#1 Principles and interpretation of immunologic tests

Immunologic tests—designed to determine presence of antigen or antibody

a.) agglutination- antigen is particulate. Reaction of antigen + antibody causes clumping because antibody cross links antigenic particles.

- used for ABO blood typing

-used to serotype bacteria

b.) precipitation—antigen is in solution. Antibody cross links with antigen

Zone of equivalence-optimal proportion of Ag and Ab for efficient lattice formation. With either too little or too much Ag, too little or too much Ab, precipitation will not be as great.

Prozone effect- too much Ag, not enough precipitate

1.) ELISA- Enzyme Linked Immunosorbent assay

uses an enyzyme to detect antigens or antibodies in a sample

prozone effect avoided by making Ag or Ab insoluble

-basis for home pregnancy tests

- detects peptide hormones (ie insulin)

a) protocol

-bound antibody in plastic well

-add sample which may or may not contain antigen

-rinse well (Ag/Ab complexes are bound to well)

- add second Ab, conjugated to a different epitope

- second Ab is also conjugated to an enzyme

- wash and add color reagent (DNP-Phosphate pe

- enzyme cleaves DNP---yellow color produced

b) used to detect insulin, exposure to hep B, HIV etc.

- in testing for hepB exposure, would start with a bound hep B Ag because you are looking for anti- Hep B Abs

2-3% False Pos. Rate in ELISA HIV test

2.) Radioimmunoassay- based on the same principle as the ELISA, but instead of using an enzyme for detection, a radioactive isotope is used.

b.) protocol - coat well w/anti-insulin

- add radiolabeled insulin in order to est a a standard binding c.

-set up a competitive binding assay w/ radiolabeled insulin and varying dilutions of unlabeled serum

- ag detection=loss of radioactive counts

concentration in serum= radiolabeled conc at half max binding * dilution factor

3) Western Blot- what you do if you get a false positive

a) protocol for HIV test- take 3 coat proteins and fract by size on a polyacrylamide gelm

- transfer proteins to nitrocellulose paper

- test paper w/ patient serum

- add antiserum AB that is linked to an enzyme

- detect via chemical reaction

- true positives have a reaction to all three proteins

- false positives have a reaction to only one protein

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4) Complement fixation tests-

a) protocol- start w/ one known and one unknown

- add a measured amt of complement (complement will fix if Ag/Ab complex present)

- add an indicator (Ab bound rbc’s)

- if all of the complement has been taken up by the intitial Ag/Ab complex, no cell lysis will occur (positive test)

- cell lysis will occur if Ab and Ag did not match in first step (negative test—no Ab in patient’s serum)

5) Direct and Indirect Coomb’s tests- Remember Hem/Onc, Dr. Gitlin (aaaagh)

a) tests for Rh incompatibility (hemolytic disease of the newborn), drug related hemolytic anemias

-Abs bind to rbc’s in asymptomatic patients, no hemolysis

b) protocols

i. direct test- add antiserum against human ab with patient’s rbc’s

ii. indirect test- add patient’s serum to normal rbc’s, add antserum to abs

iii. agglutination will occur if rbc binding Abs are present

7 ) Flow Cytometry

a) used to measure #’s of immunologically active blood cells

eg CD-4 counts

b. protocol

i. patient’s cells are labeled w/ protein specific monoclonal ab

ii. tag ab w/ fluorescent dye

iii. single cell passed through a machine that measures # of fluorescing cells

#2 Immune Complex Diseases (type III reactions)

Ag/Ab complexes cause an inflammatory response. Complexes are deposited in tissues.

Complexes bind complement, so levels of comlepemnt will be low in immune complex disease. Binding complement=activating complement=turning on inflammatory cascadeàcome hither PMN’s

Arthus reaction- repeated injections of a foreign antigen in animals elevates IgG levels. Subcutaneous injection afterwards causes edema and hemorrhage to develop. Complexes can be deposited in vessel wallsà Hypersensitivity Pneumonitis (allergic alveolitis) comes from inhaling actinomycetes

Serum Sickness- inject foreign serum, ab production starts, complexes circulate and are deposited throughout the body, reaction manifests itself a few days to weeks after injection—fever, urticaria, arthralgia, lymphadenopathy, splenomegaly, eosinophilia. Injected drugs can cause this reaction. Penicillin can do this.

Glomerulonephritis—“lumpy” subepithelial glomerular deposits.

Happens several weeks after infection w/ beta hemolytic strep

Glomerulonephritis may also follow:

Infective endocarditis

Serum sickness

W/ viral infections such as Hepatitis b

Rheumatoid Arthritis- chronic inflammationof joints, Rh factor= IgG, IgM bound to Fc of normal IgG

- deposits on synovial membranes and blood vessels

- complement activation

Sytemic Lupus Erythematosus- Immune complex developmentt and deposition in all tissues- esp affects skin (“malar rash”), joints, and kidneys

- Abs are anti nuclear

- Complexes activate complement= inflammation and tissue destruction

#3 Genetics of Ig Variety-

Ig structure- light chain, heavy chain—2 and 2

(One light chain variable domain ) *2

One light chain constant domain )*2

(One Heavy chain variable domain)*2

(Three heavy chain constant domains)*2

Variable regions at the top of the y shape of the antibody

IgG and IgA have three heavy chain constant domains

IgM and IgE have four

Variable regions bind antigen

Constant regions bind complement, cell surface receptors

Three “hypervariable” regions in the light chain variable domain

Three hypervariable regions in the heavy chain variable domain

2 Types of light chain-kappa or lambda (constant region determines)

Kappa and Lambda occur in all abs-IgG, IgM etc.

Heavy chains are unique to each type of Ab. (gamma, alpha, mu, sigma, and epsilon)

If you were to break up an antibody into two pieces:

Fab-antibody binding portion

Fc-complement activating, cell membrane binding portion

Immunoglobulin Classes

IgG-predominant in secondary response, impt defense ag. Bacteria and viruses, only ab to cross placenta, most abundant in newborns, it can activate complement (so can IgM), opsonizing Ig

IgA- main Ab in secretions—colostrum, saliva, tears, resp, intestinal tr, genital tr.

Has a joining molecule, usually forms a dimer

IgM-main Ig in primary response

-monomeric function on B cells (ag binding receptor)

-forms a pentamer

IgD-uncertian fctn, but expression of IgD is necessary for B cell maturation.

IgE -mediates hypersensitivity reactions, causes mast cell degranulation,

- causes eosinophilic degranulation w/parasite

-Fc portion is bound to mast cell, ag reception causes degranulation (allergic reaction)

Isotypes-determined by differences in constant regions

-includes the different heavy chain classes (IgG, IgA etc)

- also includes subclasses(IgG1-4), (IgA1-2)

-kappa and lambda are difft isotypes as well

- Remember that all heavy chains may bind with kappa or lambda

Allotypes- individual antigenic features (polymorphisms in heavy chains)

Idiotype- antigenic determinants formed by amino acids in hypervariable regions

DNA arrangement and RNA splicing are used

- a pool of gene segments for each type of chain (kappa, lambda, gammaH, alphaH, muH, epsilonH, and deltaH), located on different chromosomes

variable segment(s)-----(wide separation on the gene)---D(diversity segment—in H chains)---Joining segment---Constant region

Kappa

40 variable segments---5 J segments—1 constant region

Lambda

30 variable--- 20 J segments associated with 20 constant segments

Heavy chain

50 variable regions—27 D segments-6 J regions------constant regions

(every B cell makes a heavy mu chain first. If it succeeds at this task, then it attempts to make a kappa chain. It has two tries to make a working protein, and if both rearrangements fail, lambda rearrangement ensues (two tries here as well). Lambda success rate is high. 60percent kappa 40 percent lambda

allelic exclusion-only use one light chain allele and one heavy chain allele per antibody making cell

Production of a heavy chain

#1 gene rearrangement

particular V region placed next to a D region next to several J’s and a C region

#2 transcription

all of the J segments minus one are removed by splicing

#3 translation—

Production of a light chain

Variable region has two gene segments (V+J)

Heavy chain variable region has three gene segments (V+D+J)

Hypervariability

In recombination, each V, J, D segment has a “recognition sequence” that marks where recombination enzymes combine the segments. This is a very “liberal” combination, however. Recombination can occur anywhere within the sequence. Moreover, bases can be chewed off or inserted.

This is how hypervariability occurrs

DIVERSITY

-depends on a) multiple gene segments (many v regions, many j regions etc on the chromosome)

b) Possible combinations of these v, j, d, and c segments

c) combinations of different L and H chains

d) junctional diversity

ISOTYPE SWITCHING (CLASS SWITCHING)

-initially all B cells carry IgM molecules

- then antigenic driven gene rearrangement occurs

- same antigenic specificity, but Ab is of a different class (say IgG)

- Variable heavy regions recombine with a different constant region (same head but different tail)—a gene deletion event

- Occurs only with heavy chains, not light chains (B cells express only one light chain—kappa or lambda)

- Only one set of heavy chain genes expressed per B cell (maternal or paternal)

- Interleukin dependent

§ IL-4 à IgE

§ IL-5àIgA

- Interaction between CD-40 on B cell and CD40 ligand protein on Thelper cell is impt-à failure of this int happens in hyper IgM syndrome

- CD28 and B7 also interact in the heavy chain switch

Very important- lack of CD 40 ligand can lead to hypogammaglobulinemia, hyper IgM syndrome

PRIMARY RESPONSE-first Ag encounter

- with first response, abs are detected after a longer lag period (7-10 days)

- primary antibody is IgM--à later IgG

SECONDARY RESPONSE- second Ag encounter

- rapid response (3-5 days)—due to memory cells

- memory cells proliferate and form a clone of plasma cells

- much larger IgG response, lasts longer

AFFINITY MATURATION-with each exposure to Ag, Ab becomes better

-occurs only in B cells undergoin antigen driven differentation

- Due to somatic mutations in the Variable(VDJ, VJ) region genes of B cells

4. Mechanisms of antigenic variation and immune system evasion employed by bacteria, fungi, protozoa, and viruses. (source: Robbins, p. 344)

Mechanism	Mechanism (specific)	Examples
Being inaccessible to the immune response	Propagate in luminal organs	Clostridium difficile (small intestine) Salmonella typhi (gallbladder)
	Viruses shed from luminal surface of epithelial cells	CMV (in urine, milk) Poliovirus (in stool)
	Viruses that infect keratinized epithelium	Poxviruses (cause molluscum contagiosum)
	Rapid invasion of host cells	Malaria sporozoites (liver cells) Trichinella, Trypanosoma cruzi (skeletal or cardiac muscles)
	Form cysts covered by a dense fibrous capsule (walled off)	Large parasites (e.g., larvae of tapeworms)
Resisting complement-mediated lysis and phagocytosis	Carbohydrate capsule shields antigens and prevents phagocytosis by neutrophils	All major pneumonia and meningitis pathogens (pneumococcus, meningococcus, Haemophilus)
	Leukotoxin (kills neutrophils)	Pseudomonas
	Antigens that prevent complement activation	E. Coli (K antigen)
	Complement activation at a distance (fails to lyse organism)	Some gram-negative bacteria (O antigen)
	Bind the Fc portion of Ab (inhibits phagocytosis)	Staphylococci (protein A molecules)
	Proteases that degrade Abs	Neisseria, Haemophilus, Streptococcus
Varying or shedding antigens	Strains with many antigenic variants	Rhinoviruses, influenza viruses
	>80 permutations of capsular polysaccharides	Pneumococci
	Hypervariable region of pilar (attachment) proteins, changes during infxn to prevent clearance	Neiserria gonorrheae
	Switching surface antigens before each clone is cleared by host	Borrelia recurrentis, Lyme disease borreliae, African trypanosomes, Plasmodium falciparum (malaria)
Causing specific or non-specific immunosuppression	Blocking complement activation; Using complement receptors to enter B lymphocytes	Vaccinia; EBV
	Inhibiting interferon-induced antiviral responses	Adenovirus, EBV, HIV
	Blocking production of cytokines or response to cytokines	Cowpox, adenovirus, Hep B
	Suppressing MHC Class I	Adenovirus
	Reducing B-cell activation	EBV
	Invading lymphocytes and causing opportunistic infections	HIV, EBV

5. How different types of immune deficiencies lead to different susceptibilities to infection (e.g., T-cell defects and viral/fungal infection; splenectomy and encapsulated organisms).

(source: Robbins, p. 233)

To understand the principles that determine susceptibilities to infection, please review the normal functions of T cells, B cells, granulocytes, complement system and the spleen in host defense. Due to the complex interactions between T cells and B cells, defects in T cells almost always result in impaired antibody synthesis and thus present clinically just like combined immunodeficiencies.

Note: WAS = Wiskott-Aldrich syndrome, SCID = severe combined immunodeficiency

Type of deficiency	Features	Bacteria	Viruses	Fungi/parasites
T-cell - AIDS - DiGeorge syndrome - WAS - SCID	Opportunistic pathogens, failure to clear infections	Sepsis	CMV, EBV, varicella, chronic respiratory and intestinal viruses	Candida, Pneumocystis carinii
B-cell - Agammaglobulinemia (X-linked) - Common variable immunodef. - IgA def. - Hyper IgM syndrome - WAS - SCID	Recurrent sinopulmonary infections, sepsis, chronic meningitis	Streptococci, Staphylococci, Haemophilus	Enteroviral encephalitis	Severe intestinal giardiasis
Granulocyte - PMN defects		Staphylococci, Pseudomonas		Candida, Nocardia, Aspergillus
Complement -C2 most common		Pyogenic bacteria (e.g., Neisseria)
Splenectomy	Encapsulated organisms

#6 MHC/HLA serotypes: transplantation compatibility, disease associations, familial inheritance.

Major Histocompatibility complex- complex which presents antigens to TCR

MHC I coded for on 3 genes- HLA-A, HLA-B, HLA-C

MHC II coded for on three genes- HLA DP, HLA-DQ, HLA-DR

All of the genes for MHC I are located on the same chromosome.

MHC II has genes on two chromosomes.

There are polymorphisms for each gene. Each person has two sets, haplotypes

Appx 47 HLA-A, 88 HLA-B, 29 HLA-C, etc

CODOMINANT expression. Both maternal and paternal haplotypes can be expressed in a cell.

These are the major antigens responsible for graft rejection, but a number of minor antigens are also responsible.

MHC I is expressed on every cell in the body. Thus, it is important for CD-8 cells to recognize MHC as self, and not foreign.

Detect MHC type by adding lymphocytes to a series of abs + complement. The lymphocyte which reacts with a certain Ab is lysed.

MHCII is found on macrophages, dendritic cells (spleen) , Langerhans cells (skin). MHC II is highly polymorphic

Transplantation—

Syngeneic graft-tissue transferred btw genetically identical individuals

Allograft- tissue transferred between genetically different members of the same species.

REJECTION-

Primary, “first set” rejection- (T cell mediated is the main causze)

Accelerated”second set” rejection- mainly orchestrated by sensitized T cells, MHC class II plays the major role in rejection, especially DR locus.

The cycle gets started when a graftAPC presents self antigen to the host TCR.

Or graft antigen, graft MHCI, or MHC II can be shed and picked up by a host APC and then presented to a host TCR.

In tissue typing, MHC I HLA’s and HLA DR are carefully typed.

CROSSMATCHING

Also, preformed cytotoxic Abs in the host are checked for by the following test:

Graft lymphocytes and host serum are mixed to determine if abs which are cytotoxic to graft cells are present. (Lymphocytes will lyse if this is the case)

Must also make sure that ABO types agree

Graft versus host disease-Bone Marrow Transplant gone bad. Can also happen if you give an immunodeficient pt a blood transfusion.

Donor cytotoxic T cells destroy host cells: maculopapular rash, jaundice, hepatomegaly, and diarrhea.

3 Requirements for GVHD to occur:

immunocompetent T cells in graft

immunocompromised host

donor T cell recognizes host antigens as foreign

Need to immunosuppress—use Cyclosporin (NOTE, this stuff causes hypertensive nephrosclerosis)…I did my autopsy on Saturday, and the patient developed this due to chronic immunusuppression with none other than CYCLOSPORIN…I think that we talked about this in class recently.

Tacrolums(FK506), Rapamycin, corticosteroids, azathioprine, OKT3 antibody, and radiation

Cyclosporin interrupts signal transduction by inhibiting calcineurin (a piece of the chain that turns on IL-2)

Immunosuppression enhances the chance of infection and neoplasm---this woman died of widely metastatic adenocarcinoma.

Azathioprine inhibits DNA synthesis and blocks growth of T-cells.

Corticosteroids inhibit IL-1 production and TNF production by macrophages.

OKT3 is a monoclonal antibody against CDnd 3 protein. This blocks the signal transduction cascade which activates T-Cells.

HLA Haplotype disease associations

HLA-A3- Hemochromatosis

HLA-DR4- Rheumatoid Arthritis HLA-DR3 and HLA-DR-4 IDDM (Diabetes)

HLA-DR2- Goodpasture’s Syndrome HLA-DR2 and HLA-DR-3 SLE (Lupus)

HLA-B27-AnkylosingSpondylitis

-Psoriasis

-IBD

-Reiter’s

HLA-B35 and Cw04, more susc to dev AIDS w/HIV inf.

#7 Allergies

Note: I went ahead and added the other types of hypersensitivity rxns as well

TYPES of HYPERSENSITIVITY REACTIONS-

Mediator Type Reaction

Antibody (IgE)	(I) Immediate, anaphylactic ALLERGIC	IgE antibody is induced by allergen and binds to mast cells and basophils. On second exposure to allergen, allergen binds multiple IgE (crosslinking), inducing degranulation
Antibody (IgG)	(II) cytotoxic	Antigens on a cell surface combine with antibody, complement mediated lysis
Antibody (IgG)	(III) immune complex	Antigen antibody immune complexes deposited in tissues. Complement activated. PMN’s attracted. Release lysosomal contents and damage tissue.
Cell	(IV) delayed	Helper T lymphocytes sensitized by an antigen release lymphokines upon second exposure. Lymphokines cause inflammantion, activate macros etc.

Type I Reaction notes

Type I hypersensitivity reaction may produce urticaria, asthma, eczema, rhinitis, conjunctivitis

Mast cells contain histamine-vasodilation, increased capillary permeability

Prostaglandins-vasodilation, increased capillary permeability, and

bronchoconstriction

Thromboxane- platelet aggregation

AnaphylacTOID reactions are reactions that do not need to bind to IgE in order to induce mast cell/basophilic degranulation

Examples: certain drugs or iodinated contrast materials

Atopy- immediate hypersensitivity rxns with a familial disposition, associated w/elevated IgE levels

Antigens (pollen, dust, nuts, shellfish, etc)

-use radioallergoabsorbent (RAST) test to id the offending IgE’s

Penicillin can cause a type I anaphylactic reaction

Treat via desensitization- Acute desens.—give enough drug, but not enough to cause reaction

Administer very small amounts in 15 minute intervals.

Chronic desens. - give small doses so that IgG abs develop---eventually bypass the degranulation reaction

DRUGS to GIVE: Epi, Antihistamines, corticosteroids, and CROMOLYN sodium (prevents degranulation, so can only be used beforehand)

Type II reactions— Abs are directed at antigens of cell membrane. Activates complement which

causes formation of MAC, membrane attack complex, which lyses the cell.

Examples include transfusion or Rh reactions, autoimmune hemolytic anemia (Ab binds to the RBC, then complement, and then the cell lyses)

Drugs like penicillin, phenacetin, quinidine can attach to surface of rbc and cause type II rxns.

Goodpasture’s syndrome is a type II reaction

Complement at work in transfusion mismatches (type II)

Type III- see question #2

Type IV- Delayed type hypersensitivity reactions—

CD-4 mediated

Response starts from hours to days afterwards

Tuberculin Skin test is an example

1. Contact Hypersensitivity- nickel, formaldehyde (chemicals), poison ivy, poison oak (plant materials), topically applied drugs (sulfonamides, neomycin), soaps

Hapten enters skin, joins w/ body protein. Cell mediated hypersensitivity happens in skin-à rash develops

2. Tuberculin type hypersensitivity- delayed hypersensitivity to antigens of microorganisms

Infected persons do not always test positive—immunosuppression (uremia, measles, sarcoidosis, lymphoma, aids, chemo)

8. Granulomas: role of macrophages, foreign body versus immune granulomas, caseating (TB) versus noncaseating (sarcoid) granulomas, common causes (TB, sarcoid, fungi) - Robbins p. 83-84; 349-352; 734-735)

Granuloma = focal area of granulomatous inflammation, consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear

leukocytes (lymphocytes and plasma cells); may see some multi-nucleated giant cells; chronic inflammatory response

Common Causes of granulomas: M. tuberculosis, M. leprae, Treponema pallidum (syphilis), gram-negative bacillus (cat-scratch disease), sarcoid

Foreign body granulomas = form when talc (IV drug use) or sutures are large enough to preclude phagocytosis by a single macrophage and do not incite either an inflammatory or an immune response; the foreign body is usually in the middle of the granuloma

Immune granulomas = caused by insoluble particles that are capable of inducing a cell-mediated immune response; macrophages present the material to T lymphocytes, which in turn secrete IFNγ (transforms macrophages into epithelioid cells and multinucleated giant cells)

Caseating (TB) granuloma = caused by mycobacterium tuberculosis (escapes macrophage engulfment); central amorphous granular debris, loss of all cellular detail; acid-fast bacilli present

Noncaseating (sarcoid) granuloma = systemic disease of unknown cause characterized by noncaseating granulomas in many tissues and organs; diagnosis of exclusion; each granuloma is composed of an aggregate of tightly clustered epithelioid cells, often with Langerhans or foreign body-type cells + Schaumann bodies (laminated concretions of calcium and proteins) + asteroid bodies enclosed within giant cells (stellate inclusions); lungs, lymph nodes, spleen, bone marrow, skin, eye, salivary glands

9. Vaccines

Bacterial

active- vaccines from bacteria or bacterial products

passive- via preformed antibodies

Active Immunity * common usage

Capsular Polysaccharides

*Streptococcus Pneumoniae (pneumonia)- capsular polysaccharides from 23 prevalent types

Recommended: persons over 60, cirrhosis, diabetes, or splenectomized

Neisseria Meningitidis (meningitis) - capsular polysaccharide of 4 types (A, C, W-135, and Y)

Recommended: military recruits, travelers to hyperendemic areas

*Haemophilus Influenzae(meningitis)- type b polysaccharide conjugated to a carrier protein.

Recipient: children 2-15. Combined w/DPT

Toxoid Vaccines

*Corynebacterium diphtheriae(diptheria)-contains a formaldehyde treated exotoxin.

Recipient: Every child at ages 2,4,6 mos, 1yr booster.

*Clostridium tetani- contains tetanus toxoid

Whole Bacterial, Purified Protein Vaccines

*B. pertussis (whooping cough)- (2 kinds), one w/ killed bacteria, other w/ purified ptn (preferred)

Bacillus anthracis (anthrax)-partially purified proteins—hi risk occupations

Salmonella typhi (typhoid fever)- killed or live orgs.—people in hi risk areas

Vibrio cholerae (cholera)—killed orgs—give to travelers to cholera areas

Yersinia pestis (plague)—killed orgs—hi risk patients

Mycobacterium bovis (Tb)-live attenuated strain called BCG—will have a positive PPD after administration

Francisella tularensis (tularemia)-live attenuated—give to vets and hunters

Rickettsia prowazekii (typhus)-killed orgs-give to people in hi risk areas

Coxiella burnetti (Q fever)-killed orgs

Passive Immunity-

1.) Tetanus- antitoxin is used to treat infected or poorly immunized pts. Antitoxin binds to and neutralizes toxin. Also give tetanus toxoid. Sum of tmt = passive active immunity.

2.) Botulinum- antitoxin Abs to botulinum toxins A, B, and E are given. Abs made in horses—potential hypersensitivity rxn.—antitoxin made in horses

3.) Diptheria—same antitoxin story…same potential for hypersensitivity

n.b. children respond poorly to polysaccharide antigens- do not give strep pneumo until 18-24 mos of age

autoimmune disease is high in elderly, given reduced numbers of autoregulatory T cells

Viral

Active immunity

-live attenuated virus

-killed virus

Characteristic Live Vaccine Killed Vaccine

Duration of Immunity	longer	Shorter
Effectiveness of protection	greater	Lower
Immunoglobulins produced	IgA, IgG	IgG
Cell Mediated Immunity?	yes	Weakly or none
Interruption of transmission	More effective	Less effective
Reversion to virulence	possible	No
Stability at room temp	low	Hi (more eff. In tropics)
Excretion of vaccine virus And transmission to nonimmune contacts	possible	No
Mode of administration	Oral	IM

Killed vaccine does not stimulate a cytotoxic T cell response

Concerns about live vaccines- reversion to virulence (killed can’t revert)

Excretion and subsequent infection

Contamination of vaccine w/2^nd virus

Viral vaccines are grown in chick embryos—don’t give to people who are allergic to eggs

Most vaccines are pre-exposure. Rabies and Hep B can be admin. both pre and post.

Common	Measles Mumps Rubella Varicella (chicken pox) Polio Influenza Hepatitis A Hepatitis B Rabies	Live Live Live Live Both (prim. live is used) Killed Killed Killed (contains surface Ag) Killed
Special Situations	Yellow fever Japanese encephalitis Adenovirus Smallpox	Live Killed Live Live

Passive Immunity

1.) Rabies immune globulin. Made in humans (no hypersens rxn.)

2.) Hepatitis B immune globulin

3.) Varicella Zoster immune globulin

4.) Immune globulins used in prevention or mitigation of Hepatitis A or measles.

10. Macrophage/ NK Cell Characteristics and Functions

Macrophage Characteristics and Functions

i. phagocytosis—ingest bacteria, viruses, and particles. Surface Fc receptors interact with Fc portion of immunoglobulins, enhancing uptake of opsonized organisms.

ii. antigen presentation- via MHC II

iii. cytokine production- IL-1 and TNF. IL-1 helps activate T- helper cells. TNF is an inflammatory mediator.

Derived from bone marrow cells. Monocytes in blood, Kupffer cells in the liver, etc.

C5 is an important signal for migration.

Natural Killer Cell Characteristics and Functions

i. Kill virus ingested cells and tumor cells

a) by secreting cytotoxins (granzymes and perforins)

b) by Fas Fas ligand mediated apoptosis

ii. active without prior exposure, are not enhanced, are not specific

iii. ab enhances killing effectiveness

iv. IL-12 and gamma IFN activate

v. Are lymphocytes, but do not mature in the thymus, have no memory, have no T cell receptor, do not require MHC recognition.