 1. 2. 3. 4. 5.

1. Acid: Skin secretions (sweat, sebum) are slightly acidic to inhibit bacterial growth, and sebum contains chemicals toxic to bacteria (the pH of skin is 3-5). The stomach produces hydrochloric acid and proteindigesting enzymes: both of these secretions kill pathogens. 2. Enzymes: Tears, saliva, and sweat contain the enzyme lysozyme, which breaks down the cell walls of some bacteria. 3. Mucin: cells that secrete mucus: a watery fluid that traps microbes and foreign substances that might otherwise enter the body. These are produce by glands and cells (e.g. goblet cells) that line the digestive and respiratory passageways and serve to trap and wash out microorganisms. 4. Defensins: secreted by the skin and mucous membrances, defensins are broad-spectrum antimicrobial peptides that help control bacterial and fungal colonization. 5. Dermicidin: found in sweat, dermicidin is toxic to bacteria.

There are 2 categories of humoral immunity:

1. Active Immunity a. Naturally acquired: gained when you are infected with a pathogen b. Artificially acquired: gained when you receive a vaccine 2. Passive Immunity a. Naturally acquired: gained via breastmilk (mother's antibodies are passed on to the baby; this grants the baby short-term immunity until the baby's own immune system gears up; the antibodies from the mother eventually degenerate) b. Artificially acquired: gained if you are injected with the antibodies from another individual (this grants you short-term immunity; but eventually the antibodies degenerate)

Adaptive immunity differs from innate immunity in three ways:

1. Adaptive immunity is specific for particular foreign molecules (antigens). 2. It is systemic: immunity is not restricted to the initial infection site. 3. Adaptive immunity retains a memory for most previously encountered antigens, so that a second encounter provokes an even more rapid and vigorous response.

Activation and Clonal Selection of Cytotoxic T Cells Recall that this is a 2-step process:

1. Antigenic recognition: the T cell receptor and the CD8 protein bind to the MHC-I complex of the infected body cell. 2. Costimulation: cytotoxic T cells require costimulation by IL-2 (produced by active helper T cells). Once activated, cytotoxic T cells leave secondary lymphatic organs and migrate to seek out and destroy infected cells.

There are many different kinds of T cells, we discuss two here:

1. CD4 cells (naïve). When activated: become helper T cells (TH) and memory TH cells. In addition to having antigen receptors on their membranes, helper T cells have a protein called CD4. This allows them to recognize different types of antigen. The term "CD" stands for "cell differentiation glycoproteins" and is a way of organizing the many different types of cell surface receptors found in a cell. There are nearly 400 different types of CD cells in humans alone. TH cells activate B cells, other T cells, and macrophages, thus helping to direct the adaptive immune response. 2. CD8 cells (naïve). When activated, become cytotoxic T cells (TC) and memory TC cells. In addition to having antigen receptors on their membranes, cytotoxic T cells have a protein called CD8. This allows them to recognize different types of antigen. TC cells destroy cell in the body that harbor anything foreign.

MHCs are located on the plasma membranes of all body cells except for red blood cells. Thousands of MHCs are found on each cell. Their normal function is to help T cells recognize that an antigen is foreign and not part of your body. There are two types:

1. Class I MHC, or MHC-I: these are built into the plasma membranes of all body cells, except red blood cells. Each has a groove that holds an antigen. Class I MHC proteins display endogenous antigens, or intracellular antigens (bits of protein) that have been processed from inside the cell and are now on display on the MHC complex on the cell membrane for a patrolling T cell to inspect. If the cell is healthy, only "self" proteins will be displayed in the MHC on the cell surface. If the cell is infected, the MHC will display foreign protein fragments, which a passing T cell may recognize as foreign. Class I MHC proteins are recognized by naïve CD8 cells and cytotoxic T cells (the former turns into the latter when activated). 2. Class II MHC, or MHC-II: these are on the plasma membranes of antigen-presenting cells (dendritic cells, macrophages, B cells) that present antigen to CD4 cells (inactivated helper T cells). So, APCs (such as dendritic cells) possess both Class I and Class II MHCs. Class II MHC proteins display exogenous antigens, or extracellular antigens, antigens from outside the cell that have been engulfed by the cell that displays them. Class II MHC proteins are recognized by naïve CD4 cells and helper T cells.

Antigen-presenting cells include 1. 2. 3.

1. Dendritic cells (found in the skin). They engulf antigen, destroy them, and present fragments of them, like signal flags on the MHC complex of the dendritic cell surface for T cells to recognize. Once they have engulfed antigen, dendritic cells leave the skin, enter lymphatic vessels, and travel to secondary lymphoid organs to find T cells. 2. Macrophages: engulf antigen, destroy them, and present fragments of them, like signal flags, on the MHC complex of the macrophage cell surface for T cells to recognize. Macrophages can also be activated by T cells. 3. B-lymphocytes: these cells present antigen to a helper T cell, which aids in B cell activation (discussed below).

Once clonal selection begins, lymphocytes differentiate into two classes of cells: 1. A, b, c 2. A, b, c

1. Effector cells: cells that attack the antigen. These cells die once the antigen is eradicated. Effector cells include: a. Plasma cells: part of a B cell clone b. Active helper T cells: part of a helper T cell clone c. Active cytotoxic T cells: part of a cytotoxic T cell clone 2. Memory cells: these cells do not participate in the initial immune response, but if the same antigen returns later in life, memory cells can produce more effector cells (see above) at a faster rate than the initial attack - often before any symptoms even occur. Memory cells have long life spans, they can survive for decades. They include: a. Memory B cells (part of a B cell clone) b. Memory helper T cells (part of a helper T cell clone) c. Memory cytotoxic T cells (part of a cytotoxic T cell clone) The daughter cells in the cases above are all clones - they can recognize the same specific antigen as the original lymphocyte.

Cytotoxic T cells have two methods of attack:

1. Granzymes. Cytotoxic T cells, once bound to infected target cells, release protein-digesting enzymes known as granzymes that trigger apoptosis (cell death), spilling out the microbes inside, which are then killed by phagocytes. 2. Perforin & granulysin. Alternately, cytotoxic T cells release two types of proteins: i) perforin perforates the cell membrane, causing extracellular fluid to rush in and the cell to burst; and ii) granulysin which destroys the microbes directly by creating holes in their plasma membranes.

There are two categories of adaptive defenses:

1. Humoral immunity, or antibody-mediated immunity. Antibodies are made by plasma cells and float freely in the blood and lymph vessels. Plasma cells are activated B lymphocytes. Antibodies bind to extracellular pathogens: marking them for destruction by phagocytes or complement proteins. Historically, antibody-mediated immunity was called humoral immunity because the antibodies bound to antigens in the blood (bodily fluids were historically called the humors). 2. Cellular immunity, or cell-mediated immunity. Lymphocytes known as T cells that directly attack invading antigens. In this type of immunity, cells attack intracellular pathogens, be it viruses, bacteria, or fungi that reside inside cells, some cancer cells, and foreign tissue transplants (tissue rejection).

Complete antigens have two functional properties:

1. Immunogenicity: the provoke an immune response by causing lymphocytes to proliferate (multiply) 2. Reactivity: they react with the activated lymphocytes and the antibodies released

Antibody Targets and Functions

1. Neutralization: the antibody binds to sites on the antigen that the antigen would normally use to attach to other body cells. This prevents the antigen from binding to body cells. 2. Agglutination and precipitation: if two similar antigens are close together, an antibody can bind to one antigenic determinant site on each antigen. In this way, antibodies can link large amounts of antigens together causing them to either agglutinate (clump) together or precipitate out of solution (when the antigen is a soluble molecule). 3. Activating the complement system: when an antibody binds to an antigen, it causes a shape change in part of the antibody, allowing complement molecules to bind to the antibody and help destroy the antigen. 4. Attracting phagocytes: antigens covered with antibodies attract macrophages, which phagocytize pathogens. In addition, having the complement system activated enhances phagocytosis (the macrophages can also bind to the antibodies, making it easier to engulf bacteria), a process called opsonization

The primary response takes time to become fully effective because the following steps must first take place (the example used below involves B cells, but also applies to T cells):

1. The antigen must activate the appropriate B cells. 2. The B cells must differentiate into plasma cells and memory B cells. 3. Plasma cells begin secreting antibodies into the bloodstream: the concentration of circulating antibodies gradually rises. It takes 1-2 weeks to develop peak antibody levels. Immunoglobulin M, or IgM, is the first antibody to appear, followed by the more effective IgG (discussed further, below).

Humans have ______ different kinds of TLRs: one, for example, recognizes a component of gram-negative bacteria such as Salmonella, another recognizes features in cell walls in particular bacteria, such as tuberculosis.

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4. Antimicrobial Proteins: b. Complement system

: these refer to 20 different plasma proteins in blood that, when attached or "fixed" to a foreign cell. The complement proteins then become activated, unleashing inflammatory chemical that amplify all aspects of the inflammatory process (the name "complement" is because these proteins complement, or enhance, the actions of the innate and adaptive defenses). They cause microbes to burst (cytolysis), promote phagocytosis, and aid in inflammation.

2. Costimulation

A second signal is needed to fully activate the T cell, also called costimulation, of which there are many different types. Examples of these are cytokines (small protein hormones that stimulate or inhibit many normal cell functions). Lymphocytes and APCs secrete cytokines, as do many other cells types. Interferons and interleukins are but two examples of cytokines. Interleukins (IL) are secreted by white blood cells: there are many subtypes (IL-1, IL-2, IL-3, etc.), but in general they help stimulate B and T cell proliferation. If a T cell is bound to antigen but does not receive costimulation, it is in a state called anergy.

Recall that both cell types develop in the red bone marrow, but immature T cells migrate to the thymus where they complete their development. __________________________________________

A way to remember this is T cells mature in the thymus, B cells mature in the bone marrow

Second Line of Defense 2. Natural killer (NK) cells

About 5-10% of the patrolling lymphocytes in the blood are NK cells. They can kill cancer and virus-infected body cells before the rest of the immune system is enlisted. They will attack any target they consider foreign by reading the antigens (typically sugars) on the pathogen's plasma membrane.

Immunocompetent B and T cells that have not yet been exposed to antigen are called______________. They travel to secondary lymphoid organs (lymph nodes, spleen, etc.) to encounter antigen. If they encounter antigen that they recognize, the lymphocyte will activate and undergo ____________: it will make _________________________________

naïve clonal selection thousands of copies of itself to fight the invasive cells.

When an infection occurs, _______________ migrate to the infected area.

neutrophils and monocytes

Inflammation b. emigration of phagocytes from the blood to interstitial fluids

neutrophils predominate in the early stages of an infection, but they die off rapidly. Monocytes then enter in, assisting the fixed macrophages that are already present in the tissue to engulf damaged tissue and invading microbes. Eventually, these die off too: the accumulation of dead cells and fluids is called pus.

A B cell is activated when it binds antigen that is recognized by its receptors. The B cell then undergoes clonal selection. The majority ______________of activated B cells become plamsa cells (effector B cells) which will go on to secrete antibodies; a minority of the activated B cells become ____________________: these will mount a humoral response should the same antigen return in the future.

plamsa cells memory B cells

natural killer cells (NK cells)

play an important role in the killing of cancer cells and cells infected by viruses

The term antigen is a ______________________Antigen is foreign to the body and reacts with ____________________

portmanteau of "antibody generator". antibodies (produced by plasma cells).

The initial immune response to an antigen is called the ________________________ If the antigen appears again, whether days or decades later, it triggers a more extensive and prolonged ________________________, due to the large number of memory cells ready to be called into action

primary immune response. secondary immune response