Immunology (Part 1) INNATE

SEM 2 APR (acute phase reactants)

Cellular defense mechanism

IMMUNOLOGY
 Study of Immune System Phagocytosis
 Study of host’s reaction when
foreign antigens are introduced to Inflammation
the body.
Acute Phase Reactants

Categories of the Immune System

Natural Immunity

 Aka nonspecific, innate

 Ability of the individual to resist
infection by means of normally
present body function.
 NO PRIOR EXPOSURE
 Response does not change with
subsequent exposure.
- Internal defense system
- External defense system

Adaptive Immunity  C reactive protein

- Originally thought to be an
 Aka specific, acquired antibody against the c-
polysaccharide of Pneumococci
 SPECIFICITY for individual antigen
- Primitive antibody molecule
 Ability to REMEMBER a prior exposure against microorganism or
 Results in an INCREASED response foreign cells until specific
repeated exposure antibodies e produced.
 Amyloid A
Natural - Responsible of cleaning up the
area
Internal Defense System - Increased in bacterial
infection than viral
 Cellular infections.
- Phagocyte  Alpha 1 antitrypsin
- NK cell - Inhibits elastase
 Humoral  Fibrinogen
- APR - Abundant coagulation factor
- Interferons
- Defensins Cellular Defense Mechanism
- Complement protein
 Neutrophil
External Defense System - 50-70% of the total peripheral
WBC
 Physical - 2-5 lobes
- Skin and mucous membrane - Contains large number of
- Cilia lining and resp. tract neutral granules
 Biochemical
- Lactic acid GRANULE CONTENT
- Lysozymes
- Acidity of GIT ad Vagina  Primary granules
 Normal flora - Myeloperoxidase
- Elastase
- Proteinase
- Lysozymes
- Cathepsin defensins
  Secondary granules
- Collagenase
- Lactoferrin
- Lysozyme
- Reduced NADPH oxidase
 Tertiary granules
- Gelatinase
- Plasminogen activator
 Eosinophil
- Their number increases in an
allergic reaction or in
response to many parasitic
infections.
GRANULE CONTENT
4. Digestion and excretion
TAKE NOTE
 A substance released by bacteria,
injured tissue and white blood cells
that stimulates the movement of
neutrophils and othe WBC to the
injured area.
Answer:
 Substance that coat particles and
other organisms and make them more
susceptible to phagocytosis

- Major basic protein Answer:

- Eosinophil cationic protein
and peroxidase  The release of cellular substances
 Basophil contained in cell vesicles by fusion
of the vesicular membrane with the
- Smallest of the granules plasma membrane and subsequent
release of the
GRANULE CONTENT

- Cytokines Answer:
- Growth factors
- Histamine
DISEASES ASSOCIATED TO
- Heparin
PHAGOCYTOSIS
 Monocyte
- Largest cell in the peripheral
blood  Chronic Granulomatous Disease
- Affects neutrophil
GRANULE CONTENT microbicidal action
 Type 1 granules Impaired: oxygen metabolism in
- Peroxidase phagocytes
- ACP Test: NBT test (Nitro blue-
- arylsulfatase Tetrazolium Dye Test)
 Type 2 granules - Measures the ability of the
- Glucoronidase
immune system to convert the
- Lysozyme
- Lipase colorless nitro blue
tetrazolium (NBT) to a deep
ADDITIONAL NOTES blue.
- Used to test for CGD
 Dendritic cells - Normally purple/blue for +
- Covered with long membranous activated neutrophils
extensions that make them - Pink for - (no neutrophil
resembles nerve cell activation). It assesses
dendrites.
phagocytic functions. The
Main function: Phagocytose antigen and higher the blue score, the
present it to helper T lymphocytes. better the cell is at
producing reactive oxygen
 Phagocytosis species.
- Kills foreign organisms Positive result:
 STEPS: ICED
1. Initiation FLOW CYTOMETRIC ASSAY
2. Chemotaxis
3. Engulfment - Neutrophils are labelled with
 Answer: TAKE NOTE
- Neutrophil activation
Answer:  antigenic features of leukocytes
- Patient with CGD: that are differentiated by groups of
Answer: monoclonal antibodies expressing
common activity
ADDITONAL
Answer:
 Natural Killer Cells
- First line of defense against T cells B cells
Answer:  immunity  Immunity
- Releases:  Markers:  Markers:
: induce programmed cell death  Lymphokines  Antibody
in the target cell  60-80% production
Answer:  Longer life  10-20%
: Membrane-disrupting CHON span  Shorter life
Answer: span

INFLAMMATION
LYMPHOID ORGANS
CARDINAL SIGN 1. Primary lymphoid organ
a. Bone marrow
REDNESS Rubor b. Thymus
SWELLING Tumour
2. Secondary lymphoid organ
HEAT Calor
PAIN Dolor a. Spleen
LOSS OF Functio laesa b. Lymph nodes
FUNCTION c. Tonsils
d. Appendix
e. Peyer’s patches
ADAPTIVE
f. Adenoid
Types g. MAL
h. GAL
 Naturally acquired i. BAL
- Natural exposure in response j. SAL
to an infection or natural
series of infection Functions of Secondary lymphoid
 Artificially acquired organs
- Infusion of serum or plasma
containing high concentration  Trapping site of antigen
of antibody or lymphocytes  Stand-by areas of T cells, B cells
from an actively immunized and phagocyte
individual  Place of encounter for pathogens and
the cells
EXAMPLES:  Production of and
and occurs
1. Naturally acquired
 Antigenic dependent
a. Active
b. Passive
Location
2. Artificially acquired
a. Active T cells B cells
b. Passive
 ,  Follicular and
and medullary (
region of the ) of lymph
lymph nodes nodes
   Flow cytometry
regions of the And  Fluorescence microscopy
spleen of spleen
 Thoracic duct  Follicular  Rosette assay
of the region of GALT  Density gradient centrifugation
circulatory
system Immunology (Part 2)
SEM 2

T cells B cells COMPLEMENT SYSTEM

 Responsible  Precursor  A set of proteins that play a role
for immune cell in in cytolytic destruction of cellular
response and antibody antigens by specific
are involved production  Functions/examples:
in antibody  Subsets  Chemotaxin C5a, C5b, C6,C7
regulation 1.  Immune adherence C3b
 Subsets 2.  Kinin activator C2b
1.
2.  Development  Anaphylatoxin C3a, C4a, C5a
 Subpopulation: 1. Pro B  Opsonins C3b, C4b,C5b
cell - Virus neutralization C4b,C1
2. Pre B Most abundant: C3
 Development
cell Most commonly measured complement
3. Immature fragment: C3b
1. Double
negative B cell
2. Double 4. Mature B PATHWAYS OF ACTIVATION
positive cell
3. Mature T 5. Activated Three Pathways
cell 1. Classical pathway
B cell
4. Activated T  Initiated by: 2 IgG and IgM
6. Plasma
cell  Recognition Unit: C1
5. Sensitized
cell
 Activated Unit: C4,C2,C3
T cell
2. Alternative pathway
Triggers include:
 T cell receptors  Bacterial cell walls
- Sheep red blood cell receptor  Fungal cell walls
Answer:  Yeast
- Part of T cell antigen-  Viruses
receptor complex  Tumor cell lines
Answer: - Some parasites
 CD4 – receptor of MHC Class 3. Lectin Pathway
molecule (Th)  Recognition unit
 CD8 – receptor of MHC class - MASP-1,-2,-3 complex attaches
molecule (Ts and Tc) to:
1. MANNOSE/ MANNAN
2. Others include glycoprotein or
Mitogen CHO on bacteria, yeast viruses
 T cells: some parasites
1. 3. Calcium dependent
2.  MAC: C5-C9
3.
 B cells:
1.
2.

LABORATORY IDENTIFICATION OF
LYMPHOCYTES
 - LESS IMMUNOGENS:
Carbohydrate
- NOT IMMUNOGENS: Nucleic acid
and Lipids
- Foreignness
 Ability to be processed and
presented with MHC molecules

MAJOR HISTOCOMPATIBILITY COMPLEX

MHC CLASS I
 Presented in all nucleated cells
 Processed cytoplasmically derived
antigens and presented to T
CYTOLYTIC CELLS positive cells
CLINICAL SIGNIFICANCE  Genetic loci: HLA A, B, C
 Elevated complement proteins has  Chain structure: alpha chain and B2
little clinical importance microglobulin
 Decreased complement proteins:
MHC CLASS II
- Complement protein is consumed
- Complement protein may be  Present in MACROPHAGE, B CELLS,
decreased or absent due to DENDRITIC CELL AND ANTIGEN-
genetic defect PRESENTING CELLS
 Restricted to immunocompetent cells
COMPLEMENT FIXATION TEST of immune system
 Reporting: HIGHEST DILUTION SHOWING  Process extracellular derived
NO HEMOLYSIS antigens and presented to T HELPER
CELLS positive cells
 2 system involved for complement
fixation  Genetic loci: HLA DP, DQ, QR
 Test system /Bacteriolytic system  Chain structure: alpha and beta
- Indicator system/ Hemolytic chain
system
MHC CLASS III
FACTORS INFLUENCING IMMUNE RESPONSE  Minor MHC antigens
 Involves complement components C2,
 IMMUNOGENS - macromolecules capable C4 and factor B
of triggering an adaptive immunity  HLA on RBC: : BENNETT-GOODSPEED
response by inducing formation of
antibodies or sensitized T cells in HLA PHENOTYPING
an immunocompetent host
 ANTIGEN - substance that reacts F
with antibody or sensitized T cells
but may not be able to evoke an
immune response in the first place.
 HAPTEN - incomplete / partial
antigen; low molecular weight
substance, has the ability to react
with corresponding antibody but not
able to stimulate antibody
production.

IMMUNOGENS

TRAITS OF AN IMMUNOGEN
Macromolecular size IMPORTANCE OF HLA TYPING
 Chemical composition and molecular
complexity  Tissue /organ transplant
- BEST IMMUNOGENS: Proteins  Paternity testing
and Polysaccharide
  Studies of racial ancestry and
migration
 For diagnostic and genetic
counselling
 Disease association:
- HLA B27 : ANKYLOSING
SPONDYLITIS
- HLA DR3 : MULTIPLE SCLEROSIS
- HLA DR2 , DR3: SYSTEMIC
LUPUS ERYTHOMATOSUS
- HLA DR4 : RHEUMATOID
ARTHRITIS
- HLA DR3, DR4 : TYPE 1 DM

ANTIBODIES
GAMMAGLOBULIN G
IMMUNOGLOBULIN
 Smallest antibody
 Products of antigenic stimulation  Coating antibody
 Functions:  Clinically significant
- Cell cytology
- Neutralization  Associated with secondary immune
- Opsonisation response
- Agglutination
Functions:
STRUCTURE
 Provide immunity for the women
1. Heavy chain  Fixation of complement
 IgG (GAMMA heavy chain)  Opsonisation
 IgA (ALPHA heavy chain)  Neutralization
 IgM (MU heavy chain)  Participation in agglutination and
 IgD (DELTA heavy chain) precipitation reaction
 IgE (EPSILON heavy chain)
 Light chain
 Disulfide bond
2. Hinge region

DEFINITIONS

 ISOTYPE - heavy chain that

determines Ig Class
 ALLOTYPE - variation in the
constant region of both HC and LC GAMMAGLOBULIN M
 IDIOTYPE - variation in the
variable region of both HC and LC
 First to be produced after antigenic
 VALENCE - refers to number of stimulation
binding site  First to appear in phylogeny and
 MONOMER - basic Ig structure last to leave senescence
 DIMER - consist of 2 monomers
linked by J chain Functions:
 POLYMER - more than 2 monomer
 DOMAIN - sections or regions in an  Best complement fixer
Ig Class molecule  Agglutination
 Opsonisation
 Neutralization

GAMMAGLOBULIN A
 Major antibody on secretions IMMUNOLOGICAL DISORDER
 Associated with anaphylaxis

GAMMAGLOBULIN D

 Function: IMMUNOREGULATION
 Sensitive to enzymatic degradation
 Found on the surface of B Cells
 Postulated to be an ANTI IDIOPATHIC
antibody

GAMMAGLOBULIN E

 Reaginic antibody
 Has high affinity to basophils and
mast cells
 High in allergy and in parasite
infection
 Attach to eosinophil SECRETE MAJOR
AUTOIMMUNITY DISEASES
BASIC PROTEIN
 Conditions in which damage to organs
FRAGMENTATION OF MONOMER or tissues results from the presence
of AUTO ANTIBODY or AUTO REACTIVE
1. Papain : CUT MONOMER EXACTLY AT THE CELLS
HINGE REGION  SELF TOLERANCE - ability of the
- 2 Fab, 1 FC immune system to accept self-antigen
2. Pepsin : CUT MONOMER BELOW THE HINGE and not initiate a response against
REGION them.

SPECIAL TERMS CLINICAL TYPES

 Affinity - INITIAL FORCE OF

ATTRACTION BETWEEN A SINGLE Fab AND
SINGLE EPITOPE
 Avidity - SUM OF ALL ATTRACTIVE
FORCES BETWEEN AN ANTIGEN AND
ANTIBODY
- MULTIPLE

IMMUNE RESPONSE

1. Lag
2. Log
3. Stationary
4.
5. Decline

SYSTEMIC OR NON - ORGAN SPECIFIC

 SYSTEMIC LUPUS ERYTHEMATOSUS

- Immune complex disease
characterized by
overproduction of
AUTOANTIBODIES
- ARTHRITIS - most common
manifestation
 - Manifest itself by skin
lesions BUTTEFLY RASH or RED
WOLF
 Laboratory observation:
- Presence of ANTINUCLEAR
ANTIBODIES
- LE CELLS - PMN leukocyte with
ingested LE body, often
rosette formation
 Serologic Test:
- Antinuclear antibody (ANA)
Visible
Principle: Indirect Immunoenzyme
- Hep2 cells ( Nuclear Ag) + Px
serum (with ANA) + AHG + Stain
 (+) for ANA (brown
cytoplasmic or nuclear stain)
 Indirect Fluorescent Antibody Test
- Detection Of ANA
Principle: Indirect
immunofluorescent
FLUORESCENT STAINING PATTERN
Pattern Description
Uniform staining of
Homogenous the entire nucleus
Diffuse staining is
Peripheral/Outl the nucleus, but
ine/Rim Pattern greater intensity
around the outer
circle surrounding
the nucleus
Discrete, florescent
Speckled specks throughout the
nucleus
Prominent staining of
Nucleolar the nucleoli
Numerous discrete
Centromere speckles are seen.
SYSTEMIC OR NON - ORGAN
SPECIFIC
 RHEUMATOID ARTHRITIS
- Autoimmune disease causing
chronic inflammation of the
joints and per articular
tissue
- Rheumatoid factor:
: Group of immunoglobulin that
reacts specifically with the Fc
portion of IgG molecules
 Laboratory test:
- Sheep cells agglutination test
- Latex fixation test
- Sensitized alligator
erythrocytes test
- Bentonite flocculation test
SYSTEMIC OR NON - ORGAN
SPECIFIC
 GRANULOMATOSIS WITH POLYANGITIS
- Inflammation of BLOOD VESSELS
- Primarily affects the upper
respiratory tract, lungs and
kidneys
- Laboratory diagnosis:
1. Nasal or oral inflammation
with oral ulcers or
purulent or bloody nasal
discharge
2. Abnormal chest x ray,
showing presence of
nodules, fixed infiltrates
or cavities
3. Urinary sediment with
microhematuria or RBC cast
4. Granulomatous inflammatory
or biopsy
TUMOR MARKERS
 Carcinoembryinic Antigen (CEA) – GI
cancer
 AFP – hepatocellular CA
 PSA - -prostate CA
 CA 15-3 – breast CA
 CA 19-9 – pancreas, stomach, bile
duct
 CA 125 – Ovarian CA
 CA 72-4 – gastric CA
TAKE NOTE
 ONCOGENE - “a gene: potential to
cause cancer. In tumor cells:
mutated and/or expressed
 PROTOONCOGENE - normal genes
involved in cell growth and
proliferation or inhibition of
apoptosis.
 TUMOR SUPPRESSOR GENE/ ANTI
ONCOGENE - is a gene that protects
a cell from one step on the path to
cancer.