IMMUNOLOGY-SEROLOGY REVIEW NOTES
Natural immune - aka innate, inborn, non-adaptive immune system
system - ability of the body to resist infection by means of
normally present body function
- non-specific and non-adaptive immune response, same
response to all antigens. No memory cells formed
Physical barrier first line/external immune defense examples
Biological barrier
Chemical/Humoral
barrier
unbroken skin physical barriers examples
mucous membrane
ciliary action
normal flora biological barriers example
microorganisms that prevent penetration, colonization
and facilitate elimination of foreign microorganisms
S. aureus normal flora in skin
Lactobacillus normal flora in vagina
E. coli normal flora in stomach
Lysozyme chemical/humoral barriers examples
Pepsin
Lactoferrin
Acidity
Lysozyme cleaves cell wall of certain g+ bacteria
Pepsin digest bacterial surface protein
Lactorferrin binds iron which is essential for bacterial growth
pH 1 stomach acidity
pH 5.5 – 5.6 skin acidity
pH 5 vagina acidity
Cellular components Second line/internal immune defense examples
Humoral components
Phagocytes cellular component examples of second line/internal
APCs immune defense
Mast cells
NK cells
Neutrophils examples of phagocytes
Basophiles
Eosinophils
Monocytes
Macrophage
Neutrophils most effective phagocytosis
Dendritic cells examples of APCs
Macrophage
B cells
Dentritic cells most effective phagocyte followed by neutrophils
Langerhans cells dendritic cell in skin
Interdigitating dendritic cell in secondary lymphoid organs and thymus
dendritic cells
Interstitial dendritic dendritic cell in major organs
cells
Kupffer cells macrophage in liver
Microglial cells macrophage in brain
Mesangial cells macrophage in kidneys
Alveolar cells macrophage in lungs
Osteoclast macrophage in bone
Splenic macrophage in spleen
macrophage/Littoral
cells
Mast cells derived from mesenchyme
histamine granules in mast cells
Type 1 hypersensitivity mast cells are more effective to
NK cells attacks virally infected cells and tumor cells
perforins NK cells secretes ____ and _____ to kill virally infected
granzymes cells and tumor cells
ADCC NK cells kills infected cells through
recognition of stress
protein combined with
absence of inhibitory
signals
Killer Cell examples of inhibitory receptors
Immunoglobulin-line
receptor (KIR)
ILT/LIR
CD94/NKG2A
CD16 & 56 NK cells do not express CD marker for either T and B
cells but express ___ and ____
NK cells it bridges the innate and adaptive immune response
Lymphokine Activated NK cells are also called ____ when expose to IL-2 and IFN-
Killer Cells (LAKs) y
Inflammation humoral component examples of second line/internal
Complement immune defense
Cytokines
Phagocytosis
Phagocytosis engulfment and destruction of microorganism or damage
cells
ICED steps of phagocytosis
Initiation
Chemotaxis
Engulfment/Ingestion
Digestion/Killing
Initiation initiated as a result of tissue damage, either trauma or
as a result of microorganism multiplication
Chemotaxis process by which cells tend to move in a certain
direction under the stimulation of a chemical substances
known as chemotaxin
antibodies chemotaxins include
CRP
C5a
random without the influence of chemotactic substances, cell
motion is
Boyden chamber test for chemotaxis
Positive chemotaxis migration is forward the site of which chemotaxis
Negative chemotaxis migration is away from the site of which chemotaxis
Adhesion receptors of the innate immune system recognized
Pathogen Acquired Molecular Pattern (PAMPs) through
Pattern Recognition Receptor (PRR)
Toll like receptor Types of PRR
Calcium dependent,
lecithin/C-type lecithin
receptor/CLR
Scavenger receptor
Toll like receptor toll from drosophilia fly/fruit fly
TLR1 toll like receptor for mycobacteria
TLR2 toll like receptor for targeting teichoic acid of g+ bacteria
TLR4 toll like receptor for targeting LPS (lipopolysaccharide) g-
bacteria
Calcium dependent, PRR, macrophage mannose receptor
Lecithin/C-type
Lecithin Receptor/CLR
Scavenger receptor PRR, recognizes anionic polymers and protein
Engulfment/Ingestion phagocytes engulf foreign matter through membrane
invagination and eventually formation of a
phagosome/endosome
S. pneumoniae bacteria that prevent engulfment process due to the
H. influenzae presence of large capsules
N. meningitidis
Opsonins either antibodies or complement interact with surfaces
of bacteria, speeding up phagocytosis
Digestion/Killing hydrolytic enzymes and peroxidase fused with the
phagosome, forming phagolysosome, degrading and
rupturing it. Cells become degranulated as foreign
materials are digested.
Respiratory burst NADPH oxidase enzyme activity leads to formation of
Reactive Oxygen Species/ROS
O2 part of oxygen-dependent pathway
OH Reactive Oxygen Species (ROS)
Singlet OH
H2O2
O2 (superoxidase) highly toxic ROS
H2O2 (hydrogen most important ROS
peroxidase)
Myeloperoxidase leads to the production of hypochlorite
system
Defensin part of oxygen independent pathway
Cathepsin G
Lactoferrin
Lysozyme/Muramidase
Nitric oxide
Defensin cleaves bacterial cell membrane
Cathepsin G are proteases that cleaves proteins in the cell
Lysozyme/Muramidase cleaves bacterial cell wall
Nitric oxide produced by activated macrophage
Inflammation body's overall reaction to injury or invasion by an
infectious agent
Rubor Signs of inflammation
Calor
Dolor
Tumor
Functio Laesa
Rubor redness, erythema, first sign of inflammation
Calor heat
Dolor pain
Tumor swelling/edema
Functio Laesa loss of function
Acute Phase Reactants normal serum constituents that increase rapidly by 25%
because of infection, injury or trauma to the tissues
CRP examples of acute phase reactants
Serum Amyloid An
A1-antitrypsin
Fibrinogen
Haptoglobin
Ceruloplasmin
C3 (complement)
Serum amyloid A Acute phase reactant with these function:
Activates monocytes and macrophages
A1-antitrypsin Acute phase reactant with these function:
Protease inhibitor
Fibrinogen Acute phase reactant with these function:
Clot formation
Haptoglobin Acute phase reactant with these function:
binds hemoglobin
Ceruloplasmin Acute phase reactant with these function:
binds copper and oxidizes iron
C3 (complement) Acute phase reactant with these function:
opsonization, lysis
C-reactive protein originally thought to be an antibody to the C-
polysaccharide of the pneumococci
best indicator/most widely used indicator of acute
inflammation
increased in bacterial infections, viral infection,
rheumatoid fever, malignant diseases, tuberculosis
Reverse Passive Principle of CRP
agglutination
Serum amyloid A It is associated with HDL cholesterol, activates
monocytes, and macrophages
Found to be increased significantly more in bacterial
infections than in viral infections
Cytokines Polypeptide products of activated cells that
control/regulate various cellular response thereby
regulate immune response
Interferons A group of cytokines discovered in virally infected
cultured cells that interfere with viral replication, virus
non-specific but host specific
Leukocyte IFN Other name for IFN-a
Type 1 What type of interferon is IFN-a, IFN-b?
Virus induced What type of culture is IFN-a?
leukocyte
Null lymphocyte/NK Producer cells for IFN-a
cells
IFN-a, IFN-b Which IFN has the following function?
Anti-viral
Increases class I MHC expression
Activates NK cells
Kaposi sarcoma Clinical application of IFN-a
Hepatitis
Epithelial fibroblast IFN Other name for IFN-b
dsRNA induced What type of culture is IFN-b?
fibroblasts
Fibroblast Producer cells for IFN-b
Epithelial cells
Macrophages
Multiple sclerosis Clinical application of IFN-b
Immune IFN Other name for IFN-y
Type 2 What type of interferon is IFN-y?
Immunologically What type of culture is IFN-y?
stimulated lymphocyte
Th1 cells Producer cells for IFN-y
NK cells
IFN-y Which IFN has the following function?
Activation of macrophage
Increased expression of class I and II MHC molecules
Increased antigen presentation
Stimulate the cytolytic activity of NK cells
Antagonistic to IL-4
Cachectin Other name for TNF-a
Lymphotoxin Other name for TNF-b
Neutrophils TNF-a is produced by
Monocytes
Macrophage
NK cells
Activated T cells
T cells (CD 4+ and TNF-b is produced by
CD8+)
B cells
Local inflammation TNF-a functions
Endothelial activation
Killing TNF-b functions
Endothelial activation
Adaptive immune aka acquired, specific immune system
system anamnestic immune response, which results to a more
effective response to reinfection and is characterized
with the formation of memory cells
T cells Cellular component of adaptive immune defense
B cells
Plasma cells
Antibodies Humoral component of adaptive immune defense
Lymphokines
Infection Part of active natural adaptive immunity
Vaccination Part of active artificial adaptive immunity
Colostrum Part of passive natural adaptive immunity
Serum therapy Part of passive artificial adaptive immunity
Smallpox Examples of live attenuated vaccine
BCG
Polio (sabin)
Chickenpox
MMR
Hepa A Examples of inactive vaccine
Polio (salk)
Rabies
Whooping cough
Tetanus Examples of toxoid vaccine
Diptheria
Recombinant HBsAg Examples of synthetic vaccine
Live attenuated less dose vaccine, multiply in body, cannot be
administered to people with weak immune system
Inactivate vaccine high dose vaccine, cannot multiply in body, can be
administered to people with weak immune system
Toxoids vaccine where property that cause disease is removed
IL-1 Secreted by: monocytes, macrophage, dendritic cells
Action: Inflammation, fever, initiation of acute-phase
response, and regulation of hematopoiesis
IL-2 Secreted by: T cells
Action: Growth and proliferation of T and B cells
NK and Tc cell activation and proliferation
IL-3 Secreted by: Activated T cells
Action: Hematopoiesis S
IL-4 Aka: B cell growth factor I
Secreted by: Th2, mast cells
Action: Promotion of TH2 differentiation, stimulation of B
cells to switch to IgE production (isotype switching)
IL-5 Aka: B cell growth factor II
Secreted by: Th2
Action: Eosinophil generation and activation, T cell and B
cell growth and differentiation
IL-6 Secreted by: Monocyte, macrophage, endothelial cell,
Th2 cells
Action: Initiation of the acute-phase response, activation
of B cell to plasma cells
IL-7 Secreted by: Stromal cells
Action: Stimulates proliferation of lymphoid progenitors.
Important for proliferation during certain stages of B
cells maturation
IL-8 Secreted by: Macrophage and endothelial cells
Action: Potent stimulator of neutrophils in chemotaxis.
Activates respiratory burst and release of specific and
azurophilic granule contents
IL-9 Secreted by: Th cells
Action: Proliferation of T cells, thymocytes, and mast
cells
IL-10 Secreted by: Th2, monocytes, macrophage
Action: Suppression of Th2 cells, inhibition of antigen
presentation, inhibition of interferon-gamma
TGF-B Secreted by: T cells, macrophages, other cells
Action: Inhibition of both T- and B- cell proliferation,
induction of IgA inhibition of macrophages
IL-1 Proinflammatory cytokines
IL-6
IL-8
IL-15
IL-18
TNF-a
IL-10 Anti-inflammatory cytokines
TGF-13
IL-13
IL-35
Bone marrow Primary lymphoid organs
Thymus
Bone marrow site of hematopoiesis
site of B cell maturation
Bursa of fabricius: Birds
Thymus site of T cell maturation
progenitor cells form bone marrow migrate to thymus
and differentiate under the influence of thymosin
Lymph nodes Secondary lymphoid organs
Spleen
MALT
Cutaneous immune
system
Lymph nodes traps antigen entering from subcutaneous
Cortex B cells location in lymph nodes
Paracortex T cells location in lymph nodes
Medulla Macrophage location in lymph nodes
Spleen Traps antigen entering from blood (blood-borne
pathogens)
PALS T cells location in spleen
Follicular area B cells location in spleen
Marginal zone Macrophage and dendritic cells location in spleen
Peyer’s patch Organs part of MALT – Mucosal Associated Lymphatic
Tonsils Tissue
Appendix
Appendix Participate in immunological function and help maintain
normal bacteria flora in the large intestine
Epidermis Organs part of CALT – Cutaneous Associated Lymphatic
Dermis Tissue
Epidermis Has activated keratinocytes and Langerhans cells which
are a special class of APCs
Dermis Has Th, Tc cells and macrophages
B cells Antibody/humoral mediated
Primarily against bacterial infection
Bone marrow Site of maturation of B cells
CD 19 CD markers for B cells
CD 20
CD 21
CD 25
CD 40
MCH class I and II
T cells Cell mediated
Primarily against viral and fungal infections, tumor and
graft rejection
Thymus Site of maturation for T cells
CD 2 CD markers of T cells
CD 3
CD 4
CD 8
Flow cytometry It is an automated system for identifying cells based on
scattering of light as cells flow in single file through as
laser beam
Fluorescence Used of labeled monoclonal antibodies against specific
microscopy surface Ag
Rosette test Use of sheep RBCs to detect T cells by binding to the
CD2 marker; + if there are at least 3 sRBCs that attaches
to a T cells
Ficoll Hypaque Most commonly used method to collect lymphocytes
1.077-1.114 Specific gravity of Ficoll Hypaque
Defibrinated or Sample accepted to be used in Ficoll Hypaque
heparinized ACD
plasma>mononuclear layer of Ficoll Hypaque (top to bottom)
cells>Ficoll
hypaque>granulocyte
s and RBCs
2:1 Normal CD4+:CD8+ ratio
500-1200/uL Normal CD4+ count is
0.5:1 or 1:2 Ratio of CD4+:CD8+ during HIV
<200/uL CD4 during AIDs
CD8 CD marker for Tc, Ts
CD4 CD marker for Th
CD3, 4, 25 CD marker for Treg
CD4, CD8 CD marker for Tm
Tc Destroy virally infected cells, tumor cells, and allografts
through secretion of perforins and granzymes. Also,
activate macrophage through secretion of cytokines (IFN-
y)
Th Activate macrophage, and enhance cytotoxic T cell
response by secretion of cytokines (IL-2). Activate B cells
into plasma cells
Ts, Treg Limit immune response
Tm Circulating immunosurveillance and anamnestic
response
T cell maturation Double negative T lymphocyte (CD4- CD8- CD2+)
Double positive T lymphocyte (CD4+ CD8+ CD2+)
Positive selection – only T cells with both markers survive
Negative selection – cells with strong reaction to self-
markers are deleted
Clonal expansion of Double Positive T cells
Single Positive T lymphocyte, lineage determination
B lymphocyte Pro B cell
maturation Pre B cells
Naïve/Immature B cell
Mature B cell
Activated 3 cells
Plasma cell
CD19, 45R CD marker for Pro B cell
CD19, 20, 21, 35 CD marker for naïve/immature B cell
CD25 CD marker for activated B cells
MHC-1 virally infected cell is recognized by T cytotoxic CD8 +
IL 2 Tc is activated by____ produced by Th cell
Perforins, granzymes activated Tc kills virally infected cell by screening
Perforins Pore forming
Granzymes induces DNA cleavage by enzymes
Th1 cells Produce IFN-y which activates phagocytes to kill ingested
microbes.
Also stimulates secretion of antibodies which further
enhance phagocytosis by opsonization
Th2 cells Produce IL-4 which stimulate the production of IgE and
IgG4
Produce IL-5 which activates eosinophil
Both are important for mast cell degranulation and
destruction of helminths
Human leukocyte Major Histocompatibility complex aka
antigen
Chromosome 6 Genes coding for MHC are found on which chromosome
Haplotype manner Gener coding for MHC are inherited in which manner
HLA B8 Myasthenia Gravis, Addison’s Disease, Grave’s Disease
HLA B27 ankylosing spondylitis/bamboo spine disease
HLA DQ2 Celiac disease, DM I
HLA DQ8 DM I, Celiac disease
HLA DR3 SLE, DM I, Grave’s disease
HLA DR4 RA, DM I
all nucleated cells HLA-A, HLA-B, HLA-C class I found in
A chain Class 1 MHC is composed of
B2 macroglobulin
Role of MHC class I Presents antigens that attack the inside of a cell
(endogenous/cytosolic pathway) to CD8+ T cell
triggering cytotoxic response
Viral infection Class I MHC is important in
Tumar and graft
rejection
HLA-A Classic Class I MHC
HLA-B
HLA-C
HLA-E Non-classic Class I MHC
HLA-F
HLA-G
APCs (B cells, MHC Class II is found in
monocytes,
macrophage, dendritic
cells)
A chain MHC Class II is composed of
B chain
Role of MHC Class II Present antigens found outside the cell
(exogenous/endocytic pathway) to CD4+ cells triggering
antibody production
C2 MCH Class III includes
C4
Factor B
TNF
Mitomycin C or In cellular tissue matching, lymphocytes from donors are
irradiation inactivated by
Trisium (3H) labeled In cellular tissue matching, amount of lymphocyte
thymidine recipient is determined in the presence of
Bone marrow graft Cellular tissue matching is best for
HLA D Class II Cellular tissue matching tests
RFLP (Restriction Molecular tissue matching uses
Fragment Length
Polymorphism)
Complement Complement Mediated Microlymphocytotoxicity
Dependent (Antigen-Level Typing/Phenotyping)
Cytotoxicity (CDC)
1-2 mL ACD or Blood requirement for tissue typing
heparinized blood
Ficoll Hypaque In tissue typing, purified lymphocyte suspension is
obtain by
Eosin Red dye used to visualize the cells in tissue typing
Trypan Blue
Inverted phase Plate are read using _____ microscope, in tissue typing
contrast microscope
Uninjured cells In tissue typing, ____ cells are small, bright, refractile
Injured cells In tissue typing, _____ cells are flattened, large, dark, non
refractile
B cell HLA DD typing requires identification of ___ cell
Nylon wool B cell is separated from the T cell by
Antigens Substance that reacts with antibodies or sensitized T
cells but may not evoke immune response
Immunogen Substances that provoke an immune response
Antigens, immunogens All immunogens are _____ but not all antigens are ______
s
>6 kD Strong immunogen
Protein Have the highest molecular weight and are the best
immunogen
Carbohydrates In the form of glycolipids and glycoproteins are good
immunogen
Nucleic acid, lipids Are nor immunogenic
Activate B cells Immunogens that crosslink surface immunoglobulins can
Activate T cells Immunogens should be processed and combined with
MHC molecules to
Adjuvants Substances that can be mixed with antigens to enhance
and accelerate immune response by protecting
immunogen from degranulation allowing longer response
Alum precipitate An adjuvant that enhances phagocytosis by increasing
the size and prevents rapid escape from the tissue
Squalene An adjuvant derived from shark’s oil.
Used for HIV vaccines that are being developed
Freund’s complete Water in oil emulsion of killed mycobacterium
adjuvant tuberculosis or Bordetella pertussis
Autoantigen Antigen from the host
Syngeneic antigens Antigen from other individuals but the same genome
Alloantigen Antigen from other individuals but within the same
species
Heteroantigens Antigen from different species
Heterophile antigens Antigen that exist in unrelated plants or animals but
either identical or closely related, so that antibody to one
will cross react with antibody to the other
Sequestered antigen Autologous antigen that does not come in contact with
antibody producing cells
Tissue type antigen Antigen naturally present in the tissue
Tissue specific antigen Antigen unique to specific organ A
Autograph Transfer of tissue within the same individual
Isograph/Syngraft Transfer of cells or tissue to a genetically identical
individual
Allograft Transfer of cells or tissue to a genetically non-identical
member of the same species
Heterograft/Xenograft Transfer of cells or tissues to a member of a different
species
Hyperacute graft Within minutes to hours
rejection Humoral
Caused by pre-formed antibodies to donor antigens
Accelerated graft 2-5 days
rejection Cellular-mediated
Caused by previous sensitization to donor antigens
Acute 7-21 days
Cellular-mediated
Allogeneic reaction to donor antigens. Showing
interstitial cellular infiltrates, made mostly by T cells
Chronic graft rejection >3 months
cellular-mediated
Disturbance of host vs graft tolerance showing
arteriosclerosis, fibrosis, narrowing of lumen and scarring
Antibody Specific glycoproteins produced in response to an
antigenic stimulation referred to as immunoglobulins
2 light chains Antibody is a tetrapeptide that is composed of
2 heavy chains
Disulfide bonds Bond that join 2 light chains and 2 heavy chains of
antibody
Links H-H chain and H-L chain but not L-L chain
Function of antibody To neutralize toxic substances
Facilitate phagocytosis
Kill microbes
Combine with antigen on cell surface and thereby cause
destruction of the cell
Ehrlich’s Side-Chain Cells have surface receptors that were present before
Theory contact with antigen. Antigen selects the cell with
receptors specific for it then would break off and enter
the circulation as antibody molecules. New receptor
would form on the surface of the cell.
Clonal selection Lymphocytes are genetically preprogrammed to produce
one type of antibody, and that a specific antigen finds or
selects those particular cells capable of responding to it,
causing it to proliferate
Heavy chain Determines the Ig class
Light chain Either kappa or lambda but can never be present both in
a single antibody
Hinge region Provide flexibility of the antibody due to the presence of
amino acid proline
Variable region Contains the Fab region/Paratope where the antigen
binds
Constant region Contains the Fc region or fragment crystallizable
1 variable A light chain composed of
1 constant domain
1 variable A heavy chain composed of
3 or 4 constant domain
Papain Enzyme used by Rodney Porter to describe Ab structure
Yields 2 Fab portions and 1 Fc portion
Pepsin Enzyme used by Alfred Nisoff
Yield 1 F(ab), and 1 Fc portion
IgG Aka incomplete immunoglobulin
Serum IgG is most abundant in
Secondary immune IgG is the main antibody for
response
IgG1 Best IgG, crossing placenta
IgG2 Short hinge, cannot cross placenta
IgG3 Largest number of disulfide bonds, most efficient IgG in
complement fixation
IgG4 Short hinge, cannot fix complement
Precipitation IgG antibody precipitates in agglutination but best in
Protein antigens IgG antibody best against
IgM Aka macroglobulin/complete immunoglobulin
Primary/early main antibody in _____
usually indicates acute infection
Agglutination IgM antibody effective in ____ and cytolytic reaction
IgA Monomer in serum; dimer in secretions
Predominant in secretions
IgA2 More resistant to bacterial protease
IgD Antibody present in the mature B cell surface
Plays as rile in B cell maturation, differentiation and
immunoregulation
IgE Aka regain
Binds to mast cells and triggers immediate
hypersensitivity, allergic and anaphylactic response
Also plays a role in defense mechanisms to parasites
Isotype Heavy chain that determines the immunoglobulin class
Present in all normal and healthy individuals
Allotype Variation in the constant region. Genetically controlled
alternate forms, not present in all individuals
Idiotype Difference in the variable region that give individual
molecules its specificity
Monoclonal antibody Purified antibodies which are capable of reacting to
specific antigen and are derived from a single parent
antibody-producing cell
Hybridoma Are fused B cells and myeloma cells capable of secreting
antibodies indefinitely
Myeloma cell Is a cancerous plasma cell. The selected myeloma cell
should be non-secreting and are deficient of HGPRT and
thymidine kinase enzymes
PEG Is a surfactant and fusing agent
Thymidine and Is used for DNA production
hypoxanthine
Aminopterin Blocks production of new nucleotides
Uses of monoclonal For diagnosis and treatment of disease
antibodies
Part 2
1 Robert Koch cellular immunity in TB
2 Metchnikoff phagocytosis
3 Karl human blood group antigens
Landsteiner
4 Edelman, structure of antibodies
Porter, and Edelman – ultracentrifugation
Alfred Porter – Papain
Misonoff Misonoff – Pepsin
5 Rosalyn Radioimmunoassay
Yalow
6 Susumo discovered the genetic principle underlying the generation of
Tonogawa antibodies with different specificities
7 Francoise HIV
Barre-
Sinoussi
and Luc
Montagnier
8 Jenner smallpox vaccination
9 Pasteur live, attenuated chicken cholera and anthrax vaccines
1 Salk Polio vaccine
0 Sabin Salk – IM
Sabin – oral
1 Kohler, first monoclonal antibodies
1 Milstein
1 1984 Identification of genes for T cell receptor
2
1 Robert Kaus precipitins
3
1 Chinese variolation to prevent acquisition of smallpox
4
1 Neutrophils earliest and most numerous, respond to most infections
5 (bacterial)
1 Eosinophils neutralize basophil and mast cell products, kill certain parasites
6
1 Basophils participate in anaphylactic or immediate hypersensitivity
7 reactions
1 Monocytes Participate in phagocytosis and antigen presentation
8
1 Mast cells
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