-
What are the two intrinsic systems of the immune system?
- innate (nonspecific) defense system
- adaptive (specific) defense system
-
What are the two lines of defense for the innate system?
- External body membranes (skin and mucosae)
- Antimicrobial proteins, phagocytes and other cells
-
What is the most important mechanism of the secondary innate defense system?
Inflammation
-
Adaptive defense system takes-
longer to react than the innate system
-
Adaptive defense system is the _________ and attacts ________________
third line of defense, particular foreign substances
-
Internal defenses of the innate defense system include
- Phagocytes
- Natural killer cells
- inflammation
- antimicrobial proteins
- fever
-
Adaptive defenses include
- humoral immunity-B Cells
- Cellular immunity-T Cells
-
Keratin (a protein in the skin) is resistant to
weak acids and bases, bacterial enzymes and toxins
-
What are 5 surface barrier chemicals?
- Skin acidity
- Lipids in sebum and dermcidin in sweat
- HCI and ptrotein-digesting enzymes of stomach mucosae
- Lysozyme of saliva and lacrimal fluid (tears)
- Mucus
-
What are respiratory modifications of suface barrier defense systems?
- Mucos-coated haris in the nose
- Cilia od upper respiratory tract sweep dust-and bacteria-laden mucus from lower respiratory passages.
-
Macrophages develop from _____________ to become the ____________________
monocytes, chief phagocytic cells
-
What are the two types of macrophages?
- Free macrophages that wander through tissue (e.g. alveolar macrophages)
- Fixed macrophages are permanent residents of some organs (e.g. Kupffer cells (liver) and microglia (brain))
-
Neutrophils become phagocytic on ________________________
encountering infectious material in tissues
-
The first step of phagocytosis is __________________ which is facillitated by ______________
adherence of phagocyte to pathogen, opsonization-coating of pathogen by complent proteins or antibodies
-
What is the second event of phagocytosis?
Phagocyte forms pseudopods that eventually engulf the particles forming a phagosome
-
What is the third event of phagocytosis?
Lysosome fuses with the phagocytic vesicle, forming a phagolysosome
-
What is the fourth event of phagocytosis?
Lysosomal enzymes digest the particles, leaving a residual body.
-
What is the fifth event of phagocytosis?
Exocytosis of the vesicle removes indigestible and residual material
-
How do phagocytes destroy pathogens?
- By adicification and digestion by lysosomal enzymes
- Respiratory burst: release of cell killing free radicals and activation of additional enzymes
- Oxiding chemicals (e.g. H202)
- Defensins (in neutrophils)
-
Natural killer cells are
- Large granular lymphocytes
- Target cells that lack "self" cell-surface receptors
- Induce apoptosis (programmed cell death) in cancer cells and virus-infected cells
- Secrete potent chemicals that enhance the inflammatory response
-
What are the 4 aspects of the imflammatory response?
- Triggered whenever body tissues are injured or infected
- Prevents the spread of damaging agents
- Disposes of cell debris and pathogens
- Sets the stage for repair
-
What are the cardinal signs of acute inflammation?
- Redness
- Heat
- Swelling
- Pain
- (and sometimes 5. impairment of function)
-
In the inflammatory response macrophages and epithelial cells of boundary tissues bear _______________
Toll-like receptors (TRL's)
-
TRLs recognize
specific classes of infecting microbes
-
Activated TRLs trigger
the release of cytokines that promote inflammation
-
The inflammatory mediators (promote inflammation) are
- Histamine (from mast cells)
- Blood proteins
- Kinins, prostaglandins (PGs), leukotrienes, and complement (released by injured tissues, phagocytes, lymphocytes, basophils, and mast cells)
-
Inflammatory chemicals cause
- Dilation of arterioles, resulting from hyperemia
- Increased permeability of local capillaries and edema (leakage or exudate)
-
Exudate contains
proteins, cloting factors, and antibodies
-
What are the functions of the surge of exudate during the inflammatory response?
- Moves foreign material into lymphatic vessels
- Delivers clotting proteins to form a scaffold for repair and to isolate the area
-
Neutrophils, then ___________ flood to inflamed sites
phagocytes
-
What is the first event in the internal defense response?
Leukocytosis: neutrophils enter blood from bone marrow
-
What is the second event of the internal defense response?
Margination: Neutrophils cling to capillary wall
-
What is the third event of the internal defense system?
Diapededis: Netrophils flatten and squeeze out of capillaries
-
What is the fourth event of the internal defense system?
Chemotaxis: Neutrophils follow chemical trail
-
Interferons (IFNs) and complement proteins are
antimicrobial proteins
-
Interferons and complement proteins attack __________ and hinder _______________
microorganisms directly, microorganisms ability to reproduce
-
Viral-infected cells are activated to
secrete IFNs
-
IFNs enter neighboring cells, these cells produce
antipviral proteins that block viral reproduction
-
Interferons are produced by a variety of body cells:
- Lymphocytes produce gamma or immune interferon
- Most other WBCs produce alpha interferon
- Fibroblasts produce beta interfuron
-
Interferons activate
macrophages and mobilize NKs
-
Inteferon functions are
- anti-viral
- reduce inflammation
- activvate macrophages and mobilize NKs
-
What are the two types of genetically engineered IFNs for?
- Antiviral agents against hepatitis and genital warts virus
- Multiple sclerosis treatment
-
Complement is
major mechanism for destroying foreign substances
-
Complement is about
20 blood proteins that circulate in an inactive form
-
Complement includes
C1-C9, factors B, D, and P, and regulatory proteins
-
Complement amplifies _______________
kills _____________
enhances __________________
all aspects of the inflammatory response; bacteria and certain other cell types by cell lysis; both nonspecific and specific defenses
-
What are the two pathways of complement activation?
- Classical pathway
- Alternative pathway
-
During the complement activation classical pathway
- Antibodies bind to invading organisms
- C1 binds to the antigen-antibody complexes (complement fixation)
-
During complement activation alternative pathway
triggered when activated C3, B, D, and P interact on the surface of microorganisms
-
Each pathway of complement activation involves
- activationof proteins in an orderly sequence
- each step catalyzes the next
- both pathways converge on C3, which cleaves into C3a and C3b
-
Activated complement enhances___________, promotes _______ and causes_________
- inflammation
- phagocytosis
- cell lysis
-
Fever is the
systemic response to invading organisms
-
Leukocytes and macrophages exposed to foreign substances secrete
pyrogens
-
Pyrogens reset
the body's thermostat upward
-
High fevers are dangerous because
heat denatures enzymes
-
What are the benefits of moderate fever?
- Causes the liver and spleen to sequester iron and zinc (needed for microorganisms)
- Increases metabolic rate, which speeds up repair
-
The adaptive immune (specific defense) system protects against _____________, amplfies ____________ and activates ________________
- infectious agents and abnormal body cells
- the inflammatory response
- complement
-
Adaptive immune response is _________, is ____________, and has _____________
-
What are the two overlapping arms of the adaptive defense system?
- Humoral (antibody-mediated) immunity
- Cellular (cell-mediated) immunity
-
What are antigens?
- Substances that can mobilize the adaptive defenses and provoke an immune response
- Most are large, complex molecules not normally found in the body (nonself)
-
What are the important functional properties of antigens?
-
What is immunogenicity?
Ability to stimulate proliferation of specific lymphocytes and antibodies
-
What is reactivity?
Ability to react with products of activated lymphocytes and antibodies released
-
What are examples of complete antigens?
Foreign protein, polysaccharides, lipids, and nucleic acids
-
Haptens are
Small molecules (peptides, nucleotides, and hormones)
-
Haptens are not
immunogenic by themselves. They must be attached to body proteins
-
What are examples of haptens?
poinson ivy, animal dander, detergents and cosmetics
-
Antigenic determinants are certain
parts of an entire antigen that are immunogenic. Antibodies and lymphocyte receptors bind to them.
-
Most naturally occurring antigens haave
numerous antigenic determinants that mobilize several different lymphocyte populations and form different kinds of antibodies against it.
-
Self-Antigens are
protein molecules on the surface of cells
-
An example of self-antigens are
- MHC proteins
- Coded for by genes of the major histocompatability complex (MHC) and are unique to an individual
-
What are the two classes of MHC proteins?
- Class I MHC proteins, found on virtually all body cells
- Class II MHC proteins, found on certain cells in the immune response
-
MHC proteins display
peptides (usually self-antigens)
-
Ininfected cells,MHC proteins display
fragments of foreign antigens, which help mobilize
-
What are the cells of the adaptive immune system?
- B lymphocytes (humoral immunity)
- T lymphocytes (cell-mediated immunity)
- Antigen presenting cells (APCs)
-
APCs do not ________________, they play ________________
- respond to specific antigens
- essential auxillary roles in immunity
-
Lymphocytes originate in
red bone marrow
-
B cells mature in ________________
T cells mature in ________________
- red bone marrow
- the thymus
-
When mature, lymphocytes have
- immunocompetence: they are ale to recognize and bind to a specific antigen
- Self-tolerance-unresponsice to self antigens
-
Naive (unexposed) B and T cells are exported to
lymph nodes, spleen, and other lymphoid organs
-
T cells mature in the thymus under
negative and positive selection pressures
-
Positive selection selects T cells that are
capable of binding to self-MHC proteins (MHC restriction)
-
Negative selection prompts
apoptosis of T cells that bind to self-antigens diplayed by self-MHC
-
Self-reactive B cells are _________________, or undergo _____________ and are inactivated if ____________
- eliminated by apoptosis (deletion)
- receptor editing-rearrangement of their receptors
- (anergy) if they escape from the bone marrow
-
Lymphocytes make up
to a billion types of antigen receptors
-
Genes determine which
foreign substances the immune system will recognize and resist
-
APCs engulf _____________, present ______________________
- antigens
- fragments of antigens to be recognized by T cells
-
What are the major types of antigen-presenting cells?
- Dendritic cells in connective tissues and epidermis
- Macrophages in connective tissues and lymphoid organs
- B cells
-
Macrophages and dendritic cells present _________ and activate ___________
-
Macrophages mostly remain
fixed in the lympoid organs
-
Dendritic cells internalize
pathogens and enter lymphatics to present the antigens to T cells in lymphoid organs
-
Activated T cells release chemical that
prod macrophages to become instaiable phagocytes and to secrete bactericidal chemicals
-
The adaptive immunity uses
lymphocytes, APCs, and specific molecules to identify and destroy nonself substances
-
The adaptive immunity depends on the ability of its cells to
- recognize antigens by binding to them
- communicate with one another so that the whole system mounts a specific response
-
When lymphocytes are mature they have tw things
- immunocompetance: they are able to recognize and bind to a specific antigen
- Self-tolerance:unresponsive to self-antigens
-
___________________ B and T cells are exported to lymch nodes, spleen, and other lymphoid organs
Naive (unexposed)
-
T cells mature in _________ under _______________________ controls
- the thymus
- negative and postive selection presssures
-
Selects T cells capable of binding to self-MHC proteins (MHC restriction) describes
T cells positive selection
-
Prompts apoptosis of T cells that bind to self-antigens displayed by self-MHC
Ensures self-tolerance describes
T cells negative selection
-
B cells mature in
red bone marrow
-
Self-reactive B cells are eliminated by ________ or undergo ________________, are
- apoptosis (clonal deletion)
- receptor editing - rearangement of their receptors
- inactivated (anergy) if they escape from the bone marrow
-
Lymphocytes make up to ______________________ which are
- a billion different types of antigen receptors
- coded for by about 25,000 genes
-
Genes determine which
foreign substances the immune system will recognize and resist
-
Antigen presenting cells (APCs) engulf ____________, present _________________ to be recognized by _____________
- antigens
- fragments of antigens
- T cells
-
What are the major types of APCs?
- Dendritic cells in cconnective tissue and epidermis
- Macrophages in connective tissues and lymphoid organs
- B cells
-
Macrophages and dendritic cells present
antigens and activate T cells
-
what cells remain mostly fixed in lymphoid organs?
Macrophages
-
What cells internalize pathogens and enter lyphatics to present the antigens to T cells in lymphoid organs?
dendritic cells
-
An antigen challenge is
the first encounter between an antigen and a naive immunocompetent lymphocyte
-
An antigen challenge usually occurrs in the
spleen
-
If the lymphocyte is a B cell in an antigen challenge
- the antigen provokes a humoral response
- antibodies are produced
-
What is the first step of clonal selection?
B cell is activated when antigens bind to its surface receptors and cross-link them
-
What is the second step of clonal selection?
Receptor-mediated endocytosis of cross-linked antigen-receptor complexes occurs
-
What is the third step of clonal selection?
Stimulated B cell gros to form a clone of identical cells bearing the same antigen-specific receptors (T cells are usually required to help B cells achieve full activation)
-
Most clone cells become ______________ and secrete specific ____________________ at the rate of ____________________
- plasma cells
- antibodies
- 2000 molecules per second for four to five days
-
What is the fate of the clones that become secreted antibodies?
- Circulate in blood or lymph
- Bind to free antigens
- Mark the antigens for destruction
-
Clone cells that do not become plasma cells become _______________ and provide _________________ and mount an ___________________
- memory cells
- immunological memory
- immediate response to future exposures of the same antigen
-
Primary immune response occurs on ______________, has a lag period of _____________________, peak levels of plasma antibody are reaches in ____________ antibody levels then _________
- the first exposure to a specific antigen
- 3 to 6 days
- 10 days
- decline
-
Secondary immune response occurs on ____________, sensitized memory cells ______________, antibody levels peak in _____________, antibodies bind with ____________, antibody level can _______
- re-exposure to the same antigen
- respond within hours
- 2 to 3 days at much higher levels
- greater affinity
- remain high for weeks to months
-
Active humoral immunity occurs when
B cells encounter anitgens and produce specific antibodies against them
-
What are the two types of active humoral immunity?
- Naturally aquired-response to a bacterial or viral infection
- Artificially required-repsonse to a vaccine of dead or attenuated pathogens
-
Vaccines spare _____________________ and provide __________________
- us the symptoms of the primary response
- antigenic determinants that are immunogenic and reactive
-
In passive humoral immunity B cells are not ________________ and _________________ does not occur
- challenged by antigens
- immunological memory
-
What are the two types of passive humoral immunity?
- Naturally aquired-antibodies delivered to a fetus via the placenta or to infact through milk
- Artificially aquired-injection of serum, such as gamma globulin (protection is immediate but ends when antibodies naturally degrade in the body)
-
Antibodies are (3)
- immunoglobulins-gamma globulin portion of blood
- proteins secreted by plasma cells
- capable of binding specifically with antigen detected by B cells
-
What is the basic structure of an antibody?
- T or Y shaped monomer of four looping linked polypeptide chains
- Two identical heavy (H) chains and two identical light (L) chains
- Variable (V) regions of each arm combone to form two identical antigen-binding sites
-
The constant region of antibody stem determines _______________, ________________ and how
- the antibody class
- the cells and chemical that the antibody can bind to
- the antibody class functions in antigen elimination
-
What are the 5 antibody classes?
lgM, lgA, lgD, lgG and lg E
-
A pentamer; first antibody released
Potent agglutinating agent
Readily fixes and activates complement describes
lgM
-
Monomer or dimer; in mucus and other secretions
Helps prevent entry of pathogens describes
lgA
-
Monomer attached to the surface of B cells
Functions as a B cell receptor describes
lgD
-
Monomer attached to the surface of B cells
Functions as a B cell receptor describes
lgD
-
Monomer, 75-85% of antibodies in plasma
From secondary and late primary responses
Crosses the placental barrier describes
lgG
-
Monomer active in some allergies and parasitic infections
Causes mast cells and basophils to release histamine describes
lgE
-
Billions of antibodies result from
somatic recombination of gene segment
-
Hypervariable regions of some genes increase antobody variations through
somatic mutations
-
Each plasma cell can switch the type of
H chain produced, making an antibody of a different class
-
Antibodies inactivate and _________________ and form ___________________
- tag antigens
- antigen-antibody (immune) complexes
-
What are the defense mechanisms used by antibodies?
- Neutralization and agglutination (the two most important)
- Precipitation and complement fixation
-
Describe naturalization by antibodies
- Simplest 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
-
Describe agglutination by antibodies
- Antibodies bind the same determinants on more than one cell bound antigen
- Cross-linked antigen-antibody complexes agglutinate
- Ex. clumping of mimatched blood cells
-
Describe precipitation
- Soluble molecules are cross linked
- Complexes precipitate and are subject to phagocytosis
-
What is the main antibody defense against cellular antigens?
Complement fization and activation
-
Several antibodies bind close together on a cellular antigen, their complement-binding sites trigger complement fixation into the cell's surface describes _________________-- and then __________________
- Complement fization and activation
- complemet triggers cell lysis
-
Activated complement functions
- Amplifies the inflammatory response
- Opsonization
- Enlists more and more defensive elements
-
What is opsonization?
coating the pahtogen in complement and anitbodies
-
Monoclonal antibodies are _________________ and are produced by ___________________. They proliferate ____________and have the ability to ______________________. Are used in _____________________
- commercially prepared pure antibody
- hybridomas (cell hybirds: fusion of a tumor cell and a B cell
- indefinitly
- produce a single type of antibody
- research, clinical testing, and cancer treatment
-
T cells provide defense against
intracellular antigens
-
What are the two types of T cell receptors?
- T cell antigen receptors
- Cell differentiation glycoproteins
- CD4 or CD8 Play a role in T cell interactions with other cells
-
CD4 cells become
Helper T cells (TH) when activated 4+2=Helper
-
CD8 cells become
cytotoxic T cells (TC) that destroy cells harboring foreign antigens 8+1=cytotoxic
-
What are the two other types of T cells?
- Regulatory T cells (TREG)
- Memory T cells
-
Antibodies of the humoral response are
the simplest ammunition of the immune system
-
Targets of the humoral response are
bacteria and molecules in extracellular environment (body secretions, tissue fluid, blood and lymph)
-
T cells of the cell mediated response
recognize and respond only to processed fragments of antigen displayed on the surface of body cells
-
The targets of the cell mediated response are
- body cells infected by viruses or bacteria
- abnormal or cancerous cells
- cells of infued or transplanted foreign tissue
-
What are the two types of MHC proteins that are important to T cell activation?.
- Class 1 MHC proteins-displayed by all cells except RBCs
- Class II MHC proteins-displayed by APCs (dendritic cells, macrophages and B cells)
- Both types are synthized at the ER and bind to peptide fragments
-
Immunocompetent T cells are activated when
their surface receptors bind to a recognized antigen (nonself)
-
T cells must simultaneously recognize
- nonself (the antigen)
- self (an MHC protein of a body cell)
-
Class I MHC proteins bind with
fragment of a protein synthesized in the cell (endogenous antigen)
-
Endogenous antigen is a ___________________ in a normal cell; a _____________ is an infected or abnormal cell
- self-antigen
- nonself antigen
-
Class I MHC proteins inform _______________ of the presence of microorganisms hiding in cells
- cytotoxic T cells
- (cytotoxic T cells ignore displayed self-antigens)
-
Class II MHC proteins bind with
fragment of exogenous antigens that have engulfed and borken in a phagolysosome
-
Class II MHC proteins are recognized by
helper T cells
-
APCs (most often a ____________) migrate to lymph nodes and other lymphoid tissues to
- dendritic cell
- present their antigens to T cells
-
What are the two steps of T cell activation?
- Antigen binding
- Co-stimulation
-
What is MHC restriction?
CD4 and CD8 cells bind to different classes of MHC proteins
-
CD4 cells bind to
antigen linked to class II MHC proteins of APCs
-
CD8 cells are activated by
antigen fragments linked to class I MHC of APCs
-
Dendritic cells are able to obtain other cells' endogenous antigens by
- engulfing dying virus-infected or tumor cells
- importing antigens through temporary gap junctions with infected cells
-
Co-stimulation requires
T cell binding to other surface receptors of an APC
-
Dendritic cells and macrophages produce
surface B7 proteins when innate defenses are mobilized
-
Cytokines (interleukin 1 and 2 from APCs or T cells) trigger
proliferation and differentiation of activated T cell
-
Without co-stimulation, ___________ occurs and
- Anergy
- T cells become tollerant to that antigen
- are unable to divide
- do not secrete cytokines
-
T cells that are activated enlarge, _____________ and form _____________. They also _________ and perform functions according to their _______________
- proliferate
- clones
- differentiate
- T cell class
-
Once primed by APC presentation of antigen, helpter T cells (TH)
- help activate T and B cells
- Induce T and B cell proliferation
- Activate macrophages and recruit other immune cells
-
Helper T cells interact directly with ________
B cells diplaying antigen fragments bound to MHC II receptors
-
helper T cells stimulate ____________ to divide more rapidly and begin ____________
- B cells
- antibody formation
-
B cells may be activated without TH cells by
binding to T cell-independant antigens
-
Most antigens require _________________ co-stimulation to activate B cells
TH
-
________________ cause dendritic cells to express co-stimulatory molecules required for CD8 cell activation
Helper T cells
-
Cytotoxic T cells (TC) directly
Where are they found?
- attack and kill other cells
- Blood, lymph and lymphoid organs
-
Targets of cytotoxic T cells are
- virus-infected cells
- cells with intracellular bacteria or parasites
- cancer cells
- foreign cells (transfusions and transplants)
-
Cytotoxic T cells bind to ____________ and can destroy _____________-
- a self-nonself complex
- all infected or abnormal cells
-
Describe mechanisms cytotoxic cells use to kill
- Tc cells releases perforins and granzymes by exoctytosis
- Perforins create pores through which granzymes enter the target cell
- Granzymes stimulate apoptosis
-
What are the abnormal signs recognized by NK cells
- Lack of class I MHC
- antibody coating a target cell
- different surface marker on stressed cells
-
NK cells use the same mechanisms as __________ for killing their targets
Tc cells
-
Regulatory T cells (TReg) dampen the immune response by
direct contact or by inhibiting cytokines
-
TReg is important in
preventing autoimmune reactions
-
Multiple sclerosis, myasthenia gravis, Grave's disease, type I diabetes mellitus, systemic lupus erythematosus (SLE), glomerulonephritis, and rheumatoid arthritis are examples of
Autoimmune diseases
-
What is the first mechanism of an autoimmune disease?
Foreign antigens may resemble self-antigens
-
What is the second mechanism of an autoimmune disease?
New self-antigens may appear, generated by gene mutations and changes in self-antigens by hapten attachment or as a result of infectious damage
-
What is the third mechanism of an autoimmune disease?
Release of novel self-antigens by trauma of a barrier (ex. the blood brain barrier)
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