Immunology:

• Antigen
o Any identifiable moiety = “anything”
o 99% Proteins are antigens
 Cardiolipin (seen in SLE) is the ONLY FAT that is an antigen
o Antigens do not necessarily have to set off an immune response

• Immunogen
o An antigen that elicits an immune response (> 6000 D)
• Hapten
o Antigen that is too small to set off an immune response (<6000 D)
o Viruses are a common hapten, when they are small!!!
 They soon replicate and grow larger, thus setting off an immune response
 The most common virus floating around the body is CMV and then EBV
• CMV does not have much variability, therefore, can remain dormant
 Cabrini Green Analogy
• A guy waking arounf the neighbor hood dressed with a starter jacket and starter
hat won’t draw attention because he looks the same as everyone else. However, a
guy walking down the neighborhood dresses with a cowboy hat and boots looks
STRANGE and will draw attention to itself!!! WATCH OUT

• Things that can ↑ an immune response (Factors of immunogenicity):

1.) Variability - is the #1 factor in eliciting an immune response
o How different do you look?
 Think about Genetic Drift and Genetic Shift or HIV
 A virus or a toxin can contain an enzyme that is very different to your own!!!
o Anthrax has increased variability – You can recognize this because the body reacts violently to a
the strange spore → instant necrosis
o Shigella only needs 8 – 10 microbes to be induce a full infection
2.) Size
o Beware of large molecules without variability b/c smaller molecules with variability will still be
more immunogenic!!!

Dangerous Haptens:
• In order for our body to recognize haptens they must be presented
o Need for MФ participation
• Carrier Effect: Job of the Macrophage (MФ)
o MФ will ingest and digest the hapten
 Digestion is done by the lysosome
o MФ will present a piece of the antigen on the MHC - II complex
 Self is presented by MHC – I
 Foreign is presented by MHC – II

1
 o Hapten will attach to variable region of the β-chain pf MHC II (V-β region)
 Then it will displace invariant region of β-chain from the variant region
o The MФ sacrifices itself when it presents the antigen
 The T cell kills both the antigen and the MФ
o IL-1 released:
 INFLAMMATION BEGINS
 IL-1 Stimulates FEVER
• A fever alone is not diagnostic
• The pattern of the fever is useful
 It is responsible for the non-specific symptoms of illness
 Also, recruits more helper T-cells and MФ
o Signals an invader
o The carrier effect is how vaccines work

Hapten Example: Vaccination is putting a hapten on an immunogen so that the body will recognize it and then
form antibodies to BOTH!!!

Hi
B
Hapten

Immunogen

Body then destroys

Immunogen Anti-Body
Body detects this as Production
foreign!!!

• If hapten is not attached the body will still produce a primary response to immunogen but not the hapten
o The hapten MUST BE ATTACHED to stimulate memory!!!

Cell to Cell communication:

• B7 on a MФ and a CD4+ on a T cell will produce a CD28 in order to communicate with each other
• T cell – MФ uses CD28
• MФ – B cell uses CD40 ligand

2
Things that will limit infection by decreasing the amount of the pathogen
1.) Detergent
a. Impairs membrane adhesion of the pathogen – this does not kill!!!
2.) Disinfectant/Anti-septic
a. Inactivates toxins by dissolving membrane where the endotoxin anchors itself
b. This KILLS the pathogen
i. Phenol (Lysol)
ii. Iodine (Betgdine)
iii. BOTH are Fat soluble
3.) Sterilization: KILLS SPORES
a. 1210 C vaporized heat is needed to sterlize
b. Cooking/boiling does not kill pathogen
c. Autoclave
i. Autoclaved instruments have an expiration date on them to indicate how long it would take
bacteria to get toxin BACK!!!
• Charlie the T-cell Analogy
o He and another T cell are playing cards at the local lymph node and suddenly see E. coli
wandering around. Charlie says to him, “Who do you think you are wandering around here
boy!” Charlie doesn’t kill him since he is not virulent (no endotoxins) but gives him a warning
o Know that the surgeon decided to ignore the expiration date on the autoclave pack E. coli has
now gotten his endotoxin back. He encounters Charlie the T-cell again. But to Charlie’s
surprise, E. coli says to him loaded back up…”Say hello to my little friend!” and the patient is
now infected!!!

• Spores
o Are the inactive form of the pathogen therefore can not replicate
 Made of Ca2+ dipocholinic acid
o Can’t divide
o If too much taken in can still release toxin!!!
o Examples:
 Bacillus
 Clostridium
• An immunogen will try and decrease its immunogenicity by making it more like “self”
o Strep will cover itself with basement membrane so the body will form immune response to Strep
and it’s own basement membrane!!! NOT GOOD
o The Strep that tried to Sneak by the T cells Story
o After the bacteria is gone an AUTOIMMUNE response will take place since it now has formed an
immune response to “self” basement membrane
 Post strep
 Rheumatic Fever

3
  Good Pastures
o Pathogen is never present by the time Autoimmune disease presents → Ex. Post Strep GN
IMMUNE RESPONSE CONCEPT

Humoral Cell-Mediated
Origination Blood Tissue
Tests Blood Culture Biopsy
Blood test
Cells Involved • B cells • T Cells
• Neutrophils • MФ
- Blood → monocytes
- Brain → microglia
- Lung → Type I pneumo.
- Liver → Kupffer Cells
- Spleen → RES
- Lymph → Dendritic Cells
- Kidney → mesangial cells
- Skin – Langerhans
- Bone → osteoclasts
- Connective tissue:
o Histiocytes
o Giant Cells
o Epitheloid Cells

Pathogen BACTERIA 1. Virus

2. Fungus
3. Mycobacterium
4. Protozoa
5. Parasite
6. Neoplasm
ALL ELSE

Like to attack AIRWAY Likes to attack the interstium

(Obstructive Disease) (Restrictive Disease)

Examples: Respiratory
• Interstitial infection → Restrictive problem → Dx. Of SLE → cause of infection is ALL ELSE!!! →
therefore cell-mediated response involving type I pneumocytes and T-cells!!!
o Able to connect to Restrictive profile and then to low energy state!!!
o CONNECT BABY!!!!
• All persons have been exposed to a virus….therefore,
o The most common virus in a person is
 CMV – 95%, EBV – 75%
o So, when T-cells are defective or taking prednisone after transplant the cause of death is…
CMV>EBV!!!

4
INFECTION TIMELINE:

• First 24 hours: First 24 hours

o SWELLING Swelling
 Brain → papilledema, hydroic changes
 Liver → balloon degeneration
 Surgery → 3rd spacing, intestinal swelling
 Anaphylaxis
At 24 hours
o At 24 hours → Neutrophils show up
Neutrophils show
 Peak at 3 – 4 days up

• Poor nutrition affects Cell mediated > Humoral

o More succeptible to…
 Viral At 3 days
 Fungal Neutrophils peak

Bacteria ALL ELSE

Neutrophils predominate

Switch to T-cells and MФ on

Day 4
Peak on Day 7

DAY 7 Fibroblasts appear

They Peak in 1 mo.
Takes 3-6 mos. to finish
(fibrosis, sclerosis, piecemeal
necrosis)

5
IMMUNODEFICIENT STATES:

T cell Deficiency:
• HIV
o Epidemiology
 Fastest growing populations:
• Heterosexual black females – her risk is due to homosexual male
• Elderly – ↑screening d/t missed diagnosis
o HIV’s affinity
 HIV likes to attach itself to mucosal surfaces
 The rectum is mucosa, that’s why homosexual males get it
 Once virus is “inside” the CD4 cells are affected
 Areas with ↑ CD4 cells:
• Female cervix → cervical CA
• Rectum
• Testicles
• Brain → AIDS dementia
• Blood vessels → Focal segmental nephrotitis → Kapsoi Sarcoma → CNS
lymphoma
o HIV injects it’s RNA inside cell!

Proteins associated with HIV:

Protein Function
GP41 Surface marker – no known function
GP 120 Attachment to CD4 T cell
Can prevent attachment with CCR5 mutation
Pol Integration into our DNA
RNA dependant Transcription/replication
DNA polymerase
(reverse
transcriptase)
P17 Used for assembly
P24 Used for assembly
Can be used to check viral load

CD4 count and AIDS treatment

Adult Child
Normal = 800-1200 1500
Treatment <500 <300
PCP prophylaxis <200
Rx: TMX → (-)
dihyrdofolate
reductase
MAI <100
(mycobacterium avium
6
 intracellulari)
Rx:
Clarithromycin/Azithromycin
• AIDS is defined as < 200 or if > 500 but have AIDS specific infections, i.e., Toxoplasmosis

Current treatment recommendation:

1. Use 2 Nucleoside inhibitors:
a. AZT → Decreases vertical transmission; blasts BM
b. DDI, DDC, → Painful neuropathy, pancreatitis
c. 3TC, 4TC
2. And 1 protease inhibitor: Sequanvir, indinavir, rotinavir
3. ONLY TIME when monotherapy is indicated is in a HIV pregnant mom and also to the baby up
to 6 months of life, give AZT. (Vertical transmission =40%)
a. Babies have 90% mortality in 1st year of life mostly due to FTT (failure to thrive)

Screening for HIV:

1. Start with ELISA (sensitive)
i. Antibody test (IgG)
2. Prove with Western Blot
i. Testing for all the above proteins
3. PCR is the most specific for DNA/RNA (specificity) → only done if patient really wants to know,
because very expensive
i. Is done in babies up to 18 months because mom’s IgG will make ELISA positive.
Western blot  test for proteins
Southern blot  test for DNA
Northern blot  test for RNA
PCR  most specific for DNA/RNA

7
T Cell Deficiencies:
• DiGeorge Syndrome
o Thymus is missing d/t failure of 3rd pharyngeal pouch to form
o 3rd Pharyngeal Pouch is responsible for the formation of…
 Thymus
 Inferior parathyroids
o This will cause the following:
 ↓ T-cells d/t missing thymus
 ↓ Calcium

• T-cell Leukemia
o Hairy Cell Leukemia (25%)
 “hairy” projections off cytoplasm
 “fried egg” appearance
 Resistant to acid phosphate
• (+) TRAP = Marker
• T-Cell Lymphoma
o Indented cytoplasm
o Rashes:
 Mycosis fungoides → found only on skin
 Sezary → found in blood stream; worst prognosis

• Chronic mucocutaneous Candidiasis

o Present with chonic fatigue
o Think about GI/GU/RESP.

• Cyclosporin use
o Inhibits Calcinurien which produces Interleukins that signal T-cells
• Prednisone
o Kills t helper cells (5 actions of Steroids!!!)

B cell Deficiencies:

• Leukemia and Lymphoma

o Predominately B-cells

• Common Variable Immunodeficiency (CVID)

o Late onset SCID d/t a missense mutation
o 2nd messenger not working

• Bruton’s Agammaglobunemia
o X-linked
o B cells present but Tyrosine-Kinase not working

• Jobs Syndrome
o Class switching problem
 Immunoglobulins stuck in IgE stage and cannot return to IgM
8
 o Present as RED HAIRED FEMALES

• Selective IgA Defieciency

o MC transfusion related anaphylaxis

• IgG2
o MC Selective Problem b/c it’s on same chromosome as IgA
• Multiple Myeloma
o Kappa light chains
o Rouleux formation
o Hypercalciemia → metastatic calcification

• Heavy Chain Disease

o Multiple Myeloma
o IgA

Combined T-Cell and B-Cell Deficiency

• SCID
o Adenosine deaminase deficiency
o AR (recall enzyme deficiencies are mostly AR)
o Baby is dead by 18 mos.

• Wiscott-Aldridge → “TIE”
o X-linked Recessive
o Class switching problem → can’t switch back to IgM
 Fair skin
 Thrombocytopenia (platelets affected!!!)
 Infections
 Eczema
o 10% risk of lymphoma

Neutrophil Deficiency → NEUTROPENIA

• Mostly associated with S. aureus and Pseudomonas infections (Elastase + organisms)

o If fever is d/t S. aureus → use 1 antibiotic
o If fever is d/t Pseudomonas → use 2 antibiotics

• Myeloperoxidase deficiency
o Inability to make H2O2
o Therefore, susceptible to Gram + infections
Macrophage Deficiency
MCC of ….penias
1 – virus
• CGD = NADPH-oxidase deficiency
2 - drugs
o X-linked Recessive
o NBT Test, if negative = Lacking enzyme
o Succeptible to S.aureus, E.coli, Aspergillus infections
9
 • Chediak Higashi
o Lysosome Problem
 They are slow to fuse around bacteria that was just ingested
o Be careful of staphylococcus and streptococcus
The Characters of the Immune System:

The Enemy Invader

• Usually a bacteria or virus.

• Comes in many different forms and attacks the body

The Macrophage
Body's Radar

• Type of cell normally present in the blood

• Detects the enemy

The T-Helper Cell

Communication Link

• Between the body's macrophages and b-cells

The B-Cell
The War Factory

• Produces antibodies custom tailored for the type of enemy

antigen

Antibodies
Antigen Busters

• Designed to seek and destroy the specific enemy antigen

10
 Complement
Support Troops

• Assists the antibodies to neutralize the enemy antigen

Immune Complex
When antibodies and complement attack the antigen, an immune complex is formed.

Polymorph
Disposal Unit

• Detects the immune complexes and removes them

T-Suppressor Cell
Another Communication Link

• Signals to the b-cell to stop making antibodies once the antigen has been
destroyed

11
Normal Body's Immune System

12
Leukemia:
1st must determine if Acute or Chronic → Naming

If Acute… If Chronic …
Starts in Bone Marrow → problems start with BM Start in the periphery
destruction
Any cell line that becomes cancerous will “crush” Not constrained like in the bone marrow so will
other cell lines expand.

Lymphoid Myeloid
Cell Types: Cell Types:
Lymphocytes Macrophages
B-Cells Monocytes
Neutrophils
Cell lines Killed: Cell lines Killed:
Neutrophils → neutropenia Lymphocytes
RBC → anemia Platelets
Platelets → thrombocytopenia RBC

ALL AML CML CLL

Age group 0-15 15-30 30-50 >50
Gender Male Male Female Female
Cell lines Lymphoblastic Low/immature myeloid. Increase in
affected Myeloid neutrophils,
(seen on monocytes,
Biopsy) Kills: Kills: macrophages (think
neutneutropenia Monocytes neutropenia of tissue specific ones)
RBCanemia Pltthrombocytopenia Cancer already as an
Pltthrombocytopeni RBCanemia adult
a
Presentation Infection = Bacterial Infection = All else Affect: Swollen lymph
Low E state Low E state Skin nodes → b/c that is
Bleeding Bleeding Kidney where lymphoid
Liver cells mature
Spleen
Markers PAS stain ⊕ (stains Sudan Black - leukocyte Philadelphia No marker
fat of lymphoblasts) alkaline phosphatase chromosome:t(9:22
(leaked out by )
Tdt ⊕ (found only on myeoloblast)
Ig in lymphocyte)
Calla: ⊕ Auer rods →
(common ALL antigen)
→ provides good
prognosis
Testing Differentiate by: Worst prognosis
Bone marrow biopsy Associated with Down’s
Peripheral smear will Syndrome
look the same.

13
• Acute • Chronic
o Tx: Antimetabolite o Tx: Alkylating Agent
 Blocks rapidly dividing cells  Slows down dsDNA
from dividing  Chlorambucil
 Methotrexate

2 Other leukemias:
• Promyelocytic Leukemia
o Before myeloblastic stage
o Presents with DIC (90%) = M3
o M5 → more than 30% erythroblasts
o M7 → more than 50% erythroblasts
• Hairy Cell Leukemia
o “fried egg”, “sun burst” appearance
o resistant to acid phosphatase
 (+) TRAP
• Most common cause of death in Cancer is: INFECTION
o Exception:
o Cervical cancer
o Endometrial cancer

Lymphoma:
Presents with swollen lymph node
1. Supraclavicular → MC affected lymph node
2. Epitrochlear → above elbow
3. Inguinal
If anywhere else d/t infection Swollen lymph nodes

biopsy

(+)
Reed Sternberg cells
(-)
CD30 Receptors Reed Sternberg cells

Hodgkin’s Non-Hodgkin’s

14
 Hodgkin’s Non-Hodgkin’s
Presentation Obstruction in GI tract (Ileum) → recall
MC age is 20-40 y.o. that the Ileum has the most lymphoid
tissue
Exception: AIDS - will present as
multiple primaries in CNS and testicles.
Markers bcl-2 → Burkitt’s Lymphoma
c-myc → Burkitt’s Lymphoma
t(8:14) → Burkitt’s Lymphoma
t(14:18) → Follicular Lymphoma
Staging I. 1 group of lymph nodes
II. 2 groups of lymph nods (same side of
diaphragm)
III. At least 2 groups ACROSS the
diaphragm
IV. Metastases
A = without symptoms
B = with symptoms
Common Types Nodular Sclerosis → MC in females Burkitt’s Lymphoma
• Sclerosis will see fibroblasts on biopsy • “starry sky appearance” → all small
• Lacunar cell/RS cells non-cleaved lymphocytes
Lymphocyte Predominant • associated with EBV
• Best prognosis (nasopharyngeal CA)
Lymphocyte depleted • Presentation
• No lymphocytes America = abdominal mass in the ileum
• Worst prognosis Africa = jaw mass → has to do with
Mixed lymphocyte/histiocytes nutrition!!!
• Intermediate prognosis

Treatment MOPP
Mechlorethamine
O (Vincristine)
Prednisone
Procarbazine

CHOP
Cyclophosphamide
Hydroxyurea
O (Vincristine)
Procarbazine

ABVD → Current Tx:

Adriamycin
Bleomycin
Vincristine
Dacarbazine
15
 • Myelodysplastic Syndrome:
o All cell lines are involved
o Most common cause of any “penia” (decrease in any bone marrow cell line)
o #1 is virus
• B19 → Parvovirus
• Hepatitis E in pregnant women
• Ex. Mother with Hepatitis E will have a baby with aplastic anemia HFHydrops
• Hepatitis C in transfusions
o #2 is drugs.
• AZT • Chemo • Benzene
• Vinblastine • chloromphenacol

RBC WBC PLT Symptoms Treatment

Polycythemia ↑↑↑ ↑ ↑ Vasculitis, DVT, PE, Phlebotomy
rubra vera hematuria, R flank thrombus, emboli MI, cerebral/GI
pain ↑uric acid hemorrhage
gout, kidney stones
V/Q Mismatch
Essential ↑ ↑ ↑↑↑ Thrombus HF Phlebotomy
thrombocythemia > 600,000 ASA=antiplt.
Aplastic Anemia ↓ ↓ ↓
Myelofibrosis ↓ ↓ ↓ ↓bone marrow will
or cause spleen to take
Caused by CA in the bone marrow over RBC production
Myeloplastic
 splenomegaly
or
Agnogenic
myeloid dysplasia

Immune system constituents

CBC: WBC = 4,000 -12,000
o Leukocytes- 90% are marginated at any one time, along blood vessels, so they can enter circulation.
 Called on by Cortisol and Epinephrine (stress hormone) → responsible for
Demargination
• How to raise Epi/Cortisol levels:
o ↑↑ Stressors
 Cortisol also kills T-cells and eosinophils → remember it’s a steroid.
 Marginated are mostly mature neutrophils → 95%
• <5% are myeloblasts
 The body will only marginate the mature ones.
 Under extreme stress the body will demarginated even immature ones
• Immobilization:
o Pavementing:
o Selectrins  pull mature neutrophils out of cirulation
o Integrins (ICAM-1)  anchor WBC to endothelium
16
  Margination= flattening
 Diapedesis = migration process towards crack in endothelium
 Migration (into tissue)
o Differential on CBC: That’s why always get repeat CBC and
 Look for: lumbar puncture, to verify findings → it takes
72 hours to determine if infection ins bacterial
• Neutrophils
or not
• Bands
• Blasts

WBC Neutrophils Bands Blasts

Stress Increased Increased
demargination
Bacterial Increased Increased
infection with B-cells
All else: Increased Macrophage:
Fungus, virus, Increased with
etc… T-Cells
Infection Increased Increased-
immature banded
neutrophils have
max killing power
which is needed for
infection
Leukemoid Increased <5 % (extreme
Reaction → stress: burn pt,
appears like collision, severe)
leukemia
Leukemia Increased >5%
Ex. CLL -no blasts
because haven’t
matured yet
Myelodysplastic Entire bone
marrow
Lymphoma Lymph node (tonsil is a
biopsy → lymph node)
look for RS

• IL-10
o Suppresses cell-mediated system
o That is why in a bacterial infection T-cells/MФ do not show up for at least 4 days
• IL-12
o Tells T-cells/MФ to show up → enhances cell mediated response

• Steroids (like Cortisol, prednisone) will cause demargination with high neutrophils and low
eosinophils and T cells
o ↑ WBC but not blasts/bands

17
Intro to Microbiology:
Gram stain:

Gram + Gram -
Exotoxin Endotoxin
Except Listeria has Except
endotoxin
Capsules Strep pneumo VERY Dangerous:
(Some Strange Killers Have
Pretty Nice Capsules)
1. Salmonella
2. Strep
3. Kleibsiella
4. Hemophilus B
5. Pseudomonas
6. Nisseria-(largest
capsule- most likely
cause of any
toxicity)
7. Citroacter

Gram (+) Gram (-)

-Outer membrane
-Lipid A- toxic part
of endotoxin (least
variable)
-O-antigen- different
for every gram –
family
-Core Antigen-
N-acetyl muramic acid (Nam) different for every
+ family member
N-acetyl glucosamine (Nag) = Peptidoglycan wall Most variability
Contains Techtoic Acid → non-toxic - Capsule

Periplasmic Space – contains endotoxin

Steps for Gram stain
1. Crystal violet → picked up by gram (+) Destroying outer membrane will first
2. Iodine (sealant) release Lipid A causing pt to get
a. Too little won’t adhere to G+ worse before getting better
b. Too much might stain G- -Severe shock  Gram negative
3. Wash excess crystal violet with EtOH sepsis.
4. Sapphrine (pink to stain G-) -pediatrics- give steroids before
antibiotics for bacterial meningitis
(dexamethasone BEFORE
antibiotics) to keep inflammation
down and prevent hearing loss and
neuropathies.
18
Acid Fast Stain:
• For Mycolic Acid
o Mycobacteria
o Nocardia is partially acid fast and Gram +
o Cryptosporidium is protozoa that is partially acid fast.
• Only the pathogen will be pink, everything else will be blue.

Leukocytes/ Granulocytes
• Never Let Mom Eat Beans (in this order to frequency)
o Neutrophyls (60%)
o Lymphocytes (30%)
o Monocytes (8%)
o Eosinophils (2%)
o Basophiles+ Bands (<1%)

• First line of defense: neutrophils (have 2 enzymes)

o Myeloperoxidase
 H2O +O2  H2O2 (acid)
 BUT Catalase will break down acid → 2 H2O (S. aureus, pseudomonas, and Neisseria have
this)
 Will be exposed only to Gram + proteins and denature them
 Used for killing Gram +
o NADPH –Oxidase
 O2 +H2O + Cl  O-, OH, HOCl = Free radical formation
 O2  oxidative burst (will suck all the O2 around it making the area around it
anaerobic)
 Most active on day 7 when all the free radicals will kill peptidoglycan wall.
 Ex. Abscess day 2- staph, day 4-7 – strep, > day 7- only anaerobic bacteria remain, need to
D&C.
 Organ most likely to form an abscess is the brain
 Lungs are the least likely location to form an anaerobic abscess.- if there > 7days would need a
lobectomy because antibiotic won’t get to it, other wise treat with antibiotics if early
 Need free radicals for every bacteria that’s encapsulated
• Superoxide dismutase
o Free radicals  H2O2  H2O
 Bacteria that has Catalse will neutralize myeloperoxidase. But will eventually be killed by the
free radicals.
1. Staph
2. Pseudomonas
3. Neisseria
o Anaerobes nightmare is oxygen because organism doesn’t have superoxide dysmutase
• 2 ways to determine if infection is d/t anaerobic organism
o Gas formation → necrotizing enterocolitis will show air/fluid levels
o Malodorous smell → Farts/Bad breath
• Deficiency of NADPH beware of:
1. Staph (contains catalase)
2. Strep
19
 3. encapsulated Gram negatives
o NBT Test can tell if have NADPH oxidase
 If (-) → no NADPH oxidase
• Absolute Neutrophil Count (ANC)
o ANC = (% neutrophils + % bands) x WBC
 < 2500 = neutropenia
 < 1500 = moderate neutropenia
 < 1000 = severe neutropenia

• Patients with:
o DM (hyperglycemia impairs neutrophylic migration), CF (secretions gets in the way), burn patients,
neutropenia → Always worry about pseudomonas and Staph
o If they have a fever, always cover for the most lethal bugs: pseudomonas (2 antibiotics), staph (1
antibiotic)
o If fever persists:
 Its most likely a virus, but can’t kill virus so cover for fungus.
 The only time its ok, to start empiric anti-fungus
• Always treat and then culture.
• IT takes 7-10 days to wipe out BM

• Monocytes are precursors to Macrophages.

• Extreme monocytosis >15%: STELS syndrome
o Syphilis-promiscuity
o TB
o EBV- teenager sick for a month (Mono)
o Listeria – little baby who is sick
o Salmonella – food poisoning

• Macrophages:
o only has NADPH - Oxidase
o kill everything that enters tissues (usually not G+)
o doesn’t need myeloperoxidase because G+ stay in blood

• Bands = immature neutrophils (same killing system at max. power)

Mast Cells:
o 10 Response: 1st time in contact with antigen- body doesn’t react, B cells make IgE to allergen
(asymptomatic)
o 20 Response: 2nd Time IgE will grab Fab Portion of the allergen and anchor it to the Fc
portion of the mast cell → will release:
1. Histamine- (responsible for acuter response)
• Rubor-red
• Callor-
• Dolor-pain
• Tumor- swell up
2. SRS-A (Leukotrienes)
20
 • Slow reaction substance for Anaphylaxis (4-8 hours later)
• Leukotriene C4 D4 E4 → potent vasoconstrictor
• Recognize leukotriene receptor blocker with a German name.
3. Eosinophils chemotactic factor of anaphylaxis
o ECF-A
• Eosinophils: (think allergy)
o Histaminase (break down Histamine)
o Arylsulfatase (breakdown SRS-A)
 Metachromatic Leukodystrophy → arylsulfatase deficiency
o Heparin (break down ECF-A clots)
 Co-factor for anti-thrombin 3
 Inhibit entire intrinsic pathway (PTT)
Extreme Eosinophilia:
• Think NAACP
o Neoplasm (Lymphoma)
o Allergy (allergic rhinitis, nasal polyps)
o Asthma/ Addison’s disease (no Cortisol cause relative eosinophilia)
o Collagen vascular disease.
o Parasites
• Basophiles
o Precursors to mast cells
 Have the same granules

ANTI-HISTAMINES:
• Emergency
o Epi/Norepi
o Steroids
o β agonists with β2 > β1 affect
 Metaproterenol
 Isoproterenol
 Levoproterenol
o Specific β2 Agonists
 Albuterol → q 4hours
 Terbutaline q 4 hours
 Salmeterol → given BID
 Ritodine → good for pre-term labor
• Phosphodiesterase Inhibitors
o Theophyline → ↑ cAMP = Bronchodilation (p450 dependent)
• Anti – Cholinergics
o Ipratropium bromide → ↑ cAMP = Bronchodilation
• H1 Blockers → have strong anti-cholinergic effects
o Diphenhydrane
o Phenylpropranolone → can cause arrhythmias
o Hydroxyzene → indicated in vertigo
o Dramamine → indicated in motion sickness
o Phen Phen

21
 • 2nd Generation α agonists → Mydriasis without cycloplegia side effect
o Ephedrine
o Pseudoephedrine → “Pseudofed”
o Phenylephrine
o Neonephrine → neurogenic shock
• H2 Blockers
o Cimetidine → inhibit p450 o Nizatidine
o Rantidine o Famatidine
• rd
3 Generation H2 blockers → once a day b/c have long t ½ → do not mix with MACROLIDES
o These all can produce TACHYPHYLAXIS (down regulation)
o Terfenadine
o Loratidine → Claritin
o Desloratidine → Claratin D
o Citirizine → Zyrtec
o Fexfenadrine → Allegra

Lymphocyte development and maturation:

Lymphocyte Site of Site of maturation Site of Differentiate

Development
B cell BM Bursa of Fabricus Equivalent Lymph Tissue
(Germinal centers of Lymph tissue)
T cell BM Thymus (up to teenage years) Lymph Nodes
• Thymosin (Paracortical)
• Thymopoetin
Lymph Nodes (adult)
* Remember lymph nodes can be: tonsils, spleen

B Cell maturation:
• Action:
o Macrophage must come in contact with antigen
 Macrophage will present a piece of it in the MHC-II complex
• Lymphoid tissue in the GI is the only place where MФ is not the primary processor
 Hapten will attach to variable region of the β - chain of MHCII
 Will displace invariant region of β - chain → IL-1 RELEASED
o IL-1 release:
 Fever Non-specific signs of illness → indicate inflammation has begun
 Only produced by MФ
 Recruits T-cells for presentation of antigen
o Release IL-2
 Recurits EVERYONE
 Releases all cells involved in inflammation
• Most potent interleukin
• Inhibited by prednisone and cyclosporine  decrease inflammation
o Release IL-3
 B-Cell proliferation increased/enhances processing activity

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 a. Pokeweed Mitogen Isolate B cells and cause to
b. Endotoxin proliferate
 Increased Macrophage ability

o Release IL-4
 B-Cell Differentiation: 3 Levels IgM
Pre-B-cell:
µ µ o With µ-chain in cytoplasm
µ µ
Immature B-Cell:
o With IgM on surface
o Secreting IgM is a monomer with 1 Fab & 1 Fc portion
Mature B-Cell:
o With IgM and IgD on surface
IgM IgD
o IgD = surface marker

• Plasma Cell
o Starts to secrete proteins → RER (most abundant)
• Either have 1° or 2° response:
o 1st time contact with antigen-  1° response
o 2nd time contact with antigen  Memory response by Il-4

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24
First Response:

Show up Peak Gone

IgM 3 days 2 weeks- 2 months
can cause Ab excess autoimmune disease starts 2 wks
after infection when pathogen is already gone.
IgG 2 wks 2 months 1 year

• IgG production starts at 6 mo. of life

Memory Response:

Show up Peak Gone

3 days 5 years 10 years
IgG ONLY
Apply to vaccination schedule:
Remember: baby can’t make anything but IgM, that’s why baby needs new shots every 2 months until s/he 6
months old and can make IgG

2 month 4month 6 month 18 month 5-6 years 15 yrs.

Vaccination only only IgM will IgG Memory IgG Booster for
IgM IgM start making memory IgG
IgG
DPT/DTaP DPT
*Pertusis always cause of X X X X X Don’t need Purtusis
reactions protection anymore
DTaP= acellular P, less rxns.
OPV X X X X X X
Shed live virus for 2 wks
Hib (H. flu B) X X X X X Don’t need
protection anymore
MMR
Most common cause of
serum sickness 15 months X X
(measles) 2wks after
will get joint pain
Shed live virus in stool for 8 wks

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 V Light chains:
Fab V
90% are kappa
• At Age 6, 3 infections drop off V V
list for vaccination: Tetanus, Polio, 10% are lambda
Measles
8 Live viruses: MMR OR SMALL BlisteringC YELLOW Vesicles
C
1. Measles → Will shed in stool for 8 wks, need to tell pregnant mothersHeavy chains=
not to Isotypesfor
get pregnant : 2 months
G
after receiving vaccine S S A
2.EveryMumps
variable region has a C1 M
C1 Vaccine Allergies:
3.hypervariable
Rubellaregion = D
Measles  made from eggs
Idiotype S
4. OPV (Sabin) → Will shed in stool for 2 wks. E
Influenza  made from chick embryos
5.-thisRotavirus
is where the C2 C2 Hep B  made with Baker’s yeast
6.antigen
Small pox
binds.
7.Provides
BCGSpecificity Pepsin and Trypsin
8. Varicella Cut below hinge, so Fab remains
functional and will continue to ppt./
9. Yellow Fever C3 C3
agglutinate, bind complement and
The Papain
Immunoglobin:
will cut to 3 antigen.
unusable regions. Fc= complement binding
Will have useless 2 Fab

• Characteristics of the different Isotypes: Allotypes:

o IgG: - xenotype/heterotype →
 Only one that can cross placenta difference b/w individuals in 2
nd
 2 responder in 1° response different species
 Only responder in memory response - Used in paternity cases – Maury
 Is a monomer with 1 Fab and 1 Fc Povich
 Fix complement on C2
• Memory key: 2nd to show up in 1° response
 4 Subclasses:
• IgG1 - will cross the placenta because of Fc portion
• IgG2 - most common subclass deficiency
o Directed against polysaccharide antigens
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 o associated with IgA deficiency
• IgG3 - ???
• IgG4 - Does not fix complement
 Main Opsonin
 Will fix antigen with most AFFINITY (= tightly)
 Multiple Myeloma → SKY HIGH IgG spikes
 Antibodies to own IgG → RA
• Can affect Cervical spine!!!
o IgA:
 Dimer in secretions → GI, GU, Resp.
• 2 Fab 2 Fc
• 2nd Fab portion is joined by J-chain
• has secretion component
 Monomer in blood stream
 Used in Mucosal surface infections.
 Will fix complement on C1
• Memory key for IgA: ONLY ONE to show up on mucosal surface.
 RECALL: Selective IgA Deficiency → anaphylaxis with any transfusion

o IgM:
 Has µ-chains
 First to be secreted by any plasma reaction, then switch to others
 Monomer as surface marker
 Pentamer in secretions
• 5 Fab and 5 Fc
• 2 J-chains
 Will fix antigen with most avidity (=most likely to bind).
 Will fix complement on C1
• Memory Key: 1st one to show up in inflammation
 Will fix complement on C3
• Memory Key: Avidity leads to C3 (rhyme)
 Waldenstrom’s Macroglobulinemia
• Sky high IgM
• Hyperviscosity syndrome

o IgD:
 Surface Marker ONLY
o IgE:
 Monomer
 Binds allergen
 force mast cell to release
• Histamine
• SRS-A
• ECF (eosinophylic chemotactic factor)

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Transplant Terminology:
Transplant term Transplant from Transplant to Immunoglobin
Isograft Twin Twin Isotype (5)
Autograft Self Self Idiotype (2)
Allograft Same species Same species Allotype
MOST COMMON *most common is blood
Xenograft Different species Different species Xenotype
Ex. Pig Heart → * such massive doses of
human cyclosporine are needed to
overcome rejection that will
die from CMV b/c
cyclosporine takes out
immune system

T-Cell Maturation and Differentiation:

• Maturation:
o T-Cells mature in Thymus
 Thymus is derived from the 3rd brachial pouch
 If fail to develop → DiGeorge’s Syndrome
o Pre-teens → thymus disappears
o Lymph nodes (adult)
 Where the T-cell will differentiate and take up
residence in the paracortical area
 T cells surrounded by B cells

• Enzymes:
o Thymosin (Sgt.)
o Thymopoetin (Lt.)
a. 1st CD8 cells come through
• respond to MHC I = self
• All nucleated cells in body express MHC
I (except RBC, platelets)
o The young RBCs must move fast in order to avoid getting “caught”
o The older ones are slow and get caught → remember that at 120 days RBC
runs out of energy → hemolytic anemia
o Dukes of Hazard analogy
• Divide into T suppressor and Serotoxins
b. 2nd CD4 cells come through
• respond to MHC II = other
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 • divide into T-helper I (cell-mediated) and T-helper 2 (humoral)

• Immuno-privileged Sites
o No lymphatics flow through here
o If get an infection = BAD NEWS
 Brain
 Cornea → corneal transplants are very successful because no antigens are present
 Thymus
 Testes

Thymus “Boot Camp” → Education

• In the thymus the immature t-cells wear both labels (CD4/CD8)

o They need an “identity” → Who am I?
o They become the “recruits” to be trained
• Sgt. Thymosin & Lt. Thyopoeitin call them out
to be tested through an “Obstacle course”
• Those that make it out will become a T-Cell!!!
o 1st ones to make it through = CD8 T-
cells
• CD8 T-cells
o Cytotoxic/Suppressors
 Stop spread of infection and
destroy the cell
o Respond to MHC I antigens
o Role: To patrol “self”
 Able to tell when “self” is
infected
• Now those that didn’t make it through the
course the second time get a second chance
• IF they make it out → CD4 label
• CD4 T-cells
o T-helper cells
o Respond to non-self = MHC II

• Now after they are assigned an “identity” the

T-cells must be rechecked for Affinity
• If ↓ Affinity (lacking in ability) → They are
Destroyed
• Positive selection: CD4, CD8
• Negative selection: affinity

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 • ITP
o Antibodies against Platelets
o In children → 90% curable
o Adults → 10% curable
o Frequently a prelude to Lupus

• Natural Killer cells

oMade in the BM
oHave innate killing ability = Ninjas
oCD 16/56 labels
oIf wipe out BM and Thymus predispose to CA
 Why? Because NK cells are in charge of immune surveillance
 Count MHC I – approx. 100
 If MHC I count < 100 = Infection
 If MHC I count > 100 = CA
• CD4/CD8 checks “ID”
• NK cells insert perforants (throwing stars) or program the cell for apoptosis
o Or they direct B cells to coat the invader with antibody so a MФ will eat them up

• T-cells
o Until the process 1 antigen → not differentiated = Immature
o Rookies until they kill someone
• B-cells
o Also carry a CD19 and 20 label

IMMUNOLOGICAL INTERACTION SUMMARY

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Complement:

• RULE: Keep the b’s and throw away the a’s

• Fxn:
o Bust up the capsule of the organism
• C1q = platform for C1 esterase and C1 esterase inhibitor
o 40 structure
o C1 esterase cuts C4 and produces C4C2b → C3 convertase
o C1 esterase inhibitor will stop esterase after C3 convertase is formed to prevent constant
complement formation
• C1 esterase Deficiency
o Will present with recurrent spontaneous facial swelling (Classical) →
Angioedema/angioneurotic edema
 Abdominal pain ( Most Common) C3a and C5a = Stimulate Localized anaphylaxis
o Caused by ACE Inhibitor
Some Killers Have Pretty Nice Capules
Salmonella
Klebsiella
H. influenza B.
Pseudomonas
• Pharm: Neisseria
• ACE Inhibitors: Citrobacter
o Types:
 Captopril
 Enalopril
 Lisenopril
 Rinilopril
o MOA:
 Block conversion of Angiotensin I to Angiotensin II
 Increase levels of Bradykinin → potent VENOdilator
 Contain Sulfur – Be careful!!!
o Contraindication:
 Bilateral Renal Artery Stenosis
• Pt with this condition has a high velocity of blood heading through the renal artery
since it is clotted up, if the vessel is no longer constricted the velocity of blood flow
will decrease and the blood will no be able to pass over the clot → INFARCT
o ACE Inhibitors ↓ mortality in Heart failure by > 30%
 Diabetics should be on an ACE inhibitor because it will decrease proteinuria d/t
inhibition of efferent VC
• ACE Alternatives:
o MOA:

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  Angiotensin II receptor blockers
o Losartan
o Vasotan

• C4C2b → C3 convertase
• C4C2bC3b → C5 convertase
• C5 → platform for MAC Complex intiated by C5b
o MAC Complex = C5b6789
 7 – aligns capsule
 8 – Perforator
• If there is a problem with complement it will allow for recurrent infections with encapsulated
organisms
o Must worry about N. gonorrhea because it has a LARGE capsule
Blood Typing/Transplantation:
• Your Blood Type is the ANTIGEN
o Inherited antigen from parent
o Sugar – Protein
Blood Type A B O AB
Enzyme Galactoseamino Galactose Fructose Transferase
Transferase Transferase
Antigen No Antigen = A
A B UNIVERSAL B
DONOR
Antibody No antibody =
B A Both A & B UNIVERSAL
RECIPIENT
Blood Types AA BB OO AB
AO BO

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• Rh Disease:
o Only occurs if MOM is Rh- and DAD is Rh +
 If the mom is Rh+ → do nothing!!!
o 1st baby sensitizes mom – the baby not in trouble, because there are no antibodies formed yet
 Sensitization occurs when the placenta separates and 100 cc go back into the mom →
the mom will then form antibodies to Rh+
 Once this occurs, every subsequent pregnancy will be in trouble
o Treatment
 Rhogam
• Given after delivery
• Given again at week 28 of subsequent pregnancy (fetus’ circulation develops)
• And given again 72 hours prior to subsequent delivery
• Typing
o Forward Typing
 Uses anti-body to detect antigen
o Backwards Typing
 Uses antigen to dectect anti-body

Ex: Blood type A A B

Forward (using Ab) +
Backward (using Ag) B

• Cross Matching:
o Used to detect Preformed Anti-body by using the recipients serum with the donor’s lymphocytes
and complement to see if recipient has preformed Ab’s to the donor’s Antigens
If DL is destroyed, Muriel has
preformed antibody
Want to see if Muriel has If not destroyed, no preformed
antibodies to the donor → Donor antibodies present
o Example: Lymphocyte
Next add complement
33
  Muriel’s serum with Ab

• Mixed Lymphocyte Reaction

o Every donor needs to be tested, therefore, the recipient’s lymphocytes are tested to see if they will
react to the donor’s antigens
o T3 ( Labeled Thymidine) is used to detect level of reactivity
 The smallest number will represent the least reactivity and therefore, the best
donor!!!
o Transfusion can cause people to have preformed antibodies to someone who is of no relation
• HLA Typing
Muriel 2LGIT2QIT
Mom 2 2 G I S 3 PRB
Dad CXPIT2QIR
Sister 2LGITIQIT
Boyfriend 2LGIT2QIT

• Must match 60% of the sites

• Boyfriend appears to be the best donor since they match, but this can not be possible unless they are
related … Uh Oh!!!
o Parent – Child match is not good because no better than 50% can match
o Siblings – 70-80% Match
o Twins are even better (think of it as spare parts)

• Hypersensitivity
o Type I: Immediate allergic response = anaphylaxis
 Mediated mast cells, eosinophils & IgE
• Example: Bee sting
o Type II: Antibody to self
 Fix complement deliberately
 Every autoimmune except SLE & RA
o Type III: Immune-complex
 Fix complement accidentally
 Immune complex can get stuck in organs along the way causing unintended reaction
• This will LOWER COMPLEMENT LEVEL
o SLE
Diseases causing
o SBE
LOW
o RA COMPLEMENT
o Serum Sickness LEVEL
o GN
o Type IV: Delayed hypersensitivity
 Cell mediated → T-cells and MФ
34
 Ex: contact dermatitis poison ivy doesn’t respond for a few days

35
Antibody Association with Disease:
IgA Nephropathies:
Berger’s, Alport’s, HSP
Goodpasture’s
Lupus
Drug induced Lupus
MS
Pernicious anemia
Celiac sprue
Pan/Poly arteritis nodosa
Wegner’s
CREST Syndrome
Scleroderma
Mixed connective tissue disease
Progressive Systemic Sclerosis
Sjogrens
DM Type I
Primary Biliary Cirrhosis
Graves Disease
Vitiligo
Bullous Pemphigoid
Pemphigus vulgaris
Viteligo
Alopecia Areata – clean and shiny
→ Totalis = whole head is involved
→ Universalis = whole body involved
Rheumatoid Arthritis
ITP
Myasthenia Gravis
Hashimoto
IgA deposition in the Kidney
Anti – BM
Anti – Smith
Anti – dsDNA
Anti - Cardiolipin
Anti – histone
Anti – myelin receptors
Anti – parietal cell
Anti – gluten
Anti – gliaden
pANCA
cANCA
Anti - proteinase
Anti - centromere
Anti – smooth muscle
Anti – ribonucleoprotein
Anti – topoisomerase
Anti – Ro, La, SSA
Anti – Scl 70
Anti – Islet cell
Anti – mitochondrial
Anti – TSH receptor
Anti – melanocyte
Anti – epidermal BM protein
Anti – epidermal anchoring protein receptor
Anti - melanocyte
Anti – hair follicle
Anti – IgG
Anti – Platelet
Anti – ACh receptor
Anti – thyrogobulin
Anti - microsomal
36
 • Any rash that is due to a cell-mediated response is called → Erythema nodosum
o Erythema Nodosum
 Redness on the anterior portion of the leg; with tenderness and painful nodules

Allergic Reactions Type I – immediate Type IV – delayed

Uticaria Hives/wheels → dermatographia d/t
too much histamine
Red circular macules → look like
Erythema multiforme bulls-eye/targets
MCC: Virus/Drugs
Erytherma multiforme Stevens-Johnson syndrome
+ > 1 mucosa involved
Erythema multiforme and skin Toxic Epidermal Necrosis
sloughs off
Occurs when one comes in
Contact dermatitis “contact” with something, i.e.,
Poison Ivy/Diaper Rash/Latex
Gloves
Dried out patches typically on the
elbows and behind the knees
Excema - nummular = circular
lesions
- spongiotic = weeping

37