Immunology

Front 1

Innate

Back 1

Innate – non-specific; no memory; fast (hrs); constant; Protection against infections that relies on mechanisms that exist before infection, are capable of rapid responses to microbes, and react in essentially the same way to repeat infections. The innate immune system include epithelial barriers; phagocytic cells; NK cells; complement system; cytokines, largely made by mononuclear phaogcytes, that regulate and coordinate many of the activities of the cells of innate immunity.

Front 2

Adaptive

Back 2

Adaptive – highly specific; has memory; slow (days); a form of immunity that is mediated by lymphocytes and is stimulated by exposure to infectious agents. In contrast to innate immunity, adaptive immunity is characterized by exquisite specificity for distinct macromolecules, and “memory”, which is the ability to respond more vigorously to repeated exposures to the same microbe.

Front 3

Tolerance

Back 3

A state of immunologic inactivity; a state of immunologic inactivity after exposure to an antigen; immune system is tolerant (non-reactive) to self (most of the time) and destructive to non-self

Front 4

Immunogens

Back 4

Agents that provoke immune responses (ex. Influenza virus)

Front 5

Epitopes

Back 5

Specific portion of amcromeolecular antigen to which an antibody binds. In the case of a protein antigen recognized by a T cell, an epitope is the peptide portion that binds to a major histocompatability complex molecule for recognition by the T cell receptor. It is synonymous with determent.

Front 6

Haptens

Back 6

Small chemical that can bind to an antibody but must be attached to a macromelucle (carrier) to stimulate an adaptive immune response specific for that chemical. Ex. DNP immunization alone does not stimulate an anti-DNP antibody response, but immunization with the DNP hapten attached to a protein does stimulate anti-DNP antibody production.

Front 7

Antibodies

Back 7

Antigen-specific proteins secreted by B lymphocytes; Binds large and small molecules; antibodies made for a pathogen are highly specific for that pathogen; highly variable aa’s in the V regions of Ig heavy and light chains; can be enzymatically cleaved into functionally distinct fragments; Fc portions of Ig bind to Fc receptors (FcR) on phagocytes and other cells
Isotypes: IgG, IgM, IgD, IgA, IgE

Front 8

What contributes to antibody diversity?

Back 8

• Multiple V, D, J gene segments (aka recombinatorial diversity)
• Multiple heavy (8) and light (2) chains (aka combinatorial diversity)
• Junctional diversity
• Somatic hypermutation (see Ch. 7)
possible combinations: 1014!

Front 9

Allelic exclusion

Back 9

The expression of only one of two inherited alleles encoding immunoglobulin heavy and light chains and T cell receptor Beta chains; occurs when the protein product of one productively recombined antigen receptor locus onone chromosome blocks the rearrangement of the corresponding locus on the other chromosome.

Front 10

Polyclonal activators

Back 10

Agent capable of activating many clones of lymophoscytes, regarless of their antigen specificities. Anti-IgM antibodies for B cells and anti-CD3 antibodies and phytohemagglutinin for T cells

Front 11

ELISA

Back 11

Enzyme-linked immunosorbent assay; quantifies an antigen immobilized on a solid surface using a specific antibody with a covalently coupled enzyme; amount of antibody that bbinds the antigen is proportional to the amount of antigen present and is determined by spectrophotometrically measuring the conversion of a clear substrate to a colored product by the coupled enzyme.

Front 12

List other important receptors found on immune cells

Back 12

1. Fc receptors (FcR): Bind the Fc region on antibodies. Can deliver growth or inhibitory signals
2. Cytokine receptors: bind cytokines. Deliver activation, growth, and differentiation signals; some are inhibitory. Now targets of biologic therapeutics.
3. Chemokine receptors: Bind chemokines. Can trigger movement towards a site, or keeps a cell at a site.
4. Complement receptors (CR): Bind C’ components. Activate phagocytosis or clear immune complexes.
5. Pattern recognition molecules: initiate innate immune responses

Front 13

Good antigen

Back 13

Protein>carb>>lipids; large>small; route of immunization: subcutaneous, intramuscular>intraperitoneal>IV, oral
Regions of an antigen that specifically bind an antibody are antigenic determinants or epitopes
Linear (bacterial ell walls) and conformational (proteins)
Antibodies (B cells) recognize intact proteins.
T cells see degraded peptides bound by MHC molecules.
Antigens containing more than one epitope are called multivalent. (most antigens)

Front 14

Affinity vs Avidity

Back 14

Affinity is the relative strength of a single antibody binding site for antigen (a qualitative measure).
Avidity is the overall strength of the combined binding sites (2x for IgG, 10x for IgM) of a given antibody molecule (a quantitative measure).
IgM can form a pentamer and IgA can form a dimer

Front 15

Haptens

Back 15

Special class of antigen; Haptens can’t provoke antibody responses by themselves.
Haptens must be coupled to a larger molecule, often a protein called a carrier (in this case, a RBC surface molecule); Haptenylation reactions can occur for both B and T cells.

Front 16

T-cell Receptors

Back 16

Oligopeptides + MHC molecules

Front 17

Alternative Complement

Back 17

Innate immune response; Activation of the complement system does not require antibodies when the alternative and MBL* pathways are triggered; MBL is one of the acute phase proteins released by the liver early in the response to infection; The pathway starts via spontaneous cleavage of C3 to C3b (“tick-over”; occurs naturally).
C3b is rapidly degraded unless it lands on a microbial cell surface!
When C3 is cleaved to C3b, it binds factor B, which activates Factor D.
Factor B binds to C3b on microbial cell surfaces.
Factor D cleaves Factor B/C3b to Bb/C3b.
Factor P (properdin) stabilizes the Bb/C3b complex.
The Bb/C3b complex activates C3, and the remainder of C’is pathway activated.

Front 18

Cytokines

Back 18

Secreted proteins that function as mediators of immune and inflammatory reactions; innate immune responses; produced by macrophages and NK cells and in adaptive immune responses mainly by T lymphos

Front 19

Adhesion molecules

Back 19

Cell surface molecule whose function is to promote adhesive interactions with other cells or ECM; lwukocytes express various types of adhesion molecules such as selectins and integrins and these molecules play important roles in cell migration and actibation in innate and adaptive immune responses.

Front 20

Chemokines

Back 20

• Chemokines attract cells of both the innate and adaptive immune system; Chemokines recruit fresh phagocytes and lymphocytes to local sites of infections.
• Infected cells (endothelial cells, fibroblasts, keratinocytes, among others), along with monocytes, macrophages, and dendritic cells secrete chemokines.
• Local infection is thus prevented from becoming systemic.

Front 21

Defensins

Back 21

Cystein-rich peptides produced in epithelia and neutrophil granules, which act as broad-spectrum antibiotics that kill a wide variety of bacteria and fungi.

Front 22

B Lymphocytes

Back 22

secrete antibodies (as plasma cells); present antigen to T cells; capture antigens via cell surface antibody molecules

Front 23

T Lymphocytes

Back 23

• kill infected cells
• secrete cytokines activate phagocytes, T and B cells

Front 24

NK cells (large granular lymphocytes)

Back 24

• Kill tumor and virally infected cells; act as an early defense against viral infections
• Comprise about 5% of total peripheral blood lymphocytes.
• Do NOT undergo TcR or Ig rearrangement.
• Able to kill virus infected cells without prior exposure, unlike T cells.
• Able to kill tumor cells, esp. those of hemopoietic lineage.
• Have FcR, and so can kill Ig-coated cells via antibody-dependent cell-meditated cytotoxicity (ADCC).
• Can activate macrophages to kill phagocytized pathogens.
• Rare deficiencies of NK cells lead to repeated viral infections, esp. those of herpes family.

Front 25

Antigen Presenting Cells

Back 25

Take up antigen in the periphery and present antigens to T cells; activate T cells; include macrophages (phagocytosis), dendritic cells (best – most MHC, receptors, cytokine production) (phagocytosis), and B cells (antigen-specific receptor)

Front 26

Dendritic Cells

Back 26

Present antigen to T cells via MHC molecules; capture antigen by endocytosis; deliver antigen to lymph nodes; most are found in the skin or mucosal tissues as Langerhans cells; the BEST APC!!

Front 27

MHC’s

Back 27

Oligopeptides; Cluster of genes on Chr 6 that encode proteins which (1) control T cell mediated immune responses (2) determine the fate of transplanted tissues; MHC genes are co-dominant and inherited as haplotypes; expression on MHC molecules differs btw tissues and cell types; MHC II = APC & MHC I = every tissue; erythrocytes and neurons do not have MHC’s; MHC’s bind peptides and present them to T cells
MHC I = CD8
MHC II = CD4

Front 28

polymorphism

Back 28

The existence of two or more alternative forms, or variants, of a particular gene, which are present at stable frequencies in a population. Each common variant of a polymorphic gene is called an allele, and one individual may carry tow different alleles of a gene, each inherited from a different parent. The MHCs are the most polymorphic genes in the mammalian genome.

Front 29

alloantigen

Back 29

Cell or tissue antigen that is present in some members of a species and not others and which is recognized as foreign on an allograft; products of polymorphic genes.

Front 30

T cell Effector Functions

Back 30

1. Macrophage activation: destruction of phagocytosed microbe
2. B cell antibody secretion: antibody binding to microbe
3. Killing of antigen-expressing infected cell

Front 31

Granulocyte vs. Agranulocyte

Back 31

Granulocytes: Neutrophils; Eosinophils; Basophils (NEBS); Specific granules and non-specific granulues (lysosomes)
Agranulocytes: Monocytes; Lymphocytes; non-specific granules (lysosomes)

Front 32

Neutrophil

Back 32

Granulocyte; phagocytic; most numerous WBC found in the blood. They comprise 60-70% of the WBCs in the blood. Neutrophils are 9-12 m in diameter (compare to RBCs) and contain a multilobed nucleus. Neutrophils contain three types of granules- small specific granules, larger nonspecific secondary granules (lysosomes), and also tertiary granules. The small specific granules contain enzymes and pharmacological agents that help Neutrophils phagocytose and destroy bacteria. The tertiary granules contain membrane and secreted proteins that help Neutrophils migrate to sites of infection; Neutrophil production is stimulated in the BM by G-CSF (granulocyte-colony stimulating factor).

Front 33

Eosinophil

Back 33

Granulocyte; constitute less than 4% of the WBC population. They are round cells in the blood and pleiomorphic as they migrate into the blood. Eosinophils are 10-14 m in diameter, and contain a bilobed nucleus. Esosinophils contain numerous specific pink-orange staining granules, as well as larger nonspecific granules (lysosomes). Eosinophils function in phagocytosis of antibody-antigen complexes and of parasitic invaders such as worms. Eosinophil granules contain major basic protein, eosinophilic cationic protein and eosinophil-derived neurotoxin. Eosinophils usually act in response to signals released by other cells such as Mast cells, Neutrophils and Basophils. Specific granules: MBP, peroxidase, histaminases, arylsulfatase, acid phosphatase, eosinophil derived inhibitor

Front 34

Basophil

Back 34

Granulocyte; similar to Mast cells in function, but are thought to have a different developmental origin. Basophils constitute less than 1% of the WBC population. They have an S-shaped nucleus which is usually obscured by their intensely dark- staining specific granules. Basophil specific granules contain heparin, histamine, hemotactic factors, and peroxidase (similar in composition to Mast cell granules). Basophils function as initiators of the inflammatory process and can result in an anaphylactic response, similar to Mast cells. Similar to Mast cells, Basophils will bind antigens, and then release their granules, causing effects such as vasodilation, smooth muscle contraction, and leakiness of blood vessels.

Front 35

Lymphocytes

Back 35

Agranulocyte; the largest WBC and constitute 3-8% of the WBC population. Monocytes are precursor cells for Macrophages. Monocytes will migrate into the connective tissue and then become Macrophages. Monocytes are twice as large as RBCs. They have an acentric indented nucleus and bluish-grey cytoplasm. Macrophages function in phagocytosis, inflammatory cytokine production, and also presentation of epitopes to T-lymphocytes. Granules: hydrolytic enzymes, heparin, histamine, chondroitin sulfate, ECF-A

Front 36

Monocytes

Back 36

Agranulocyte; phagocytic cells that present antigens to T cells; capture antigen by phagocytosis of pathogens; constitute the second largest population of WBCs (20-25%). Lymphocytes are round cells in blood, but may be pleiopmorphic in connective tissue or when activated. Lymphocytes are 1-1.5 X as large as RBCs, and contain a dark nucleus that usually (but not always) is round and fills almost the entire cytoplasm of the cell, leaving only a little rim of pale blue-grey cytoplasm showing. There are two types of lymphocytes T- and B-lymphocytes. With routine histological stains, T- and B-cells are indistinguishable. However, T- and B-cells express different cell surface proteins. B-cells are responsible for the humorally (antibody) mediated immune response while T-cells are responsible for the cellularly-mediated immune response.

Front 37

Platelets

Back 37

Small non-nucleated cell fragments that derive from cells called Megakaryocytes found in the bone marrow. Platelets are 2-4 m in size in the blood. In theory, platelets display a peripheral clear region (hyalomere) and a central dark region (granulomere). (Often the hyalomere is not visible.) Platelets function in coagulation of blood in response to damage to the endothelial lining of blood vessels. Platelets contain granules with various clotting factors (including thrombospondin, and thromboplastin). Platelets also have a system of tubules that open up into their membrane, dramatically increasing their surface area.

Front 38

Mast Cells

Back 38

Inflammatory responses; innate immunity; anti-helminth immunity; Mast cell activation leads to release of chemokines, cytokines, and other inflammatory agents.

Front 39

Humoral Immunity

Back 39

B-lymphocytes; adaptive immune response mediated by antibodies that are produced by B cells; principal defense mechanism against extracellular microbes and their toxins.

Front 40

Cell mediated immunity

Back 40

T-lymphocytes; adaptive response mediated by T cells and serves as the defense against microbes that survive within phagocytes or infect nonphagocytic cells; includes CD4 T cell mediated activation of macrophages that have phagocytosed microbes and CD8 cytolytic T lymphocyte killing of infected cells.

Front 41

Lymphatic system divisions

Back 41

1. Primary: a. Bone marrow (B/T lymphocyte formation) and B cells immunocompetent; b. Thymus (T cells immunocompetent)
2. Secondary: where lymphocytes contact antigens; lymph nodes, spleen, MALT

Front 42

Thymus organization/functions

Back 42

Two-three lobes, surrounded by a connective tissue capsule. Capsule sends trabeculae that subdivide cortex into lobules.
• Cortex-site of T-cell maturation, dense T-cells.
• Medulla-fewer T-cells.
• BloodThymic Border: Continuous capillaries with tight junctions. Epithelial reticular cells line up along the capillaries. Thick basal lamina formed by capillary endothelium and epithelial reticular cells. **Prevents immature T-cells from contacting foreign antigens.

Front 43

Path of Tcells through thymus and staining

Back 43

T-cells enter the cortex from capillaries. Migrate to the outer edge of the cortex. Mature from the outer cortex inwards towards the medulla. Mature, surviving T-cells leave the thymus through the veins in the medulla. Cortex stains dark but does NOT contain follicles. Medulla stains lighter.

Front 44

Hassall’s Corpuscles

Back 44

Found in thymic medulla; Concentric arrangements of remnants of apoptotic epithelial reticular cells and T-cells.

Front 45

Lymph Node Organization

Back 45

Capsule of connective tissue surrounding cortex (paracortex-Tcells) and medulla.
Function in filtering lymph borne antigens. Lymphoid follicles: In Cortex of lymph node.
Contain B-Lymphocytes.Following stimulation, B-cells proliferate and rearrange. Follicles develop a lighter-staining germinal center with B-lymphoblasts surrounded by a darker corona of B- lymphocytes.

Front 46

Describe Lymphoid vascularization and staining

Back 46

Afferent lymphatic vessels enter on convex side; drain into subcapsular sinuses that drain to trabecular and medullary sinuses.
Efferent lymphatic vessels exit at the hilum of the node. Cortex stains dark and contains follicles. Medulla appears lighter

Front 47

Reticular fibers

Back 47

Surround and support the cells of the lymph node; Collagen Type III

Front 48

Organization of the Spleen

Back 48

Surrounded by connective tissue capsule with trabeculae that penetrate into parenchyma. Subdivided into White pulp (the pruple dots) and Red pulp.Filters blood-borne antigens.
White pulp = PALS (T-cells) + follicles (B-cells) + central arteries
Red pulp = Cords of Cells + Venous Sinuses

Front 49

Describe the path of blood flow in the spleen and staining

Back 49

From white pulp to red pulp; Central arteries (in WP) branch into penicillar arteries which give rise to sheathed capillaries (in RP). Blood drains from sheathed capillaries into cords of cells and/or venous sinuses in the red pulp. Appears as light background (red pulp) with dark areas (white pulp) randomly positioned. Follicles in white pulp

Front 50

Functions of the Lymphatic system

Back 50

1. Maintaining fluid balance- transports interstitial fluid back to circulation; transports protein back to circulation
2. Purification and defense- clears extracellular space of particulate matter, exudates, bacteria; brings immune cells in contact with invaders
3. Nutrition- absorption of fats from the small intestine

Front 51

What are the factors that affect lymph flow

Back 51

1. Factors influencing interstitial pressure: capillary hydrostatic pressure, plasma protein, interstitial protein, capillary permeability, interstitial hydrostatic pressure
2. Lymphatic pumping: intrinsic pumping by smooth muscle, extrinsic pumping

Front 52

Know how a lymphocyte responds to a particular antigen or pathogen?

Back 52

Lymphocyte clones with diverse receptors arise in generative lymphoid organs; clones of mature lymphocytes specific for many antigens enter lymphoid tissue; antigen-specific clones are activated (“selected”) by antigens; antigen-specific immune responses occur; Process can also occur with lymphocytes; multiple daughter cells with different specificities; proliferation and differentiation of pathogen-specific lymphocytes; happens for multiple clones of lymphocytes, thus any immune response is polyclonal; effector cells eliminate antigens and pathogens

Front 53

Primary vs Secondary lymphoid organs

Back 53

Primary – bone marrow, thymus
Secondary – spleen, lymph nodes, lymphoid tissus, Peyers Patches; tonsils

Front 54

Memory responses

Back 54

Ability of innate immune system to mount more rapid, larger, and more effective responses to repeat encounters with the same antigen; Faster induction; longer-lasting; more potent

Front 55

What are the steps in infection and immune responses

Back 55

Adherance to epithelium; penetration of epithelium causing local infection; local infection of tissues, innate immunity; increasing infection with lymphatic spread; adaptive immunity

Front 56

Barriers to infection

Back 56

1. Mechanical – skin and mucous membranes; mucous + ciliated cells
2. Chemical – lysozyme; skin oils; defensins (antibacterial peptides); stomach acid (low pH) + digestive enzymes
3. Microbiological – normal flora of the skin and GI tract; occupy niches that pathogens may otherwise exploit

Front 57

Steps of neutrophil migration

Back 57

1. Rolling: selectin (endothelium); CD15 (leukocytes)
2. Tight binding: ICAMS and integrins (both leukocytes and endothelial cells ex. LFA-1 and ICAM1)
3. Diapedesis: chemokines (IL8, RANTES, eotaxin, MIP)
4. Migration: chemokines
TNF causes leucopenia by stimulating extravasation of leukocytes; adhesion molecules arenow the targets of immunotherapeutics

Front 58

Describe the events that take place when phagocytes ingest micro-organsims

Back 58

• Acidic environment of phagolysosome (ph 3.5-4) helps break down bacteria.
• Toxic O2 derivatives; myeloperoxidase; peroxides; superoxides; oxygen radicals. These kill bacteria via the respiratory burst.
• Defensins (bacteriocidal peptides)
• Lactoferrin (competes for iron)
• Hydrolytic enzymes; proteases
• Microbes are internalized into phagosomes, which fuse with lysosomes to form phagolysosomes, where the microbes are killed by reactive oxygen and nitrogen intermediates.

Front 59

Pathogen components that trigger inflammatory responses to infection

Back 59

LPS and other bacterial cell wall components
-Bacterial DNA and flagella
-Viral double-stranded RNA
-Bacterial toxins
• All interact with receptors on phagocyte surfaces (see slide 17)
Phagocytosis of bacteria (esp. non-encapsulated) triggers...
-signaling pathways that result in the secretion of inflammatory cytokines.
-changes in surface molecules, allowing for transit into tissues to reach sites of infection (see slides 13-15).

Front 60

List inflammatory cytokines/mediators and the reactions they produce in reaction to alternate complement pathway

Back 60

• IL1 (fever, induces acute-phase proteins by liver, and prostaglandin synthesis)
• IL6 (fever, induces acute-phase proteins, increased antibody production)
• TNF (fever, induces acute-phase proteins, vascular permeability Ý, shock)
• IL12 (activates NK cells; CD4+ Th1 cells)
In addition to these, C’ activation produces inflammatory mediators such as
C3a and C5a; C5a can trigger mast cells, releasing histamine and LTB4
Acute phase proteins = C-reactive protein, fibrinogen, α1-antitrypsin, and serum amyloid A. All are markers of inflammation and infection when increased.

Front 61

Clinical signs resulting from immunological events:

Back 61

Calor: heat increased blood flow IL1, IL6, C3a, C5a
Rubor: redness increased blood flow TNF, C3a,C5a, histamine
Dolor: pain prostaglandins IL1
Tumor: swelling vascular permeability IL1, TNF, C3a, C5a, histamine, chemokines

Front 62

TNF

Back 62

• At low concentrations, TNF acts on leukocytes and endothelium to induce acute inflammation.
• At moderate concentrations, TNF mediates the systemic effects of inflammation.
• At high concentrations, TNF (and other cytokines) causes the pathologic abnormalities of septic shock.

Front 63

IFN

Back 63

• Induce resistance to viral replication in all cells
• Up-regulate MHC class I and antigen processing in all cells
• Activate degradation of viral RNA
• Activate NK cells

Front 64

Describe how T cells recognize peptides

Back 64

• Peptides bind to the MHC molecules via anchor residues.
• The T cell receptor (TcR) sees both the peptide and the MHC molecule.

Front 65

Describe antigen uptake by APC’s

Back 65

1. Macrophages – phagocytosis
2. Dendritic cells – phagocytosis by tissue dendritic cells/ viral infection
3. B cells – antigen-specific receptor (Ig)
Different types of antigens reach different lymphoid tissues by...
• lymphoid drainage
• transport via APCs
• bloodstream

Front 66

1. Live attenuated vaccines

Back 66

a. Smallpox (as vaccinia = cowpox), rubella, mumps, measles
b. Live virus has been mutated  reduced ability to grow; nonpathogenic to humans
c. Viruses are still capable of replication, but are avirulent or minimally virulent
d. More potent at eliciting protective immunity than a killed virus because mimics a real infection
e. CANNOT be used in pregnant or immunocompromised patients because will induce illness

Front 67

2. Killed, whole organism vaccines

Back 67

a. Influenza
b. Treated with chemicals, heat or radiation so that the cannot replicate

Front 68

3. Subunit or recombinant vaccines

Back 68

a. Use only the antigenic viral components
b. Protein and/or polysaccharides, hepatitis B
c. Use only a single protein derived and derived from the pathogen

Front 69

4. Toxoids (denatured toxins)

Back 69

a. Tetanus
b. Undergo chemical modification to produce toxoid from toxin  elimination of toxin moiety, while keeping antigenic determinants

Front 70

Know how vaccines prevent infection

Back 70

– Unvaccinated individuals are protected when a certain threshold number of people are vaccinated
– Ex: For MMR, threshold is 95%  elimination of disease; If only 70% vaccinated, pathogen can maintain itself by continual infection of non-vaccinated people
– Vaccines are a form of active immunization (in contrast to passive immunization)
– Elicit a new immune response
– Delayed protection
– Memory
– Generally permanent
– Used proactively (prior to occurrence of infection)
– NOTE: Passive immunization does not elicit a new immune response.
– Uses preformed gammaglobulin injections to offer immediate protection AFTER exposure to pathogen
– No memory or secondary response
– Ex: maternal AB  placenta via placenta

– Vaccinations can be used actively or passively soon after pathogen exposure  prevents or diminishes disease expression

Front 71

Know how vaccines are used

Back 71

- Vaccines may be administered with adjuvants  increase efficacy
o Aluminum phosphate = primary adjuvant; only one approved for humans
o Turns a soluble protein into a particle, and makes it easier for APCs to phagocytose
o Activates inflammatory immune responses, especially IL-1

- May use a conjugate vaccine utilized in children < 2 y.o. because they have poor anti-carbohydrate antibody reactions
o Covalently link polysaccharide to carrier protein (ex: toxoid)
o B cell binds and endocytoses the linked molecule presents peptide to T cell  activates polysaccharide specific B cell  differentiation into plasma cell  production of anti-polysaccharide antibodies

Front 72

Current issues in vaccine safety

Back 72

• Greatest risk = active disease in immunocompromised patients
• Minor increase in risk of febrile seizures with MMR and DPT vaccines, but will NOT result in long term consequences

• False risks that may prevent parents from immunizing children:
• Deaths from measles vaccine  NO CREDIBLE DATA
• Neuropathology or autism from thimerosal (mercury containing vaccine preservative)  7 STUDIES DO NOT SUPPORT
• Vaccination causes type 1 diabetes, MS, or autoimmune diseases  NO CAUSAL LINK IN 10 STUDIES
• Autism resulting from MMR vaccine  REFUTED BY MULTIPLE STUDIES

• Need patients to realize that temporal sequence does not demonstrate causality
• Just because A precedes B, it does not mean that A caused B