Immunology Part 1

IMMUNOLOGY

PHYSIOLOGY

1.    IMMUNOGENS

Chemical compounds that cause specific immune response

2.    ANTIGENS

Chemical compounds that BIND TO THE PRODUCTS of an immune response

3.    IMMUNOGEN-ANTIGEN

Compound associated with or secreted by parasitic bacteria, protozoa, fungi and viruses an of MW >5,000 daltons

n  For the cmpd to be immunogenic,it must contain protein or peptide

n  Insulin

4.    HAPTENS

Low MW cmpds that act as immunogens after COVALENTLY binding to a larger molecule or cell surface.

After they stimulate the immune system in this complex, these compounds can act as ANTIGENS in the unbound or bound state

n  May be present in environment (EX: Pentadecacatechol of poison ivy)

n  Drugs such as PENICILLIN

5.    TOLEROGENS

Chemical compounds that elicit specific nonresponsiveness. This specific nonresponsiveness may be caused by the ability of the compound to be broken down by the body or by the route of administration of the compound

n  Oral adminstration

 

 

Cells of the immune system

1.    B lymphocyte and T lymphocytes

Primary cells of specific immune responses.

ANTIGEN-specific

Antigen Receptors of B-CELLS

Different B cells have different antigen specificities, but each B cell has ONE specificities

n  B cells that recognize specific antigens divide to form new Bcells (memory B cells) and plasmacells (antibody-forming cells), which secrete free,soluble (humoral) antibody molecules into extracellular fluids

 

n  Virgin B cell have not responded to an antigen since their release into the circulation from bone marrow

 

Ø  Membrane antibodies:  IgM, IgD

n  Memory B cells- derived by cell division from another B cell that has responded  to an antigen.

Ø  Ig A, G,E

 

Antigen receptors of T-CELL

n  Have two (2) membrane proteins  (α and β or γ and δ),which define the antigen specifity of each T-cell and several other integral membrane proteins known as CD3 complex

n  T-cells are CD3+

 

A.   Major Histocompability Complex *MHC) proteins. The antigens of Tcells do not recognize antigens alone.

n  THEY NORMALLY RECOGNIZE PEPTIDE EPITOPES (fragment of antigens) that are  chemically combined with MHC proteins on the surface of other body cells

à TWO MAJOR CLASSES

1.    Class 1 proteins- present on the surfaces of all body cells

2.    Class II proteins- present on the surface of special antigen-presenting cells APC

B.    THYMUS GLAND

Ø  T cells do not enter the circulation directly from bone marrow but first enter the thymus gland to mature. Most developing T-cells die in THYMUS.

Ø  T-CELLS released from thymus into circulation= VIRGIN T CELL

Ø  T-cells  that originate through cell division from the response of the other T cells are= MEMORY T CELLS or EFFECTOR T CELLS

C.   GLYCOPROTEINS.

Ø  T-cell classification by the presence of a membrane glycoprotein CD4—the helper or the presence of CD8 or the cytotoxic T cell.

Ø  T-HELPER CELLS

-          TH1 cells-activate other cells, including some TH cells, Tc cells and macrophages. Decrease ANTIBODY (Ab) production by inhibiting the formation of TH2cells

-          TH2 cells- activate B cells and produce Ab. Inhibit formation of Th1 cells

Ø  T-CYTOTOXIC CELLS

-          Are able to KILL CELLS that are infected BY VIRUSES.

Ø  T REGULATORY CELLS

-          Most are CD4+

-          Suppress Immune response through the secretion of IL-10 and transforming growth factor B TGFB

Ø  Cytokines

 

 

 

 

 

 

3.      NATURAL KILLER CELLS- large granular lymphocytes without specific T or Bcell antigen receptor. Their cytotoxicity is similar to that of CTL (Tc) cells.-

-          NK cells kills DESTROY TUMOR

-          Important in viral infections prior to dev’t adaptive immunity

4.      APC- essential for most immune response and are found in the sites at which these responses originate

a.     EX: MACROPHAGES, DENDRITIC CELLS

5.      Neutrophils, macrophages, eosinophils, basophils, platelets, and mast cells - -assist in ELIMINATING ANTIGENS FROM THE BODY.

FIVE CLASSES OF ANTIBODIES/IMMUNOGLOBULINS

1.      Ig M - first to be secreted during primary immune responses

-          Accounts 20% of the adult serum Ig

-          Can’t leave blood

-          MOST POTENT ACTIVATOR OF THE COMPLEMENT SYSTEM

2.    IgG – predominant serum immunoglobulin secreted at the end of primary immune response and during memory responses

-          can diffuse from blood into extracellular fluids; crosses placenta

-          Account 70% of adult Ig

-          OPSONIZES antigens for phagocytosis and activates the complement system

3.    Ig E – Binds to IgE receptors located on the cell surface, blood basophils ans on mucosal and connective tissue

-          To trigger secretion of inflammatory mediators

-          Mediates Allergic reaction

-          Less 1%

4.    Ig A- Secreted in large quantities across mucosal surfaces into GI, respiratory, lachrymal, mammary and genitourinary secretions, where it protects mucosa from colonization of bacteria and others

-          10%

5.    Ig D- NO KNOWN FUNCTION

-          less 1%

HYPERSENSITIVITY REACTIONS- exaggerated, inappropriate or prolonged immune responses that cause damage to otherwise normal tissue

FOUR TYPES

1.      Ig E mediated TYPE I- hypersecretion of IgE (tendency is heritable)

-          Does not usually occur on the first exposure to a specific allergen

-          TX:

o   Epinephrine Kits- reverses anaphylaxis

o   Competitive H1 antagonist

o   Cromolyn Na- inhibit mast cell degranulation

-          Note: Non- IgE mediated Type 1 reaction- anaphylactoid reaction

2.      TYPE II Hypersensitivity Reactions-  occurs through the production of Ig M and Ig G

-          Antigens: transfusion mismatches, Rh disease, drug allergens, autoimmune conditions

-          MAJOR SIGNS: Hemolytic anemia and thrombocytopenia

3.      TYPE 3 Reactions- persistence of immune complexes in the circulation or at local tissue sites when they are not removed after production of specific  antibodies ad antibody-antigen complexes

-          IMMUNE COMPLEXES ACTIVATE COMPLEMENT , cause  inflammation and induce positive chemotaxis in neutrophils.

-          SIGNS: Lymphadenopathy, splenomegaly, fever, rash

4.      Type IV Hypersensitivity reactions- prolonged inappropriate and appropriate immune responses mediated by ANTIGEN-SPECIFIC TH1 cells in concert with activated macrophages

-          Tuberculin test (Mantoux reaction)

-          Common antigens: Mycobacterium tb. M. leprae, Listeria monocytogenes

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Infectious Diseases and Preferred Treatments (Status: Incomplete)

Table 29-5. Treatment of Tuberculosis

Disease stage

Treatment

Duration

Latent (probably isoniazid sensitive)

Isoniazid

9 months (6 months possible except for children and HIV-positive persons)

Latent (probably isoniazid resistant)

Rifampin + apyrazinamide

2 months

Active disease

Isoniazid + rifampin + pyrazinamide

2-4 months

 

Table 29-1. Empiric Treatment of Meningitis

Age of patient

Most likely organism

Empiric treatment

Newborn to 1 month

Gram-negative enterics (Escherichia coli), group B streptococci, or Listeria monocytogenes

Ampicillin and aminoglycoside, cefotaxime, or Ceftriaxone

1 month to 4 years

Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae

Cefotaxime or ceftriaxone, plus vancomycin

5-29 years

N. meningitidis, S. pneumoniae, or H. influenzae

Cefotaxime or ceftriaxone, plus vancomycin

30-60 years

S. pneumoniae or N. meningitidis

Cefotaxime or ceftriaxone, plus vancomycin

> 60 years

S. pneumoniae, Gram-negative enterics (E. coli), or L. monocytogenes

Cefotaxime, ceftriaxone, or ampicillin and aminoglycoside-vancomycin

 

NOTES:

ü  Empiric therapy hallmarkà coverage of the most common pathogen associated with the infection

ü  Most cellulitis infections are associated with Staphylococcus aureus and Streptococcus pyogenes.

ü  Cant be cultured in cell media

o   Rickettsia rickettsii.

o   Ehrlichia phagocytophila.

o   Francisella tularensis.

ü  Staphylococcus and Bacillus diarrheas are an intoxication not caused by a living organism. Both Salmonella and E. coli diarrheas should be treated only if severe or if signs of systemic infection are present. Vibrio cholerae causes a severe diarrhea requiring anti-infective treatment.

ü  P.carinii as many HIV patients (Oppurtunistic infections)

ü  Most common organisms associated with COMMUNITY ACQUIRED PNEUMONIA IN ADULTS

o   Chlamydia pneumoniae is not a pathogen associated with adult pneumonia.

o   Answer:  Mycoplasma pneumoniae, Streptococcus pneumoniae, and Haemophilus influenzae.

 

 

 

 

Gonorrhea

Syphilis

Neisseria gonorrheae

Treponema pallidum- cannot grown in culture, dark field fluorescent antibody exam

 VDRL test

Rapid plasma regain test (RPR

Gonorrhea- Gram negative; gram stain)

Penicillin

Tick borne Systemic Febrile Syndromes

Lyme disease

 

Borrelia burgforfei

Doxycycline

Rocky mountain spotted fever

Rickettsia rickettsii

Ehrlichiosis

Erlichia phagocytophila

Tularemia

Francisella tularensis

Gentamicin

 tobramycin

Hepatitis

Hepa B

Chronic

Interferon alfa 2b

Lamivudine

Hepa C

Chronic

INF alfa 2b

RIBAVIRIN

Hepa C

Acute

INF a2b

Influenza

Influenza A

 

Oseltamivir -mivir

Rimantadine

Influenza B

Prohylaxis

Oseltamivir

Herpes Virus

Herpes Simplex

Initial

Acyclovir

Recurrence

Famciclovir

Chronic suppresion

Valacyclovir

Immunocompromised

Acyclovir

Resistance to Acyclovir

FOSCARNET

Varicella zoster

 

Acyclovir/ Foscarnet

UTI

Cystitis

Pylonephritis

Prostatitis

 

QUINOLONE

TMP-SMX

 

 

 

Endocarditis

 

Penicillins

allergic: vancomycin

Hospital acquired pneumonia

 

aminoglycoside and one other Gram-negative agent, such as cefepime.

:MRSA vancomycin

Prostate infections

4-6 weeks

CIPROFLOXACIN: concentrate in prostate fluid

TMP-SMX reasonable chice

Candida infections

 

Amphotericin and Fluconazole

 

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Disperse Systems to be continued...

DISPERSE SYSTEMS

 

SUSPENSION

-          Finely divided particles distribute somewhat uniformly  throughouta vehicle in which the drug exhibits a minimum degree of solubility

-          GOOD SUSPENSION: particle diameter: 1 to 50 micrometer

-          MICROPULVERIZATION;Producing fine powders: 10 to 50 micrometer

-          FLUID ENERGY/JET MILLING/ MICRONIZING--Under 10 um

     ……Floc/floccules- intentional formation of loose aggregates of particles, forming type of lattice that resist complete settling. It breaks up easily with small amount of agitation

EMULSIONS

-          Dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible

 

Theories of Emulsification

1.       Surface tension theory

 

2.       Oriented wedge theory

Assumes mono-molecular layers of emulsifying agent curved around the droplet of the internal phase of the emulsion

3.       Interfacial film theory

Places the emulsifying agent  at the interface between theoil and water, surrounding the droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops

 

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