reflection
w651374616
Microbiology_course_materals_SpecificImmunity.pdf
Welcome to Immunology…
Round Two! Bio120: Introduction to Microbiology
City College of San Francisco Matthew Schweitzer
Where were we? Oh Yes! Ralph!
He has evaded your innate defenses… now what?
Ralph is dipping, diving, dividing, and generally running amok in your body now. He has bypassed your innate defenses. Time
to send in the calvary!
The Host Defenses – Three Levels of Protection First Line (Innate)
× Any barrier that blocks invasion at the portal of entry
× Limits access to the internal tissues of the body
× Not considered a true immune response because it does not involve recognition of foreign substances
× Very general in action
Second Line (Innate)
× Internalized system of protective cells and fluids
× Includes inflammation and phagocytosis
× Acts rapidly at both the local and systemic levels once the first line of defense has been circumvented
Third Line (Specific)
× Acquired on an individual basis as each foreign substance is encountered by lymphocytes
× The reaction with each different microbe produces unique protective substances
× Provides long-term immunity
Crash! Burn!
WSQ1: How does the third line of defense differ from the first two? Be general and then see if you can come up with some specific examples.
Specific Immunity: The Third and Final Line of Defense Immunocompetence: the ability of the body to react to/with countless foreign substances Adaptive immunity acquired only after an immunizing event such as an infection
Your body has noticed Ralph!
Ah-Ha!
What Do We See? × Antigens or immunogens: molecules that stimulate a response
by B and T cells × Protein or polysaccharide molecules on or inside cells and
viruses × Any exposed or released protein or polysaccharide is
potentially an antigen × Foreign molecules that stimulate an immune response × Unlike PAMPs, antigens are highly individual and stimulate
specific immunity.
Two features that characterize the specific immune response are specificity and memory POW!
Zap!
BAM!
Specificity × Lymphocytes and
antibodies only recognize one epitope or antigenic determinant each
Memory × Your adaptive immune
system will remember pathogens it has encountered before and react faster and stronger than before!
Who Are Our Heroes?
B Lymphocytes T Lymphocytes
WSQ2: What is the difference between
cell-mediated immunity and humoral immunity?
The Players: × Principal stages of immunologic development and
interaction: × Lymphocyte development and differentiation × Presentation of antigens × Challenge of B and T cells by antigens × T-lymphocyte response: cell-mediated immunity
(Cell-Mediated) × B-lymphocyte response: production and
activities of antibodies (Humoral)
Lymphocyte Development × All lymphocytes arise from the same basic stem cell type. × B cells mature in specialized bone marrow sites. × T cells mature in the thymus. × Both cell types migrate to separate areas of lymphoid
organs.
× B and T cells constantly recirculate through the circulatory system and lymphatics, migrating into and out of the lymphoid organs.
Entrance and Presentation of Antigens and Clonal Selection × When pathogens carrying antigens cross the first line of
defense: × Resident macrophages migrate to the site. × Tissue macrophages ingest the pathogen and
initiate an inflammatory response. × Dendritic cells ingest the pathogen and process it to
present it to T and B lymphocytes. × Gamma-delta cells can be activated by PAMPs
The Role of Markers and Receptors in Presentation and Activation × All cells have a variety of different markers on their
surfaces for: × Detection × Recognition × Cell communication
× These markers play an important role in activating different components of the immune system
Wait! Whaaaaaat?
Hruuuuuh?
How Does It Know? × Basically, your immune system has
the equivalent of facial recognition software! It is able to identify pathogens based on their unique and specific features. Much more individualized that PAMPs.
What are they looking for? Immunogen: synonymous with antigen
× Substances that can elicit an immune response
× Must meet certain requirements in foreignness, shape, size, and accessibility
× Must not be a normal constituent of the body
WSQ3: What are some examples of antigens that you can think of?
What does Ralph “look” like to your
body?
Examples of Immunogens: × Whole microbes or their parts × Cells or substances that arise from other
humans, animals, plants, and various molecules × Complex proteins and protein-containing
molecules are more immunogenic than repetitious polymers composed of a single type of unit
Most antigens fall into the following categories:
× Proteins and polypeptide: enzymes, cell surface structures, and exotoxins
× Lipoproteins: cell membrane × Glycoproteins: blood cell markers × Nucleoproteins: DNA complexed to proteins, but
not pure DNA × Polysaccharides (certain bacterial capsules) × Lipopolysaccharides
Does Size Matter? Of Course! × To initiate an immune response, a substance must be large
enough to “catch the attention” of surveillance cells:
× Large, complex macromolecules of 100,000 Daltons are the most immunogenic.
× Size alone is not sufficient for antigenicity. × Highly repetitious structures such as glycogen are not
immunogenic.
× Insulin at 6,000 Daltons is immunogenic.
The Face Of It All
Epitope × The portion of an antigenic
molecule to which a lymphocyte responds
× Primary signal to the immune system that the molecule is foreign
What If It Is Only A Piece? Haptens
× Small foreign molecules that are too small by themselves to elicit an immune response
× If this incomplete molecule is linked to a larger carrier molecule, the combination develops immunogenicity.
× The carrier group contributes to the size of the complex and enhances the proper spatial orientation of the determinative group.
× The hapten serves as the epitope
The Happening Haptens! × Examples of haptens:
× Drugs × Metals × Ordinarily innocuous household, industrial,
and environmental chemicals
× Many haptens develop antigenicity in the body by combining with large carrier molecules such as serum proteins.
The Shape Of It All Alloantigens:
× Cell surface markers and molecules that occur in some members of the same species, but not in others
× The basis for an individual’s blood group and major histocompatibility profile
× Responsible for incompatibilities that can occur in blood transfusion or organ grafting
Causing Crime With That! × Superantigens:
× Bacterial toxins that are potent stimuli for T cells × Activate T cells at a rate 100 times greater than
ordinary signals × The result can be an overwhelming release of
cytokines and cell death × Toxic shock syndrome and certain autoimmune
diseases are associated with superantigens
Give It To Me! × In most immune reactions, the antigen must be further acted upon
and formally presented to lymphocytes by antigen presenting cells (APCs).
× Examples of APCs: × Macrophages × B cells × Dendritic cells
× After processing is complete, the antigen will be bound to the MHC receptor and moved to the surface of the APC so it will be readily accessible to T lymphocytes
Give It To Me! × Most antigens must be presented first to T cells,
even though they will eventually activate both the T-cell and B-cell systems.
× T-cell-independent antigens: antigens that can trigger B cells directly without APCs or T helper cells × Carbohydrates with many repeating and
invariable determinant groups
WSQ4: What are MHC Markers and how do they work?
The Major Histocompatibility Complex (MHC) × One set of genes that codes for human cell
markers or receptors: × Found on all cells except red blood cells × Also known as the Human Leukocyte Antigen
(HLA) system × These markers play a vital role in recognition
of self by the immune system and in rejection of foreign tissue.
× Three classes of MHC genes have been identified: × Class I genes: code for markers that appear on all
nucleated cells, display unique characteristics of self, allow for recognition of immune reactions
× Class II genes: also code for immune regulatory markers found on macrophages, dendritic cells, and B cells, and are involved in presentation of antigens to T cells
× Class III genes: encode proteins involved with the complement system
The Major Histocompatibility Complex (MHC)
The MHC: A Bit Deeper
× The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells
The MHC: A Bit Deeper × The human MHC is also called the HLA (human leukocyte
antigen) complex (often just the HLA) × In a cell, protein molecules of the host's own phenotype or of
other biologic entities are continually synthesized and degraded × Each MHC molecule on the cell surface displays a molecular
fraction of a protein called an epitope × An epitope is like a face! × This presented face can be self or non-self
× If non-self, the immune system gets all rowdy!
Self Non-SelfVS
MHC: Self Vs. Non-Self
× The presented antigen can be either self or non-self, thus preventing an organism's immune system targeting its own cells
× In its entirety, the MHC population is like a meter or a gauge, indicating the balance of proteins within the cell
WSQ5: What are receptors and
co-receptors? How do they function with
regard to the immune system?
Receptors Vs Co-Receptors
× Receptor – a receptor, usually on a cell membrane, which binds to a substance (for example, a cytokine) and causes a response in the immune system
× Co-Receptor - a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell
Physiology Question….
What is a ligand and how does it work?
It’s like buying tamales in Texas at
Christmas time! YUM!
Cluster of Differentiation (CD) Receptors× In terms of physiology CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell
× A signal cascade is usually initiated, altering the behavior of the cell
× Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion
× CD for humans is numbered up to 371 (as of 21 April 2016)
CD Receptors in Humans × Two commonly used CD molecules are CD4 and
CD8, which are, in general, used as markers for helper and cytotoxic T cells, respectively
× These molecules are defined in combination with CD3+, as some other leukocytes also express these CD molecules (some macrophages express low levels of CD4; dendritic cells express high levels of CD8)
CD Receptors in Humans
Putting it into context: Human immunodeficiency virus (HIV) binds CD4 and a chemokine receptor (co-receptor) on the surface of a T helper cell to gain entry. The number of CD4 and CD8 T cells in blood is often used to monitor the progression of HIV infection
Lymphocyte Receptors Major role is to “accept” or “grasp” antigens in some form:
× B cells have receptors that bind antigens. × T cells have receptors that bind antigens that
have been processed and complexed with MHC molecules on the presenting cell surface.
× Receptors have the capacity to respond to a nearly infinite number of unique antigens
Lymphocyte Differentiation Specific events in T-Cell Maturation
× Maturation of T cells and development of their receptors is directed by the thymus gland and its hormones. × CD3 receptors: surround the T-cell receptor and assist
in binding × CD4 receptors: accessory receptor proteins that binds
to MHC II molecules × CD8 receptors: found on cytotoxic T cells and binds to
MHC I molecules
Lymphocyte Differentiation Specific Events in B-cell Maturation:
× First discovered in birds in the bursa × Occurs in certain bone marrow sites that
harbor stromal cells in humans (Stromal cells provide chemical signals that initiate B-cell development.)
× Naïve lymphocytes circulate in the blood, “homing” to specific sites in the lymph nodes, spleen, and GALT
The Origin of Immunological Diversity × By the time B and T cells reach lymphoid tissues, each one
is equipped to respond to a single unique antigen.
× Diversity is generated by rearrangement of gene segments that code for antigen receptors on T and B cells:
× Every possible recombination occurs, leading to a huge assortment of lymphocytes.
× It is estimated that each human produces antibodies with 10 trillion different specificities.
WSQ6: What is an immunoglobulin?
What Is An Immunoglobulin? Immunoglobulin (Ig): × Large glycoprotein molecules
that serve as the antigen receptors of B cells
× When secreted are antibodies
What Is An Immunoglobulin? Immunoglobulin structure:
× Antigen binding sites: pockets in the ends of the forks of the molecules that can be highly variable in shape to fit a wide range of antigens
× Variable regions: areas of extreme versatility from one clone to another
× Light chains, heavy chains, constant regions: amino content does not vary greatly from one antibody to another
T Cell Receptors × Belongs to the same family as the B-cell
receptor
× Similar to B cells: × Formed by genetic recombination × Has variable and constant regions × Inserted into membrane × Has an antigen binding site × Relatively small and never secreted
Clonal Selection × The mechanism by which the exactly correct B or T
cell is activated by any incoming antigen
× Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the tissues.
× Each genetically distinct lymphocyte expresses only a single specificity and can react to only one type of antigen
Clonal Expansion
The rapid multiplication of B or T cell clones after activation by an antigen
Cell-Mediated Immunity
WSQ7: What are the different types of T cells and what are their roles in immunity?
It’s All About Those T’s, About Those T’s! The three functional types of T cells are as follows:
× Helper T cells: activate macrophages, assist B-cell processes, and help activate cytotoxic T cells
× Regulatory T cells: control the T-cell response × Cytotoxic T cells: lead to the destruction of infected host
cells and other “foreign” cells
× T cells secrete cytokines to help destroy pathogens, but they do not produce antibodies.
T-Cells × T-cell reactions are the most complex and diverse in the
immune system and involve several subsets of T cells. × Actions of T cells are dictated by the APCs that activate them. × Restricted: require some type of MHC (self) recognition before
they can be activated × All T cells produce cytokines with a spectrum of biological
effects. × End result of T-cell stimulation is the mobilization of other T
cells, B cells, and phagocytes
Helper T Cells × Arguably the most important cells in adaptive
immunity, as they are required for almost all adaptive immune responses × Help activate B cells to secrete antibodies × Help macrophages to destroy ingested
microbes × Help activate cytotoxic T cells to kill
infected target cells
Helper T-Cells × Three types of T helper cells that all bear the CD4 marker and
are critical in regulating immune reactions to antigens × Also involved in activating macrophages × Directly by receptor contact × Indirectly by releasing cytokines such as interferon gamma
(IFNγ) × Secrete interleukin 2 (IL-2), which stimulates primary growth of
T cells, including cytotoxic T cells × Secrete IL-4, IL-5, and IL-6, which stimulate B cells × Make up about 65% of the T-cell population
Helper T Cells × Can only function when activated to become
effector cells
× Activated on the surface of antigen-presenting cells, which mature during the innate immune responses triggered by an infection
× The innate responses also dictate what kind of effector cell a helper T cell will develop into and thereby determine the nature of the adaptive immune response elicited
Presenting to the Presenter
× To activate a cytotoxic or helper T cell to proliferate and differentiate into an effector cell, an antigen-presenting cell provides two kinds of signals: × Signal 1 × Signal 2
Presenting to the Presenter × Signal 1 – provided by a foreign
peptide bound to an MHC protein on the surface of the presenting cell × This peptide-MHC complex
signals through the T cell receptor and its associated proteins
Presenting to the Presenter × Signal 2 - provided by costimulatory proteins, especially
the B7 proteins (CD80 and CD86), which are recognized by the co-receptor protein CD28 on the surface of the T cell × The expression of B7 proteins on an
antigen-presenting cell is induced by pathogens during the innate response to an infection
× Effector T cells act back to promote the expression of B7 proteins on antigen-presenting cells, creating a positive feedback loop that amplifies the T cell response
Regulatory T Cells × The regulatory T cells (T-Regs) formerly
known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease
Regulatory T Cells × T-Regs are immunosuppressive
and generally suppress or downregulate induction and proliferation of effector T cells
Saaaaaaay Whaaaaaat?
Regulatory T Cells × Downregulation is the process by which a
cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus.
× The complementary process that involves increases of such components is called upregulation
Cytotoxic T Cells
× Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also implicated in transplant rejection
× These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surfaces
Cytotoxic T Cells Target cells that TC cells can destroy include:
× Virally infected cells: recognize virus peptides displayed on the cell surface
× Cancer cells: TC constantly survey the tissues and immediately attack any abnormal cells they encounter
× Cells from other animals and humans: the most important factor in graft rejection
Cytotoxic T Cells
× These cells recognize their targets by binding to antigen associated with MHC class I molecules, which are present on the surface of all nucleated cells
× Through IL-10, adenosine, and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state, which prevents autoimmune diseases
https://www.youtube.com/watch?v=WdCiaIS2LV4
WSQ8: What cells are a bridge between the innate and specific immune systems?
Gamma-Delta T Cells × Distinct from other T cells: × Have T-cell receptors arranged to recognize a wide range of
antigens × Frequently respond to certain kinds of PAMPs in the same way
as nonspecific WBCs × Respond more quickly and produce memory × Particularly responsive to certain types of phospholipids and
react to tumor cells × Considered the bridge between nonspecific and specific
immune responses
Natural Killer Cells × Lack specificity for antigens × Circulate through the spleen, blood, and lungs × Probably the first killer cells to attack cancer cells and
virus-infected cells
× Destroy these cells in a similar fashion as TC cells × Not part of specific immunity, but sensitive to IL-12 and
interferon
https://www.youtube.com/watch?v=HNP1EAYLhOs
Natural Killer T (NKT) Cells × Hybrid cell that is part killer cell and part T cell × Has T-cell receptors for antigen and the ability
to release large amounts of cytokines very quickly, leading to cell death
× Another bridge between nonspecific and specific immunity
T cells secrete cytokines to help destroy pathogens, but they do not produce
antibodies
Humoral Immunity
WSQ9: What are the components of humoral immunity, and what is so
special about it?
Humoral Immunity – B Cells × When activated, B cells divide and give rise to
plasma cells. × Plasma cells release immunoglobulins
(antibodies) into the tissue and the blood. × Antibodies attach to the antigen for which
they are specific, and the antigen is marked for destruction or neutralization
What is this thing we call an Antibody??? × Symmetrical Y-shaped
arrangement
× Antigen-binding fragments (Fabs) × End of each Fab fragment folds
into a groove that can accommodate an epitope
× Crystallizable fragment (Fc)
What is this thing we call an Antibody??? × Pair of identical heavy chains (H): bonded
together with disulfide bonds
× Pair of identical light chains (L): one light chain bonded to one heavy chain with disulfide bonds
× Region between the Fab and Fc regions allows swiveling of the Fab fragments
Antibodies, Antibodies Everywhere! × Hypervariable region:
× The site on the antibody where the epitope binds × Amino acid content of this region is extremely
varied × Specificity of antigen binding sites for antigens is
very similar to enzymes and substrates × Specificity on the two Fab sites is identical, so an
Ig molecule can bind epitope on the same cell or on two separate cells, and bind them.
×
WSQ10: How do antibodies work?
Neutralization
× Antibodies bind with the pathogen and form antibody/pathogen complexes × These complexes incapacitate the pathogen
by preventing it from communicating with other cells in the body
× If the pathogen cannot communicate, it dies off
Neutralization
× Imagine a computer system with a sophisticated firewall. The firewall detects an intrusion and closes the port before the virus or Trojan horse can invade the computer and communicate with the other files.
Opsonization
× Antibodies bind to the pathogen and release a chemical to attract the phagocytic cells
× Imagine a guard dog (antibodies) cornering a burglar and barking to signal his location until someone arrives to take the burglar to jail
Complement Activation
× Some antibodies perform double duty by binding and marking intruders and by activating complement… do you remember which ones????
× Imagine that the guard dog (antibodies) corners the burglar and signals his location. The security guard (complement) arrives on the scene and handcuffs the burglar. Then, the police (phagocytes) arrive to take the burglar to jail.
Antitoxins × An antitoxin is an antibody with the
ability to neutralize a specific toxin × Antitoxins are produced by certain
animals, plants, and bacteria × Although they are most effective in
neutralizing toxins, they can kill bacteria and other microorganisms
Agglutination × The clumping of cells such as bacteria or red blood
cells in the presence of an antibody or complement
× The antibody or other molecule binds multiple particles and joins them, creating a large complex which increases the efficacy of microbial elimination by phagocytosis as large clumps of bacteria can be eliminated in one pass, versus the elimination of single microbial antigens
Functions of the FC × Fc end contains an effector portion that can bind to
receptors on the membranes of cells, such as macrophages.
× Effect of Fc binding depends on the cell’s role: × Opsonization: attachment of antibody to foreign
cells is followed by binding of the Fc portion to phagocytes
× Fc end of IgE binds to basophils and mast cells, causing release of allergic mediators
The Variable Region
× Very specific conformation
× Recognizes SPECIFIC antigens × Epitopes and haptens
WSQ11: What are the different classes of
antibodies and what do they target/assist with?
Immunoglobulin A - IgA × Second most common human immunoglobulin
in serum × Secreted in milk and is also the most prevalent
lg in secretions (e.g. tears, saliva and mucous) × Resistant to digestion and can activate the
complement pathway when aggregated × both subclasses of IgA (IgA1 and IgA2) bind
fragment crystallization (Fc) receptors
Immunoglobulin D - IgD × Expressed on the surface of mature
B cells, human immunoglobulin D (IgD) works with IgM in B cell development
× IgD is found in very low levels in serum and does not activate the complement pathway
Immunoglobulin E - IgE × Expressed on the surface of mature B cells × The least abundant Ig in the serum and does not activate
the complement pathway × Fc receptors for IgE are found on eosinophils and IgE binds
Fc receptors on mast cells and basophils even before interacting with antigen
× As a result of its binding to basophils and mast cells, IgE is involved in allergic reactions
× This happens when allergen is bound to IgE on cells and releases various pharmacological mediators which cause allergies
Immunoglobulin G - IgG × Expressed on the surface of mature B cells and is
the most prevalent Ig in serum and the major Ig in extravascular spaces. IgG1, IgG2 and IgG3 are complement activators, with IgG3 being the strongest
× Human immunoglobulin subclasses IgG1 and IgG3 tend to strongly bind fragment crystallization (Fc) receptors, whereas subclasses IgG2 and IgG4 bind weakly
× IgG is also the only human immunoglobulin to pass from mother to fetus to transfer immunity
× It should be noted, the human immunoglobulin subclass IgG2 does cross the placenta, but it does so weakly
Immunoglobulin G - IgG
Immunoglobulin M - IgM × expressed on the surface of immature and mature B
cells as monomers
× IgM is the third most abundant human immunoglobulin.
× IgM is also the first human immunoglobulin to be made by a fetus and virgin B cells which are challenged with antigen
× IgM is a strong complement activator and agglutinator due to its pentameric structure and binds fragment crystallization (Fc) receptors
Innate Immunity - Part 2
WSQ12: What are Type 1 Hypersensitivity
Responses, and what are allergies?
The Immune Response: A Two-Sided Coin × The human immune system is powerful and intricate, having the
potential to cause injury and disease.
× Defects in the immune system can range from hay fever to dermatitis.
× Abnormal or undesirable immune functions can result in: × Asthma × Anaphylaxis × Diabetes × Rheumatoid arthritis × Graft rejection
The Immune Response × Immunopathology: the study of disease associated with the
overreactivity or underreactivity of the immune response
× Hypersensitivity: × Allergy and autoimmunity × Tissues are attacked by immunologic functions that
can’t distinguish between self and nonself.
× Hyposensitivity or immunodeficiency: immune system is incompletely developed, suppressed, or destroyed
Hypersensitivity – 4 Types × Type I: anaphylaxis, allergies such as hay fever,
asthma
× Type II: blood group incompatibility, pernicious anemia, myasthenia gravis
× Type III: systemic lupus erythematosus, rheumatoid arthritis, serum sickness, rheumatic fever
× Type IV: Infection reactions, contact dermatitis, graft rejection
Allergy or Hypersensitivity? × Allergy vs. Hypersensitivity:
× Allergy: exaggerated immune response that is manifested by inflammation
× Hypersensitivity: delayed reactions × Allergens: innocuous substances that induce allergy in sensitive
individuals
× Atopy: chronic local allergy such as hay fever or asthma
× Anaphylaxis: systemic, sometimes fatal reaction that involves airway obstruction and circulatory collapse
Who Gets Allergies?
× Allergists estimate that 10 – 30% of the population is prone to atopic allergy
× Self-treatment with over-the-counter medications makes this a low estimate
Type I Hypersensitivity/Allergy
× Relatively mild × Asthma and anaphylaxis may require
hospitalization and can cause death. × Some allergies last for a lifetime, some are
“outgrown,” others develop later in life.
Who Gets Type I Hypersensitivity/Allergies? × Generalized susceptibility to allergens is inherited, not
the allergy to a specific substance.
× Genetic basis for atopy: × Increased IgE production × Increased reactivity of mast cells × Increased susceptibility of target tissue to allergic
mediators
× The prospect of a child’s developing atopic allergy is 25% if parents are afflicted and 50% if siblings or grandparents are afflicted.
Hygiene hypothesis: × The industrialized world has created a hygienic
environment: antimicrobial substances, insulated homes, etc.
× Immune systems need to be “trained” by interaction with microbes as they develop.
× It has been shown that children who grow up on farms have lower incidences of several types of allergies.
× Delivery by caesarian section and maternal history of allergy elevates childhood risk of allergy by a factor of eight.
Who Gets Type I Hypersensitivity/Allergies?
× Effect of breastfeeding: × Newborns breastfed for the first 4 months have a
lower risk of asthma and eczema.
× Cytokines and growth factors in human milk act on the baby’s gut mucosa to induce tolerance to antigens.
× Human Microbiome Project: 600 species of bacteria can be transferred to infants through breast milk.
Who Gets Type I Hypersensitivity/Allergies?
Allergens
Allergens have certain immunogenic characteristics:
× Proteins × Haptens × Organic and inorganic chemicals
Allergen Portals of Entry × Mucosa of the gut and respiratory tract:
× Thin, moist surface that is normally quite penetrable
× Skin: × Dry, tough keratin is generally less permeable × Access occurs through tiny breaks, glands, and hair
follicles
Allergen Portals of Entry × Inhalants: airborne environmental allergens such as
pollen, house dust, dander, or fungal spores × Ingestants: allergens that enter by mouth that cause food
allergies × Injectant: allergies triggered by drugs, vaccines, or
hymenopteran (bee) venom × Contactants:
× Allergies that enter through the skin × Many are type IV (delayed) hypersensitivities
IgE- and Mast-Cell-Mediated Allergic Conditions: Atopic Diseases × Hay fever:
× A generic term for allergic rhinitis × Seasonal reaction to inhaled plant pollen or molds × Year-round reaction to airborne allergens or inhalants × Targets: respiratory membranes × Symptoms: nasal congestion, sneezing, coughing, profuse
mucus secretion, itchy, red, and teary eyes, mild bronchoconstriction
Atopic Diseases (cont’d) × Asthma:
× Respiratory disease characterized by episodes of impaired breathing due to severe bronchoconstriction
× Airways of asthmatics are extremely sensitive to minute amounts of inhalants, ingestants, or other stimuli and are chronically inflamed.
× Asthma: × Symptoms range from
labored breathing to fatal suffocation.
× Rales: clicking, bubbling, or rattling sounds in the lungs
× Lungs are overreactive to leukotrienes and serotonin.
× Natural killer cells are also recruited and activated.
Atopic Diseases (cont’d)
Atopic Diseases (cont’d) × Atopic dermatitis/eczema:
× Intensely itchy inflammatory condition of the skin
× Sensitization occurs through ingestion, inhalation, and skin contact with allergens
Atopic Diseases (cont’d) × Atopic dermatitis/eczema:
× Usually begins in infancy and is characterized by reddened, weeping, encrusted skin lesions on the face, scalp, neck, and inner surfaces of limbs and trunk.
× Lesions are itchy, painful, and predisposed to secondary bacterial infections.
Food Allergies × Most common food allergens come from peanuts, fish,
cow’s milk, eggs, shellfish, and soybeans. × Symptoms include vomiting, diarrhea, and abdominal
pain, hives, rhinitis, asthma, and occasionally anaphylaxis.
× Hypersensitivity involves IgE and degranulation of mast cells, but not all reactions involve this mechanism.
Drug Allergies × Drugs are foreign compounds
capable of stimulating allergic reactions.
× Allergen is not the intact drug itself, but a hapten given off when the liver processes the drug
Drug Allergies × Drug allergy is one of the most common side effects of treatment,
affecting 5 – 10% of hospitalized patients.
× Reactions range from a mild rash to fatal anaphylaxis. × Compounds implicated:
× Antibiotics: penicillin × Synthetic antimicrobials: sulfa drugs × Aspirin × Opiates × Contrast dye used in X rays
Anaphylaxis: An Overpowering IgE-Mediated Allergic Reaction × Anaphylaxis/anaphylactic shock:
× Cutaneous anaphylaxis: wheal-and-flare inflammatory reaction to the local injection of allergen
× Systemic anaphylaxis: characterized by sudden respiratory and circulatory disruption that can be fatal within minutes due to airway blockage
× Anaphylaxis/anaphylactic shock: × Result of the sudden, massive
release of chemicals into the tissues and blood, which act rapidly on target organs
× Bee stings and injection of antibiotics or serum are most commonly implicated
Anaphylaxis: An Overpowering IgE-Mediated Allergic Reaction
Diagnosis of Allergies – In Vitro × Radioallergosorbent (RAST) test: measures levels of IgE
to specific antigens × Tryptase test: measures tryptase, an enzyme released by
mast cells that increases during an allergic response × Differential blood cell count can reveal high levels of
basophils and eosinophils. × Leukocyte histamine-release test: measures the amount
of histamine released from the patient’s basophils when exposed to a specific allergen
Diagnosis of Allergies – In Vivo × Skin Testing: In vivo method to detect precise atopic or
anaphylactic sensitivities × Skin is injected, scratched, or pricked with a small
amount of pure allergen extract. × 20 minutes after antigenic challenge, a wheal and flare
result shows sensitivity. × The diameter of the wheal is measured and rated on a
scale from 0 (no reaction) to 4 (greater than 15 mm).
Treatment and Prevention of Allergies × Duh! Avoid the allergen, although this may be
difficult in many instances. × Take drugs that block the action of lymphocytes,
mast cells, or chemical mediators. Ex. Benedryl × Use injections that short-circuit the allergic
reaction
Using Drugs to Block Allergies × Corticosteroids: inhibit the activity of lymphocytes and
reduce the production of IgE × Have dangerous side effects and should not be taken
for long periods
× Some drugs block the degranulation of mast cells and reduce the levels of inflammatory cytokines.
× Other drugs block synthesis of leukotriene or are monoclonal antibodies that inactivate IgE
GIVE ME DRUGS!!! × Antihistamines:
× Most widely used medications for preventing symptoms of atopic allergy
× Bind to histamine receptors on target organs
× Aspirin and acetaminophen: reduce pain by interfering with prostaglandins
× Theophylline: bronchodilator that reverses spasms in respiratory smooth muscles
× Epinephrine (adrenaline): reverses constriction of airways and slows the release of allergic mediators
Allergy “Vaccines”? × Desensitization or hyposensitization:
× Therapeutic way to prevent reactions between allergen, IgE, and mast cells
× Allergen preparations include pure, preserved suspensions of plant antigens, venoms, dust mites, dander, and molds.
× Blocking antibodies: one hypothesis is that injected allergens stimulate formation of these allergen-specific IgG antibodies
× Also hypothesized that allergen delivered in this fashion combines with IgE itself, taking it out of circulation
Allergy “Vaccines”? × “Decoy” allergy vaccines
× Allergy shot contains an innocuous molecule that resembles a bacterium.
× Engages components of the immune system that are active in allergy, causing them to stop reacting inappropriately to specific allergens
WSQ13: Explain the role of Rh factor in hemolytic
disease development and how it is prevented in
newborns
Type II Hypersensitivities: Reactions That Lyse Foreign Cells × A complex group of syndromes that
involve complement-assisted destruction (lysis) of cells by antibodies (IgG and IgM) directed against those cells’ surface antigens: × Transfusion reactions × Some types of autoimmunities
× Alloantigens: × Molecules that differ in the same species
that are recognized by the lymphocytes of the recipient
× Not an immune dysfunction; the immune system is functioning normally by reacting to foreign cells in an organ or tissue transplant
Type II Hypersensitivities: Reactions That Lyse Foreign Cells
WSQ14: What are Type III Hypersensitivity reactions
and what are some examples?
Type III Hypersensitivities: Immune Complex Reactions
× Involves the reaction of soluble antigen with antibody, and deposition of resulting complexes in various tissues in the body: × Involves the production of IgG and IgM antibodies × Also involves the activation of complement × Unlike type II hypersensitivities, antigens are not
attached to the surface of a cell.
Type III Hypersensitivities: Immune Complex Reactions
× Immune complex reaction: produces free floating complexes that are deposited into tissues
Mechanisms of Immune Complex Disease
× Large quantities of antibodies are produced in response to an exposure to a profuse amount of antigen.
× Upon second exposure, antigen-antibody complexes are formed. These recruit complement and neutrophils that would normally eliminate these complexes.
Mechanisms of Immune Complex Disease
× In immune complex disease, these complexes are deposited in the basement membrane of epithelial tissues: × Neutrophils release lysosomal granules that
digest tissues and cause a destructive inflammatory condition.
Types of Immune Complex Reactions × Arthus reaction and serum sickness are
associated with certain types of passive immunization. × Similar to anaphylaxis in that all require sensitization
and preformed antibodies
× Differences from anaphylaxis: × Depend on IgG, IgM, or IgA rather than IgE × Require large doses of antigen × Symptoms are delayed hours to days
The Arthus Reaction × Localized dermal injury due to
inflamed blood vessels
× Usually an acute reaction to a second injection of vaccines (boosters) or drugs at the same site as the first injection
The Arthus Reaction × Area becomes red, hot to the touch, swollen, and
painful × Symptoms are due to the destruction of tissues
in and around blood vessels, and the release of histamine from mast cells and basophils.
× It is self-limiting and usually rapidly cleared, but occasionally intravascular blood clotting, necrosis, and loss of tissue can occur.
Serum Sickness
× Named for a condition in soldiers treated with horse serum for tetanus: × Also caused by injections of
animal hormones and drugs
Serum Sickness × A systemic injury initiated by
antigen-antibody complexes that circulate in the blood and settle into membranes at various sites: × Kidney, heart, skin, and joints × Condition can become chronic causing enlarged lymph
nodes, rashes, painful joints, swelling, fever, and renal dysfunction
WSQ15:What characterizes Type IV Hypersensitivity
responses and what are some examples?
Type IV Hypersensitivities: Cell-Mediated (Delayed) Reactions
× Involves primarily the T-cell branch of the immune system.
× Results when T cells respond to antigens displayed on self tissues or transplanted foreign cells
× Traditionally known as “delayed hypersensitivity”: × Symptoms arise one to several days
following the second contact with antigen
Infectious Allergy
× Tuberculin reaction: × Acute skin inflammation at
the injection site following an extract of Mycobacterium tuberculosis
Contact Dermatitis
× Caused by exposure to resins in poison ivy and poison oak, haptens in household and personal articles, and drugs
× Requires a sensitizing dose followed by a provocative dose.
Contact Dermatitis × Allergen penetrates the outer
skin layers: × Processed by skin dendritic cells and
presented to T cells × Subsequent exposures attract
lymphocytes and macrophages. × Cells release enzymes and cytokines
that damage the epidermis and vicinity
Transplant Rejection × Transplantation or grafting of organs is a common
medical procedure.
× Although it is life-giving, it is plagued with the natural tendency of lymphocytes to seek out and destroy foreign antigens.
× The bulk of the damage that occurs in graft rejections are attributed to cytotoxic T-cell action
Types of Grafts: × Autograft: tissue transplanted from one site on an
individual’s body to another site × Isograft: tissue from an identical twin is used × Allograft: exchanges between genetically different
individuals belonging to the same species; the most common types of grafts
× Xenograft: a tissue exchange between individuals of a different species
Types of Transplants × Transplantation has been performed on
every major organ, but most often involves the skin, liver, heart, kidney, coronary artery, cornea, and bone marrow.
× Sources of organs: × Live donors: kidney, skin, bone
marrow, and liver × Cadavers: heart, kidney, and cornea × Fetal tissue: stem cells
Types of Transplants × Bone marrow transplantation:
× Used in individuals with immune deficiencies, aplastic anemia, leukemia, and other cancers
× Patient is treated with chemotherapy and whole-body irradiation to destroy their own blood cells, preventing rejection.
× Closely matched donor marrow is infused. × GVHD can still occur, and antirejection drugs
may be necessary. × After transplantation, a recipient’s blood type
may change to the blood type of the donor
WSQ16: What is an Autoimmune
disorder and what are some examples?
An Inappropriate Response to Self: Autoimmunity × Autoimmune diseases: individuals
actually develop hypersensitivity to themselves × Autoantibodies, T cells, or both mount an
abnormal attack against self antigens. × Systemic: involves several major organs × Organ specific: involves only one organ or tissue
Genetic and Gender Correlation in Autoimmune Disease × Cases cluster in families, and even unaffected
members tend to develop autoantibodies for the disease.
× Particular genes in class I and II MHC coincide with certain autoimmune diseases:
× Rheumatoid arthritis and ankylosing spondylitis are more common in persons with B-27 HLA type.
× X-chromosome inactivation in females may also play a role in autoimmunity.
× Molecular mimicry: × Microbial antigens bearing molecular determinants similar
to human cells induce the formation of autoantibodies. × One explanation for the pathology of rheumatic fever × Psoriasis flare-ups after strep throat infections may also
be due to T cells primed to react with keratin in the skin. × Type I diabetes and multiple sclerosis may be triggered
by a viral infection
Genetic and Gender Correlation in Autoimmune Disease
Examples of Autoimmune Diseases:Systemic Autoimmunities × Systemic lupus erythematosus
(SLE or lupus): × Name originated from the characteristic
butterfly-shaped rash that drapes across the nose and cheeks.
× Manifestations vary, but all patients develop autoantibodies against organs, tissues, or intracellular materials
Systemic Autoimmunities (cont’d)× Rheumatoid arthritis: × Causes progressive, debilitating damage to the joints
and at times to the lungs, eyes, skin, and nervous system
× Autoantibodies form immune complexes that bind to the synovial membrane of joints, activating cytokine release by macrophages.
× Chronic inflammation develops, leading to scar tissue and joint destruction.
× Cytokines trigger additional type IV delayed hypersensitivity responses.
× Epstein-Barr virus has been implicated as a precipitating cause.
Ughhhhh! What is this Epstein-Barr Virus? × Epstein-Barr virus (EBV), also known as human
herpesvirus 4, is a member of the herpes virus family × One of the most common human viruses × EBV is found all over the world × Most people get infected with EBV at some point in their
lives × EBV spreads most commonly through bodily fluids,
primarily saliva × EBV can cause infectious mononucleosis, also called
mono, and other illnesses
× The EBV is being linked to many other diseases and disorders, including many forms of cancer
× The cells infected by the EBV in its lysogenic state can be determinative regarding disease/disorder manifestation
Ughhhhh! What is this Epstein-Barr Virus?
Autoimmunities of the Endocrine System × Graves’ disease:
× Attachment of autoantibodies to receptors on thyroxin-secreting follicle cells of the thyroid gland
× Abnormal stimulation of these cells causes over- production of the thyroid hormone and the symptoms of hyperthyroidism
Who has/had Grave’s disease?
Who has/had Grave’s disease?
Who has/had Grave’s disease?
Autoimmunities of the Endocrine System × Type I Diabetes:
× Molecular mimicry has been implicated in sensitization of cytotoxic T cells to attack and lyse insulin-producing beta cells.
× A recent study showed permanent reversal of type 1 diabetes by re-infusion of stem cells after complete immune suppression
Neuromuscular Autoimmune Diseases × Myasthenia gravis:
× Autoantibodies bind to receptors for acetylcholine, a neurotransmitter required for muscle stimulation.
× First effects felt in the muscles of the eyes and throat, but eventually progresses to complete loss of skeletal muscle function and death.
× Current treatment includes immunosuppressive drugs and therapy to remove autoantibodies from circulation.
Neuromuscular Autoimmune Diseases × Multiple sclerosis:
× Paralyzing neuromuscular disease associated with lesions on the myelin sheath of nerves and white matter of the nervous system.
× T cell and autoantibody-induced damage compromises the capacity of neurons to send impulses.
× Symptoms include muscle weakness, tremors, difficulties in speech and vision, and paralysis.
× Possible association between infection with human herpesvirus 6
× Treatments include immunosuppresants and interferon beta.
Hyposensitivity of the Immune System × Occasionally, an individual is born with or develops weakened
immune responses. × Predominant consequences of immunodeficiencies are recurrent,
overwhelming infections with opportunistic microbes. × Primary immunodeficiencies: present at birth (congenital), usually
stemming from genetic errors × Secondary immunodeficiencies: acquired after birth and caused by
natural or artificial agents
Primary Immunodeficiency Diseases
× Because of an inherited abnormality × In some diseases, the lymphocytes are absent, or
present at low levels. × In other diseases, the lymphocytes are present, but do
not function normally. × An individual can lack either B or T cells, or both. × Some deficiencies can affect other cell functions as
well.
Clinical Deficiencies in B-Cell Development or Expression × Genetic deficiencies in B cells usually result in
abnormal immunoglobulin (Ig) expression: × In some cases, certain classes of Igs are absent. × In other cases, all levels of Ig are reduced.
× Agammaglobulinemia: absence of gamma globulin; it is very rare for Ig to be completely absent.
× Hypogammaglobulinemia: abnormally low levels of gamma globulin
Clinical Deficiencies in B-Cell Development or Expression (cont’d) × Symptoms of hypogammaglobulinemia:
× Recurrent, serious bacterial infections appear about 6 months after birth.
× Pyogenic cocci, Pseudomonas, and Haemophilus influenzae are most often implicated; infections with viruses and protozoa are common as well.
× Most common infection sites: lungs, sinuses, meninges, and blood
× Current treatment is passive immunotherapy with immune serum globulin and continuous antibiotic therapy
Clinical Deficiencies in B-Cell Development or Expression (cont’d) × Lack of a particular class of immunoglobulin is a relatively
common condition: × IgA deficiency is the most prevalent form. × Individuals have normal quantities of B cells and other
immunoglobulins. × Lack protection against local microbial invasion of mucous
membranes, suffer recurrent respiratory and gastrointestinal infections.
× Usual treatments do not work because passive antibody therapy is high in IgG, not IgA
Clinical Deficiencies in T-Cell Development or Expression × Defects in T-cell development result
in a broad spectrum of diseases: × Severe opportunistic infections × Cancer × More devastating than B-cell deficiencies,
because T helper cells are required to assist in most specific immune functions
Abnormal Development of the Thymus × DiGeorge syndrome or thymic aplasia:
× Congenital absence or immaturity of the thymus gland
× High susceptibility to infections by fungi, protozoa, and viruses
× Vaccinations using attenuated microbes pose a danger and common childhood infections can be fatal.
× Reduced antibody production allows for transplantation of thymic tissue
Severe Combined Immunodeficiencies (SCIDs)× Most serious form of immunodeficiency: × Involve dysfunction in both lymphocyte systems × Some SCIDs are due to the lack of lymphocyte
stem cells in the bone marrow; others due to dysfunction of B and T cells later in development
× Infants with SCID usually develop candidiasis, sepsis, pneumonia, or systemic viral infections within days after birth
SCIDs (contd)
× Two most common forms: Swiss-type agammaglobulinemia and thymic alymphoplasia: × Genetic defects in the development of the lymphocyte stem cell
in the bone marrow
× Extremely low numbers of all lymphocyte types × Poorly developed humoral and cellular immunity
× Adenosine deaminase deficiency: lymphocytes develop but a metabolic product builds up and selectively destroys them
SCIDs (contd) × SCID children require rigorous aseptic
techniques to protect them from opportunistic infections:
× Only serious option for longtime survival is total replacement or correction of lymphoid cells: × Infants can benefit from fetal liver or stem cell grafts × X-linked and ADA types of SCID can be treated with gene
therapy; insertion of normal genes to replace the defective genes
https://www.youtube.com/watch?v=B84GJOsioSA
The Story of David Vetter – The Bubble Boy
Secondary Immunodeficiency Diseases× Caused by one of four general agents: × Infection × Organic disease × Chemotherapy × Radiation
× Most recognized infection-induced immunodeficiency is AIDS: × T helper cells, monocytes, macrophages, and antigen-presenting
cells infected by HIV × Depletion of T-helper cells and impairment of immune responses
account for cancers and opportunistic infections caused by AIDS
Secondary Immunodeficiency Diseases × Cancers that target the bone marrow can be responsible for
malfunction of humoral and cellular immunity: × Leukemia: cancer cells outnumber normal cells,
displacing them from bone marrow and blood × Plasma cell tumors: produce large amounts of
nonfunctional antibodies × Thymus gland tumors: cause severe T-cell deficiencies
Secondary Immunodeficiency Diseases (cont’d) × An ironic outcome of lifesaving medical
procedures is the suppression of the immune system:
× Drugs that prevent graft rejection can also suppress beneficial immune responses.
× Radiation and anticancer drugs are damaging to the bone marrow and other body cells.
Innate Immunity - Part 3
HIV
HIV – By the Numbers × 37.9 M people are infected with HIV
worldwide as of 2018 × 1.7 M new infections each year
× About 4700 new infections per day × 770,000 deaths each year attributed to
HIV (down from 1.7 million in 2010)
History of HIV
https://www.youtube.com/watch?v=ph6_Z6NIx98
Please watch the video on the history of the HIV pandemic before we have our zoom meeting. IT IS ABOUT AN HOUR AND A HALF LONG.
HIV Subtype Distribution
HIV Structure
× Retro-virus × gp120 - binds CD4
on target cells
× Packaged with assistant enzymes
HIV Life Cycle
https://www.youtube.com/watch?v=ng22Ucr33aw
HIV Pathogenesis × HIV enters mucous membrane or skin × Infects dendritic cells which are CD4+, grows and is
shed × Is amplified by macrophages (also CD4+) × Infects CD4+ T-lymphocytes (helper T-cells) × Also needs the CCR-5 coreceptor present to enter
the cell × Ironic that HIV infects the very cells needed to combat
it…..
HIV Transmission × Direct and specific contact × High levels of virus in blood - any trauma,
needle sharing, blood transfusion × Semen and vaginal secretions harbor
virus and infected white blood cells × Breast milk - via white blood cells × NOT BY saliva, urine, tears (viral load is
too × low)
HIV Treatment
× Anti-HIV meds that treat the HIV infection × Drugs that treat side effects of the
disease or HIV treatment × Drugs that treat the opportunistic
infections that result from a weakened immune system
HIV Treatment
× The FDA has approved more than 25 antiretroviral drugs to treat HIV infections
× Things they can do: × Lower the viral load in the patient’s system × Fight infections × Improve patient’s quality of life
HIV Treatment × Even when HIV medications are effective, the patient
can still transmit HIV to others × There currently is no proven cure for HIV × Current ideal medications do the following:
× Control the growth of the virus × Improve overall immune system function and status × Suppress symptoms × Produce as few side effects as possible
× HAART × Highly Active Antiretroviral Therapy
Classes of HIV Medications × 1. Reverse transcriptase (RT) inhibitors help block
an important step in the HIV life cycle. There are two types of RT inhibitors. × Nucleoside/nucleotide reverse transcriptase inhibitors
(NRTIs) stall reproduction of HIV. They force the virus to use faulty versions of building blocks.
× Non-nucleoside RT inhibitors (NNRTIs) bind to the RT protein. This disables it, keeping HIV from making copies of itself.
× 2. Protease inhibitors interfere with an enzyme that HIV uses to create infectious viral particles.
Classes of HIV Medications × 3. Fusion inhibitors help block HIV's entry into healthy cells.
× At this time, Fuzeon (enfuvirtide), ENF, is the only one the FDA has approved.
× 4. Entry Inhibitors also help block HIV's entry into healthy cells. × Currently, maraviroc (Selzentry) is the only FDA-approved drug, but
others are in late stage clinical trials
× 5. Integrase inhibitors block insertion of viral DNA into the host cell DNA. × Currently, Isentress (raltegravir), Vitekta (elvitegravir), and Tivicay
(dolutegravir) are the only FDA-approved drugs, but others are in clinical trials
× Dolutegravir is part of a combination pill called Triumeg, which also includes abacavir and lamivudine
HIV Cure?
× What are we looking for? × Sterilizing cure
× Means total eradication of HIV from the body × Functional cure
× Prevent disease progression × Have long periods (years) that are treatment
free (remission)
HIV Cure?
The Berlin Patient × Received bone marrow transplant
× Caused functional cure × Leukemia × Donated marrow had mutation in CCR5...HIV can’t
bind to his immune cells
× Not practical for most people….
HIV Cure? 2015 × A drug used to treat alcoholism - called disulfiram - could bring
us closer to a cure for HIV × Antiretroviral therapy (ART) is the primary treatment for HIV,
involving a combination of at least three antiretroviral drugs that slow disease progression.
× While the treatment has led to reductions in HIV death rates worldwide, it is not a cure.
HIV Treatment × ART is unable to eliminate HIV from patients completely
× the virus can lay dormant in cells, hiding from immune system attack.
× But in phase 2 clinical trial, the researchers found disulfiram helped "wake up" dormant HIV cells, allowing them to be destroyed - a "shock-and-kill" approach that researchers believe is key to curing the virus
WSQ17: What are vaccinations and
what is their purpose?
Natural vs Artificial Immunity
× Natural immunity: any immunity that is acquired through the normal biological experiences of an individual
× Artificial immunity: protection from infection obtained through medical procedures such as vaccines and immune serum
Specific Immunity Active immunity: × Occurs when an individual receives immune stimulus that
activates B and T cells to produce immune substances such as antibodies
× Creates memory that renders the person ready for quick action upon re-exposure to the same antigen
× Requires several days to develop × Lasts for a relatively long time × Can be stimulated by natural or artificial means
Specific Immunity Passive immunity:
× Recipient is protected for a short period of time, even though they have not had prior exposure to the antigen
× Lack of memory for the original antigen × Lack of antibody production against the disease × Immediate onset of protection × Short-term effectiveness × Can be natural or artificial in origin
Immunization – A Lively History! First recorded attempt at immunization occurred in 6th century China:
× Consisted of drying and grinding up smallpox scabs and blowing them with a straw into the nostrils of vulnerable family members
Variolation in the 10th century • Deliberate inoculation of dried pus
from smallpox pustules of one patient into the arm of a healthy person
• Used in parts of the Far East until Lady Montagu brought it to England in 1721
• Unfortunately, many recipients and their contacts still died of smallpox
Edward Jenner × 1796
× Inspired by a dairymaid who had been infected by cowpox and who was immune to smallpox
× Tested his theory by injecting a young boy with material from human cowpox lesions, exposed him to smallpox 2 months later, and was immune to the disease
× Use of this vaccine was first regarded with skepticism, but later adopted when it proved successful
× Vaccination: any immunity obtained by inoculation with selected antigens
Passive Immunization × First attempts involved the
transfusion of horse serum containing antitoxins to prevent tetanus and treat diphtheria.
× Antisera from animals has now been replaced with human products, or genetically engineered products.
Passive Immunization Gamma globulin:
× Immunoglobulin extracted from the pooled blood of many human donors
× Used to treat specific infections in high-risk neonates and other immunocompromised patients
× Useful when there is no effective treatment available or to treat immune deficiencies
Artificial Active Immunity × Basic principles behind
vaccination: × Stimulate a primary response and a
memory response × Prime the immune system for future
exposure to a virulent pathogen × If the pathogen enters the body, the
response will be immediate, powerful, and sustained
Artificial Active Immunity
× Vaccines have profoundly reduced the prevalence and impact of many infectious diseases that were once common and deadly
What To Look For In A Vaccine: × Protect against exposure to natural, wild forms of the
pathogen × Have a low level of adverse side effects or toxicity, and not
cause harm × Stimulate both antibody (B-cell) and cell-mediated (T-cell)
response × Long-term, lasting effects (produce memory) × Does not require numerous doses or boosters × Inexpensive, have a relatively long shelf life, and be easy to
administer
Vaccine Types:
× Whole cell or virus vaccines: × Live, attenuated cells or viruses × Killed cells or inactivated viruses
× Examples include: × MMR × Pertussis
Vaccine Types: × Antigenic molecules derived from
bacterial cells or viruses (subunits): × Subunits derived from cultures of cells or viruses × Subunits synthesized to mimic natural molecules × Subunits manufactured via genetic engineering × Conjugated vaccines: subunits conjugated with
proteins to make them more immunogenic
Vaccine Side Effects: × Vaccines must go through years of trials in
experimental animals and human volunteers before they are licensed for general use.
× Still some complications occur: × Local reactions at the injection site × Fever × Allergies × Other adverse reactions
Vaccine Side Effects: × Rare reactions:
× Panencephalitis (measles vaccine) × Back-mutation to a virulent strain (polio vaccine) × Disease due to contamination with dangerous
viruses or chemicals × Neurological effects of unknown cause (pertussis
and swine flu vaccines) × Allergic reactions to the medium rather than
vaccine antigens (egg or tissue culture)
WSQ18: What is the Anti-vaxx Movement and
why has it gained a foothold in the USA?
Anti-Vaxx Movement × No link between autism and MMR
vaccine: × 1998 paper linking autism to MMR was entirely
discredited and the principal author’s medical license was revoked.
× Scores of studies have studied these negative associations and found they are unsupportable.
× 2011: Institute of Medicine stated unequivocally that MMR vaccine does not cause autism
Why Vaccinate?
× Price of not vaccinating: × Outbreaks of measles, mumps, diphtheria,
polio, typhoid fever, and whooping cough × Decrease in the level of herd immunity, a
phenomenon in which a certain percentage of the population is vaccinated, making it impossible for the microbe to circulate
Why Vaccinate?
× Getting vaccinated serves the common good, as well as the individual good
× Many young parents have no memory of the pre-vaccination era and don’t appreciate the greater risk of not vaccinating their children
Why Vaccinate? × In the decade before the
measles vaccine was available: × 3 – 4 million cases of measles per
year × 300 – 400 children died annually × 1000 more chronically disabled due
to measles encephalitis
Why Vaccinate?
× Childhood vaccines save the lives of 2.5 million children a year worldwide (UNICEF).
× Risks from infectious disease almost always outweigh the chance of an adverse vaccine reaction
When To Not Vaccinate?
× Caution must be exercised in giving live vaccines to immunocompromised or pregnant patients.
When To Vaccinate?
× Recommendation has been vaccination for all typical childhood diseases for which a vaccine is available: × Adults, only in certain circumstances: health workers,
travelers, military personnel
× Revised recommendation: vaccination in adults to “boost” older immunizations, protect against adult infections, and to provide special protection in people with certain medical conditions
Innate Immunity - Fin
