Chapter 34
Friday, November 30, 2012
8:36 PM
 Innate Immunity
 Phagocytosis by WBCs and tissue macrophage system
 Destruction by acid secretions of the STM and digestive enzymes
 Resistance of skin
 Presence in the blood of certain chemical cpds
o Lysozyme - mucolytic polysaccharide attacks bacteria and cause them to dissolute
o Basic polypeptides - gram + bacteria
o Complement complex
o Natural killer lymphocytes - can recognize/destroy foreign cells, tumor cells, even some

infected cells
Acquired (Adaptive) Immunity
 Initiated by Ags - proteins or large polysaccharides, usually high molecular weight 8000 or
greater, usually depends on epitopes (regularly recurring molecular group)
 Both types of lymphocytes derived from
o Pluripotent hematopoietic stem cells -> common lymphoid progenitor cells
 Gene segments - hundreds, but not whole genes, which mix randomly and form whole genes
o Millions of different combos
o When lymphocytes is formed gene structure codes for only a single Ag specificity
 Humoral Immunity/B-cell Immunity
o B lymphocytes - produce the Abs, recognize intact Ags
 Preprocessed in liver during mid-fetal life, then in BM in late-fetal life and after
birth
 Greater diversity than T lymphocytes
 100,000 Ab molecules, Ag immediately attaches to Ab in cell membrane
 Plasma Cells
 Macrophages phagocytize Ag, present Ag to B cells and T cells
 activated T helper cells are formed
 B cells take appearance of lymphoblasts
 Some differentiate to plasmablasts = precursors of plasma cells
 Cytoplasm expands, rER proliferates
 Divides once every 10hrs 9X (total 500 in 4 days)
 Produces gamma globulin Abs ~2000 molecules/sec
 Memory Cells
 Some of the lymphoblasts don't differentiate into plasmablasts and become
memory cells
 Spread thruout the body and remain dormant until activated
 Primary exposure (Primary Response)
 1 wk delay, weak potency, short life
 Subsequent exposure (Second Response)
 More rapid (w/in hours) and potent Abs response, forms Abs for
many months rather than weeks (b/c more memory cells than there
were original B lyphocytes)
 Antibodies (Abs)
 Gamma globulins (immunoglobulins-Ig), 20% of all plasma proteins



Composed of light and heavy polypeptide chains
 Each heavy chain is paralleled by light chain at one of the ends
 At least two pair, up to 10 pair - held together by disulfide bonds
 Variable portion (light and heavy chains)
 Different for each Ab, attaches to Ag
 Constant portion (heavy chains)
 Diffusivity of Ab in tissues
 Adherence of Ab to specific structures w/in tissues
 Attachment to complement complex
 Ease of Abs passing thru membranes
Specificity - based on unique structural organization of aa's in variable
portion
 Different steric shape for each Ag specificity
 Fits as a mirror image - rapid/tight bonding b/w Ab and Ag
 Hydrophobic bonding
 Hydrogen bonding
 Ionic attractions
 Van der Waals forces
 Ka = affinity constant, measure of how tightly Ab binds w/Ag
 Bivalent- two variable sites
Mechanisms of Action
 Direct attack on invader
 Agglutination - large particles w/surface Ags are bound
together in a clump
 Precipitation - Ag/Ab complex (i.e. tetanus toxin) becomes so
large its rendered insoluble and precipitates
 Neutralization - Abs cover toxic sites of antigenic agent
 Lysis - cause rupture of agent
 Activation of Complement System
 System of ~20 proteins, 11 principal proteins (C1-C9, B and D)
 Activated via classic pathway - initiated by Ag-Ab rxn
 Specific reactive site on constant portion of Ab is
uncovered/activated and binds directly w/C1 molecule ->
cascade
 Opsonization and phagocytosis
 C3b-strongly activates phagocytosis by
neutrophils/macrophages of cells w/Ag-Ab
complexes attached
 Lysis
 C5b6789-directly ruptures cell membranes of
bacteria/invaders
 Agglutination
 Changes invaders surfaces -> adhere to one
another
 Neutralization of viruses
 Attack viral structures and render them nonvirulent
 Chemotaxis





C5a-initiates chemotaxis of
neutrophils/macrophages -> large #'s migrate into
tissue area adjacent to antigenic agent
Activation of mast cells and basophils
 C3a, C4a, C5a-activate mast cells/basophils ->
release histamine, heparin -> increased local blood
flow, increased leakage of fluid and plasma protein
into the tissue (major role in allergy and
inflammation)
Inflammatory effects
 In addition to mast cells and basophils, several
products contribute to local inflammation ->
 Increased blood flow increases more
 Capillary leakage of proteins to increase
 Interstitial fluid proteins coagulate in tissue
spaces, preventing movement of invader thru
tissues
Classes
 IgM - large share of primary response, 10 binding sites, not many of
them
 IgG - bivalent, 75% Abs in normal person
 IgA
 IgD
 IgE - small percentage, involved in allergies
Cell-mediated Immunity/T-cell Immunity
o T lymphocytes - activated lymphocytes
 Originate in BM, preprocessed in thymus gland (shortly before birth, and for few
months after birth) then spread thruout the body
 Thymus Selection
 T cells are mixed w/all the specific "self-Ags" from body's tissues. If the T
cell reacts it is destroyed and phagocytized. 90% of cells are lost this way.
 Removal of thymus several months before birth can prevent development of all
cell-mediated immunity
 Mainly responsible for rejection of transplanted organs
 Surface receptor proteins (T-cell markers)
 Macrophages - line sinusoids of LNs, spleen and lymphoid tissues
 Invading organisms are phagocytized and partially digested
 Antigenic products liberated in cytosol, Ags are passed by cell-to-cell
contact directly to lymphocytes -> activation of specified lymphocytic
clones
 Secrete interleukin-1 -> promotes further growth and reproduction of
specific lymphocytes
 T-lymphocyte Memory Cells - formed same as B memory cells
 Ag Recognition (as many as 100,000 receptors on a single T cell)
 T lymphocytes respond to Ags only when they're bound to MHC proteins on
APCs
 Antigen Presenting Cells (APCs)
 Macrophages, B lymphocites, Dendritic Cells





Tolerance
Major Histocompatibility Complex (MHC)
 Bind peptide fragments of Ag proteins degrade inside APCs and
transport them to the cell surface
 MHC I proteins - present Ag to cytotoxic T cells
 MHC II proteins - present Ags to T helper cells
Helper T cells
 Most numerous of T cells
 Major regulator of almost all immune functions
 secrete lymphokines (protein mediators)
 Interleukin- 2
 Interleukin-3
 Interleukin-4
 Interleukin-5
 Interleukin-6
 Granulocyte-monocyte colony-stimulating factor
 Interferon-gamma
 Absence of lymphokines -> paralyzed immune system
 AIDS inactivates/destroys T helper cells
 Stimulates growth/proliferation of cytotoxic T cells and suppressor T
cells
 IL-2
 Stimulation of Bcell growth/differentiation to form plasma cells and
Abs
 IL-4, 5, 6 (B cell stimulating factors), but all IL participate
 Activation of Macrophage System
 Lymphokines slow/stop migration of macrophages after they
are attracted to inflamed tissue - activate more efficient
phagocytosis
Positive Feedback on T helper cell activation

 Some lymphokines, esp IL-2
Cytotoxic T cells
 Direct attack cell, "assassin/killer cells"
 Receptor proteins on surface cause them to bind tightly to appropriate Ag
 Secretes perforins (hole-forming proteins) - punch round holes in attached
cell's membrane, allows fluid to rush into cell - swells
 Releases cytotoxic substances into attacked cell
 Especially lethal to viral infected cells
 Virus particles become entrapped in membranes of tissue cells and
attract killer cells
 Important for destroying cancer cells, heart transplant cells, and other
foreign cells
Suppressor T cells
 Capable of suppressing cytotoxic and helper T cells
 Prevents killer cells from excessive immune rxns
 Classified as regulatory T cell (w/T helper cells)
 Important in immune tolerance (limiting ability of IS to attack person's own
body tissues)
o
o



Most develops during preprocessing of T cells in thymus and B cells in BM
Failure causes autoimmune dzs
 Rheumatic fever - body become immunized against tissue in joints and heart
 Streptococcal toxin-epitope that is molecular structurally similar to some of
body's self-Ags
 Glomerulonephritis - immunized against basement membranes of glomeruli
 Myasthenia gravis - immunized against Ach receptor proteins of the
neuromuscular junction-> paralysis
 Lupus erythematosus - immunized against many tissues at once -> extensive
damage, rapid death
Immunization by Injection of Ags
o Injecting dead organisms no longer capable of causing dz, still have chemical Ags
 bacterial dzs (i.e. whooping cough, diphtheria)
o Injecting toxins tx w/chemicals so toxic nature is destroyed, Ags still intact
 Toxic dzs (i.e. tetanus, botulism)
o Injecting live organisms that are attenuated, mutated enough that they will not cause
dz
 Viral dzs (i.e. smallpox, yellow fever, measles)
Passive Immunity
o Infusing Abs, activated T cells or both obtained from the blood of someone else or from
an animal that has been actively immunized against the Ag
o Abs lasts in recipient for 2-3 weeks
o Activated T cells last for few hours to a few days
Allergy/Hypersensitivity
o Delayed-reaction allergy - caused by activated T cells (not Abs)
 i.e. poison ivy - doesn't cause much harm to tissues
 Cause formation of activated helper and cytotoxic T cells
 Subsequent exposure w/in ~1 day activated T cells diffuse from blood to
skin in large #'s
 T cells elicit cell-mediated type immune rxn -> release of many toxic
substances, invasion of macrophages
 Damage occurs in tissue area where Ag present
o Allergic Person - excess IgE
 Atopic allergies - caused by nonordinary response of IS
 Genetically passed parent to child
 Characterized by presence of large quantities of IgE in blood (reagins or
sensitizing Abs)
 Allergen - Ag that reacts specifically w/specific type of IgE reagin Ab)
 IgE Abs
 Strong propensity to attach to mast cells and basophils (one of them can
bind ~500,000 IgEs)
 Many mast cells/basophils will rupture and others will release special
agents:
 Histamine, protease, slow-reacting substance of anaphylaxis (mixture
of toxic leukotrienes), eosinophil chemotactic substance, neutrophil
chemotactic substance, heparin, and platelet activating factors
 Dilation of local blood vessels
 Attraction of eosinophils and neutrophils to reactive site


o
o
o
o
Increased permeability of capillaries w/loss of fluid into tissues
Contraction of local smooth muscle cells
Anaphylaxis
 Allergen reacts w/basophils of blood and mast cells of tissue immediately outside
small blood vessels if sensitized by attachment of IgE reagins
 Widespread allergic rxn occurs thruout vascular system = anaphylaxis
 Histamine released into circulation causes body-wide vasodilation, increase
permeability of capillaries w/marked loss of plasma from circulation
 Pt dies of circulatory shock w/in a few min unless tx w/epinephrine
 Activated basophils/mast cells release slow-reacting substance of anaphylaxis cause spasm of smooth muscle of bronchioles -> asthma like attack -> sometime
death by suffocation
Urticaria
 Ag entering specific skin areas -> localized anaphylactoid rxns
 Histamine released locally causes
 Vasodilation -> immediate red flare
 Increased local permeability of capillaries -> local areas of swelling of the
skin w/in minutes
 Swellings=Hives  Antihistamines used to prevent hives
Hay Fever
 Allergen-reagin rxn occurs in nose
 Histamine released in response to rxn causing local intranasal vascular dilation
w/resultant increase capillary pressure and permeability. -> rapid fluid leakage
into nasal cavities, nasal linings become swollen and secretory
 Antihistamines used to prevent swelling rxn
 Other products can still cause typical sneezing syndrome
Asthma
 Often occurs in "allergic" type person
 Allergen-reagin rxn occurs in bronchioles
 Mast cells release slow-reacting substance of anaphylaxis -> spasm of bronchiolar
smooth muscle
 Pt has difficulty breathing until cause is removed
 Antihistamines don't work b/c histamine does NOT appear