intro to serology immuno and serology exam 4

Colonization

The presence of bacteria on a body surface (like on the skin, mouth, intestines or airway) without causing disease in the person.

Pathogenicity

refers to the ability of an organism to cause disease (i.e, harm the host).

Virulence

term often used interchangeably with pathogenicity, refers to the degree of pathology

caused by the organism.

• Avirulent - does not cause disease

Virulence factors

a structure, toxin, adhesin, etc that contibutes to the ability of a pathogen to cause disease.

Normal flora

Innate Defenses include

Mucous membranes, skin and microbes

Epithelial lining of the

Respiratory tract: frequently used entry site

for microbes.

• Gastrointestinal tract: common entry site. Enter through water, food, contaminated fingers and fomites (fecal-oral route); survive stomach HCl, enzymes, and bile.

• Genitourinary tract: entry site for most sexually transmitted diseases (STDs).

Innate defenses, skin:

Unbroken skin is impenetrable by most microbes

• Some microbes gain access through hair follicles and sweat glands.

• Some microbes gain access through insect vectors

• Necatoramericanus (hookworm) can bore through intact skin.

•Certain fungi (dermatophytes) grow on skin and produce enzymes that break down keratin.

How microorganisms can cause disease

Number of Invading Microbes Higher number of pathogens increase the likelihood of developing disease.

LD50: Lethal dose for 50% of hosts. Number of microbes that will kill 50% of inoculated test animals.

ID50: Infectious dose for 50% of hosts. Number of microbes that will cause a demonstrable infection in 50% of inoculated test animals

LD50 Meaning

Lethal dose for 50% of hosts. Number of microbes that will kill 50% of inoculated test animals.

ID50 means

Infectious dose for 50% of hosts. Number of microbes that will cause a demonstrable infection in 50% of inoculated test animals.

First step of infection is usually

Adherence

Adherence: Adhesins or Ligands

Surface molecules on pathogen that bind specifically to host cell surface molecules. May be located on glycocalyx, fimbriae, viral capsid, or other surface structure

Adherence: Receptors

Surface molecules on host tissues to which pathogen adhesins bind.

Bacteria examples with polysaccharide capsules

Streptococcus pneumoniae, Haemophilus influenzae, Treponema palladium, Klebsiella pneumoniae

M protein and Fimbriae of Group A strep are

Examples of phagocytic inhibitors

How does protein A by Staph aureus work?

P aeruginosa has what as an inhibitor for phagocytosis

Formation of polysaccharide biofilm

Survival inside of cells

Bacterial Kinases

Break down clots produced by body to isolate infection. Made by streptococci and staphylococci.

Phospholipases

produced by Clostridium perfringens, hydrolyze phospholipids in cell membranes by removal of polar head groups.

Lecithinases

also produced by Clostridium perfringens, destroy lecithin (phosphatidylcholine) in cell membranes

Neuraminidase produced by Vibrio cholerae and Shigella dysenteriae

degrades neuraminic acid of intestinal mucosa

Three mechanisms in which bacterial damage can affect host cells

Three mechanisms:

• Direct damage, include viral cytopathic effect

• Toxins (Most bacterial damage is carried out by toxins) • Hypersensitivity and/or inflammatory reactions

Cytotoxin

An exotoxin that disrupts host cells

Seen in gas gangrene, diptheria, and scarlet fever

enterotoxin

An enterotoxin that disrupts the lining of the gastrointestinal tract

Anti toxin

Antibodies that bind to exotoxins, thus activating the exotoxin. Transfusion of anti-toxin is a means of providing passive immunity

Toxoid

Physically or chemical inactivated exotoxin

Employed as vaccines

Endotoxins and the pyrogenic response

Bacteremia is

Bacteremia presence of viable bacteria in circulating blood. May not have any indication of disease, which is a difference to septicemia

Septicemia

Presence of bacteria in blood (bacteremia) and is associated with disease

Septic shock

Sepsis that occurs when blood pressure is dangerously low, as a result, internal organs typically receive too little blood, causing them to malfunction. Life threatening

An antibody titer is a

measurement of how much antibody was produced that recognizes a particular antigen.

• Antibody titers are often expressed as the inverse of the greatest dilution (in a serial dilution) that still gives a positive result.

• ELISA and agglutination are a common means of determining antibody titers.

What is the value of antibody titer test?

An antibody titer test is used to determine if you’ve had previous infections and whether or not you need certain immunizations. This test can be used to determine the following:

• if there is a need for a booster shot

• whether the patient recently had or currently has an infection

• whether the patient’s immune system has a strong response to your own tissues, possibly indicating an autoimmune disorder

Primary versus secondary antibody

responses

Serum IgG has a longer half life than IgM.

• IgG half life = 21 days • IgM half life = 5-6 days

• This figure is a bit deceptive, as you can still have specific IgG in serum from a infection/vaccine after IgM is below detection.

Because IgM is usually produced in significant quantities during first exposure in a patient with an infectious agent, detection of

specific IgM can be of diagnostic significance.

IgM is still produced during second exposures. IgM titers may be helpful in cases where the patients do not manifest decisive clinical signs or under conditions requiring rapid therapeutic decisions.

• IgG responses may indicate past exposure or vaccination, especially in the absence of an IgM response.

IgG responses may indicate past exposure or vaccination, especially in the

absence of an IgM response.

Significance of antibody titer

• “A single titer result does not differentiate between vaccine status and exposure”

Therefore, when being used as a tool to diagnose clinical disease, it is often useful to have paired samples (acute and convalescent) drawn approximately 2 weeks apart to monitor any significant changes in antibody titers.

• Testing of a single specimen is not recommended.

• Generally, a 4 fold increase in titers between paired samples is a good indication of recent infection.

Generally, a _________ in titers between paired samples is a good indication of recent infection.

4 fold increase

The ability of an organism to cause disease is known as

pathogenicity

A primary disadvantage of using serology in the diagnosis of an infection is

delayed appearance of antibodies after onset of infection

A newborn suspected of
having a congenital viral
infection. Serologic test for
IgG is positive for viral-
specific antibody. Which of
the following statements is
true?

A. Newborn has viral infection.
B. Mother is immune to the virus.
C. Baby has another disease.
D. Retest serum for another antibody
class.

Retest serum for another antibody
class.

Which of the following
positive antibody tests may
be an indication of recent
vaccination or early primary
infection in a patient with
no clinical symptoms?

A. Only IgG positive
B. Only IgM positive
C. Both IgG and IgA antibodies positive
D. Fourfold rise in titer for IgG

Only IgM positive

Strawberry tongue, Erythema (redness), tonsillar exudate, and petechiae on palate, tonsils and/or posterior pharynx (Symptoms can vary with age) are associated with

Strep throat caused by Group A streptococcus

Strep A Capsule (hyaluronic acid)

prevents phagocytosis

M protein Of Strep A

inhibits complement activation and phagocytosis

• Antibodies against M protein aids in destroying organism

• Has over 60 serotypes which can be used for additional subclassification

• Individual can be infected with more than one GAS in their lifetime

Group A strep Streptokinase

Dissolves clots

Erythrogenic toxin

released from scarlet fever strains and responsible for rash

Hyaluronidase (spreading factor)

breaks down hyaluronic acid found in host’s connective tissue

Streptolysin O (SLO) and Streptolysin S

• O is oxygen labile, S is oxygen stable

• Lysis of red and white cells, responsible for beta hemolysis

• SLO is antigenic and antibody response is frequently used as serologic indicator of recent infection.

• Most widely used strep test (RST)

• Lateral flow test (immunochromotography), which is currently the most widely used RST.

• The sample is applied to a strip of film and, if GAS antigens are present, these will migrate along the film and localized to form a visible line of antigen bound to labeled antibodies.

Lateral flow test

The sample is applied to a strip of film and, if GAS antigens are present, these will migrate along the film and localized to form a visible line of antigen bound to labeled antibodies

ASO titers can have false negatives when patients have skin infections, rheumatic fever, or post-streptococcal glomerulonephritis.

•so… Anti-DNase B antibody test is assay of choice for acute rheumatic fever and acute glomerulonephritis after S. pyogenes infection.

S. pyogenes produces the enzyme DNase B, and the ADN-B neutralization test demonstrates recent or previous infection.

• Anti-DNase-B antibodies stay elevated longer than ASO

• Test can be done using polystyrene beads coated with DNase B and monitoring agglutination by nephelometry.

• Neutralization of enzyme activity is an alternative used in the past.

• ASO and ADN-B tests are often run in parallel.

Spirochetes

Tiny gram-negative bacteria that look like corkscrews

•Motile with axial filaments winding around organism

•Contraction causes spinning motion

Treponema pallidum causes

Syphilis

Borrelia

•B. burgdorferi – Lyme disease (tick-borne)

•Rash, neurologic infections, cardiac infection, arthritis

Diagnostic tests for Syphilis: nonspecific screening tests

For secondary stage,

• RPR – Rapid Plasma Reagin test

• VDRL – Venereal Disease Research Laboratory test

• High sensitivity (detects most cases)

• Low specificity (detects other diseases, false positives with pregnancy, elderly, viral infections, etc)

• Antigen is nonspecific; antibodies are not to treponemes

• Because of the potential of false positives, need to confirm diagnosis using a specific treponemal test.

Specific treponemal tests are done as a confirmatory test is done because

of the potential of false positives