Edward Jenner

 He noticed that milkmaids exposed to cowpox are immune to smallpox.

 He coined the term vaccination (vacca – cow)

Louis Pasteur

 Started the first attenuated vaccine by noting that older cultures of vibrio cholera does not cause
chicken cholera.
 Father of Immunology

Year Event
1888 Eljie Phagocystosis
Metchnikoff (Transparent
Starfish Larvae)
1891 Robert Koch Demonstration of
Cutaneous
(Delayed Type)
Hypersensitivy
1894 Jules Bordet Discovered
Complement
1897 Robert Kaus Discovered
Precipitins
1900 Paul Ehrlich Antibody
Formation Theory
1949 Salk and Development of
Sabin Polio Vaccine
1951 Reed Vaccine Against
Yellow Fever
1957 Burnet Clonal Selection
Therapy
1975 Kohler and First Monoclonal
Meilsten Antibody
(Hybridoma)
1977 Rosalyn Radioimmunoassay
Yellow
1987 Susumu Nobel Priza for
Tonegawa Antibody Diversity
2005 Frazer Human
Papillomavirus

Natural Immunity (external)

Natural:

External:

 Skin
  Mucosal Membrane
 Lactic Acid and Fatty Acid
 Mucus Secretion and Cilia
 Flushing Action of Urine
 Acidity in Stomach (PH1)
 Acidity in Vagina (PH 5)
 Lysozyme
 Normal Flora

Internal

 Cellular
o White Blood Cells
o Macrophage
 Humoral
o Acute Phase Reactants
o Complement

Acute Phase Reactants

 Normal Serum Constituents that increase rapidly by at least 25 percent due to infection, injury, or
trauma to the tissues.
 They are produced primarily by hepatocytes (liver parenchymal cells) within 12 to 24 Hours in
response to an increase in certain intercellular signaling polypeptides called cytokines.

Characteristices of Acute Phase Reactants

C-reactive Protein 6-10 0.5 1000x Opsonization,

complement activation

Serum amyloid A 24 3.0 1000x Removal of Cholesterol

Alpha-antitrypsin 24 200-400 2-5x Protease inhibitor

Fibrinogen 24 110-400 2-5x Clot formation

Haptoglobin 24 40-200 2-10x Birds Hemoglobin

Ceruloplasmin 48-72 20-40 2x Binds Copper and

Oxidizes iron
Complement C3 48-72 60-140 2x Opsonization, lysis
Mannose-binding ? 0.15-1.0 ? Complement activator
protein
C – Reactive Protein

Elevated levels are found in conditions such as bacterial infections, rheumatic fever, viral
infections, malignant diseases, tuberculosis, and after a heart attack.

It is capable of opsonization (The coating of foreign particales), agglutination, precipitation, and

activation of complement by the classical pathway.

It also binds to small, ribonuclear proteins; phospholipids; peptidoglycan; and other constituents
of and organism.

The most widely used indicator of acute inflammation.

Serum Amyloid A

Acts by removing cholesterol, from cholesterol-filled macrophages at the site of tissue injury,
serum amyloid A contributes to the cleaning up of the area

It has been found to increase significantly more in bacterial infections than in viral infections.

Mannose-Binding Protein

Acts as an opsonin

Also called Mannose Binding lectin

Lack of MBP has been associated with recurrent yeast infections

It is widely distributed on mucosal surfaces throughout the body.

Alpha 1 – antitrypsin

It is a general plasma inhibitor of proteases released from leukocytes, especially elastase.

Acts to “mop up” or counteract the effects of neutrophil invasion during an inflammatory
response.

Alpha 1 – antitrypsin deficiency can result in premature emphysema, especially in individuals who
smoke or who are exposed to a noxious occupational environment.

Haptoglobin

Its primary function is to bind irreversibly to free hemoglobin released by intravascular hemolysis.

The rise in plasma haptoglobin is due to de novo synthesis by the liver and does not represent
release of previously formed haptoglobin from other sites.
 Increase in haptoglobin can be seen following inflammation, stress or tissue necrosis.

Fibrinogen

Most abundant of the coagulation factors in plasma and it forms the fibrin clot.

Ceruloplasmin

Principal Copper-Transporting protein in human Plasma

A depletion of ceruloplasmin is found in wilson’s disease.

Neutrophil

 50% - 70%
 Rise in bacterial infection

Eosinophil

 1% - 3%
 Rise in parasitic infection or allergy
 Takes up the acid eosin dye
 Reddish orange in color

Basophil

 Less than 1%
 Contains heparin and histamine inside and IgE on cell Surface
 Smallest of the granulo??

Mast Cell

 Not A WBC
 Connective tissue cell
 Contains granules like histamine
 Contains IgE on cell surface

Monocyte

 4% - 10%
 Largest cell in peripheral blood
  Horse shoesshaped nucleus
 Fines dustlike granules

Macrophage

 Monocytes in tissues
 Slow motility
 Lifespan of months

Liver Kupffer cell

CNS Microglial Cell
Bones Osteoclast
Lung Alveolar Macrophage, Dust cell
Connective Tissue Histiocye
Placenta Hofbauer Cell
Spleen Littoral Cell
Kidney Mesangial Cell
Sunovial Type A lining Cell

Dendritic cell

Most potent APC

How do lymphocytes be a:

B – Cell

T – Cell

NK Cell

Cytokines

Lymphoid Organ

Primary:
Bone Marrow

Thymus

Secondary:

Spleen

Lymph Nodes
 Appendix

Tonsils

Peyer’s Patches

Mucosal – Associated Lymphoid Tissue ( Malt )

Comparison of T and B Cells

Develop in the thymus Develop in the bone marrow

Found in blood ( 60% - 80% of circulating
lymphocytes), thoracic duct fluid, lymph nodes
Identified by rosette formation with SRBC’s
End products of activation are cytokines
Antigens include CD2, CD3, CD4, CD8
Located in paracortical region of lymph nodes
Found in bone marrow, spleen, lymph nodes
Identified by surface immunoglobulin
End product of activation is antibody
Antigens include CD19, CD20, CD21, CD40, MHC
class II
Located in cortical region of lymph nodes

NK CELL

HOW DO WE KNOW IF ITS IS A “B”, “T”, or “NK” Cell?

By using cluster differentiation protein on cell surface.

1. Isolation through density gradient centrifugation with ficoll – hypaque

2. Separation of lymphocytes into diff subsets through flow cytometer or manual method
3. Detection of CD Marker

Antigens are substances that react with antibodies.

Immunogens are antigens that triggers immune response.

All immunogens are antigens but not all antigens are immunogens.

Macromolucular size, Chemical composition and molecular complexity, foreignness, The ability to be
processed and presented with MHC molecules.

Types of Antigen:

Autoantigens – antigens that belong to the host

Alloantigens – other members of the host’s species

Heteroantigens – from other species

Haptens

Adjuvants

MHC MOLECULES = HLA

MHC CLASS 1

 Present on all nucleated cell and highest on lymphocyte and low or undetected on liver
hepatocytes, neural cells, muscle cells and sperm.
 Binds to endogenous antigen
 Locus/Ag = HLA – A,B,C
 Chain Structure = alpha-chain + Beta 2 microglobulin
 Presents antigen to CD8+ cells

MHC CLASS 2

 Found primarily on antigen-presenting cells ( B lymphocytes, monocytes, macrophages, and

dendritic cells)
 Binds antigen found on surface of the cell
 Locus/Ag = HLA – DP, DQ, DR
 Chain structure = alpha chaon + beta chain
 Presents antigen to CD4+ cells

Human Leukocyte Antigen Disease Palatandaan

B27 Ankylosing Spondilits
DR15 Goodpasteur Syndrome Si DR. 15 is a good doctor
DR3 Grave’s, Hashimoto’s 3 feet below the grave
B8, DR3 Myasthenia Gravis Gravi kasi dalawang HLA
DR2 Multiple Sclerosis Multiple kaya 2
DR4 Rheumatoid Arthritis Yung number 4 is parang
matandang nakayuko at
nakahawak sa tuhod na may
arthritis
DR3 SLE 3 letters

END PRODUCT OF B CELL STIMULATION OR DIFFERENTIATION

MADE UP OF 2 HEAVY AND 2 LIGHT CHAIN

 Constant region of L chain – can be kappa type or lambda type.

 Variable region of L chain – amino terminal end.
 Constant region of H chain – can be gamma, alpha, mu, delta or epsilon type.
 o Allotype is the variation in constant region.
 Variable region of H chain – unique and what we call idiotype of an antibody molecule.

IgA – sedimentation coefficient of 7s

Has 2 subclasses:

IgA1 – mainly found in serum, a monomer

IgA2 – usually found in mucus membranes or surfaces, a dimer with J chain

Synthesized at a greater rate than IgG

Synthesized in plasma cells found in mucosal associated lymphoid tissue (MALT)

Functions are:

Patrol mucosal surfaces

Act as first line of defense

Neutralize toxins

Prevent adherence of organism on mucosal surface/membrane

Cannot start complement pathway that is why you don’t usually get inflammation if there is an
infection in mucosal surface/membrane

IgM – known as macroglobulin because it has sedimentation coefficient of 19s

Half life is 10 days.

5 to 10% of total Ig

Has two forms:

Pentamer – found in secretions and fluids of the body such as saliva and blood

Monomer is found on surface of 8 cells

Has 10 functional binding sites but only 5 is usually used unless antigens are very small.

Star like shaped

Cannot cross placenta

First to appear in maturing infant

First to appear after infection

Synthesized only as long as antigen presence because there is no memory cells for IgM.
IgG – sedimentation coefficient of 7s

Predominant immunoglobulin in humans

75% to 8-% of total Ig.

Has longest lifespan of 23 to 25 days.

Functions are:

Provide immunity for newborn since it can cross placenta

Starts complement pathway

Coats antigen for enhanced phagocytosis

Neutralize toxins and viruses

Participate in aggluntination and precipitation reactions

Has 4 subclasses:

IgG1 – has a large hinge region compared to IgG3

IgG2 – has short hinge region, least effective in crossing placenta

IgG3 – has the largest hinge region

IgG4 – has short hinge region

IgD – almost the same sedimentary coefficient as gamma globulin

Has half-life of 2 days (because of long hinge region)

Found on immunocompetent but unstimulated B cells.

Second to appear after IgM on an onset of infection

Function is:

B (memory) cell activation, maturation and differentiation

Does not cross placent

Does not start complement pathway

Does not bind neutrophils or macrophages

IgE – sedimentary coefficient of 8s

Lease abundant of all immunoglobulin

Most heat labile of all immunoglobulin

Cannot start complement pathway

 Cannot agglutinate

Cannot opsonize

Cannot cross placenta

Found on basophil and mast cells

Mast cells are foun in lining of respiratory and alimentary traacts, and the skin.

Synthesized by plasma cell found in lung and skin

Functions are:

Destruction of large antigen such as parasitic worm triggering of acute inflammatory

reaction.

SIDE CHAIN THEOR

CLONAL SELECTION THEORY

ANTIBODY DIVERSITY

RUBOR
COLOR
DOLOR
TUMOR

Laboratory Safety:

 Always wear PPE

 Chain of infection: source, method of transmission and susceptible host.
 Universal Precaution: Instituted by CDC for bloodborne pathogens
 Body substance isolation: replacement of UP not limited to bloodborne pathogens.
 Sodium Hypochlorite: also known as household bleach 1:10
 Material safety data sheet (MSDS) – required for chemicals greater than 1% concentration
 Biohazard symbol – fluorescent-orange or orange-red

ANTIGEN
ANTIBODY
REACTION

SOLUBLE ANTIGEN SOLUBLE ANTIBODY

AFFINITY

 The initial force of attraction that esists between a single site on an antibody molecule and a
single site on an antibody molecule and a single epitope or determinant site on the corresponding
antigen
 Ionic bonds, hydrogen bonds, hydrophobic bonds, and van der Waals forces

AVIDITY

 Avidity represent the sum of all the attractive forces between an antigen and an antibody
 It is a measure of the overall stability on an antigen-antibody complex

Prozone-> Zone of Equivalance <- Postzone

Aggluntination – aggregation of particles caused by combination with an antibody

Involves two-step process:

 Sensitization – initial binding between one Ab and one Ag

 Lattice formation – binding of Ab-Ag complex to another Ab-Ag complex

KINDS OF AGGLUTINATION

DIRECT AGGLUTINATION

 Occurs when antigens are found naturally on the surface of a particle/cell

 Unknown is the presence or absence of antibody
 If the direct agglutination reaction involved red cells, then it is called hemagglutination

PASSIVE AGGLUTINATION

 Occurs when antigens are not found naturally on the surface of a particle/cell
 Unknown is the presence or absence of the antibody
 Uses particles to increase the size of antigen (latex, red cell, gelatin, silicates)

REVERSE PASSIVE AGGLUTINATION

 Antibody rather than antigen is attached to a carrier particle

 Unknown is the presence or absence of antigen
 Uses particles to increase the size of antigen (latex, red cell, gelatin, sillicates)

AGGLUTINATION INHIBITION

 Based on competition between particulate and soluble antigens for limited antibody
combining sites
 Unknown is the presence or absence of antigen
  Lack of agglutination is an indicator of a positive reaction

COAGGLUTINATION

 Uses bacteria as the inert particles to which antibody is attached

 Unknown is the presence or absence of antigen
 Staphylococcus aureus is frequently used because if its protein A on its surface

Direct Agglutination
Passive Agglutination
Reverse Passive Agglutination
Agglutination inhibition
Coagglutination
Principle
Antigens are found naturally on
the surface
Antigens are not found naturally
on the surface
Antibody rather than antigen is
attached to a carrier particle
Competition between antigens
for limited antibody-combining
sites
Uses bacteria as the inert
particles
Unknown
Presence or absence of
antibody
Presence or absence of
antibody
Presence or absence of antigen
Presence or absence of antigen
Presence or absence of antigen

SOMETIMES, AGGLUTINATION DOES NOT HAPPEN

Ways to increase agglutination:

 Increase viscosity – by addition of dextran or polyethylene glycol (PEG)

 Using enzymes – reduces surface charge of cells
 Agitating – provides physical means for cells to come closer
 Centrifuging- provides physical means for cells to come closer
 Altering temperature – temperature must be suited to the type of antibody
 Altering pH – optimal for most reactions is between 6.5-7.5 except Anti-M and anti-P1 which
react at lower pH
 Coomb’s test – technique that detects nonagglutinating antibody by means of coupling with a
second antibody
o Direct coomb’s test – in vivo sensitization
o Indirect coomb’s test – in vitro sensitization

Preparation of AHG Reagent

POLYCLONAL AHG PRODUCTION

 Uses rabbits
 Prepared by convention technique
o Sheep or goats may be used when large volumes of antibody are required
 Rabbits are injected with complement and IgG
 Antibody produced is collected and purified:
o Anti-IgG
 o Anti-CeB/C3d
 Monospecific antibodies are pooled together to form AHG Polyspecific reagents

MONOCLONAL AGH PRODUCTION

 Uses mice
 Employs the use of hybridoma technology
o Spleen Cells + Myeloma Cells = HYBRIDOMA CELLS
o Clone cells that produce only one type of antibody
 Fused cells are placed in a HAT medium
o Hypoxanthine, aminopterin, and thymidine
o Only allows growth of Hybridoma cells

How do we measure or quantify precipitation/agglutination?

 Turbidimetry
 Nephelometry
 Immunodiffusion Technique

Turbidimetry

 Measure of the turbidity or cloudiness of a solution

 Detection device is put in direct line with the source of light

Nephelometry

 Measures the light that is scattered at a particular angle from the incident beam as it passes
through a suspension
 Detection device is put in perpendicular line with the source of light

Immunodiffusion

 Requires the use of agar with or without electricity

1. Immunodiffusion without electrophoresis
a. Uses agar and agarose
b. Other name is passive immunodiffusion
c. Rate of diffusion is affected by the size of the particles, the temperature, the gel
viscosity, and the amount of hydration.
d. Divided into two:
i. Single diffusion
ii. Double diffusion

1A. Single Immunodiffusion

o Pioneered by James Oudin

o Antibody is mixed with agarose gel and put into tube. Antigen is layered on top and
moves down in proportion to the amount of antigen present or layered
 o The distance of precipitin bands from the top of the gel is directly proportional to
amount of antigen

1B. Radial Immunodiffusion

o Modification of single immunodiffusion

o Antibody is mixed with agarose gel and put into plate/slide. Antigen is put into the well
cut in the gel. Antigen moves sideways in proportion to the amount of antigen present
or put.
o The area of the ring formed is directly proportional to amount of antigen.

1C. Ouchterlony Double Diffusion

o Multispecific antibody is put on the center well

o Antigens are put on wells surrounding the antibody
o Arc line is observed if both antigens are the same
o Cross line is observed if antigens are not the same or not share a similar epitope
o Spur formation is seen for partial similarity
2. Immunodiffusion with electrophoresis
a. The same with passive diffusion but has the presence of electrical charge.

2A. Rocket Immunoelectrophoresis

o Adaptation of radial immunodiffusion

o Developed by Laurell in 1960
o The end result is a precipitin line that is conical in shape, resembling a rocket

2B. Immunoelectrophoresis

o A double diffusion
o Two-step process
 Antigens are separated through electrophoresis
 Trough is made between specimens and antiserum is put in it and incubated
from 18 to 24 hours
o These lines or arcs can be compared in shape, intensity, and location to that of a normal
serum control to detect abnormalities.

2C, Immunofixation Electrophoresis

o Procedure is same as Immunoelectrophoresis but instead of putting antiserum in the

trough, antiserum is put directly on the gel’s surface
o Faster results of around 1 hour only.

SOMETIMES, NEPHELOMETRY, TURBIDIMETRY AND IMMUNODIFFUSION IS NOT ENOUGH TO TELL IF

THERE IS A REACTION
Label immunoassay is the key

Types of label immunoassay:

 Radioactive
 Enzyme
 Fluorescent
 Chemiluminiscent

NUMEROUS MATERIALS, SUCH AS POLYSTERENE TEST TUBES, MICROTITER PLATES, GLASS OR

PLYSTYRENE BEADS, MAGNETIC BEADS, AND CELLULOUSE MEMBRANES, HAVE BEEN USED FOR THIS
PURPOSE.

Radiactive Immunoassay

 First type of immunoassay

 125 132 3
I, I, H (from most to least popular)
 Unknown is presence or absence of patient’s antigen
 Result is read using Schilling’s counter
 Advantage:
o Extremely sensitive
 Disadvantage:
o Expensive to maintain
o Requires special license
o Shelf life of radioactive chemicals
o Health hazard

Enzyme Immunoassay

 Enzyme is used as labels

 Results are read using spectrophotometer

I. Competitive Enzyme immunoassay (Heterogenous)

 Two antigens compete for the binding site on the antibody fixed on the media.
 Unknown is presence or absence of patient’s antigen

II. Noncompetitive Enzyme immunoassay (Heterogenous)

 Has higher sensitivity than competitive

 Also known as indirect enzyme linked immunosorbent assay or indirect ELISA
 Unknown is the presence or absence patient’s antibody
 Used to test for Hepa A, Hepa B and HIV
 III. Capture assay – (Heterogenous)

 Also known as sandwich immunoassays

 Almost the same as indirect elisa but the antibody is the one attached to solid media
 Unknown is presence or absence of patient’s antigen
 Can undergo hook effect

Fluorescent Immunoasay (immunofluorescent assay)

 Uses fluorophores or fluorocromes, they are organic molecules that emits light after absorbing
energy from the incident light.
 Example: fluorescein (green), rhodamine(red)
 Results is read using fluorescent microscope, spectrofluorometer, flow cytometer or
fluorometer.
 Can be classified into two:
1. Direct immunofluorescent assay
a. Best suited in detection of antigen in tissue
2. Indirect immunofluorescent assay
a. More sensitive than direct immunofluorescent assay
b. Same principle as indirect elisa

Chemiluminiscent immunoassay

 Emission of light caused by a chemical reaction, commonly oxidation.

 Most common examples:
o Luminol
o Acridinium
o Esters
o Ruthenium derivatives
o Nitrophenyl oxalates

MOLECULAR DIAGNOSTICS

Below are some ways to amplify target sequence:

 Polymerase Chain Reaction

 Nucleic acid sequence based …….????
 Strand displacement amplific…..???
 Transcription mediated ampli….???
 Ligase chain reaction
Automated system in which single cells in a fluid suspension are analyzed in terms of their intrinsic light-
scattering characteristics and are simultaneously evaluated for extrinsic properties (I.E., the presence of
specific surface proteins) using fluorescent labeled antibodies or probes.

Major components of a flow cytometer:

 Include the fluidics

 Laser light source
o Light souce to be used should be matched with fluorochromes to be used.
o Argon that emits at 488nm is commonly used.
o Light is measured at forward angle (cell size) or orthogonal right angle (cell granularity
or intracellular complexity)
 Optics (photodetectors)
 Computer for data analysis and management

Specimen considerations:

 Can use whole blood, bone marrow aspirate, and fluid aspirates. Can also use tissue specimens
but cells should be disintegrated first.
 Use EDTA or Heparin as anticoagulant.

HYPERSENSITIVY

HEIGHTENED STATE OF IMMUNE RESPONSIVENESS

TYPE 1 HYPERSENSITIVITY

 Other name is anapnylactic/ atopic

 Mediated by IGE
 Trigger is atopic antigen or allergens
 Atopy – refers to inherited tendency to react to normal allergens.
 Anaphylaxis is the most severe type of allergic response.

Testing for IGE:

1. Radioimmunosorbent Test (RIST) – test all IGE or total IGE. Uses radioactive labels
2. Radioallergosorbent Test (RAST) – test for antigen-specific IGE. Use enzyme of
Fluorescent Labels.

Type 1 Type 2 Type 3 Type 4

Other Anaphylatic/ Cytotoxic Immune Complex Delayed/cell
Name atopic mediated
Mediator IgE IgM / IgG IgM / IgG T cell(th1)
 Effector cell Basophil / Mast RBC, WBC, Platelet Host tissue cell APC,
cell Macrophage,
Tcell
Antigen Allergen Cell-bound antigen Soluble antigen Sensitized
Involved antigen
Complemen No Yes Yes No
t
Involvemen
t
Mechanism Release of Cell lysis Deposition of Ag-Ab Release of
inflammatory complexes cytokines
mediators

Examples Anaphylactic  AIHA  Serum sickness  Contact

 Bee sting  HTR  Arthus reaction Dermatit
 Food/dru  HD  SLE is
g  ITP  Post  Poison
allergies  Goodpastu streptococcal Ivy
Allegic/atopic re glomerulonephri  GVHD
 Rhinitis  Rheumatic tis  PPD test
 Hives fever  Polyarteritis
 Hay nodosa
fever
 Eczema
 asthma

AUTOIMMUNITY

Central Tolerance – this destruction of potentially self-reactive lymphocytes in bone marrow

Peripheral Tolerance – this destruction of potentially self-reactive lymphocytes in secondary lymphoid

organ

Caused by presence of Autoantibody which happens if:

 Self-reactive T cells
 Presence of Certain MHC Molecule
o HLA b27 – Ankylosing Spondylitis
 Release of Sequestered Antigens
o Myelin Basic Protein
o Sperm
 Molecular Mimicry
o Poliovirus VP2 and Acetylcholine
o Measles Virus P3 and Myelin Basic Protein
o Papilloma Virus E2 and Insulin Receptor
 Polyclonal B cell activation

1. Systemic Lupus Erythematosus

a. Caused by genes (Inherited Deficiency of CQ1, C2 and C4 or Environmental Factors such
as UV Light Exposure, Drugs or Organism)
b. Typical Patient has average of three circulation antibodies.
c. Clinical Signs:
i. Weight loss, malaise, fever
ii. Joint involvement
iii. Erythematosus rash on skin exposed to UV Light
iv. Classic Butterfly rash on nose and cheek
v. Renal involvement due to deposition of complexes
d. Laboratory Diagnosis:
i. Demonstration of Le Cell – Neutrophil that has engulfed the antibody-coated
nucleus of another Neutrophil
ii. Fluorescent anti-nuclear antibody testing – most used screening
iii. Indirect Immunofluorescnece – benchmark in identification of Autoantibodies
for SLE

Patterns Autoantibody Disease Associations

Homogenous or Peripheral Anti-dsDNA Most Diagnostic for SLE
Anti-histone Drug-induced SLE
Anti-DNP Drug-induced SLE
Coarseley Speckled Anti-SM Diagnostic for SLE
Anti-RNP SLE, RA, systemic sclerosis,
Sjogren’s Syndrome
Finely Speckled Anti-SS-A (Ro) Cutaneous SLE, Scleroderma,
Anti-SS-B (La) Sjogren’s Syndrome
Homogenous nucleolus Anti-nucleolar SLE, Scleroderma, Systemic
sclerosis
Atypical speckled Anti-Sci-70 Scleroderma,Systemic sclerosis
Fine cytoplasmic speckling Anti-Jo-1 Polymyositis
No fluorescene Anti-centromere CREST
2. Rheumatoid Arhtritis
a. Autoimmune disease that affects the synovial membrane of multiple joints
b. Characterized by presence of Rheumatoid factor which is an igm that targets IGG FC
Region
c. Rheumatoid Factor can also be seen in:
i. Chronic Hepatitis
ii. Systemic Lupus Erythematosus
iii. Syphilis
iv. Hypo/Hypergammaglobulinemia
d. Anti-CCP is more specific for Rheumatoid Arthritis than Rheumatoid Factor
e. Laboratory Diagnosis:
 i. Detection of RF in serum of Synovial Fluid
ii. Latext Test is more sensitive but Sheep Cell Agglutination more specific
1. 2A Latext Fixation Test
a. Positive Titer: >= 80
b. Weake Positive: 20-40
c. Negative: No Agglutination at 1:20 even if subsequent dilution
shows agglutination
2. 2B Sheep cell Agglutination
a. Use of Sheep red cell coated with IGG
3. Myasthenia Gravis
– Autoimmune that affects the neuromuscular junction
4. Goodpasture Syndrome
– Presence of autoantibody to glomerular, renal tubular, and alveolar basement
membranes, immune deposits accumulate, and complement fixation causes injury
because of the release of oxygen species and proteolytic enzymes.

Autoantibody Associated disorder

Anti-dsDNA, Anti-smith SLE
Anti-acetylcholine receptor Myasthenia Gravis
Anti0basement membrane Goddpasture
Anti-centromere CREST syndrome
Anti-histone Drug-induced SLE
Anti-insulin, Anti-beta cells, Anti-GAD Type I DM
Anti-mitochondrial Primary Biliary Cirrhosis
Anti-myelin sheath Multiple sclerosis
Anti-parietal cell Pernicious anernia
Anti-smooth muscle Chronic active hepatits
Anti-SSA, Anti SSB Sjogren’s syndrome
Anti-thyroglobulin, Anti-thyroid peroxidase, Anti- Hashimoto’s thoiditis
microsomal
Anti-TSH receptor Grave’s disease
Cold/warm autoantibodies AIHA/WAIHA
Rheumatoid factor, Anti-CCP Rheumatoid Arthritis

IMMUNOPROLIFERATIVE DESEASES
1. Leukemia – lymphoid malignant cells are in the bone marrow or peripheral blood
2. Lymphoma – lymphoid malignant cells are in lymphoid tissues such as lymph node, tonsil,
spleen
3. Plasma cell dyscrasias – Characterized by the overproduction of an immunoglobulin
component called a myeloma protein (M protein), or paraprotein, by a clone of plasma cells.

LEUKEMIA

 Acute Lymphoblastic Leukemia (ALL)

o Presence of very poorly differentiated precursor cells (blast cells)
o Occur usually in children
 o Curable
o Divided into 4 types : (CD10)-expressing immature B cell ALL (CALLa), pre-B cell
ALL, T-cell ALL, B-cell ALL (most common to rare)
 Chronic
o Mature cells present
o Occur usually in adult
o Not curable
o Divided into 4 types: chronic lymphocytic leukemia (CLL), small lyhphocytic
leukemia (SLL), prolymphocyticleukemia, and hairy cell leukemia.

LYMPHOMA

 Hodgkin’s lumphoma
o Highly treatable and highly communicale
o Characterized by presence of Reed-Sternberg cells in lymphoid organ. (own
eye’s appearance)
 Non-Hodgkin’s lymphoma
o Absence of reed Sternberg cell

Disease Defect Presentation/Symptoms Findings

Bruton’s  Failure of B cell  Recurrent  Absence of B
Agammaglobulinem precursors to bacterial and cell in the
ia mature enteroviral blood
infections after 6  Lowering of
months immunoglobuli
(depleted ns
maternal IgG)
Selective IgA  Most common  Aysmptomatic  Lowering of IgA
deficiency congenital with normal
immunodeficien IgG and IgM
cy
Common variable  Normal number  Can be acquire in  Lowering of
immunodeficiency of B-cells in the 20s-30s plasma cells
blood but  Immunoglobuli
unable to ns
differentiate
into plasma cells
DiGeorge Synrome  Absent thymus  Tetany due to  Lowering of
and parathyroid hypocalcemia Tcelss and PTH
 Deficiency in and CA
Th17
Jcb syndrome  Impaired  Dermatologic  Rising of IgF
chemotaxis of problems and lowering of
neutrophils to I5Ny
site of infection  Normal IgG,
IgA, IgM
 Severe combined  Most severe  Failure to thrive  Absence of
immunodeficiency immunodeficien  Need bone germinal
cy marrow centers to
 Adenosine transplant lymph node
deaminase  Absence of T
deficiency cell in floow
cytometer
Ataxia-  Defect in a gene  Triad of Ataxia,  +AFp
Telangectasins that is Spider angima,  - IgG, IgA, IgF
apparently IgA def
essential to the
recombination
process for
genes in the
immunoglobulin
superfamily
Wiskott-Aldrich  Abnormality of  Triad of  - or Normal
Syndrome the integral Thrombocytopen IgG, IgM
membrane ia, Eczema,  + IgF, IgA
protein CD43 Recurrent  Fewer and
because of infection smaller
WASp gene. platelets
Leukocyte Adhesion  Proetein (CD18)  Abnormal vessel  + neutrophil
Deficiency that is a wall adhesion blod
component of and chemotixs  ????
adhesion
receptors on
neutrophils and
monocytes and
on T cells is
defective
Chediak-Higashi  Defect in LYST  Recurrent  Giant granukes
syndrome gene pyogenic of granulocytes
 Dysfunction in infection by and platelets
phagosome- staph and strep
lysosome organism
dysfunction
Chronic  Inability of  Recurrent  Cannot reduce
Granulomatous neutrophils to infection NST dye
disease produce the  Abnormal
reactive forms neutrophil
of oxygen phagocytosis
necessary for
normal bacterial
killing