Transcript Cellular Biology

INFECTION AND DEFECTS IN
DEFENSE
Paula Ruedebusch, ARNP, DNP
IMMUNE DEFICIENCY
Defense system protects body
 Occasional breakdowns
 Mild defects or life-threatening defects
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MICROORGANISM AND HUMAN RELATIONSHIP

Mutual relationship
Normal flora
 Relationship can be breached by injury
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Leave their normal sites and cause infection elsewhere
Opportunistic microorganisms
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OPPORTUNISTIC INFECTIONS
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INFECTION
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Developed countries
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US = heart disease and malignancies
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India, Africa, Southeast Asia, etc.
Vaccines and antimicrobials
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Deaths greatly surpass deaths from infectious disease
Infectious disease
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Sanitary living conditions, clean H20, uncontaminated
food, vaccinations, antimicrobials
Alter prevalence of some infectious diseases
New diseases
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Mutant stains and new diseases, drug-resistant TB, etc.
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INFECTIOUS DISEASE, MISC.
https://www.youtube.com/watch?v=6xxd63o7Usg
 http://www.google.org/flutrends/about/how.html
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FACTORS FOR INFECTION
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Communicability
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Ability to spread from one individual to others and cause
disease: measles and pertussis spread very easily, HIV is of
lower communicability
Immunogenicity
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Ability of pathogens to induce an immune response
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FACTORS FOR INFECTION (CONT’D)

Infectivity
Ability of pathogen to invade and multiply in the host
 Involves attachment to cell surface, release of
enzymes, escape phagocytes, spread through lymph
and blood to tissues
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Pathogenicity
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Ability of an agent to produce disease
Success depends on communicability, infectivity,
extent of tissue damage, and virulence
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FACTORS FOR INFECTION (CONT’D)
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Mechanism of action

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How the microorganism damages tissue
Portal of entry

Route by which a pathogenic microorganism infects
the host
Direct contact
 Inhalation
 Ingestion
 Bites of an animal or insect
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FACTORS FOR INFECTION (CONT’D)
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Toxigenicity
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Ability to produce soluble toxins or endotoxins, factors that
greatly influence the pathogen’s degree of virulence
Virulence

Capacity of a pathogen to cause severe disease; for example,
measles virus is of low virulence; while rabies virus is highly
virulent
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CLASSES OF INFECTIOUS MICROORGANISMS AND
EXAMPLES
Virus (poliomyelitis, influenza)
 Bacteria (Staph, Cholera, Strep pneumonia, TB)
 Fungi (tinea pedis, candidiasis)
 Protozoa (giardiasis, sleeping sickness)
 Chlamydia (Urethritis)
 Rickettsia (Rocky Mountain Spotted Fever)
 Mycoplasma (Atypical pneumonia)
 Helminths (Filariasis)
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PATHOGEN DEFENSE MECHANISMS

Bacteria

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Produce surface coats that inhibit phagocytosis and
toxins
Viruses
Many can mutate within cells where they are not
available to immune and inflammatory mechanisms
 Not available to antibodies in circulation
 Antigenic variations:

Antigenic drift
 Antigenic shifts
 http://www.cdc.gov/flu/about/viruses/change.htm
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BACTERIA
Prokaryotes
 Aerobic or anaerobic
 Motile or immotile
 Shapes:

Spherical = cocci
 Rodlike – bacilli
 Spiral = spirochetes
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Gram stain
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BACTERIAL VIRULENCE AND INFECTIVITY
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Toxin production
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Exotoxins (cytotoxins, neurotoxins, pneumotoxins,
enterotoxins, hemolysins)
Enzymes released during growth, causing specific responses
 Immunogenic
 Antitoxin production
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Ex. Tetanus, diptheria, pertussis, group A streptococci (flesh
eating bacteria)
Endotoxins
Lipopolysaccharides contained in the cell walls of gramnegative organisms released during cell destruction
 Pyrogenic effects
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ENDOTOXINS
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BACTERIAL VIRULENCE AND INFECTIVITY
(CONT’D)

Bacteremia (presence) or septicemia (growth)
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A result of a failure of the body’s defense mechanisms
Usually caused by gram-negative bacteria
Toxins released in the blood cause the release of
vasoactive peptides and cytokines that produce
widespread vasodilation leading to septic (endotoxic)
shock
https://depts.washington.edu/idhmc/guidelines/hospital
/hmc_sepsis.html (UW Sepsis protocol)
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SEPTIC SHOCK
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https://www.youtube.com/watch?v=NKtiC0HRrqc
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VIRAL INFECTION
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Characteristics:
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Dependent on host cells
No metabolism
Simple organism
Spreads cell to cell
Usually a self-limiting infection
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VIRAL REPLICATION
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Not capable of independent reproduction
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Need permissive host cell
Begins when virion binds to a specific receptor on
the plasma membrane of a host cell penetrates
the plasma membrane
 Virus then uncoats in cytoplasm
 DNA virus replicates in nucleus
 RNA virus replicates in cytoplasm
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VIRAL REPLICATION (CONT’D)
Copies of genetic material made
 New virions released from cell to infect other host cells
 Some remain latent in host cell until activated by stress,
hormone changes, disease (e.g., herpes virus and cold
sore)
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CELLULAR EFFECTS OF VIRUSES
Inhibition of host cell DNA, RNA, or protein
synthesis
 Disruption of lysosomal membranes release
enzymes that damage host cell
 Transformation of host cell to cancer cell
 Promotion of secondary bacterial infection
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SECONDARY BACTERIAL INFECTIONS
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FUNGAL INFECTION
Large microorganisms with thick rigid cell walls
without peptidoglycans (resist penicillin and
cephalosporins)
 Eukaryotes
 Exist as single-celled yeasts, multi-celled molds,
or both
 Reproduce by simple division or budding
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FUNGAL INFECTION (CONT’D)
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Pathogenicity
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Adapt to host environment
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Wide temperature variations, digest keratin, low oxygen
Suppress the immune defenses
 Usually controlled by phagocytes, T lymphocytes
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FUNGAL INFECTION (CONT’D)
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Diseases caused by fungi are called mycoses
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Superficial, deep, or opportunistic
Fungi that invade the skin, hair, or nails are known as
dermatophytes

The diseases they produce are called tineas (ringworm)

Tinea capitis, tinea pedis, and tinea cruris
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FUNGAL INFECTION AND INJURY
Deep fungal infections are life threatening and are
commonly opportunistic (e.g., with antibiotics or pH
changes)
 Changes that alter normal flora foster fungal infections
 Candida albicans
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PARASITIC INFECTION
 Symbiotic
 Unicellular
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protozoa to large worms (helminths)
Flukes, nematodes, tapeworms
 Protozoa
include malaria, amoebae, flagellates
 More common in developing countries
 Spread human to human via vectors
 Usually ingested
 Tissue damage is secondary to infestation itself
with toxin damage or from inflammatory/immune
response
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PARASITIC INFECTION
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CLINICAL MANIFESTATIONS OF INFECTIOUS
DISEASE

Variable depending on the pathogen
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Directly caused by the pathogen or indirectly caused
by its products
Fever
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COUNTERMEASURES (CONT’D)
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Antimicrobials
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Bacteriocidal vs. bacteriostatic
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Inhibit synthesis of cell wall
Damage cytoplasmic membrane
Alter metabolism of nucleic acid
Inhibit protein synthesis
Modify energy metabolism
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COUNTERMEASURES (CONT’D)
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Antimicrobial resistance
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Can destroy normal flora
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Genetic mutations
Inactivation
Multiple antibiotic-resistance bacteria (e.g., MRSA)
Clostridum difficile
Why?
Overuse!
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COUNTERMEASURES
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Vaccines
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Induction of long-lasting protective immune responses
that will not result in disease in a healthy recipient
Attenuated organism
Killed organisms
Recombinant viral protein
Bacterial antigens
Toxins
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COUNTERMEASURES (CONT’D)
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Vaccines
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Biologic preparations of weakened or dead pathogens
Long lasting immunity
CDC schedules = http://www.cdc.gov/vaccines/
Development expensive
Reluctance to vaccinate but complications rare
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IMMUNE DEFICIENCIES
Failure of immune
mechanisms of selfdefense
 Primary (congenital)
immunodeficiency
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Genetic anomaly
Secondary
(acquired)
immunodeficiency
Caused by another
illness
 More common
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IMMUNE DEFICIENCIES (CONT’D)
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Clinical presentation
Development of unusual or recurrent, severe infections
 T cell deficiencies
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Viral, fungal, yeast, and atypical microorganisms
B cell and phagocyte deficiencies
 Complement deficiencies
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SECONDARY DEFICIENCIES (CONT’D)
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Causes:
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Normal physiology conditions
Psychologic stress
Dietary insufficiencies
Malignancies
Physical trauma
Medical treatments
Infections
Acquired immunodeficiency syndrome (AIDS)
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ACQUIRED IMMUNODEFICIENCY SYNDROME
(AIDS)

Syndrome caused by a viral disease
Human immunodeficiency virus (HIV)
 Depletes the body’s Th cells
 Incidence:

Worldwide: 33.4 million (2008)
 United States: about 56,000 (2008)
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ACQUIRED IMMUNODEFICIENCY SYNDROME
(AIDS) (CONT’D)
Effective antiviral therapies have made AIDS a
chronic disease
 Epidemiology

Blood-borne pathogen
 Heterosexual activity is most common route worldwide
 Increasing faster in women than men especially in
adolescents
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ACQUIRED IMMUNODEFICIENCY SYNDROME
(AIDS) (CONT’D)

Pathogenesis

Retrovirus
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Genetic information is in the form of RNA
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HUMAN IMMUNODEFICIENCY VIRUS
(HIV)
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)
(CONT’D)

Structure

protein binds to the CD4 molecule found primarily on
surface of helper T cells
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Destroys CD4+ Th cells
Typically 800 to 1000 cell/mm3
 Reverses CD4/CD8 ratio
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AIDS = < 200 cell/mm3 of CD4 + T cell
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)
(CONT’D)
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Clinical manifestations
Serologically negative, serologically positive but
asymptomatic, early stages of HIV, or AIDS
 Window period
 Th cells <200 cells/mm3 diagnostic for AIDS
 Diagnosis of AIDS is made in association with various
clinical conditions and lab tests:

Atypical or opportunistic infections, and cancer
 Presence of antibodies against HIV (4 to 7 weeks after blood
transmission, 6-14 months after sexual intercourse)
 Western blot analysis
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)
(CONT’D)

Treatment and prevention

Highly active antiretroviral therapy (HAART)
Reverse transcriptase inhibitors
 Protease inhibitors
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New drugs
Entrance inhibitors
 Integrase inhibitors
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Vaccine development
Genetically and antigenically variable
 Antibodies may not be protective
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HYPERSENSITIVITY
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Altered immunologic response to an antigen that
results in disease or damage to the host
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HYPERSENSITIVITY (CONT’D)
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Allergy
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Autoimmunity
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Deleterious effects of hypersensitivity to environmental
(exogenous) antigens
Disturbance in the immunologic tolerance of selfantigens
Alloimmunity
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Immune reaction to tissues of another individual
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HYPERSENSITIVITY (CONT’D)
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Characterized by the immune mechanism:
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Type I
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Type II
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Tissue-specific reactions
Type III
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IgE mediated
Immune complex mediated
Type IV
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Cell mediated
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HYPERSENSITIVITY (CONT’D)
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Immediate
hypersensitivity
reactions
Anaphylaxis
 Types I, II, III
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Delayed
hypersensitivity
reactions
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Type IV reactions
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TYPE I HYPERSENSITIVITY
IgE mediated
 Against environmental antigens (allergens)
 IgE binds to receptors on surface of mast cells
 Food allergies
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Kids: Milk, chocolate, citrus fruits, eggs, wheat, nuts,
peanut butter, fish
 Adults: shellfish

Urticaria
 Histamine release
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H1 and H2 receptors
Antihistamines
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TYPE I HYPERSENSITIVITY (CONT’D)
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Manifestations:
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Itching
Urticaria
Conjunctivitis
Rhinitis
Hypotension
Bronchospasm
Dysrhythmias
GI cramps and malabsorption
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TYPE I HYPERSENSITIVITY (CONT’D)
Genetic predisposition- atopic
 Tests:
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Food challenges
Skin tests
Laboratory tests
Desensitization
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Cautiously
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TYPE I HYPERSENSITIVITY (CONT’D)
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TYPE II HYPERSENSITIVITY
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Tissue specific

Specific cell or tissue (tissue-specific antigens) is the
target of an immune response
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TYPE II HYPERSENSITIVITY (CONT’D)
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Five mechanisms:
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Cell is destroyed by antibodies and complement
Cell destruction through phagocytosis
Soluble antigen may enter the circulation and deposit
on tissues; tissues destroyed by complement and
neutrophil granules
Antibody-dependent cell-mediated cytotoxicity (ADCC)
Causes target cell malfunction (e.g., Graves)
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TYPE III HYPERSENSITIVITY
Immune complex mediated
 Antigen-antibody complexes are formed in the
circulation and are later deposited in vessel walls
or extravascular tissues
 Not organ specific
 Serum sickness
 Raynaud phenomena
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TYPE IV HYPERSENSITIVITY
Does not involve an antibody!
 Cytotoxic T lymphocytes or lymphokine producing
Th1 cells
 Examples:


Acute graft
rejection
 Skin test for TB
 Some autoimmune disorders
 Contact allergic reactions (chemicals,
cosmetics, detergents, clothing, food,
metals, topical meds)
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PPD TEST
Intradermal injection of tuberculin antigen
 Delayed hypersensitivity skin test (24-72 hours)
 Influx of T lymphocytes and macrophages
 Induration (clear hard center)
 Erythema (surrounding)
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ALLERGY
Most common hypersensitivity and usually type I
 Environmental antigens that cause atypical
immunologic responses in genetically predisposed
individuals


Pollens, molds and fungi, foods, animals, etc.
Often allergen is contained within a particle too
large to be phagocytosed or is protected by a
nonallergenic coat
 Bee stings
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EPIPENS
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AUTOIMMUNITY

Breakdown of tolerance
Body recognizes self-antigens as foreign
 Self-antigens not normally seen by the immune system


Infectious disease (e.g., rheumatic fever,
glomerulonephritis)
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AUTOIMMUNE EXAMPLES

Systemic lupus erythematosus (SLE)
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Chronic multisystem inflammatory disease
Autoantibodies against:
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Nucleic acids
Erythrocytes
Coagulation proteins
Phospholipids
Lymphocytes
Platelets, etc.
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AUTOIMMUNE EXAMPLES (CONT’D)

Systemic lupus erythematosus (SLE)
Deposition of circulating immune complexes containing
antibody against host DNA
 More common in females
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SYSTEMIC LUPUS ERYTHEMATOSUS
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Clinical manifestations:
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Arthralgias or arthritis (90% of individuals)
Vasculitis and rash (70%-80%)
Renal disease (40%-50%)
Hematologic changes (50%)
Cardiovascular disease (30%-50%)
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SYSTEMIC LUPUS ERYTHEMATOSUS (CONT’D)
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Eleven common findings:
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Facial rash (malar rash)
Discoid rash
Photosensitivity
Oral or nasopharyngeal
ulcers
Nonerosive arthritis
Serositis
Renal disorder
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Neurologic disorder
Hematologic disorders
Immunologic disorders
Presence of antinuclear
antibodies (ANA)
Serial or simultaneous presence of at least four
indicates SLE
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ALLOIMMUNITY

Immune system reacts with antigens on the tissue
of other genetically dissimilar members of the
same species

Transplant rejection and transfusion reactions:
Major histocompatibility complex (MHC)
 Human leukocyte antigens (HLA)


Transfusion reactions

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ABO blood groups
Rh incompatibility

Hemolytic disease of newborn
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GRAFT REJECTION

Transplant rejection is classified according to time

Hyperacute
Immediate and rare
 Preexisting antibody to the antigens of the graft


Acute

Cell-mediated immune response against unmatched HLA antigens
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GRAFT REJECTION (CONT’D)

Transplant rejection is classified according to time

Chronic
Months or years
 Inflammatory damage to endothelial cells of vessels as a
result of a weak cell-mediated reaction against minor HLA
antigens
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GRAFT-VERSUS-HOST DISEASE (GVHD)

Immunocompromised individuals are at risk for
GVHD
T cells in the graft are mature and capable of cellmediated destruction tissues within the recipient
 Not a problem if patient is immunocompetent
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QUESTIONS?
Thank you for a fantastic quarter!!
 Study hard, you can do it!!
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