Introduction To BMS-clinical Immunology-Bb

IMMUNOLOGY
•Innate
•Adaptive
Primary and secondary immune tissues
Lymphatic system to the pressurized

blood system - leaked blood plasma
collected and returned as lymph
T-CELLS
• Immature cells - T-lymphocytes - Bone marrow - Thymus as thymocytes - T-cell receptor.

• Maturation - The response pathway: T-cell receptor activated - differentiated
o CD4 antigen (cluster differentiation antigen 4) T-helper cells and express cytokines
o CD8 (cluster differentiation antigen 8) cells kill any cell which their T-receptor binds.
• Antigen naive T-cells - the thymus to the secondary lymphatic tissue awaiting encounter with foreign antigens.
• Primary function of the T-cell receptor is to drive this antigen naive first generation effector T---cell into a
replication - generating clones executed CD4þ or CD8þ cells expressing cytokines to aid the immune response or
kill the antigen expressing cells.
• A few of the daughter cells not executed T-cells and will migrate into the spleen and lymph nodes as CD4 and
CD8 memory cells for the antigen.
B CELLS
• Progenitor B lymphocytes undergo maturation and differentiation within the
bone marrow.
• B-cells expressing an antibody (usually surface expressed in these
immature B-cells) reacting against self antigens are deleted by apoptotic
mechanisms.
• The antigen-specific naive B-cells migrate from the bone marrow and
populate the follicular centres of lymph nodes and other lymphoid tissues
waiting to react to passing antigens which bind to their surface membrane
bound antibody.
B CELLS
• Naive B-cells to the antibody binding of its specific target antigen - the
primary B-cell - replication of genetic clones - antibody factories (plasma
cells), the antibody - monoclonal antibodies.
• A few of the daughter cells will not be plasma cells and will migrate to the
spleen and lymph nodes as memory B-cells.
B CELLS
Genetic rearranging occurs within the component domains that make up an antibody, both
antigen binding Fab portions and the structural Fc domains that determine whether the
immunoglobulin is as an IgM, IgA, IgG, IgE or IgD subtype, produced by this gene
rearrangement.
IMMUNOGLOBULINS
foamy body immunology
Ko ed IGG s is weak
IGG
your
-
the
↳
taking
Dominant class of antibody

Vibrio pharahaemolytieus
-
feit to detect -7
Agriculture ← BMS → Pharmaceutical -
A-
gram
-
negative marine
. v
\ development bacterium
Epitope
(
Innmramglagy
) U
monoclonal ( determinate)
ekingCasandra
atom
Antigone
-
: =
Whole
polyclonal eta
doing Ag
V -
:
=
( Arthritis )
molecular diagnoses Cancer. . . . .
. .
.
2¥
.
Antibodies
→ PIC -
Ab - s others (false positives
↳ Me -
Ab → VP (
specifies
IGA
Crosses into mucous membrane secretions

IGD
Found predominately on lymphocyte membranes

IGE
• Allergy specific Ig,

• Designed to work in defence of nematode infections
IGM
Produced first to response to a new immune

antigen
VACCINATION - SUCCESS T -
cell and B -
cell
memory
-
?
because B cell neutralise
antigen
-
→
MONOCLONAL ANTIBODY
MONOCLONAL ANTIBODY STRUCTURES
A VARIETY OF ANTIBODY FRAGMENTS
Applications
To detect the presence and quantity of this
substance, for instance in a Western blot test (to
detect a protein on a membrane) or an
immunofluorescence test (to detect a substance
in a cell).
Useful in immunohistochemistry which detect

antigen in fixed tissue sections.
Monoclonal antibodies for cancer treatment
Monoclonal antibodies that bind only to cancer cell-specific

antigens and induce an immunological response against the
target cancer cell.
Such mAb could also be modified for delivery of a toxin,

radioisotope, cytokine or other active conjugate; it is also possible
to design bispecific antibodies that can bind with their Fab regions
both to target antigen and to a conjugate or effector cell.
Every intact antibody can bind to cell receptors or other proteins

with its Fc region
Drug
Monoclonal antibody
Cell surface protein
Target cell
Prodrug
drug
Enzyme
Treatment →
target
§ heart
s
cancer
Monoclonal antibody
Cell surface protein
Target cell
IMMUNITY TO There are three main forms of bacterial
BACTERIA immunity:
1. Immunity to bacterial toxins
2. Immunity to extracellular bacteria
3. Immunity to intracellular bacteria
Immune evasion via multiple antigenic variants of
microbes (serotypes).
Immune evasion via
multiple antigenic
variants of microbes
(serotypes).
Immune evasion via
multiple antigenic
variants of microbes
(serotypes).
Antibody-mediated immunity
• Antitoxins
• Antibodies: acquired by immunization or previous infection
or given passively as antiserum, are able to neutralize
bacterial toxins.
• Quantity
• Faster produced than toxin
Previous exposure -----Immunological memmory

Immunization
IMMUNITY TO CANCER
Humans have 100 or so specialized genes that control the
growth of cells
o Mutation-à a single DNA base may change or whole

sections of the message are lost.
o Virus oncogenes are inserted into the DNA-à Harmful
mutation
Adoptive
transferof
tumor specific
T cells
Immunodiagnosis
o Alpha-Fetoprotein
o Beta-subunit of human chorionic gonadotropin
o (B-HCG)
o Prostate-specific antigen (PSA)
o CA 125
o Radio-labeled monoclonal antibody B72.3
o Carcinoembryonic Antigen (CEA)
o Protein-polysaccharide complex in colon carcinomas
o Immunoassay can detect increased levels in blood
o Specificity is low in certain cases, such as heavy cigarette smokers, others
Diagnostics
• Ideal Tumor Marker

1. Specific for tumor type.
2. Released only in response to tumor.
3. Results proportional to tumor mass.
4. Quantitatively reflects tumor response.
5. Elevated with low tumor burden.
Prognostic roles of tumor markers
Immunological related
diseases
Psoriasis
Type 1 diabetes do
immune
systems
Pemphigus vulgaris
Autoimmune- hepatitis
Rheumatoid arthritis
vieunldiop
Laboratory tests evaluating the immune system
o C-reactive protein
o Complement C3
o C4 Immunoglobulins
o IgE
o Neutrophil respiratory burst
o T-cell proliferation
o Neutrophils
o Eosinophils
o CD4 T cells
o Rheumatoid factor and antiCCP autoantibodies
o Double-stranded DNA antibodies
o Acetylcholine receptor antibodies
o Raised levels indicative of infection or inflammation
o Low levels indicate consumption in immune complex disease
o Low levels indicate antibody deficiency, usually due to underlying disease
or immunodeficiency
o Elevated levels, particularly IgM, indicate acute infection
o Raised levels in autoimmunity, can pinpoint allergen specific IgE responses
o Absent in immune deficiency chronic granulomatous disease
o Low in primary T-cell immunodeficiencies
o High levels in bacterial infections low in secondary immunodeficiency
o High levels in parasite infections or allergic reactions
o Low levels in HIV infections
o Rheumatoid arthritis
o Systemic lupus erythematosus (SLE) Myasthaemia gravis
•Immunoassay
•Colorimetric protein and specific immunoassay
•Immunoassays
•Functional assay
•Functional assay Haematological cell count
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IMMUNOLOGY

Lymphatic system to the pressurized

• Immature cells - T-lymphocytes - Bone marrow - Thymus as thymocytes - T-cell receptor.

Dominant class of antibody

Crosses into mucous membrane secretions

Found predominately on lymphocyte membranes

• Allergy specific Ig,

Produced first to response to a new immune

Useful in immunohistochemistry which detect

Monoclonal antibodies that bind only to cancer cell-specific

Such mAb could also be modified for delivery of a toxin,

Every intact antibody can bind to cell receptors or other proteins

Cell surface protein

Cell surface protein

Previous exposure -----Immunological memmory

o Mutation-à a single DNA base may change or whole

• Ideal Tumor Marker

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