Innate Defense System (nonspecific)

Innate Defense System (nonspecific)

is always prepared, responding within minutes to protect the body from all foreign substances. This system has two “barricades.” The first line of defense is the external body membranes—intact skin and mucosae. The second line of defense, called into action whenever the first line has been penetrated, uses antimicrobial proteins, phagocytes, and other cells to inhibit the invaders’ spread throughout the body. The hallmark of the second line of defense is inflammation.

Adaptive Defense System (specific)

Adaptive Defense System (specific)

is more like an elite fighting force equipped with high-tech weapons that attacks particular foreign substances and provides the body’s third line of defense. This defensive response takes considerably more time to mount than the innate response. Although we consider them separately, the adaptive and innate systems always work hand in hand.

Immune System

Immune System

is a functional system rather than an organ system in an anatomical sense. Its “structures” are a diverse array of molecules plus trillions of immune cells (especially lymphocytes) that inhabit lymphoid tissues and circulate in body fluids.

Phagocytes

Phagocytes

(phago = eat) Engulf and destroy pathogens that breach surface membrane barriers; macrophages also contribute to adaptive immune responses

Pathogen

Pathogen

A bacterium, virus, or other microorganism that can cause disease.

Macrophages

Macrophages

(“big eaters”) The chief phagocytes which derive from white blood cells called monocytes that leave the bloodstream enter the tissues.

Neutrophils

Neutrophils

the most abundant type of white blood cell, become phagocytic on encountering infectious material in the tissues.

Phagocytosis

Phagocytosis

The ingestion of bacteria or other material by phagocytes and ameboid protozoans.

Phagosome

Phagosome

A vacuole in the cytoplasm of a cell, containing a phagocytosed particle enclosed within a part of the cell membrane.

Phagolysosome

Phagolysosome

A cellular body that is formed by the union of a phagosome or ingested particle with a lysosome that contains hydrolytic enzymes

Adherence

Adherence

phagocyte must adhere or cling to the pathogen

Opsonization

Opsonization

complement proteins or antibodies coat foreign particles

Natural killer (NK) cells

Natural killer (NK) cells

“police” the body in blood and lymph, are a unique group of defensive cells that can lyse and kill cancer cells and virus-infected body cells before the adaptive immune system is activated. Non-specific - they can eliminate a variety of infected or cancerous cells by detecting the lack of “self” cell-surface receptors and by recognizing certain surface sugars on the target cell.

Inflammatory Response

Inflammatory Response

triggered whenever body tissues are injured by physical trauma (a blow), intense heat, irritating chemicals, or infection by viruses, fungi, or bacteria.

The inflammatory response has several beneficial effects:
1. Prevents the spread of damaging agents to nearby tissues
2. Disposes of cell debris and pathogens
3. Sets the stage for repair

Toll-Like Receptors (TLRs)

Toll-Like Receptors (TLRs)

surface membrane receptors that play a central role in triggering immune responses.

Mast cells

Mast cells

a key component of the inflammatory response, release the potent inflammatory chemical histamine

Histamine

Histamine

Granules of mast cells and basophils. Released in response to mechanical injury, presence of certain microorganisms, and chemicals released by neutrophils. Promotes vasodilation of local arterioles. Increases permeability of local capillaries, promoting exudate formation.

Kinins

Kinins

A plasma protein, kininogen, is cleaved by the enzyme kallikrein found in plasma, urine, saliva, and in lysosomes of neutrophils and other types of cells. Cleavage releases active kinin peptides. Promotes vasodilation of local arterioles. Increases permeability of local capillaries, promoting exudate formation. Also induce chemotaxis of leukocytes and prompt neutrophils to release lysosomal enzymes, thereby enhancing generation of more kinins. Induce pain.

Prostaglandins

Prostaglandins

Fatty acid molecules produced from arachidonic acid found in all cell membranes; generated by enzymes of neutrophils, basophils, mast cells, and others. Promotes vasodilation of local arterioles. Increases permeability of local capillaries, promoting exudate formation. Also induce neutrophil chemotaxis. Induce pain.

Platelet

Platelet

derived growth factor (PDGF) - Secreted by platelets and endothelial cells. Stimulates fibroblast activity and repair of damaged tissues.

hyperemia

hyperemia

congestion with blood, accounting for the redness and heat of an inflamed region.

Intact skin epidermis

Intact skin epidermis

Forms mechanical barrier that prevents entry of pathogens and other harmful substances into body

Acid mantle Skin secretions

Acid mantle Skin secretions

(sweat and sebum) make epidermal surface acidic, which inhibits bacterial growth; also contain various bactericidal chemicals

Keratin

Keratin

Provides resistance against acids, alkalis, and bacterial enzymes

Intact Mucous Membranes

Intact Mucous Membranes

Form mechanical barrier that prevents entry of pathogens

Mucus Traps

Mucus Traps

microorganisms in respiratory and digestive tracts

Nasal Hairs

Nasal Hairs

Filter and trap microorganisms in nasal passages

Cilia

Cilia

Propel debris-laden mucus away from nasal cavity and lower respiratory passages

Gastric Juice

Gastric Juice

Contains concentrated hydrochloric acid and protein-digesting enzymes that destroy pathogens in stomach

Acid Mantle of Vagina

Acid Mantle of Vagina

Inhibits growth of most bacteria and fungi in female reproductive tract

Lacrimal Secretion (tears), saliva

Lacrimal Secretion (tears), saliva

Continuously lubricate and cleanse eyes (tears) and oral cavity (saliva); contain lysozyme, an enzyme that destroys microorganisms

Urine

Urine

Normally acid pH inhibits bacterial growth; cleanses the lower urinary tract as it flushes from the body

Interferons

Interferons

Proteins released by virus-infected cells and certain lymphocytes that protect uninfected tissue cells from viral takeover; mobilize immune system

Complement

Complement

complement system, or simply complement, refers to a group of at least 20 plasma proteins that normally circulate in the blood in an inactive state. Lyses microorganisms, enhances phagocytosis by opsonization, and intensifies inflammatory and immune responses

Leukocytosis

Leukocytosis

an increase in WBCs that is a characteristic of inflammation.

Fever

Margination

Systemic response initiated by pyrogens; high body temperature inhibits microbial multiplication and enhances body repair processes

Margination

clinging of phagocytes to the inner walls of the capillaries and postcapillary venules

Diapedesis

Diapedesis

the outward passage of blood cells through intact vessel walls

Chemotaxis

Chemotaxis

The characteristic movement or orientation of an organism or cell along a chemical concentration gradient either toward or away from the chemical stimulus

Antimicrobial Proteins

Antimicrobial Proteins

enhance the innate defenses by attacking microorganisms directly or by hindering their ability to reproduce.

Viruses

Viruses

essentially nucleic acids surrounded by a protein coat—lack the cellular machinery to generate ATP or synthesize proteins. They do their “dirty work,” or damage, in the body by invading tissue cells and taking over the cellular metabolic machinery needed to reproduce themselves.

Interferons (IFNs)

Interferons (IFNs)

help protect cells that have not yet been infected. The IFNs diffuse to nearby cells, where they stimulate synthesis of proteins which then “interfere” with viral replication in the still-healthy cells by blocking protein synthesis and degrading viral RNA

Complement Classical Pathway

Complement Classical Pathway

involves antibodies, watersoluble protein molecules that the adaptive immune system produces to fight off foreign invaders.

Complement Alternative Pathway

Complement Alternative Pathway

is triggered when spontaneously activated C3 and factors B, D, and P interact on the surface of certain microorganisms.

MAC (membrane attack complex)

MAC (membrane attack complex)

forms and stabilizes a hole in the membrane that ensures lysis of the target cell by inducing a massive influx of water.

Pyrogen

Pyrogen

a fever-producing chemical

Antigens

Antigens

substances that can mobilize the adaptive defenses and provoke an immune response. They are the ultimate targets of all adaptive immune responses.

Humoral immunity

Humoral immunity

also called antibodymediated immunity, is provided by antibodies present in the body’s “humors,” or fluids. Though they are produced by lymphocytes (or their offspring), antibodies circulate freely in the blood and lymph, where they bind primarily to bacteria, to bacterial toxins, and to free viruses, inactivating them temporarily and marking them for destruction by phagocytes or complement.

Cellular Immunity

Cellular Immunity

cell-mediated immunity. When lymphocytes themselves rather than antibodies defend the body. The protective factor is living cells. Cellular immunity also has cellular targets—virus-infected or parasiteinfected tissue cells, cancer cells, and cells of foreign grafts. The lymphocytes act against such targets either directly, by killing the foreign cells, or indirectly, by releasing chemical mediators that enhance the inflammatory response or activate other lymphocytes or macrophages.

Hapten

Hapten

incomplete antigen; a specific nonprotein substance which does not itself elicit antibody formation but does elicit the immune response when coupled with a carrier protein

Immunogenicity

Immunogenicity

the property enabling a substance to provoke an immune response, or the degree to which a substance possesses this property

Self-Antigens

Self-Antigens

are not foreign or antigenic to you, but they are strongly antigenic to other individuals.

MHC proteins

MHC proteins

proteins that mark a cell as self is a group of glycoproteins

Major Histocompatibility Complex (MHC)

Major Histocompatibility Complex (MHC)

genes that code for MHC proteins

B lymphocytes

B lymphocytes

B cells oversee humoral immunity.

T lymphocytes

T lymphocytes

T cells are non-antibody-producing lymphocytes that constitute the cell-mediated arm of adaptive immunity.

Immunocompetence

Immunocompetence

The ability of a lymphocyte to recognize its one specific antigen by binding to it.

Self-tolerance

Self-tolerance

lymphocyte is relatively unresponsive to self-antigens so that it does not attack the body’s own cells.

Primary Lymphoid Organs

Primary Lymphoid Organs

The lymphoid organs where the lymphocytes become immunocompetent—thymus and bone marrow

Naïve

Naïve

Immunocompetent B and T cells that have not yet been exposed to antigens

Positive Selection

Positive Selection

identifies T cells whose receptors are capable of recognizing (binding) self-MHC molecules

Negative Selection

Negative Selection

T cells that make it through positive selection are then tested to make sure that they do not recognize (bind tightly) self-antigens displayed on self-MHC. If they do, they are eliminated by apoptosis

Somatic Recombination

Somatic Recombination

gene segments are shuffled and combined in different ways to produce functional antibody genes

Antigen

Antigen

Presenting Cells (APCs) - major role in immunity is to engulf antigens and then present fragments of them, like signal flags, on their own surfaces where they can be recognized by T cells.

Antigen Challenge

Antigen Challenge

the first encounter between an immunocompetent but naive lymphocyte and an invading antigen

Clonal Selection

Clonal Selection

B cell grow and then multiply rapidly to form an army of cells all exactly like itself and bearing the same antigen-specific receptors

Hormonal Immunity

Hormonal Immunity

The component of the immune system involving antibodies that are secreted by B cells and circulate as soluble proteins in blood plasma and lymph.

Plasma Cells

Plasma Cells

the antibody-secreting effector cells of the humoral response.

Memory Cells

Memory Cells

Clone cells that do not become plasma cells They are longlived and can mount an almost immediate humoral response if they encounter the same antigen again at some future time

Primary Immune Response

Primary Immune Response

occurs on first exposure to a particular antigen, has a lag period of 3 to 6 days after the antigen challenge.

Secondary Immune Response

Secondary Immune Response

If (and when) someone is reexposed to the same antigen, whether it’s the second or the twenty-second time. These responses are faster, more prolonged, and more effective, because the immune system has already been primed to the antigen, and sensitized memory cells are already in place “on alert.”

Immunological Memory

Immunological Memory

Memory cells that have been primed to the antigen, and cells are already in place “on alert.

Active Humoral Immunity

Active Humoral Immunity

When your B cells encounter antigens and produce antibodies against them

Active Humoral Immunity Naturally Acquired

Active Humoral Immunity Naturally Acquired

when you get a bacterial or viral infection, during which time you may develop symptoms of the disease and suffer a little (or a lot).

Active Humoral Immunity Artificially Acquired

Active Humoral Immunity Artificially Acquired

when you receive vaccines.

Passive humoral immunity

Passive humoral immunity

The antibodies are harvested from the serum of an immune human or animal donor. As a result, your B cells are not challenged by antigens, immunological memory does not occur, and the protection provided by the “borrowed” antibodies ends when they naturally degrade in the body. Differs from active immunity, both in the antibody source and in the degree of protection it provides. Instead of being made by your plasma cells

Antibodies

Antibodies

also called immunoglobulins constitute the gamma globulin part of blood proteins. antibodies are proteins secreted in response to an antigen by effector B cells called plasma cells, and they are capable of binding specifically with that antigen

Antibody Monomer

Antibody Monomer

four looping polypeptide chains linked together by disulfide (sulfur-to-sulfur) bonds to form an antibody molecule

Heavy (H) Chains

Heavy (H) Chains

two chains of an antibody that are identical to each other and contain more than 400 amino acids each.

Light (L) Chains

Light (L) Chains

two chains of an antibody that are identical to each other, but they are only about half as long as each H chain.

Antigen

Binding Site In each arm of the monomer, the V regions of the heavy and light chains combine shaped to “fit” a specific antigenic determinant.

C-Region

C-Region

These are the effector regions of the antibody that dictate

1. the cells and chemicals of the body the antibody can bind to
2. how the antibody class functions in antigen elimination.

Monoclonal Antibodies

Monoclonal Antibodies

used in research, clinical testing, and treatment.

Hybridomas

Hybridomas

fused tumor cells and B lymphocytes

Neutralization

Neutralization

the simplest defensive mechanism, occurs when antibodies block specific sites on viruses or bacterial exotoxins (toxic chemicals secreted by bacteria). As a result, the virus or exotoxin loses its toxic effect because it cannot bind to receptors on tissue cells to cause injury. The antigen-antibody complexes are eventually destroyed by phagocytes.

Agglutination

Agglutination

cell-bound antigens are cross-linked, the process causes clumping,

Precipitation

Precipitation

soluble molecules (instead of cells) are cross-linked into large complexes that settle out of solution.

Complement fixation and activation

Complement fixation and activation

is the chief antibody defense used against cellular antigens, such as bacteria or mismatched red blood cells. When several antibodies bind close together on the same cell, the complement-binding sites on their stem regions align.

Antibodies PLAN of Action

Antibodies PLAN of Action

precipitation, lysis (by complement), agglutination, and neutralization.

Class I MHC proteins

Class I MHC proteins

are displayed by virtually all body cells except red blood cells and are recognized by cytotoxic (CD8) T cell

Class II MHC proteins

Class II MHC proteins

typically found only on the surfaces of cells that present antigens to CD4 cells: dendritic cells, macrophages, and B cells.

Cytokines

Cytokines

a general term for mediators that influence cell development, differentiation, and responses in the immune system.

Endogenous Antigen

Endogenous Antigen

a bit of a cellular (self) protein or a peptide derived from a foreign protein synthesized in a body cell.

CD4+ T cells

CD4+ T cells

T helper cell (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. They express the CD4 protein on their surface.

CD8+ T cells

CD8+ T cells

Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. They express the CD8 glycoprotein at their surface.

Memory T cells

Memory T cells

are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells).

Regulatory T cells

Regulatory T cells

(Treg cells) are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.

Natural killer T cells

Natural killer T cells

(NKT cells) bridge the adaptive immune system with the innate immune system.

Autografts

Autografts

tissue grafts transplanted from one body site to another in the same person.

Isografts

Isografts

grafts donated to a patient by a genetically identical individual, the only example being identical twins.

Allografts

Allografts

grafts transplanted from individuals that are not genetically identical but belong to the same species.

Xenografts

Xenografts

grafts taken from another animal species, such as transplanting a baboon heart into a human being.

Immunodeficiency

Immunodeficiency

Any congenital or acquired condition that causes immune cells, phagocytes, or complement to behave abnormally

Hodgkin’s disease

Hodgkin’s disease

a cancer of the B cells, can lead to immunodeficiency by depressing lymph node cells.

Acquired Immune Deficiency Syndrome (AIDS)

Acquired Immune Deficiency Syndrome (AIDS)

which cripples the immune system by interfering with the activity of helper T cells.Cripples the immune system by destroying helper T cells

• Characterized by severe weight loss, night sweats, and swollen lymph nodes
• Opportunistic infections occur, including pneumocystis pneumonia and Kaposi’s sarcoma
• Caused by human immunodeficiency virus (HIV) transmitted via body fluids—blood, semen, and vaginal secretions
• Treatment with antiviral drugs
• Incurable, and massive infection or cancer kills the sufferer

HIV (human immunodeficiency virus)

HIV (human immunodeficiency virus)

destroys TH cells, depressing cell-mediated immunity. Although B cells and TC cells initially mount a vigorous response to viral exposure, in time a profound deficit of B cell and cytotoxic T cell function develops. The whole immune system is turned topsy-turvy.

Autoimmune Diseases

Autoimmune Diseases

Occasionally the immune system loses its ability to distinguish friend (self) from foe (foreign antigens). When this happens, the artillery of the immune system, like friendly fire, turns against itself. The body produces antibodies (autoantibodies) and cytotoxic T cells that destroy its own tissues.

Multiple sclerosis

Multiple sclerosis

which destroys the myelin of the white matter of the brain and spinal cord (see p. 405)

Myasthenia gravis

Myasthenia gravis

which impairs communication between nerves and skeletal muscles (see p. 285)

Graves’ disease

Graves’ disease

which prompts the thyroid gland to produce excessive amounts of thyroxine (see p. 611)

Type 1 (insulindependent) diabetes mellitus

Type 1 (insulindependent) diabetes mellitus

which destroys pancreatic beta cells, resulting in a deficit of insulin and inability to use carbohydrates

Systemic lupus

Systemic lupus

erythematosus (SLE), a systemic disease that particularly affects the kidneys, heart, lungs, and skin

Glomerulonephritis

Glomerulonephritis

a severe impairment of renal function

Rheumatoid arthritis

Rheumatoid arthritis

which systematically destroys joints

Hypersensitivities

Hypersensitivities

allergies, Immune responses to a perceived (otherwise harmless) threat (usually involves haptens)

Allergen

Allergen

is an antigen that causes an allergic reaction.

Anaphylactic Shock

Anaphylactic Shock

typically occurs when the allergen directly enters the blood and circulates rapidly through the body, as might happen with certain bee stings or spider bites. It may also follow injection of a foreign substance (such as penicillin or other drugs which act as haptens). Essentially the same as that of local responses, but when mast cells and basophils are enlisted throughout the entire body, the outcome is life threatening.

Subacute Hypersensitivities

Subacute Hypersensitivities

caused by antibodies (IgG and IgM rather than IgE) and can be transferred via blood plasma or serum. However, their onset is slower (1–3 hours after antigen exposure) and the duration of the reaction is longer (10–15 hours).

Cytotoxic (type II) Reactions

Cytotoxic (type II) Reactions

occur when antibodies bind to antigens on specific body cells and subsequently stimulate phagocytosis and complement-mediated lysis of the cellular antigens.

Immune

Immune

Complex (type III) Hypersensitivity - results when antigens are widely distributed through the body or blood and the insoluble antigen-antibody complexes formed cannot be cleared from a particular area.

Delayed Hypersensitivity (type IV) Reactions

Delayed Hypersensitivity (type IV) Reactions

are slower to appear (1–3 days) than antibody-mediated hypersensitivity reactions. The mechanism is basically that of a cell-mediated immune response, which depends on helper T cells. Inflammation and tissue damage comes about through the action of cytokineactivated macrophages, and sometimes cytotoxic T cells.

Allergic Contact Dermatitis

Allergic Contact Dermatitis

which follow skin contact with poison ivy, some metals (nickel in jewelry), and certain cosmetic and deodorant chemicals. These agents act as haptens, and after diffusing through the skin and attaching to self-proteins, they are perceived as foreign by the immune system.