ch 21

resistance to disease

• innate (nonspecific) defense system
• adaptive (specific) defense system

• functional system rather than organ system
• innate and adaptive defenses intertwined 
• release and recognize many of same defensive molecules
• innate defenses do have specific pathways for certain substances
• innate responses release proteins that alert cells of adaptive system to foreign molecules

• first - external body membranes:skin and mucosa
• second -antimicrobial proteins, phagocytes, other cells: inhibit spread of invaders; inflammation most important mechanism

• adaptive defense system
• it attacks particular foreign substances, so it takes longer to react than the innate system

antimicrobial peptides which inhibit growth

• mucus coated hairs in nose
• cilia of upper respiratory tract sweep dust and bacteria mucus toward mouth

• phagocytes
• natural killer (NK) cells
• antimicrobial proteins (interferons and complement proteins)
• feber
• inflammatory response (macrophages, mast cells, WBCs and inflammatory chemicals)

• neutrophils: most abundant but die fighting. become phagocytic on exposure to infectious material
• macrophages: develop form monocytes -chief phagocytic cells. free macrophages wander through tissue spaces, while fixed macrophages permanent residents of some organ e.g. kupffer cells (liver)

• phagocyte must adhere to particle
• some microorganisms evade adherence with capsule.
• cytoplasmic extensions bind to and engulf particle in vesicle
• phagosome fuses with lysosome

marks pathogens; coating by complement proteins or antibodies

helper t cells cause release of enzymes of respiratory burst, which kill pathogens resistance to lysosomal enzymes.

yes, it pierces the membrane of the pathogen

• nonphagocytic large granular lymphocytes
• attack cells that lack "self" cell surface receptors (induce apoptosis)
• secrete potent chemicals that enhance inflammatory response

controlled cell suicide

• triggered whenever body tissues injured
• prevents spread of damaging agents
• disposes of cell debris and pathogens
• alerts adaptive immune system
• sets the stage for repair

• redness
• heat
• swelling
• pain
• sometimes impairment of function

• kinins, prostaglandins, and complement.
• -dilate local arterioles
• -make capillaries leaky
• -many attract leukocytes to area
• -some have inflammatory roles

• scaffold for repair
• isolates injured area so invaders cannot spread

• 1. leukocytosis: release of neutrophils from bone marrow in response to leukocytosis inducing factors from injured cells
• 2. margination: neutrophils cling to walls of capillaries in inflamed area in response to CAMs
• 3. diapedesis of neutrophils
• 4. chemotaxis: inflammatory chemicals promote positive chemotaxis of neutrophils

• attack microorganisms directly
• hinder microorganisms' ability to reproduce

• family of immune modulating proteins
• viral infected cells secrete IFNs to warn neighboring cells.
• IFNs enter neighboring cells, produce proteins that block viral reproduction and degrade viral RNA; also activate NK cells

• 20 blood proteins that circulate in inactive form
• major mechanism for destroying foreign substances
• our cells contain complement activation inhibitors
• unleashes inflammatory chemicals that amplify all aspects of inflammatory response
• kills bacteria and certain other cell types by cell lysis
• enhances both innate and adaptive defenses

• classical: antibodies bind to invading organisms and to complement componenets, called complement fixation, first step in activation
• lectin pathway: lectins produced by innate system to recognize foreign invaders, when bound to foreign invaders can also bind and activated complement
• alternative: triggered when activated C3, B, D, P interact on surface of microorganisms

• abnormally high body temperature
• systemic response to invading microorganisms
• leukocytes and macrophages exposed to foreign substances secrete pyrogens
• pyrogens act on body's thermostat in hypothalamus, raising body temperature

• causes liver and spleen to sequester iron and zinc
• increases metabolic rate for faster repair

• protects against infectious agents and abnormal body cells
• amplifies inflammatory response
• activates complement
• must be primed by initial exposure to specific foreign substances (priming takes time)

recognizes and targets specific antigens

not restricted to initial site

stronger attacks to known antigens

antibody mediated immunity

cell mediated immunity

• antibodies produced by lymphocytes circulating freely in body fluids
• bind temporarily to target cells, temporarily inactivate, mark for destruction by phagocytes or complement

ability to stimulate proliferation of specific lymphocytes

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

• small molecules not immunogenic by themselves 
• e.g. peptides, nucleotides, some hormones
• (incomplete antigens)
• may be immunogenic if attached to body proteins and combination is marked foreign
• cause immune system to mount harmful attack
• examples: poison ivy, animal dander, detergents, cosmetics

• only certain parts (antigenic determinants) of entire antigens are immunogenic
• antibodies and lymphocyte receptors bind tot hem as enzyme binds to substrate

• protein molecules (self antigens) on surface of cells not antigenic to self but antigenic to others in transfusions or grafts
• ex. MHC glycoproteins

• two types of lymphocytes: B (humoral immunity) and T (cell mediated immunity)
• antigen presenting cells (APCs)

• origin: all originate in red bone marrow
• maturation
• seeding secondary lymphoid organs and circulation
• antigen encounter and activation
• proliferation and differentiation

• T cells: thymus
• B cells: bone marrow

• lymphocyte can recognize one specific antigen by binding to it.
• B or T cells display unique receptor on surface when achieve maturity, bind only one antigen

lymphocytes unresponsive to own antigens

selects t cells capable of recognizing self-MHC proteins; failures destroyed by apoptosis

• prompts apoptosis of t cells that bind to self antigens displayed by self MHC
• ensures self tolerance

• mature in red bone marrow
• positively selected if successfully make antigen receptors
• those that are self reactive are eliminated by apoptosis

when the immunocompetent B and T cells ahve not yet been exposed to antigens

• naive lymphocyte's fire encounter with antigen, selected for further development
• if correct signals present, lymphocyte will complete its differentiation

• activated lymphocytes proliferates > exact clones
• most clones > effector cells that fight infections
• few remain as memory cells 
• B and T memory cells and effector T cells circulate continuously

able to respond to same antigen more quickly second time

genes

• engulf antigens
• present fragments of antigens to T cells for recognition
• major types: dendritic, macrophages, B cells

• dndritic cells phagocytize pathogens, enter lymphatics to present antigens to T cells in lymph node
• macrophages widespread in lymphoid organs and connective tissues
• can activate naive T cells
• present antigens to T cells to activate themselves into voracious phagocytes that secrete bactericidal chemicals

no

• b cell activated when antigens bind to its surface receptors and cross-link them
• receptor mediated endocytosis of cross linked antigen receptor complexes
• proliferation and differentiation into effector cells

• most clone cells become plasma cells: secrete specific antibodies at rate of 2000 molecules per second for four to five days then die
• antibodies circulate in blood or lymph: bind to free antigens and mark for destruction by innate or adaptive mechanisms

• memory cells
• provide immunological memory
• mount an immediate response to future exposures to same antigen

• cell proliferation and differentiation upon first antigen exposure
• lag period: three to six days
• peak levels of plasma antibody are reached in 10 days
• antibody levels then decline

• re-exposure to same antigen gives faster, more prolonged, more effective response
• sensitized memory cells respond within hours
• antibody levels peak in two to three days at much higher levels
• antibodies bind with greater affinity
• antibody level can remain high for weeks to months

• naturally acquired: response to bacterial or viral infection
• artificially acquired: response to vaccine of dead or attenuated pathogens

• most of dead of attenuated pathogens
• spare us symptoms of primary response
• provide antigenic determinants that are immunogenic and reactive
• can cause illness trying to vaccinate against; can cause allergic responses

• naturally acquired: anitbodies delivered to fetus via placenta or to infant through milk
• artificially acquired: injection of serum, such as gamma globulin

• immunoglobulins
• proteins secreted by plasma cells
• capable of binding specifically with antigen detected by B cells
• grouped into one of five Ig classes

IgM, IgG, IgB, IgA, IgD

• pentamer
• larger than the rest
• first antibody released
• potent agglutinating agent
• readily fixes and activates complement

• monomer or dimer
• in mucus and other secretions
• helps prevent entry of pathogens

• monomer attached to surface of B cells
• functions as B cell receptor

• monomer; 75-85% of antibodies in plasma
• from secondary and late primary responses
• crosses placental barrier

• monomer active in some allergies and parasitic infections
• causes mast cells and basophils to release histamine

• neutralization and agglutination are the most important
• precipitation and complement fixation

• simplest defensive mechanism
• antibodies block specific sites on viruses or bacterial exotoxins
• prevent these antigens from binding to receptors on tissue cells
• antigen antibody complexes undergo phagocytosis

• antibodies bind same determinant on more than one cell bound antigen
• crosslinked antigen antibody complexes agglutinate

• soluble molecules are cross linked
• complexes precipitate and are subject to phagocytosis

• main antibody defense against cellular antigens
• several antibodies bind close together on a cellular antigen > complement binding sites on stem regions align which triggers complement fixation into cell's surface to cause cell lysis

yes

some do. others release chemicals that regulate immune response

• helper T: CD4 usually become helper T, which activate B cells, other T cells, macorphages, and direct adpative immune response. some beomce regulatory T cells which moderate immune response
• Memory T cells

• cytotoxic t cells
• destory cells harboring foreign antigens
• also become memory T cells

true

displayed by all cells except RBC

displayed by APCs (dendritic, macrophages, B cells)

MHC I

MHC II

• antigen binding and costimulation
• both occur on surface of same APC
• both required for clonal selection

dendritic cells and macrophages produce surface B7 proteins when innate defenses mobilized. it is crucial for a co-stimulatory signal

• they become tolerant to that antigen
• are unable to divide
• do not secrete cytokines

• enlarge and proliferate in response to cytokines
• differentiate and perform functions according to their T cell class

• chemical messengers of immune system
• mediate cell development, differentiation, and responses in immune system
• include interferons and interleukins

• play central role in adaptive immune response
• activate both humoral and cellular arms
• without them, there is no immune response

false; CD8 cells do that

• directly attack and kill other cells
• activated T cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize

• virus infected cells
• cancer cells
• foreign cells
• cells with intracellular bacteria or parasite

create pores through which granzymes enter target cell

stimulate apoptosis

from one body site to another in same person

between identical twins

between individuals who are not identical twins

from another animal species

none; they die from an opportunistic disease because of the weakened immune system due to AIDS

CD4

• systemic response to allergen that directly enters blood and circulates rapidly
• basophils and mast cells enlisted throughout body
• systemic histamine release ay cause constriction of bronchioles, tongue may swell, circulatory collapse and death
• treatment: epinephrine