Chapter 21: The Immune System: Innate and Adaptive Body Defenses

natural killer (NK) cells

"police" the body in blood and lymph, are a unique group of defensive cells that can kill cancer cells and virus-infected body cells before the adaptive immune system in activated - part of a small group of large granular lymphocytes

Where do these protein fragments come from?

- All antigens displayed on class I MHC proteins are endogenous antigens - endogenous antigens: fragments of protein synthesized inside the cell --> in a healthy cell these are all self-antigens, generally bits of digested cellular proteins --> in an infected cell, these may also include fragments of foreign antigens that are synthesized within the infected cell but "belong to" the pathogen

Activation of CD8 cells

- CD8 cells require help from Th cells to activate into destructive cytotoxic T cells - Th cells cause dendritic cells to express on their surfaces the co-stimulatory molecules required to activate CD8 cells

how do IFNs work?

- IFNs diffuse to nearby cells, which they stimulate to synthesize proteins that block further protein synthesis and degrade viral RNA - in this way they interfere with viral replication - IFN protection is NOT virus specific

NK cells use similar mechanisms to kill their target cells. What is the similarity and difference?

- Nk cells do not look for foreign antigen displayed on class I MHC proteins - search for signs of abnormality, including LACK of class I MHC or the presence of antibodies coating the target cell - stressed cells also often express different surface markers - NK cell stalk abnormal or foreign cells in the body that Tc can't "see"

antigen binding

- T cell antigen receptors (TCRs) bind to an antigen-MHC complex on the surface of an APC - TCRs must perform double recognition: they must recognize both MHC (self-antigen) and the foreign antigen it displays

amplification of innate defenses

- Th cells also amplify the responses of the innate immune system - cytokines released by Th cells not only mobilize lymphocytes and macrophages but also attract other types of white blood cells into that area

Toll-like receptors (TLRs)

- a central in triggering immune responses - 22 types of human TLRs, each recognizing a particular class of attacking microbe - allow the cells to recognize invaders and sound a chemical "alarm" that initiates inflammation

what is the most devastating of the acquired immunodeficiencies?

- acquired immune deficiency syndrome (AIDS) - cripples the immune system by interfering with the activity of helper T cells

cytotoxic T (Tc) cells

- activated CD8 cells - T cells that can directly attack and kill other cells - roam the body, circulating in and out of the blood and lymph and through lymphoid organs in search of body cells displaying antigens that the Tc cells recognize - main targets are virus-infected cells, but can attack tissue cells infected by certain bacteria or parasites, cancer cells, and foreign cells

CD8 cells (cytotoxic T cells)

- activated by antigen fragments on class I MHC proteins, also found on the surface of APCs - once activated, cytotoxic T cells look for this same antigen presented on class I MHC proteins located on any cell in the body

approaches still being developed include reestablishing self-tolerance by:

- activating regulatory T cells - inducing self-tolerance using vaccines - destroying self-reactive immune cells by directing antibodies against them

Class II MHC proteins

- are typically found only on the surfaces of cells that present antigens to CD4 cells: dendritic cells, macrophages, and B cells - synthesized in the ER and bind to peptide fragments (longer peptides) and come from exogenous antigens - exogenous antigens: come from outside the cell that have been engulfed by the cell that displays them

why is HIV DNA highly mutated?

- because the reverse transcriptase enzyme is very inaccurate and produces errors frequently

CD4 cells (helper T cells) are restricted to...

- binding antigens only on class II MHC proteins, which are typically displayed on antigen-presenting cell (APC) surfaces

mechanism for anaphylactic shock

- bronchioles constrict (tongue may swell) - makes it difficult to breathe - sudden vasodilation and fluid loss from the bloodstream may cause circulatory collapse (hypotensive shock) - dead within minutes - treatment: epinephrine

how are engulfed exogenous antigens broken down?

- by proteases inside a phagolysosome - vesicles from the ER containing class II MHC proteins fuse with the phagolysosome, and the antigen fragments bind to the groove of the MHC proteins - vesicle is then exported to the cell surface, where the class II MHC protein displays its prize for CD4 cells to recognize

Delayed type IV hypersensitivity reaction

- caused by T cells and take longer to appear (1-3 days) - inflammation and tissue damage result from the action of cytokine-activated macrophages, and sometimes cytotoxic T cells

subacute hypersensitivities

- caused by antibodies (IgG and IgM) - slower onset (1-3 hours after antigen exposure) - reaction lasts longer (10-15 hours)

basic antibody structure

- consists of 4 looping polypeptide chains linked together by disulfide bonds - 4 chains combined form a antibody monomer with 2 identical halves - The molecule is T or Y shaped

how do APCs obtain endogenous antigens from another cell and display them on class I MHCs to activate CD8 cells?

- dendritic cells have the special ability to do this - they obtain other cells' endogenous antigens either by engulfing dying virus-infected or tumor cells, or by importing antigens through temporary gap junctions with infected cells - dendritic cells then display these antigens on BOTH class I and II MHCs

macrophages

- derived from monocytes that leave the bloodstream, enter the tissues, and develop into macrophages

variable (V) region and constant (C) region

- each chain forming an antibody has this region at one end and a constant (C) region at the other - antibodies responding to different antigens have very different V regions, but their C regions are the same in all antibodies of a given class

negative selection of the thymus

- ensures that T cells do not recognize self-antigens displayed on self-MHC - if they do they are eliminated by apoptosis - this is the basis for immunological self-tolerance, making sure that T cells don't attack the body's own cells, which would cause autoimmune disorders - clonal deletion

IgM (pentamer)

- first immunoglobulin class secreted by plasma cells during the primary response - readily activates complement - exists in monomer and pentamer forms - monomer serves as an antigen receptor on B cell surfaces - pentamer circulates in blood plasma - numerous antigen-binding sites make it a potent agglutinating agent

allergic contact dermatitis (ACD)

- follow skin contact with poison ivy, some metals (nickel in jewelry), and certain cosmetic and deodorant chemicals - agents diffuse through the skin and attach to self-proteins as haptens

like the boss of an assembly line, the Th cell signals...

- for antibody formation to begin. - helper T cells interact directly with B cells displaying antigen fragments bound to class II MHC receptors - whenever a Th cell binds to a B cell, the Th cell releases cytokines that prod the B cells into dividing more rapidly

dendritic cells

- found at the body's frontiers where they act as mobile sentinels - once they have internalized antigens by phagocytosis, they enter nearby lymphatics to get to a lymph node where they will present the antigens to the T cells

IgD (monomer)

- found on the B cell surface - functions as a B cell antigen receptor

Class I MHC proteins

- found on the surface of virtually all body cells except red blood cells - each class I MHC protein has a groove that holds an antigen - protein fragment-

what are the most devastating congenital immunodeficiencies?

- group of related disorders called severe combined immunodeficiency syndromes (SCID)

how does hyperemia help an injured site?

- hyperemia brings more cells and chemicals of the immune system to the injured area - it accounts for two of the cardinal signs of inflammation: redness and heat of inflamed region

foreign antigens resemble self-antigens

- if the determinants of a foreign antigen resemble those on a self-antigen, antibodies made against the foreign antigen can cross-react with the self-antigen

treatment of autoimmune disease

- immunosuppressive drugs - such as anti-inflammatory drugs (corticosteroids)

Some activated T cells directly kill body cells that are:

- infected by viruses or bacteria - cancerous or abnormal - foreign cells (transplanted)

Innate and adaptive defenses are deeply intertwined, specifically:

- innate and adaptive systems release and recognize (bind to) many of the same defense molecules - innate responses are not as nonspecific as once thought. Indeed, they have specific pathways to target certain foreign substances - proteins released during innate responses alert cells of the adaptive system to the presence of specific foreign molecules in the body

immunodeficiency

- is a cogential or acquired condition that impairs the production or function of immune cells or certain molecules, such as complement or antibodies

positive selection in the thymus

- it ensures that only T cells with receptors that are able to recognize self-MHC proteins survive - T cells that are unable to recognize self-MHC are eliminated by apoptosis

AIDS is caused by what?

- it is caused by HIV (human immunodeficiency virus) - a virus transmitted in body secretions - especially blood, semen, and vaginal secretions

inflammation has several beneficial effects:

- it prevents the spread of damaging agents to nearby tissues - it disposes of cell debris and pathogens - it alerts the adaptive immune system - it sets the stage for repair

respiratory burst promotes killing of pathogens by:

- liberating a deluge of highly destructive free radicals - producing oxidizing chemicals (hydrogen peroxide and a substance identical to household bleach) - increasing the phagolysosome's pH and osmolarity, which activates other protein-digesting enzymes that digest the invader

Th17 cells

- link together adaptive and innate immunity by releasing IL-17, which promotes inflammatory responses against extracellular microbes and may underlie most autoimmune diseases

macrophages (APCs)

- macrophages often present antigens to T cells for other reasons - to maintain T cell activation or to be activated themselves - certain effector T cells release chemicals that prod macrophages to become activated macrophages - true "killers" - insatiable phagocytes that can trigger powerful inflammatory responses and recruit additional defenses

Th2 cells

- mainly defend against parasitic worms - they mobilize eosinophils and activate immune responses that depend on B cells and antibody formation - they are also cells that promote allergies

how do lymphocytes fail self-tolerance?

- maturing lymphocytes undergo extensive education that weeds out self-reactive cells - it is thorough, but not super thorough so some lymphocytes that identify pathogens that are self, but look like pathogens can exist - if they are activated, this could cause problems

IgG (monomer)

- most abundant antibody in plasma, accounting for 75-85% of circulating antibodies - main antibody of both secondary and late primary responses - readily activates complement - protects against bacteria, viruses, and toxins circulating in blood and lymph - crosses placenta and confers passive immunity from mother to fetus

T cell-dependent antigens

- most antigens are T cell-dependent antigens that require T cell help to activate the B cells to which they bind

severe combined immunodeficiency syndrome (SCID)

- most devastating congenital immunodeficiencies - group of disorders, which result from various genetic defects that produce a marked deficit of B and T cells

cytotoxic (type II) reactions

- occur when antibodies bind to antigens on specific body cells and stimulate phagocytosis and complement-mediated lysis of the cellular antigens - may occur after a patient has received a transfusion of mismatched blood and complement lyses the foreign red blood cells

primary immune response

- occurs on first exposure to a particular antigen. The primary response typically has a lag period of 3 to 6 days after the antigen encounter - lag time corresponds to B cells specific for that antigen to proliferate and for their offspring to differentiate into plasma cells - after mobilization period, plasma antibody levels rise, reach peak levels in 10 days, and decline

Co-stimulation

- once antigen binding has occurred, the T cell is stimulated but still "idling" - an "idling" T cell can be activated and proliferate to form a clone, it must also bind one or more co-stimulatory signals - these signals are yet other molecules that appear on the surfaces of APCs in tissues that are damaged or invaded by pathogens

helper T (Th) cells

- play a central role in adaptive immunity, mobilizing both its humoral and cellular arms - activates macrophages - once activated by APC presentation of antigen, Th cells help activate B and T cells, and induce B and T cells to proliferate - without the help of "director" Th cells, there is no adaptive immune response

how do these endogenous antigens end up attached to class I MHCs on the outside of our cell?

- proteases degrade cytoplasmic proteins as part of their natural recycling, a random sample of the resulting protein fragments is transported into the ER. these peptides bind to newly synthesized class I MHC proteins and transport vesicles export the loaded class I MHC proteins to the cell surface

IgA (dimer)

- referred to as a secretory IgA, is found in body secretions such as saliva, sweat, intestinal juice, and milk - secretory IgA helps stop pathogens from attaching to epithelial cell surfaces - monomer exists in limited amounts in plasma

immune-complex (type III) hypersensitivities

- result when antigens are widely distributed through the body or blood and the huge number of insoluble antigen-antibody complexes formed cannot be cleared from a particular area - intense inflammatory reaction occurs, complete with complement-mediated cell lysis and cell killing by neutrophils that severely damages local tissues

hypersensitivities

- result when the immune system damages tissue as it fights off a perceived threat that would otherwise be harmless to the body (pollen or animal dander)

What are examples of some important autoimmune diseases?

- rheumatoid arthritis (joints) - myasthenia gravis (impairs nerve and skeletal muscle communication) - multiple sclerosis (destroys myelin of white matter in the brain and spinal cord)

new self-antigens appear

- self-proteins not previously exposed to the immune system may appear in the circulation - they may be generated by (1) gene mutations that cause new proteins to appear at the external cell surface (2) changes in the structure of self-antigens as a result of happen attachment or infectious damage (3) novel self-antigens, normally hidden behind barriers that are released by trauma

interferons (IFNs)

- small proteins - proteins released from virus-infected (and other) cells that protect uninfected cells from viral takeover. also inhibit some cancers

precipitation

- soluble molecules are cross-linked into large complexes that settle out of solution - precipitated antigen molecules are much easier for phagocytes to capture and engulf than are freely moving antigens

T cell-independent antigens

- some B cells may be activated solely by binding to certain antigens - T cell-independent antigen responses tend to be weak and short-lived

IgE (monomer)

- stem end binds to mast cells or basophils. Antigen binding to its receptor end triggers these cells to release histamine and other chemicals that mediate inflammation and an allergic reaction - secreted by plasma cells in skin, mucosae of the gastrointestinal and respiratory tracts, and tonsils - only traces of IgE are found in plasma - levels rise during severe allergic attacks or chronic parasitic infections of the gastrointestinal tract

anaphylactic shock

- systemic response - occurs when the allergen directly enters the blood and circulates rapidly through the body

why are Treg cells important?

- they are important in preventing autoimmune reactions because they suppress self-reactive lymphocytes in the periphery - that is, outside the lymphoid organs

How do NK cells kill?

- they are not phagocytic - they kill by directly contacting the target cell, inducing it to undergo apoptosis (programmed cell death) - also secrete potent chemicals that enhance the inflammatory response

how do cytotoxic T cells begin to kill?

- they must "dock" on the target cell by binding to a self non self complex

what are the 5 major immunoglobulin classes?

IgM, IgA, IgD, IgG, IgE on the basis of the C regions in their heavy chains

the adaptive immune system involves 3 crucial types of cells:

two distinct populations of lymphocytes, plus antigen-presenting cells (APCs) B and T lymphocytes and APCs

In clonal selection, "who" does the selecting? What is being selected?

In clonal selection, the antigen does the selecting. What is being selected is a particular clone of B or T cells that has antigen receptors corresponding to that antigen.

what happens if a T cell binds to antigen without receiving the co-stimulatory signal?

In this case, the T cell becomes tolerant to that antigen and is unable to respond - anergy

CD4 cells

usually become helper T (Th) cells that help activate B cells, other T cells, and macrophages, and direct the adaptive immune response

immune surveillance

NK and Tc lymphocytes roam the body, adhering to and crawling over the surfaces of other cells, examining them for markers they might not recognize

free macrophages

wander throughout the tissue space in search of cellular debris or "foreign invaders"

What is opsonization and how does it help phagocytes? Give an example of a molecule that acts as an opsonin.

Opsonization is the process of making pathogens more susceptible to phagocytosis by decorating their surface with molecules that phagocytes can bind. Antibodies and complement proteins are examples of molecules that act as opsonins.

Under what circumstances might NK cells kill our own cells?

Our own cells are killed by NK cells when they have been infected by viruses or when they have become cancerous.

a quick and dirty way to remember how antibodies work is to remember they have a PLAN of action...

P - precipitation L - lysis (by complement) A - agglutination N - neutralization

agglutination

when cell-bound antigens are cross-linked, the process causes clumping of the foreign cells

cellular or cell-mediated immunity is when...

when lymphocytes rather than antibodies defend the body, the immunity is called cellular because living cells provide the protection

active humoral immunity

when your B cells encounter antigens and produce antibodies against them - acquired in 2 ways: 1. naturally acquired 2. artificially acquired

What marks a cell as "self" as opposed to "nonself"?

Self-antigens, particularly MHC proteins, mark a cell as self.

how does the inflammatory response begin?

with a chemical "alarm" - a flood of inflammatory chemicals released into the extracellular fluid - inflammatory chemicals are released by injured or stressed tissue cells and immune cells

anergy

State of unresponsiveness to antigenic stimulation.

What is the first line of defense against disease?

Surface barriers (the skin and mucous membranes) constitute the first line of defense.

once cytotoxic T cells recognize their targets, how do they deliver a lethal hit?

TWO major mechanisms 1. involves performs and grazymes 2. involves binding to a specific membrane receptor on the target cell that stimulates the target cell to undergo apoptosis

Which of the following T cells would survive education in the thymus? (a) one that recognizes neither MHC nor self-antigen, (b) one that recognizes both MHC and selfantigen, (c) one that recognizes MHC but not self-antigen, (d) one that recognizes self-antigen but not MHC.

The T cell that would survive is (c), one that recognizes MHC but not self-antigen.

What distinguishes the innate defense system from the adaptive defense system?

The innate defense system is always ready to respond immediately, whereas it takes considerable time to mount the adaptive defense system. The innate defenses consist of surface barriers and internal defenses, whereas the adaptive defenses consist of humoral and cellular immunity, which rely on B and T lymphocytes.

Why is the secondary response to an antigen so much faster than the primary response?

The secondary response to an antigen is faster than the primary response because the immune system has already been "primed" and has memory cells that are specific for that particular antigen.

How do vaccines protect against common childhood illnesses such as chicken pox, measles, and mumps?

Vaccinations protect by providing the initial encounter to an antigen—the primary response to that antigen. As a result, when the pathogen for that illness is encountered again, the pathogen elicits the much faster, more powerful secondary response, which is generally effective enough to prevent clinical illness.

if pathogens provoked the inflammation...

a group of plasma proteins known as complement is activated to form potent inflammatory chemicals

fever

abnormally high body temperature, is a systemic response to invading microorganisms

what protective chemicals does the skin and mucous membranes produce?

acid, enzymes, mucin, defensins, other chemicals such as sebum and dermcidin

pyrogens

act on the body's thermostat - a cluster of neurons in the hypothalamus - raising the body's temperature above normal

immediate hypersensitivities (acute or type I hypersensitivities)

allergies - an allergen is an antigen that causes an allergic reaction - allergic reactions begin within seconds after contact with the allergen and last about half an hour

hapten or incomplete antigen

an incomplete antigen; has reactivity but not immunogenicity

exudate seeps from blood into the tissue spaces which causes?

an influx of protein-rich fluids into the tissues spaces that sweeps foreign material into the lymphatic vessels so that it can be processed in the lymph nodes - it also delivers important proteins such as complement and clotting factors to interstitial fluid

antibodies (immunoglobulins (Igs)

antibodies are proteins secreted in response to an antigen by effector B cells called plasma cells, and the antibodies bind specifically with that antigen.

what do lymphocytes produce?

antibodies that circulate freely in the blood and lymph

what two-step process occurs where T cells are activated by APCs?

antigen binding and co-stimulation - both occur on the surface of the same APC, and both steps are required for clonal selection

opsonization

any pathogen can be coated with opsonins, a process called this, it greatly accelerated phagocytosis of that pathogen

light (L) chains (2 of them) - pink

are also identical to each other, but they are only about half as long as each H chain

Opsonins

are complement proteins or antibodies - both provide "handles" to which phagocyte receptors can bind

heavy (H) chains (2 of the chains)

are identical to each other - has a flexible hinge region at their approximate middles - loops are created by disulfide bonds that cause the intervening parts of the polypeptide chains to loop out

T lymphocytes (T cells)

are non-antibody-producing lymphocytes that constitute the cellular arm of adaptive immunity

self-antigens

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

monoclonal antibodies

are pure antibody preparations specific for a single antigenic determinant - produced by descendants of a single cell - used to diagnose pregnancy, certain STIs, some cancers, hepatitis, and rabies - more specific and sensitive and rapid than other tests

antigens

are substances that can mobilize the adaptive defenses - they are the ultimate targets of all adaptive immune responses

what is the result of ready-made antibodies being introduced to your body instead of being made by your plasma cells?

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

when naive T cells are simply called CD4 or CD8 what does that mean?

because they are not activated

why are natural killer (NK) cells called natural killer cells?

because they are not picky in who they eliminate - they identify infected or cancerous cells by detecting general abnormalities such as the lack of "self" cell-surface proteins called MHC

CD8 cells

become cytotoxic T (Tc) cells that destroy cells in the body that harbor anything foreign

passive humoral immunity differs from active immunity:

both in the antibody source and in the degree of protection it provides

how is passive immunity conferred artificially?

by administering exogenous antibodies (from outside your own body) as gamma globulin, harvested from the plasma of an immune donor - exogenous antibodies are used to prevent Hep A and treat poisonous snake bites, botulism, rabies, and tetanus because these rapidly fatal diseases would kill a person before active immunity could be established

inflammatory chemicals also increase the permeability of local...

capillaries and venules

cytokines

chemical messengers involved in cellular immunity belong to a group of molecules, a general term for mediators that influence cell development, differentiation, and responses in the immune system Ex: interferons and interleukins

Antigens can be ____ or ____

complete or incomplete

Innate (nonspecific) defense system

constitutes first and second lines of defense 1st line of defense consists of surface barriers, intact skin and mucosae 2nd line of defense, called into action whenever the first line has been penetrated, relies on internal defenses such as antimicrobial proteins, phagocytes, and other cells to inhibit the invaders' spread throughout the body - inflammation

diapedesis

continued chemical signaling prompts the neutrophils to flatten and squeeze between endothelial cells of capillary walls

Class I MHC proteins are crucial for...

crucial for both activating naive CD8 cells and "informing" cytotoxic T cells that infectious microorganisms are hiding in body cells - without them, viruses and certain bacteria that thrive in cell could multiply unnoticed and unbothered

most vaccines contains pathogens that are:

dead or attenuated (living, but extremely weakened) or their components

what do neutrophils use to pierce the pathogen's membrane?

defensins - an antimicrobial peptide

what are on of the key links between innate and adaptive immunity?

dendritic cells

what are the major types of cells acting as APCs?

dendritic cells, macrophages, and B lymphocytes

antigen-presenting cells (APCs)

engulf antigens and then present fragments of them, like signal flags, on their own surfaces where T cells can recognize them - Naive T cells can only be activated by antigens that are presented to them on MHC proteins by APCs

antimicrobial proteins

enhance our innate defenses by attacking microorganisms directly or by hindering their ability to reproduce - most important antimicrobial proteins are interferons and complement proteins

once activated by antigen binding and co-stimulation, a T cell...

enlarges and proliferates

the inflammatory response enlists who to help repair tissue?

enlists macrophages, mast cells, all types of white blood cells, and dozens of chemicals that kill pathogens

In response to leukocytosis-inducing factors, neutrophils do what?

enter the blood from red bone marrow and within a few hours, the number of neutrophils in blood increases four- to fivefold

Exudate

fluid containing clotting factors and antibodies

MAC - membrane attack complex

forms and stabilizes a hole in the membrane that allows a massive influx of water, lysing the target cell

2 types of macrophages

free macrophages and fixed macrophages

Adaptive (specific) defense system

functions like an elite fighting force equipped with high-tech weapons to attack identified foreign substances. The adaptive defense response, which provides the body's third line of defense, takes considerably longer to mount than the innate

pathogens

harmful or disease producing microorganisms

3 major groups of effector T cells

helper, cytotoxic, and regulatory T cells

mast cells and basophils secrete what chemicals to initiate an inflammatory response typical of allergies?

histamine

vasodilation of local arterioles causes local what?

hyperemia (increased blood flow)

secondary immune response

if (and when) someone is reexposed to the same antigen, the second immune responses are faster, more prolonged, and more effective, because they immune system has already been primed to the antigen, and sensitized memory cells are already "on alert"

complete antigens have two important functional properties:

immunogenicity or reactivity

memory cells provide what?

immunological memory

antigen-binding site location

in each arm of the monomer, the V regions of the heavy and light chains combine to form this region shaped to "fit" a specific antigenic determinant - each antibody monomer has 2 such antigen-binding regions

leukocytosis

increase in white blood cells, is a characteristic of inflammation

splitting C3 initiates a common terminal pathway that enhances what?

inflammation, promotes phagocytosis, and can cause cell lysis

chemotaxis

inflammatory chemicals act as homing devices, or more precisely chemotactic agents

classical pathway

involves antibodies, water- soluble protein molecules that the adaptive immune system produces to fight off foreign invaders - when antibodies bind to pathogens, they can also bind complement components - double binding is the first step in this complement activation pathway

lectin pathway

involves lectins, water soluble protein molecules that the innate immune system produces to recognize foreign invaders - when lectins bind specific sugars on the surface of microorganisms, they can then bind and activate complement

inflammation

is a nonspecific response to any tissue injury - causes include physical trauma, intense heat, irritating chemicals, or infection

hummoral immunity (antibody mediated immunity)

is provided by antibodies present in the body's humors or fluids (blood, lymph)

reactivity

is the ability to react with the activated lymphocytes and the antibodies released by immunogenic reactions

immunogenicity

is the ability to stimulate specific lymphocytes to proliferate (multiply)

complement 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 and complement is activated - molecules released during complement activation tremendously amplify the inflammatory response and promote phagocytosis by opsonizing pathogens

alternative pathway

is triggered when spontaneously activated C3 and other complement factors interact on the surface of microorganisms - microorganisms lack the complement activation inhibitors our own cells have

the clotting factors form a gel-like fibrin mesh (clot) that acts as a scaffold for permanent repair that also...

isolates the injured area and prevents bacteria and other harmful agents from spreading - walling off the injured area is such an important defense strategy that some bacteria have evolved enzymes that break down the clot, allowing them to invade

what are examples of inflammatory chemicals?

kinins, prostaglandins, cytokines

most antigens are

large, complex molecules (natural or synthetic) that are foreign - they are non self or intruders

when pyrogens are released what is happening?

leukocytes and macrophages are exposed to foreign substances in the body

injured cells release chemicals called?

leukocytosis-inducing factors

what types of allergic reactions can there be?

local or systemic (bodywide)

what secretes immune interferon (IFN gamma)?

lymphocytes secrete this chemical and it has widespread immune mobilizing effects

how are some bacteria able to elude capture?

many bacteria have external capsules that conceal their carbohydrate signatures, they cannot be captured because phagocytes cannot bind to them

what is an example of the inflammatory response?

mast cells, a key component in the inflammatory response, release the potent inflammatory chemical histamine

An immunocompetent but naive B lymphocyte is activated when...

matching antigens bind to its surface receptors and cross-link adjacent receptors together

memory cells

members of T and B cell clones that provide for immunological memory

MHC proteins (major histocompatibility complex)

molecules on the outer surface of the plasma membrane of all cells; help the immune system distinguish self from non self. T cells recognize antigens only when combined with these proteins

when is passive immunity conferred naturally?

on a fetus or infant when the mother's antibodies cross the placenta or are ingested with the mother's milk - for several months after birth, the baby is protected from all the antigens to which the mother has been exposed

antigenic determinants

only certain parts of the antigen are immunogenic - antibodies or lymphocyte receptors bind to these antigenic determinants in much the same manner that an enzyme binds to a substrate

B lymphocytes (B cells)

oversee humoral immunity

as a rule, small molecules such as what are not immunogenic?

peptides, nucleotides, and many hormones

pathogens that get through the skin or mucosae into the underlying connective tissue are confronted by what?

phagocytes

what are examples of immunogenic microorganisms or pollen grains?

pollen grains, bacteria, fungi, and virus particles because their surfaces bear many different foreign macromolecules

regulatory T (Treg) cells

population of T cells (usually expressing CD4) that suppress immune response

what does T cell education consist of?

positive and negative selection in the thymus

autoimmunity (autoimmune disease)

production of antibodies or effector T cells that attack a person's own tissue

pattern recognition receptors

protective tactics identify potentially harmful substances by recognizing (binding to) molecules with specific shapes that are part of infectious organisms (bacteria, viruses, fungi, and various parasites) but not normal human cells

complement system

refers to a group of at least 20 plasma proteins that normal circulate in the blood in an inactive state - major mechanism for destroying foreign substances in the body - it "complements" the effectiveness of BOTH innate and adaptive defenses

margination

refers to the phenomenon of phagocytes clinging to the inner walls (margins) of the capillaries and postcapillary venules

Some CD4 cells become...

regulatory T (Treg) cells, which moderate the immune response

clonal deletion

self-reactive lymphocyte and all of its potential progeny are eliminated - if the T cells attack the body cells

the development, maturation, and activation of B and T cells share these 5 general steps:

1. Origin: both B and T cell precursors originate in red bone marrow 2. Maturation: lymphocyte precursors destined to become T cells migrate to the thymus and mature there. B cells mature in the bone marrow. during maturation lymphocytes develop immunocompetence and self-tolerance. 3. Seeding secondary lymphoid organs and circulation: immunocompetent, but still naive lymphocytes leave the thymus and bone marrow. They seed the secondary lymphoid organs and circulate through blood and lymph 4. antigen encounter and activation: when a lymphocyte's antigen receptors bind its antigen, that lymphocyte can be activated 5. proliferation and differentiation: activated lymphocytes proliferate and then differentiate into effector cells and memory cells - memory cells and effector T cells circulate continuously in th blood and lymph and throughout the secondary lymphoid organs

the same general events occur in cellular immune response:

1. a primary response sets up a pool of effector cells 2. generates memory cells that can then mount secondary responses

In this signaling, the class I MHC proteins both...

1. act as antigen holders 2. form the self part of the self-nonself complexes that cytotoxic T cells must recognize in order to kill

Clonal selection of T cells involves simultaneous recognition of self and non self..

1. antigen presentation: dendritic cell engulfs an exogenous antigen, processes it, and displays its fragments on class II MHC protein 2. double recognition: 2a. CD4 T cell recognizes antigen-MHC complex. Both TCR and CD4 proteins bind to antigen-MHC complex 2b. Co-stimulatory molecules bind their receptors 3. clone formation: activated CD4 T cells proliferate (clone) and become memory and effector cells

two widely used therapeutic approaches involve:

1. blocking the actions of various cytokines using antibodies against them or their receptors 2. blocking the co-stimulatory molecules required to activate effector cells

one of the following conditions or events may trigger self-reactive lymphocytes slipping out of control:

1. foreign antigens resemble self-antigens 2. new self-antigens appear

the adaptive immune response has 4 key characteristics:

1. it involves lymphocytes called B and T lymphocytes 2. it is specific 3. it is systemic 4. it has "memory"

phagocyte mobilization

1. leukocytosis- neutrophils enter blood from bone marrow 2. margination - neutrophils cling to capillary wall 3. diapedesis - neutrophils flatten and squeeze out of capillaries 4. chemotaxis - neutrophils follow chemical trail

active immunity is acquired in 2 ways:

1. 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) 2. artificially acquired: when you receive a vaccine

phagocytosis steps

1. phagocyte adheres to pathogen or debris 2. phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome 3. lysosome fuses with the phagocytic vesicle, forming a phagolysosome 4. toxic compounds and lysosomal enzymes destroy pathogens 5. sometimes exocytosis of the vesicle removes indigestible and residual material

how can you tell if inflammation is present? There are 4 cardinal signs of acute inflammation:

1. redness 2. heat 3. swelling 4. pain

what are the different types of hypersensitivity reactions?

1. their time course 2. whether they involve antibodies or T cells - immediate and subacute occur with antibody-associated reactions - delayed hypersensitivities occur because of T cells

vaccines provide 2 benefits:

1. their weakened antigens provide functional antigenic determinants that are both immunogenic and reactive 2. they spare us most of the symptoms and discomfort of the disease that would otherwise occur during the primary response

interferon mechanism against viruses

1. virus enters cell and replicates 2. interferon genes switch on 3. cell produces interferon molecules 4. interferon binding stimulates cell to turn on genes for antiviral proteins 5. antiviral proteins block viral reproduction

passive immunity definition

short-lived immunity resulting from the introduction of "borrowed antibodies" obtained from an immune animal or human donor; immunological memory is not established

each plasma cell functions at a rate of 2000 molecules/second for how many days before it dies?

4-5 days before it dies

how many classes of antibodies are there?

5 classes

What is the difference between a complete antigen and a hapten?

A complete antigen has both immunogenicity and reactivity, whereas a hapten has reactivity but not immunogenicity.

Immune system

A functional system whose components attack foreign substances to prevent their entry into the body

Julian has a mutation in the gene that codes for interferon. What type of pathogen is Julian particularly susceptible to?

A mutation in the gene that codes for interferon would make Julian particularly susceptible to viruses.

what determines the ability of a molecule to act as an antigen?

size and complexity

What is the body's first line of defense?

skin and mucous membranes, along with the secretions these membranes produce

what releases cytokines?

APCs or T cells

Immunity

Ability of the body to resist many agents (both living and nonliving) that can cause disease; resistance to disease

List four ways in which antibodies can bring about destruction of a pathogen.

Antibodies can bring about destruction of pathogen via "PLAN"—phagocytosis, lysis (via complement), agglutination, or neutralization.

Th1 cells

stimulate inflammation, activate macrophages, and promote differentiation of cytotoxic T cells. - they mediate most aspects of cellular immunity

fixed macrophages

such as stellate macrophages in the liver, are permanent residents of a particular organ

C regions that form the stem of the antibody monomer determine...

the antibody class and serve common functions in all antibodies: 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 to eliminate antigens

plasma cells

the antibody-secreting effector cells of the humoral response - develop the elaborate internal machinery (largely rough endoplasmic reticulum) needed to secrete antibodies at the unbelievable rate of about 2000 molecules per second

What event triggers the release of histamine from mast cells in an allergic response?

Binding of an allergen onto specific IgE antibodies attached to mast cells triggers the mast cells to release histamine.

what is the common event in all antibody-antigen interactions?

the formation of antigen-antibody (immune) complexes - defense mechanisms used by antibodies include neutralization, agglutination, precipitation, and complement activation, with the first two most important

MHC restriction

CD4 and CD8 cells have different requirements for MHC protein that presents antigens to them

two major classes of T cells (two structurally related cell differentiation glycoproteins)

CD4 or CD8

When activated, CD4 and CD8 cells differentiate into the three major kinds of effector cells of cellular immunity:

CD4, CD8 and some CD4 cells become regulatory T cells

two classes of MHC proteins

Class I and Class II

Class II MHC proteins display what kind of antigens? What class of T cell recognizes antigens bound to class II MHC? What types of cells display these proteins?

Class II MHC proteins display exogenous antigens. Class II MHC proteins are recognized by CD4 T cells. APCs display class II MHC proteins.

In order for a phagocyte to ingest a pathogen, what must happen?

the phagocyte must first adhere to that pathogen - by recognizing the pathogen's carbohydrate signature

increased tissue fluid causes local swelling that presses on adjacent nerve endings, contributing to a sensation of pain, but pain also results from...

the release of bacterial toxins, and the sensitizing effects of released prostaglandins and kinins

neutralization

the simplest defense mechanism, occurs when antibodies block specific sites on viruses or bacterial exotoxins - as a result, the virus or exotoxin cannot bind to receptors on tissue cells. phagocytes eventually destroy the antigen-antibody complexes

somatic recombination

DNA segments are shuffled and combined in different ways - the information of the newly assembled genes is then expressed as the surface receptors of B and T cells and as the antibodies later released by the B cell's "offspring"

Name three different APCs. Which is most important for T lymphocyte activation?

Dendritic cells, macrophages, and B cells can all act as APCs. Dendritic cells are most important for T cell activation.

What event (or observation) signals that a B or T cell has achieved immunocompetence?

Development of immunocompetence of a B or T cell is signaled by the appearance on its surface of specific and unique receptors for an antigen. In the case of a B cell, this receptor is a membranebound antibody. (In T cells, it is simply called the T cell receptor.)

What do phagocytes do when they are unable to ingest their targets?

they can release their toxic chemicals into the extracellular fluid - neutrophils kill themselves in the process - macrophages do not kill themselves in the process

B lymphocytes (APCs)

they present antigens to a certain kind of T cell (a helper T cell) in order to obtain "help" in their own activation

what structural modifications does the respiratory tract mucosae have that counteract potential invaders?

tiny mucus-coated hairs inside the nose trap inhaled particles, and cilia on the mucosa of the upper respiratory tract sweep dust- and bacteria-laden mucus toward the mouth, preventing it from entering the lower respiratory passages

what is the ultimate goal of an inflammatory response?

to clear the injured area of pathogens, dead tissue cells, and any other debris so that tissue can be repaired - once this occurs healing happens quickly

Name four key characteristics of adaptive immunity.

Four key characteristics of adaptive immunity are that it involves B and T lymphocytes, it is specific, it is systemic, and it has memory.

What makes HIV particularly hard for the immune system to defeat?

HIV is particularly hard for the immune system to defeat because (1) it destroys helper T cells, which are key players in adaptive immunity and (2) it has a high mutation rate and so it can avoid detection by the immune system by changing its surface antigens.

Which type of T cell is the most important in both cellular and humoral immunity? Why?

Helper T cells are central to both humoral and cellular immunity because they are required for activation of both cytotoxic T cells and most B cells.

what is an example of an acquired immunodeficiency?

Hodgkin's lymphoma - a cancer of B cells

vaccine booster shots are used in some cases to do what?

to intensify the immune response at later encounters with the same antigen