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IMMUNITY
I. First we want to review the types of plasma proteins:
A. Albumins & clotting factors – synthesized in the liver
B. Immunoglobulins – synthesized by lymphocytes in the lymph nodes; these are the proteins responsible
for much of our immunity.
II. Responsibilities of the Immune system – 3 main jobs
A. Defense against pathogens (“self vs. non-self”) – get rid of non-self
1. Bacteria
a) -2 variants of regular bacteria
2. Spirochetes (syphilis & lyme)
3. Mycoplasms (pneumonia & TB)
4. Viruses
5. Rickettsia & Chlamydia (b/w a bacteria & a virus)--Rocky Mountain spotted fever
6. Fungi (molds & yeasts)
7. Protozoa (parasites): malaria, giardiasis
8. Helminths (worms)
9. Arthropods: mites, chiggers, scabies
B. Removal of worn-out cells & tissue debris (e.g. spleen & old RBC’s)
C. Identification & destruction of abnormal or mutant cells (CA)
III. Mechanisms of defense (how the immune system defends the body)
A. Physical & chemical barriers: 1st line of defense; non-specific
1. E.g. Intact skin & mucous membranes; sphincters; epiglottis; gastric acidity; normal intestinal flora
of GI
B. Inflammatory response: non-specific; “--itis” (non-specific) - innate
1. 2nd line of defense: reaction to local injury (surgery, trauma, microorganisms, ischemia) when
something gets beyond 1st defense
a) Defends even when has never seen the invader before – doesn’t have to ID the foreign object
b) From small insect bites to major inflammations (appendicitis)
c) Important in wound healing
2. 3 events take place (when injury occurs or foreign agent enters)
a) Increased vascular permeability
i) Vasodilation caused by a release of chemical mediators (chemokines) from surrounding cells,
bacteria, mast cells, skin cells, etc
ii) Chemical mediators – histamine (from mast cells), prostaglandins, and leukotrienes cause
vasodilation and increases vascular permeability
iii) Larger blood volume to the area also increases hydrostatic pressure which also causes fluid to
shift out into the tissues
iv) Contributes to the edema, redness, pain, and warmth
v) Platelets move to the site and adhere to the exposed vascular collagen
b) Emigration of leukocytes (within a few minutes to hours after injury) – called in by chemokines
i) Neutrophils move to the sides of the blood vessels and roll along the endothelium of the
blood vessel wall – known as margination (step 1); they stop and adhere (adhesion)
ii) They push through the blood vessel wall (transmigration – step 2)
iii) Biochemical mediators - chemokines (bacterial toxins, degenerative products of the
inflamed tissue, and the C5a complement fragment) attract the neutrophils to the
inflamed tissue – this is known as chemotaxis (step 3)
iv) Neutrophils are first on the scene; Monocytes are slower; Eosinophils and NK cells also
respond (NK cells recognize virally infected cells)
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c) Phagocytosis
i) Neutrophils and Monocytes (macrophages) produce phagocytosis
ii) Neutrophils produce enzymes which lead to digestion and degradation of foreign and
inflammatory debris
iii) Macrophages remove spent neutrophils and prepare the site for healing
3. Lab Tests
a) ESR: erythrocyte sedimentation rate increases; increases in chronic inflammation
b) CRP (C-reactive protein): increases in acute inflammation
IV. Immune response: 3rd line of defense; specific
A. Overview
1. Selective to specific invaders
2. Requires initial contact to initiate development of this response (builds up immunity)
B. Organs involved
1. Lymph vessels & nodes (increased size in children)
a) Drain extra interstitial fluid to cluster of nodes located throughout body (esp. neck, maxillae,
groin) and onto vascular
b) Contain lymphocytes (B & T) & macrophages in the nodes
c) Act as filters: trap and remove foreign material
2. Thymus: in mediastinal area (lower neck region, over heart, under sternum)
a) Matures pre-T lymphocytes into types of T cells until puberty, then decreases function b/c
immune system is established (have been exposed to most antigens)
3. Spleen: largest (LUQ of abdomen)
a) Reservoir for RBC’s: macrophages break down old RBCs & then clear out the cellular debris
b) Lined with B & T lymphocytes, as well as macrophages for phagocytes
c) Abnormal RBC’s or platelets tend to collect in the spleen in excessive amounts (sickle cell
anemia & ITP = bleeding)
d) Splenectomy - increased risk of infection
4. Mucosa-associated: at portals for entry of microorganisms
a) Tonsils/ adenoids contain WBCs
b) Peyer’s patches : ileum/ appendix; lymph nodules in ileum (si)
C. Leukocytes (WBC): major cells of immune system; total WBC is 5-10,000
1. Part of the hematopoietic (blood-forming/producing) & lymphoid tissues
a) WBC’s are formed in the bone marrow (myeloid) from a hematopoietic (blood forming) stem
cell; there are several types of WBC’s
b) Some WBC’s circulate & mature in the lymphoid tissues (macrophages, T lymphocytes)--lymph
nodes, thymus, spleen
i) Lymphadenopathy: enlarged lymph nodes that are
2. Types of WBCs (5 total) (Nl lab range 5-10,000)
a) Granulocytes (granules present in cytoplasm that contain enzymes for killing and catabolizing):
life span approx. 10 hrs; circulate in blood & travel to tissues
i) Neutrophils (50-70%) a.k.a. polymorphonuclear neutrophil (PMN) =“segs”; “bands” =
immature neutrophils; increased bands = bacterial infection.
(a) 1st defenders for bacterial infection; major scavengers (phagocytes)
(b) A differential WBC count tells the % of each type of WBC; if there is an abnormal
increase in neutrophils, MD can make a reasonable dx as to whether infection is bacterial
or viral; can know whether or not to start Abx
ii) Eosinophils (1-5%): function not well-known; ingest antigen-antibody complexes
(a) Allergic conditions (asthma, hay fever)  IgE stimulates eosinophils (elev with allergies)
(b) Internal parasites (helminths)
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iii) Basophils (0-1%); function poorly understood; act similarly to tissue mast cells located just
outside capillary
(a) Mast cells: cellular bags in connective tissue containing lg. basophilic granules with
heparin, serotonin, bradykinin, & histamine (substances released in response to
injury/infection)
(b) Release histamine & heparin – inflammation; prevents clotting in microcirculation
1. Inflammatory reaction
2. Increased capillary permeability (red flush)
3. Increased gastric secretion
b) Agranulocytes: no granules in cytoplasm; WBC’s proliferate/clone in spleen
i) Monocytes (1-6%) – kidney shaped
(a) Mature (morph) into macrophages in the tissues; “professional phagocytes” – fewer
digestive vacuoles than granulocytes, but larger
1. Macrophages: recognize & ingest foreign antigens
2. Ingest large particles & debris/ old & damaged cells – esp. blood cells
3. Kuppfer cells in liver
ii) Lymphocytes (20-40%)
(a) Programmed for specific targets; mature in thymus
(b) Immunocytes, not phagocytes (no digestive vacuoles)
(c) Travel to lymph system (only sm. % circulate in the blood)
(d) Types
1. B lymphocytes
2. T lymphocytes
(e) Major cells of the specific immune response = B&T lymphocytes
1. A specific lymphocyte attacks & destroys a specific antigen after prior exposure to it
(memory) to prevent disease = immunity; identifies the antigen as “non-self”; if this
is the first exposure to it, this process takes several days; Lymphocytes are able to
recognize “self” vs. “non-self”
2. Remember, this specific immune reaction is aided by the non-specific inflammatory
response (neutrophils & macrophages)
D. Humoral Immunity: B lymphocytes (B&T lymphocyte maturation)
1. Both B & T lymphocytes start out as a generic stem cell in the bone marrow; travel to lymph tissue
(spleen, lymph, mucous)
a) All blood cells start out as stem cells, then differentiate
b) B lymphocytes mature into plasma cells with help from T helper cells; plasma cells produce
antibodies (immunoglobulin or gammaglobuline)-- IgG; these coat the antigen & target it for
destruction by macrophages & entropies
i) Antigen-antibody complexes – membrane bound antibodies bind to pathogen at the epitope
(binding area). B-cell will engulf and break up pathogen and present on MHC to flag for
destruction. B-cells become activated . B-cells either become effector (plasma) cells which
produce free floating antibodies that bind to or tag the pathogen (opsonization) for
destruction; others will become memory cells.
2. Types of antibodies (5 major classes)
a) IgG (75-80%): major antibacterial & antiviral antibody; moves out of vascular into ISF; crosses
placenta to baby; activates complement system & promotes phagocytes
b) IgM (10%), largest Ig: 1st to be produced during an immune reaction; then replaced by IgG;
usually stays in vascular b/c too large to cross membrane; can lyse cell walls of antigen
i) -Increased IgM at birth = intrauterine infection
ii) -Sign of recent infection
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c) IgA: defends against pathogens on body surfaces (esp. respiratory & GI tracts); found in
secretions (saliva, sweat, tears, colostrum, mucous)
d) IgE: involved in allergic reactions; antigen stimulates mast cells (basophils) & eosinophils to
release histamine & heparin (asthma, hay fever)
i) Increased IgE = allergies & parasitic infections
e) IgD: function not totally known; may act as an antigen receptor on B cells; stimulates them to
turn into plasma cells
3. Major Ig’s are specific for specific antigens (esp. bacteria)
a) B lymphocytes circulate throughout vascular & lymphoid tissue & rapidly convert to plasma
cells & produce specific antibodies once a familiar antigen is encountered (some B cells become
“memory” cells after the initial contact so subsequent contacts can result in immediate release of
large quantities of Ig)
b) Primary response: 6-10 days after initial contact
c) Secondary response w/subseq. contacts = immediate production (memory cells)
i) Idea behind “booster” vaccinations (e.g. Td)
4. Passive vs. active immunity
a) Passive: transfer of the antibody to individual (starts working immediately); only stays in body
for a few weeks or months; artificial vs. natural
i) E.g. Through placenta or breast milk; IgG infusion or injection; HBIg if exposed to HBV
(specific anti-serum antibodies), TIg for tetanus exposure
b) Active: transfer of the antigen to individual who then builds up his own T cells, B cells, or
antibodies (actively works, but takes time-- days to weeks); stays in body much longer--
sometimes entire life; natural vs. artificial
i) E.g. Exposure to a disease or getting an immunization
E. T lymphocytes (cell-mediated): no antibodies formed; direct contact (ø antibodies)
1. Overview
a) Provide long-term immunity and originate from bone marrow pre-T stem cells which travel to
thymus & mature into T cells (instead of B) (T=thymus)
b) T cells mature in thymus with specific receptors on surfaces which allow them to recognize
specific antigens (develop into sub-types)
c) T cells mount a direct assault on the antigens they match (viruses, parasites, CA, transplants);
takes a few days to mount this assault (delayed)
d) T cells must be able to recognize “self” & distinguish between foreign matter & normal body
(e.g. transplant rejection) (autoimmune d/o = body attacks “self”)
e) T cells leave thymus & enter lymphoid tissue/ circulation/ ISF
2. 3 types of T cells
a) Killer cells (cytotoxic T-cell; CD8 receptors): *must be activated by helper T cells; attacks
infiltrated antigens (able to recognize by presentation on MHC); binds to the MHC and releases
cytotoxin into the antigen which kills antigen
b) Helper T cells = CD4: receptor on helper cells (major problem in AIDS)
i) Activates B-cells into plasma cells to make antibodies (binds to MHC II on B-Lymphocyte).
Release cytokines (interferon) – makes other cells more active (macrophages, killer-T-cells)
ii) Macrophages produce phagocytosis
c) Suppressor T cells
i) Decrease the humoral response (suppresses both B cells & helper T cells)
ii) Provide limits (esp. on “self” tissue) so body doesn’t destroy itself.
(a) *Master Switch”--balance between helper T cells and suppressor T cells
d) Natural killer cells (NK): neither B or T, but are leukocytes; kill antigen viruses & tumors
directly, esp. if antigen is coated with Ig (helper T cells not needed, cells activated)
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3. Definition of terms (involving WBC’s) and labs
a) WBCs:
i) Neutrophil = bacterial (increased bands)
ii) Lymphocyte = viral
iii) Eosinophil = helminthes, parasitic, asthmatic response
b) Leukocytosis: WBC > 10,000 (normal protective response to stressors, invaders, surgery, drugs)
c) Leukopenia: WBC < 5000 (usually d/t decreased neutrophils); never normal response; response
to chemo, radiation, anaphylactic shock, lupus Leukopenia may occur if body is overwhelmed by
infection & neutrophils are depleted (bad sign) e.g. septic newborn
d) Neutropenia: Neutrophils < 1500 (also called granulocytopenia) – granulocyte production does
not keep up with demand
e) Agranulocytosis: granulocytic levels that are life-threateningly low of all –phils (esp.
neutrophils); ANC (absolute neutrophil count) <500 (segs + bands x WBC / 100 = ANC)
f) Band cells: immature neutrophils; see increased numbers of bands with bacterial infection d/t
bone marrow making increased numbers & kicking them out into the circulation (demand is
exceeding supply); similar to what you see in leukemia. Increased band cells: immature
neutrophils rise in presence of infection (horseshoe-shaped) “Leukocyte shift” or “Shift to the
left” ( immature neutrophils)

ALTERATIONS IN IMMUNE RESPONSE

V. -3 categories of problems
A. Impaired immune response (under-response; gets sick a lot)
B. Hypersensitivity response: small stimulus with major response (overreaction, e.g., anaphylaxis)
C. Autoimmune response: loses ability to recognize “self” from “non-self”; attacks “self”; drugs are given
to suppress this reaction
VI. Impaired immune response
A. -Disorders of WBC
1. Infectious mononucleosis (“mono”)-- “kissing disease”; not really all that contagious
a) Viral infection caused by Epstein-Barr (EBV)
b) Contaminated saliva: often spread by asymptomatic carrier who is healthy
c) Often asymptomatic in kids, but more severe in young adults (may provide immunity to later
infections)
d) The EBV invades & kills some of the B lymphocytes
i) Anti-viral antibodies develop
ii) Stimulates production of T lymphocytes (atypical appearing ones) which show up in blood
(atypical increased lymphocytes Dx
2. Symptoms: fever, lymphadenopathy, pharyngitis (sore throat), atypical lymphocytes, fatigue
a) May see hepatosplenomegaly: liver & spleen enlarged (rupture most common cause of death):
risk of hepatitis – liver inflammation (nausea, jaundice) & splenic rupture (no rough activities;
can be spontaneous)
3. Treatment: symptomatic; analgesics, antipyretics, steroids, rest
4. Acute phase: 2-3 weeks; recovery may take up to 2-3 months
B. Neoplastic disorders of WBC
1. Leukemia (actually, any cell coming from hematopoietic stem cell in bone marrow could be the
malignant one; but mostly WBC); uncontrolled proliferation; overcrowds bone marrow  
production of all normal blood cells: pancytopenia
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a) “Blast cell”-- leukemia CA cell; immature, poorly differentiated WBC
b) 4 major types
i) Acute (rapid proliferation of immature blast cells; common in children, as well as adults)
ii) Chronic (slower proliferation; cells are more mature/ differentiated; seen in adults, esp.
elderly; may convert to acute type at some point)
iii) Lymphocytic (CA of lymphocyte-- B or T or pre-B/ T)-- better prognosis; common in kids
iv) Myelocytic (non-lymphocytic): CA of one of the other blood cells (granulocytes, monocytes,
erythrocytes, thrombocytes
v) *ALL or CLL (best) vs. AML (ANLL) -worst or CML
2. Lymphoma (has seen most significant advances in CA Tx)
a) Solid Ca of lymphoid tissue (includes lymphocytes & macrophages/precursors & derivatives) –
change to DNA of lymphocytes; painless lymphadenopathy, fever, night sweats, wt loss, malaise
b) Hodgkin vs. Non-Hodgkin (can transform into leukemia)
i) Hodgkin – presence of Sternberg-Reed cells (malignant atypical macrophages) 70% cured if
localized (better prognosis that Non); grows and spreads predictably
ii) Non-Hodgkin – many different sub-types; lymphosarcoma (malignancy of connective tissue);
no RS cells; Burkitt’s is a type of non-Hodgkin
3. Multiple myeloma
a) CA of the plasma cells that secrete IgG & IgA (type of B lymphocyte) in osseous tissue; can
disseminate to other tissue
b) Causes bone destruction with pathological fractures & hypercalcemia: confusion, lethargy, renal
dz
C. -Immunodeficiency syndromes
1. Primary (congenital) vs. secondary (loss of previously normal immune function); acquired d/t
exposure to CA, drugs (immunosuppressants), radiation, viruses, aging; increased susceptibility to
infection
2. B-cell deficiencies (lack of antibodies)  risk of bacterial infections
a) IgA deficiency (IgA lines resp./GI tract: increased respiratory, sinus, ear infections; GI problems
(ulcerative colitis, malabsorption) – failure of B cells to mature and secrete IgA
b) X-linked Agammaglobulinemia or hypogammaglobulinemia: absence of B cells or plasma cells;
no Ig’s, selective IgG disorders – lack of B cell development from the bone marrow
3. T-cell deficiencies: can have effect on B-cell function too (b/c helper cells  Ig production)
a) DiGeorge syndrome: congenital absence of thymus = decreased mature T- cells; frequently fatal;
thymic transplantation
i) -Also, absence of parathyroid gland with hypocalcaemia (tetany) & heart defects
4. Combined deficiencies (both B and T lymphocytes)
a) SCID (severe combined immune deficiency): decreased stem cells that form the B & T
lymphocytes; “bubble boy” – protective isolation; symptoms by 3 months
i) Severe risk of infection – candida, pneumonia, otitis, diarrhea
ii) Treat with bone marrow transplant
b) Wiskott-Aldrich: blood coagulation d/o (x-linked recessive seen in first 6 mo of life)
i) Eczema
ii) Decreased platelets  bleeding
iii) Decreased immune function (B & T)
D. HIV/AIDS (*CEU’s required to renew nursing license)
1. AIDS: acquired immunodeficiency syndrome; 1st recognized in 1981/1982 among male homosexuals
a) 1983: virus was discovered that caused AIDS; retrovirus; now called HIV 1 (HIV 2 more
prevalent in W. Africa; less virulent)
b) *Retrovirus: contain the enzyme reverse transcriptase; genetic info stored in a molecule of
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single-stranded RNA; during replication, the viral DNA becomes integrated into the DNA of the
host cell; can synthesize DNA from an RNA template (oppposite of the usual process)
c) -Because of the modes of transmission & b/c of the fast spread of AIDS, this disease is 1 of the
major PH issues today; AIDS has become the leading cause of death nationally in all people 25-
44 years of age with ½ of the new cases affecting those under 25 years of age (80% are male, but
women & children are contracting AIDS more frequently)
2. Patho:
a) Virus binds to CD4 receptor on T lymphocyte (attachment)
b) Viral contents (RNA) enters the cell along with enzymes (protease, RT, integrase)
c) The virus changes RNA to DNA using RT – backwards (needed for reproduction of the virus)
d) Viral DNA enters the nucleus and becomes a part of the DNA of the cell (integration)
e) DNA forms a single strand of mRNA with instructions for building a new virus (normal cell
process)
f) RNA creates a protein chain needed to make a new virus (translation)
g) The protease enzyme cuts the chain into individual proteins that will make up the new virus
(cleavage)
h) Proteins migrate to cell membrane and buds off – becomes systemic by the end of the first week;
most CD4 have been infected within 10 days
3. Modes of transmission
a) Not casual contact or insect bites (no evidence)
b) Sexual activity ( ø just a homosexual disease)
i) Vaginal intercourse, anal intercourse (increased risk due to mucosal trauma)
ii) In the past, most reported cases in the US occurred among gay/bisexual men, but these
numbers are changing
c) Blood-to-blood (Body fluids: blood, semen, vaginal secretions, saliva, tears, urine, CSF, feces),
some fluids have low concentrations of the virus
i) Only blood, semen, vaginal secretions, & breast milk have been directly implicated (highest
concentration of HIV) – IV drug users
(a) Contracted through drug users sharing needles
(b) Those who receive blood products/ transplanted tissue (all donor blood now tested, but
there is a window of time b/w contact and infection with HIV
1. Seroconversion: when blood tests HIV+
(c) Health care workers
(d) Women are at risk b/c they don’t consider themselves at risk & often don’t find out until
baby tests HIV+
d) Vertical transmission: mom to baby (before or during delivery, breast feeding)
i) Prenatal (placenta), L&D, breastfeeding (avoid)
ii) Those who become pregnant soon after infection have decreased risk of transmission than
those who have been HIV+ for a long time
iii) Mom should start on drug therapy (AZT: anti-retroviral) immediately to decrease risk to
unborn baby – c-section; bottle feed
4. Target cells
a) After virus gets in, circulates through blood & lymph and binds with CD4 (receptor) found on
helper T cells and macrophages; virus then enters & destroys cells, but continues to replicate;
affects T&B cell function (helper cells signal B-cell maturation)
b) Increased numbers of viruses (viral load) and decreased CD4 cells (destroyed by virus) breaks
down cell-mediated and humoral immune systemsinfections (esp. if CD4<200)
i) *Normal CD4 = 650-1200
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5. Classic S&S of AIDS are called diagnostic indicators
a) Healthy person wouldn’t normally be infected; immune system is weak & infections grab the
opportunity to invade (opportunistic infections)
b) 2 requirements for AIDS diagnosis
i) HIV+
ii) CD4<200 or AIDS defining disease
(a) *Treatment & therapy decisions are based on actual numbers of CD4 cells
6. Time frame: AIDS is terminal; always ends in death; usually predictable course; average time from
exposure to virus & development of AIDS = 8-10 years (less in children)
7. Stages of progression
a) Acute retroviral syndrome (acute primary HIV infection)
i) Within 3 weeks, 90% develop mono-like S&S: fever, pharyngitis, H/A, malaise, rash
ii) Goes away in 1-2 weeks
iii) Seroconversion: generally 6-12 weeks (up to 35 months--rarely); antibodies develop
iv) Testing recommended at 3 months
(a) ELISA x 2: enzyme linked immunosorbent assay (screening antibody test); then:
(b) Western blot x 1 (confirmatory antibody test--more specific)
v) *These antibodies are unable to inactivate the virus
vi) *Neonates born to HIV+ moms often test HIV+ for up to 10 months (antibodies present in
their system), even though they may not have the virus (PCR can now detect the virus right
away)
b) Asymptomatic stage (incubation period)
i) Sometimes enlarged lymph nodes, but no obvious S&S
ii) Decreased CD4 (Helper T cells)
iii) Can transmit the disease even though no S&S
iv) Can last as long as 12 years
c) Early symptomatic HIV
i) Decrease in CD4 continues
ii) Opportunistic infections--not normally seen in people with healthy immune function (viruses,
fungi, protozoa)
iii) Fever, night sweats, chronic diarrhea, fatigue, H/A
d) Late symptomatic stage (AIDS)
i) With CD4<200, susceptible to more severe diseases & opportunistic infections malignancies,
HIV wasting, lymphomas, neurological disorders
8. AIDS-defining diseases
a) Pneumocystis jiroveci pneumonia (PCP)  caused by fungus
i) Most common & life-threatening?
ii) Persistent non-productive cough, SOB, increased RR, fever
iii) HAART and prophylaxis have decreased incidence
b) Recurrent pneumonias: bacterial or viral (CMV) at 2 years or more
i) CMV symptoms: fever, hepatosplenomegaly, possible blindness, gastroenteritis
c) TB – HIV infection causes reactivation of dormant TB
i) May be presenting illness, especially with IV drug users
ii) Increased resistance to drugs
iii) S&S: cough, fever, night sweats, fatigue, weight loss
iv) Leading cause of HIV death world-wide
d) Toxoplasmosis
i) 2nd most common neurologic disease
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ii) Protozoan found in domestic cats: ova ingested from cat feces (gardening/litter) or
undercooked meat (pork; lamb)
iii) S&S: H/A, fever, hemi plesgia, seizures, altered mental states, visual disturbances
e) Malignancies
i) Kaposi’s sarcoma (angiosarcoma): higher in gay/bisexual men
i. CA of endotheleial cells lining small blood vessels. Lesions of skin, oral
cavity, GI tract. lungs
ii) CA of cervix seen in women
f) Neurologic: encephalopathy, dementia (caused by viruses & infections of the brain cells)
g) HIV wasting: cause unknown; similar to anorexia/cachexia; diarrhea
9. Treatment: depends on each disease or infection person may have
a) 2 approaches
i) Restoration of immune function (interferon)  prevents viral spread
ii) Prevention of viral replication (anti-retroviral drugs)
b) AZT (zidovidine): Neucleoside Reverse Transcriptase Inhibitor: antiretroviral that blocks reverse
transcription of DNA from RNA & prevents intracellular viral replication
i) Tolerance develops in 18-33 months
ii) S/E: bone marrow depressionanemia
(a) Blood transfusion may be needed
(b) Epoetin alpha (epogen)--erythropoietin: stim. RBC production in bone marrow
c) Protease inhibitors: inhibit HIV protease activity, leading to the formation of immature,
noninfectious virus particles
i) *Protease: an enzyme necessary for cutting large viral peptides into smaller functional units
to create active new viral particles
d) Fusion Inhibitors – prevents fusion of HIV to the CD4 receptor on the T lymphocyte
e) Use of multiple drugs (“cocktails”) to controls HIV in several different ways (may require many
drugs/day; very expensive)--highly active antiretroviral therapy (HAART) – usually 2 NTIs and
one other
VII. Hypersensitivity = altered immune. rx. to an antigen causing disease or damage to host
A. Major Types:
1. Allergy = hypersensitivity of environmental antigens (allergen)
2. Autoimmunity = problem with tolerance to self-antigens. Develop autoantibodies or auto-T cells
against own tissues resulting in damage.
3. Alloimmunity = (isoimmunity) = immune sys. of one person develops immune rx. against tissues of
a 2nd person. (transfusions, fetus, transplanted tissue)
4. Many factors play a role: genetic, environmental, infectious
B. Four Types of Hypersensitivity Reactions (multiple can be involved in one disease)
1. Type I = Ig-E Mediated
a) Most common type & considered an “allergy” rx. since usually against an environmental antigen
b) Note: Some allergic rxs. (i.e. poison ivy) are not type I
c) Primary exposure to antigen: IgE attachs to mast cells (sensitizes them)
d) Subsequent exposure to antigen: mast cells degranulate and release cytokines, especially
histamine  causes massive inflammation (also promotes chemotaxis of eosinophils)
e) Major example is anaphylaxis
i) Major symptoms are GI (N/V), dermal (urticaria), and respiratory (bronchoconstriction) 
because these tissues have a lot of mast cells
ii) Requires epinephrine to resolve. Once histamine has bound to receptors, anti-histamines
don’t help any more
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2. Type II = Tissue Specific/Antibody Mediated
a) Specific tissues have their own antigens (more than just HLA) which can be targeted by
antibodies
b) IgM or IgG respond to the antigen and cause tissue destruction or dysfunction
i) Destruction occurs because of the complement system, phagocytosis, or NL cells (like ABO
mismatched blood)
ii) Dysfunction occurs when the antibody stimulates or blocks receptors on the target cell (like
in myasthenia gravis or Grave’s disease)
3. Type III = Immune-Complex Mediated
a) A soluble antigen is released in the body  antibodies form and bind to the antigens  antigen-
antibody complexes form
b) These antibody-antigen complexes deposit in vessel walls or tissues (this triggers the
complement system which results in neutrophils trying to phagocytize and ultimately releasing
lysosomal enzymes which damage tissues)
c) Inflammation occurs
d) Examples: (RA is technically III and IV)
i) Systemic Lupus Erythematosis
ii) Celiac Disease (gluten = antigen)
iii) Rheumatic Fever/Heart Disease
iv) Acute/poststreptococcal glomerulonephritis (antigen-antibody complexes clog kidneys,
neutrophils can’t phagocytize  kidney inflammation/damage)
4. Type IV = Cell-Mediated
a) Cytotoxic-T-cells directly attack antigens; Helper-T-cells produce cytokines and activate
macrophages
b) Examples
i) Rheumatoid Arthritis: T-cells attack collage in joints
ii) Type I Diabetes Mellitus: T-cells attack pancreatic beta cells
iii) Hashimoto’s Hypothyroidism: T-cells attack thyroid cells
iv) Contact dermatitis: small antigen in skin binds to carrier protein in the skin and causes a local
response
c) Graft-Versus-Host Disease (GVHD)
i) Alloimmunity – risk is highest in immunocompromised people (those with normal immune
systems are not at risk
ii) Cells are transplanted into a host  T-cells in the graft are mature and begin to attack the
host cells (cell-mediated tissue destruction)
iii) Can occur with blood transfusions or with stem cell transplants
d) Transplant (Graft) Rejection
i) Alloimmunity
ii) HLA antigens on a donated organ trigger the host’s T-cells to attack the tissue
iii) Hyperacute: due to prior antibodies (blood transfusions or previous transplant), attack occurs
immediately (blocks blood flow due to clotting cascade)
iv) Acute: days to months after transplant
v) Chronic: months to years later, T-cells attack lining of blood vessels, weak attack
vi) Immunosuppressants (like cyclosporine) can be given to manage acute or chronic rejection
VIII. Autoimmunity
A. Body forms antibodies against own cells & tissues: these tissues have sometimes been altered or
damaged by a virus which results in the body’s no longer recognizing them as “self”
1. 2 types
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a) Organ-specific diseases
i) Pancreas: IDDM, Graves’ disease
b) Non-organ-specific diseases: can affect multiple organs or have system-wide effects (RA, lupus,
myasthenia gravis); many are immune- complex hypersensitivity reactions (Type III), more
common in women
i) *Myasthenia gravis: chronic fatigue and muscle weakness, especially in face & throat,
because of defective conduction of nerve impulses at the neuromuscular junction
B. *Graves’ disease: antibodies bind to TSH sites, pronounced hyperthyroidism, enlarged thyroid gland,
exophthalmos (COVERED UNDER ENDOCRINE)
C. Systemic lupus erythematosis: systemic type involves many systems with relapses & remissions; usually
women 20-40 y.o.
1. Widespread degeneration of connective tissue, esp. heart, glomeruli, blood vessels, skin, spleen,
brain (antibodies develop against many different tissues; almost any organ can be affected)
2. S&S
a) Stiffness & pain of hands, feet, large joints (no deformities, but warm & tender)
b) Malar (Butterfly) rash
c) Systemic: fever, fatigue, anorexia, weight loss
d) Renal complications are serious: from precipitations of immune complexes in glomeruli to total
renal failure
i) Use of dialysis, NSAID’s, glucocorticoids (steroids), and renal transplants can greatly
improve renal function, but not a cure
e) Also treat symptomatically (e.g. hypertension)
3. Dx – antinuclear antibodies
D. Rheumatoid arthritis
1. Chronic, systemic inflammatory disease that affects small joints of hands & feet (early) & large
joints later
a) Results in destruction of cartilage & joints
b) The body forms antibodies against its own IgG (rheumatoid factor – an antibody that reacts with
IgG to form immune complexes)  Nl antibodies become autoantibodies
c) -These RF/ IgG complexes activate complement & other substances (e.g.
prostaglandins)encourages inflammatory response (chronic)
2. Acute attacks occur as these complexes precipitate in synovial fluid; joint space & cartilage
destroyed by scarring (chronic inflammatory reaction & tissue damage
a) Pannus: mass of inflamed tissue that erodes the cartilage
b) Progresses to fibrous (cartilage) ankylosis, then bony ankylosis (fixation of a joint, often in an
abnormal position, usually resulting from destruction of articular cartilage and subchondral bone)
c) SC nodules sometimes seen on elbow or other tendons (firm, non-tender)
3. S&S: r/t systemic & local inflammation--fatigue, weakness, joint stiffness, vague arthralgias,
worsened stiffness in a.m., inflamed & swollen joints
4. Lab:
a) +RF; increased ESR (chronic inflammation)
b) Anti-CCP antibodies (textbook says ACPA) – 98% specificity, can predict severity
5. Some people have relatively simple cases, while others may progress to severe deformity &
disability (remissions & exacerbations)
6. Treatment: NSAID’s (ASA), immunosuppressants, balance exercise (ROM)/ rest/ splinting, surgery
a) -New drugs have become available d/t the research into the immune system b/c of AIDS