BIOCHEMISTRY NOTE: The flow of this trans is based

on Dr. Echavez’s lecture incorporated

Immunochemistry Part 1 with information from the Manual 

Dr. Echavez
 Antigen
CASE:
o Any substance (a foreign macromolecule), capable of
An apparently healthy medical student came in due to cough, cold, and on
inducing a specific immune response and reacts by
and off fever for 3 days
binding selectively with the products of that response (a
specific antibody)
DEFINITION OF TERMS o In a physiological context, if the binding of the foreign
 Immunocompetent molecule stimulates an immune response, that molecule
o The ability to develop an immune response following is called an immunogen
exposure to antigen o An antigen may be a soluble substance (toxin or foreign
 Immunocompromised protein), or particulate (bacteria and tissue cell)
o Having the immune response attenuated by o The site on the antigen to which an antibody binds is
administration of immunosuppressive drugs, by termed an epitope
irradiation, by malnutrition and by some disease process  Antibody
(e.g. cancer) o A glycoprotein secreted by plasma cells, which are derived
 Immunodeficient from B lymphocytes (BLs) , a part of the acquired immune
o A deficiency in immune response system
o It is a gamma globulin, called an immunoglobulin
Explanation during lecture: molecule, functioning as recognition elements that bind
Sa immunocompetent, when exposed to an antigen, kaya niyang to foreign molecules and serve as markers signaling
mag-respond doon foreign invasion
Sa immunocompromised, yung immune response nababawasan. o Antibodies have specific amino acid sequence that allow
Mas mahina ang immune response due to different reasons: it to interact only with the antigen that induced their
malnourished siya, you are sick (cancer), taking synthesis
immunosuppressive drugs, you had kidney transplant and your o They have molecular weights between 160,000 and
body do not want to reject it, all these weakens your immune
970,000
response
o They usually constitute about 20% of all the plasma
Sa immunodeficient, everything is working fine except for a
portion of your immune system. For example, in AIDS – ang CD4 proteins
cells ang may problema. The rest of your immune cells are working o Antibodies are found in high levels in plasma and other
normally except for your CD4 cells body fluids
o The specific affinity of an antibody is not for the entire
What is the difference between immunocompromised and macromolecular antigen but for a particular site on the
immunodeficient? antigen called the epitope or antigenic determinant
In immunocompromised, it means across all – lahat (global). In
immunodeficient, isang part lang ang problema (specific) NATURAL IMMUNITY vs. ACQUIRED IMMUNITY
Characteristics Natural Immunity Acquired Immunity
CASE QUESTION: Innate, native or Adaptive or specific
Other names
What is the immune status of the student? nonspecific immunity immunity
Answer: IMMUNOCOMPETENT. The student is healthy and has a normal Appearance in
Present prior to exposure Stimulated by exposure to
relation to
reaction to the antigen to fight it off (coughing, colds, & fever). If the student to antigen antigen
exposure
was said to be immunocompromised, the immune reaction should be lesser
Effect of Increase in magnitude with
which means that if he/she was exposed to the antigen it will already create Not amplified by exposure
exposure each successive exposure
an illness such as pneumonia.
Does not discriminate Specific for distinct
Specificity
Definition of Terms continued… among most antigens macromolecules
 Immunity Involves physicochemical
barriers such as skin and Cutaneous and mucosal
o Defined as resistance to infectious disease Physical
mucous membranes and immune systems; antibody
 Immune system barriers
their associated secreted in mucosal secretions
o The collection of cells, tissues and molecules that mediate products
resistance to infections through recognition, reaction with Circulating
and elimination of antigens (foreign and non-self Complement Antibodies
molecules
substances), that may disturb the homeostasis of the Phagocytes (macrophages,
body Cells involved neutrophils) Lymphocytes
o Immune response is the coordinated reaction of these Natural killer cells
cells and molecules to infectious microbes Soluble Macrophage-derived Lymphocyte-derived
 Immunology mediators cytokines cytokines
o Is the branch of biomedical science concerned with the
study of the immune system and its responses to invading CASE QUESTION:
pathogens. The physiologic function of the immune What branch of the immune system is the first to kick in?
system is to prevent infections and to eradicate Answer: NATURAL IMMUNITY (INNATE IMMUNITY)
established infections

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Immunochemistry Part 1
Dr. Echavez
CASE QUESTIONS:
What cellular components are part of natural immunity?
Answer: PHAGOCYTES & NK CELLS
What is the first immune cell encountered by the pathogen?
Answer: ANTIGEN PRESENTING CELLS
COMPONENTS OF NATURAL IMMUNITY
 Natural immunity’s main effect cells are: macrophages, neutrophils,
dendritic cells, and natural killer (NK) cells
 Main mechanism involved are:
o Phagocytosis
o Release of inflammatory mediators
o Activation of complement system proteins, as well as
synthesis of acute phase proteins
o Cytokines and chemokines
 Phagocytosis
o Begins with adhesion of the phagocyte surface receptors
to the pathogen  it is then internalized into vesicles
called phagosomes  inside the phagocyte, the
phagosome fuses to lysosomes  In the lysosomes,
contents are released with consequent digestion and
pathogen elimination
DENDRITIC CELLS
 Act as a bridge between natural and acquired immunity by being
attracted and activated by elements of natural immunity and permit
TL mobilization of acquired immunity
o DCs capture antigens and become activated and migrate
to regional lymph nodes where they process and present
protein antigen or lipid to T lymphocytes (TLs)
o The captured antigens are processed inside the cell and
presented on its surface, bound to MHC molecules
o They can receive signals from mature NK, NK/T, and TL
cells, and pro-inflammatory molecules (cytokines,
prostaglandins, interferons, and pathogen-associated
molecular patterns)
o DCs contribute to immunological memory by retaining
antigen in lymphoid organs for extended periods
Functions of Dendritic Cells: OAR
 Orchestrates the arrival of other immune cells within the lymph
nodes by secreting chemokines
Chemokines are important because it is the one responsible
for the migration of leukocytes into the site of inflammation
 Antigen-presenting cells (APC) to lymphocytes
o Immature dendritic cells are highly efficient in capturing
antigens
o Mature dendritic cells are very efficient in antigen
presenting to lymphocytes
Immature DCs become Mature DCs when they
capture antigens. So if the Immature DC has no
antigen, it will not mature
 Regulate the activity of differentiation, maturation and functions of
T lymphocytes
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MACROPHAGES
 Monocytes constitutes 3-8% of circulating leukocytes
 If monocytes are in connective tissue or parenchyma of organs, they
give rise to macrophages and myeloid dendritic cells
Functions of Macrophages: PPP
 Phagocytes, act as APC in inflammation
o Monocytes and macrophages are efficient phagocytes,
engulfing pathogens and cellular debris
o Macrophages, unlike neutrophils, can remain in tissue for
months to years
o Aside from its role in natural immunity, macrophages
process and presents antigens (they are also APC) via MHC
molecules, thus inciting the response mediated by TLs
 Potentiates the activation of lymphocytes (TL and BL)
o They potentiate the activation of TL and BL by the
expression of co-stimulatory molecules and release pro-
inflammatory cytokines (Interleukins 1, 6, 12, TNF-α) and
chemokines
 Produce Reactive Oxygen Species (ROS)
o Example of ROS are superoxide anion, hydroxyl radical,
hydrogen peroxide (H2O2), and reactive nitrogen
intermediates whose main representative is nitric oxide
(NO)
o ROS will help in the killing or digestion of whatever is
ingested by the macrophage
Three Subpopulation of Macrophages:
 Activated Macrophage – tumoricidal and microbicidal activity
 Tissue Repair – activated by IL-4, stimulates fibroblasts and
promoting extracellular deposition
 Regulator Macrophage – release of IL-10, an anti-inflammatory
cytokine
OTHER COMPONENTS OF NATURAL IMMUNITY:
 Neutrophils
 Natural Killer Cells
 Mast Cells Will be tackled
 Basophils later in the trans
 Eosinophils
 Complement System
 Chemokines
Question:
How do APCs communicate with the other cells?
Answer: They communicate through the Major Histocompatibility Complex
MAJOR HISTOCOMPATIBILITY COMPLEX
 Major histocompatibility complexes are displayed on the surface of
cells
 They act as “signposts” that serve to alert the immune system if
foreign material is present inside a cell
 The human major histocompatibility complex (MHC) is composed of
a set of highly polymorphic genes called human leukocyte antigen
(HLA) and comprises more than 120 functional genes, of which about
20% are associated with immunity
 In humans, these genes are located on chromosome 6 and are
traditionally divided into classes I, II and III
 Only the genes of class I and class II are involved in presenting antigen
protein to TLs
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Major Histocompatibility Complex continued…..
 The association between autoimmune diseases and MHC genes
reflects the important role of these molecules in carrying out one
cardinal feature of immune response: discrimination of self from
nonself
 Another cardinal feature of immune response is diversity, because
MHC genes must defend against a great diversity of microbes in the
environment, the MHC molecules they encode must present a wide
range of peptides
Class I and Class II MHC Proteins
Class I MHC protein: (A)
 Its α-chain has three extracellular domains α1, α2, and α3, encoded
by separate exons
 It is noncovalently associated with a smaller polypeptide chain,
ß2-microglobulin , which is not encoded within the MHC
 The α3 domain and ß2-microglobulin are Ig-like
 While ß2-microglobulin is invariant, the α-chain is extremely
polymorphic, mainly the α1 and α2 domains
 There are about 20 genes in HLA region class I, and three of them
(HLA-A, B, and C) are called classics. The genes that encode the
classical MHC molecules are highly polymorphic
Class II MHC protein: (B)
 Both chains (α and ß) are polymorphic, mainly the α1 and ß1
domains
 The α2 and ß2 domains are Ig-like, thus, there are striking
similarity between the class I and class II MHC proteins
 HLA class II molecules are encoded by polymorphic genes in MHC
class II complex regions. In the nomenclature of genes in class II,
the first letter indicate the class (D), the second indicates the
family (M, O, P, Q, R)

In both MHC proteins, the two outermost domains interact to form a groove
(peptide binding region) that binds peptide fragments of foreign proteins and
present them to T cells

Both molecules of classes I and II are expressed as heterotrimers in which

two chains are from MHC molecule and the third is the peptide presented to
the TL

Comparison of MHC Class I and II Molecules

Characteristics MHC Class I
 α-chain encoded by the
Detailed Explanation of Picture Above:
genes HLA-A, B, or C,
and a small invariant
(A) Class I MHC protein has only one Parts
chain
transmembrane peptide which is the
 B2-microglobulin
α-chain (boxed in red). You also have
 Peptide
a ß2-microglobulin (boxed in blue)
which is attached noncovalently to
the α-chain. Another part is the Genes have codominance
peptide binding region (boxed in  Each individual may have ß-chain of the same type),
green). 3-6 different types of HLA but
class I on the surface of his heterologous pairing;
Expression cells, encoded by
maternal and paternal
alleles of the HLA-A, B, and
C genes
(B) Class II MHC protein has two
transmembrane peptide which is the α-
chain (boxed in red) and the ß-chain
Found on the surface of all
(boxed in blue). And the last part is the
Location nucleated cells including
peptide binding region (boxed in green)
platelets
Present endogenous
peptides to CD8 TLs, i.e.,
Surveillance peptides derived from
autologous proteins in
cytoplasm
MHC Class II
 α-chain and ß-chains,
both encoded by genes
HLA-DR, DP, and DQ
families
 Peptide
Homologous pairing (an α-
chain of any type [ex: DR
types] is associated with a
there may be
o Depending on the
degree of homozygosity
or heterozygosity, an
individual may develop
on the surface of his
APCs 10 to 20 different
class II molecules
Found on the surface of
antigen presenting cells
(APCs) [BMED]
B lymphocytes,
Macrophages, some
Endothelial cells,
Epithelium of thymus and
Dendritic cells
Present exogenous
peptides to CD4 TLs, i.e.,
derived from proteolysis of
non-autologous proteins in
phagolysosomes

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Dr. Echavez
Exercise: ENDOGENOUS Antigens
What MHC Class protein does NEUTROPHIL has? Class I  These are antigens generated within the cells.
How about MACROPHAGES? Class I and II  The following sequence occurs:
o Why does macrophages have class I? It’s because macrophage is 1. Proteins are degraded into fragments or short peptides
an APC. And APCs are also nucleated. So it means that 2. Displayed at the surface of cell by class I MHC
macrophages and other APCs have both Class I and II MHC
3. Antigenic peptides recognized b CD8 TLs
proteins
4. These CD8 TLs are cytotoxic
How about EOSINOPHILS? Class I 5. Infected cells are destroyed

Explanation during lecture:

MHC Class I Expression: Usually, it is codominantly expressed, meaning you
can have 3-6 different types of the surface of your cells. Galing kay mama at
kay papa. Ibigsabihin, if you inherit from both sides of your parents, and these
(HLA class I) are found on your cells, kapag kailangan mo ng liver or kidney
transplant, sino kaya ang posibleng ka-match mo when you talk about this?
Yung siblings, kasi you inherit from both of your parents. So which means,
yung combination ng HLA mo is a combination of your parents. So kung
kailangan mo ng transplant, hahanap ka ng ka-match sa kapatid mo kasi siya
yung nag-inherit din sa parents mo

Is there a possibility that you may not have a match from your siblings? Yes.
Posible yun kasi you have many combinations – 3 up to 6 different types.
What if your siblings inherited all the same combination? Pero ikaw
nagkataon na yung na-inherit mo eh yung combination na hindi nakikita sa
kanila, then that means that THERE IS A POSSIBILITY that you may not have
a match from your siblings
Your MHC Class I is being checked by your CD8. Your CD8 is a cytotoxic cell.
Ano and trabaho ni CD8? To identify body cells that have become abnormal.
Bakit naging abnormal yung cell? Kasi may infection o kaya naging malignant
siya
So, the function of your MHC Class I interacting with CD8 is to protect you
from infections and cancers. It’s a natural mechanism
MHC Class II Expression: It is being encoded by your D region (HLA-DR, DP, &
DQ). It has 10-20 different combinations. The important thing here is that it
will facilitate EVEN MORE response whenever there is invasion of foreign or
nonself antigens
Sino and taga inspect ng peptide sa MHC Class II? CD4. Bakit kailangan
makipag-cooperate ni MHC Class II kay CD4? Para hindi atakihin ng sarili
nating katawan ang mga cells niya, in other words, it is to prevent your cells
from killing your other cells in the body
NOTE: Just remember the magic number 8.
For MHC Class 1, it is checked by CD8 (1 x 8 = 8)
For MHC Class 2, it is checked by CD4 (2 x 4=8)
Picture Above: Generation of MHC Class I
1. Newly synthesized MHC Class I α-chain is first partnered with calnexin
2. Calnexin will be released when ß2-microglobulin binds to the MHC class I
creating the α chain-ß2 microglobulin complex. Calnexin is then replaced by
calreticulin and tapasin to keep the MHC complex in its properly folded state.
It binds to TAP 1 and 2 via tapasin
3. Proteasome will degrade defective proteins into peptide fragments and it
will be delivered by TAP to the ER, loading it to the groove on the MHC class
I (peptide binding protein)
4. After the peptide fragment bind to groove, the MHC Class I molecule will
be released from TAP and is exported to the cell membrane where it will be
presented to CD8
EXOGENOUS Antigens
 These antigens are inhaled, ingested, or introduced beneath the skin
 It follows the following steps:
1. Antigen engulfed by endocytosis
2. Endosome fuses with lysosome
3. Antigen degraded into short peptides
4. Antigenic peptides displayed at cell surface by class II MHC
5. Antigen recognized by CD4 TLs

ANTIGEN PRESENTATION
 Antigens can be distinguished by their route of entry into the body:
o Inhaled macromolecules (e.g. proteins on cat hairs)
o Ingested macromolecules (e.g. shellfish proteins)
o Introduced beneath the skin (e.g. injected vaccine)

Note: The above mentioned is true for exogenous antigen

 Antigens can be either Endogenous (generated within the cell) or

Exogenous (inhaled, ingested, or introduced beneath the skin)

Explanation on next page…..

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Picture on Lower Right (Page 4): Generation of MHC Class II Alternative/Properdin Pathway
1. Newly synthesized MHC Class II is combined first with li molecule (invariant 
Key features:
chain) to prevent binding of proteins in the ER. If li molecule is not attached o Ability to be spontaneously activated
there, autoimmune response can happen o Unique C3 convertase (C3bBb) – act as amplification
2. Eventually MHC Class II will meet up with a lysosome which digested an loop to generate more C3b → stabilized by Factor P or
exogenous protein into peptides Properdin
3. The peptide fragment will be loaded to the groove of the MHC Class II (CLIP o Factor B cleaved by Factor D
fragment of li molecule on the groove will be released and be replaced by the o C5 convertase: C3bBb3b
peptide fragment)  Activated in two ways:
4. After the peptide fragment bind to groove, the MHC Class II molecule will 1. Spontaneous hydrolysis (“tick over”) of thioester bond
be exported to the cell membrane where it will be presented to CD4 in C3 to form C3(H2O) → abundant in plasma
2. By the action of lectin or the classical pathway
OTHER COMPONENTS OF NATURAL IMMUNITY (continued)  C3b produced binds to Factor B (cleaved by
Factor D to Ba and Bb) → produce C3bBb
CHEMOKINES C3 convertase: C3bBb
 Chemokines is a short cut for chemotactic cytokines C5 convertase: C3bBb3b
 A large family of homologous cytokines structurally responsible for Membrane Attack Complex (MAC): C5b6789
the movement of leukocytes, including their migration from the
blood to sites of tissue inflammation Biological Effects of Complement Fragments:
 They are small polypeptides of 8 to 12 kDa with two internal disulfide Biological Effect Fragment
bonds Vascular Permeability C2a, C4a
 About 50 different chemokines have been identified and classified Activation of Macrophages Bb
Anaphylatoxin (induce activation of mast cells &
into families by the number of location of N-terminal cysteine C5a > C3a > C4a
neutrophils)
residues
Chemotactic activity (stimulates motility and
 The two main family are: adhesion of neutrophils to inflammatory foci)
C5a
1. CC chemokines with adjacent cysteine residues (having 2 Opsonins (enhances the process of phagocytosis) C3b, C4b
cysteines) Promotes clearance of immune complexes which are
2. CXC family, such as IL-8, where these residues are CR1-C3b
carried by RBC and removed by phagocytes in the liver
separated by one amino acid (in between the cysteines is interaction
and spleen
an amino acid) Membrane Attack Complex (promotes osmotic lysis
C5b6789
 Chemokine receptors are expressed on leukocytes, dendritic cells, of target-cell)
and Langerhans cells
CASE QUESTION:
CASE QUESTION:
What is the first responder in natural immunity?
What is the circulating component of natural immunity?
Answer: NEUTROPHILS. How is this possible? They are among the first to
Answer: COMPLEMENT SYSTEM
migrate because they have chemokine receptors

COMPLEMENT SYSTEM NEUTROPHILS

 Synthesized by the liver, macrophages and fibroblasts  Most abundant leukocyte in peripheral blood
 The following are the 3 forms of activation:  Has an important role in the early stages of inflammatory reaction
Mannose-Binding Lectin Pathway (MBL) and sensitive to chemotactic agents
Mannose on the microorganism surface by MCL bound  Are among the first cells to migrate from vessels to tissues attracted
Major activator:
to MASP1 and MASP2 serine protease by chemokines (e.g. IL-8)
C3 convertase: C4b2a  Activated by various stimuli ( e.g. bacterial products, complement
C5 convertase: C4b2a3b proteins (C5a), immune complex, chemokines, and cytokines)
Membrane Attack Complex (MAC): C5b6789 Functions of Neutrophils: PADNet
 Phagocytosis
Classical Pathway o Stimulated by binding of its receptors to opsonins, IgG-
Major activator: Ag-Ab complex (IgM & IgG) Fc, C3b and TLRs
 Involves activation from C1  Antimicrobials
 Requires calcium for activation
 Undergo Degranulation, releasing three classes of granules
 Composed of C1q, C1r, and C1s → recognition unit
1. Primary or azurophilic granules that contain important
o C1q – pathogen sensor
mediators, such as myeloperoxidase, defensins,
o C1r – activates C1s
o C1s – activates C4 and C2 neutrophil elastase, permeability-increasing protein, and
 C1 binds to the Fc portion of IgM and IgG bacterial cathepsin G
 Sequence of activation: C1 → C4 & C2 → C3 → C5 + C6-C9 2. Secondary granules with components specifically
secreted by neutrophils, with lactoferrin is a prime
C3 convertase: C4b2b example
C5 convertase: C4b2b3b 3. Tertiary granules with cathepsins and gelatinases as main
Membrane Attack Complex (MAC): C5b6789 proteins

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Functions of Neutrophils continued…..
 Generate Neutrophil Extracellular Traps (NETs)
o NETs is a web of fibers formed by granular substances and
nuclear components (serine proteases and chromatin)
capable of degrading virulence factors and destroying
extracellular bacteria
o NETs are present in large quantity in inflammatory sites,
acting directly on microorganisms and also serving as a
physical barrier that prevents spreading
NATURAL KILLER (NK) CELLS
 Originate in the bone marrow from a common precursor to TLs
 Makes up 5-20% of mononuclear blood cells
 An important line of natural immunity:
o Recognizing and Lysing cells infected by virus, bacteria
and protozoa, as well as tumor cells
o Recruit neutrophils and macrophages
o Activate dendritic cells, T and B lymphocytes
The expansion and activation of NKs are stimulated by:
o IL-15 – produced by macrophages
o IL-12 – potent inducer of IFN-γ and cytolytic action
Once NKs are activated, the NKs lyse infected and tumoral cells and secrete
proinflammatory cytokines (IL-1, IL-2, and IFN-γ)
Functions of NK Cells: EAR
 Enzymes causing cytolysis:
o Perforins create pores in membrane of target-cells
o Granzymes will penetrate into cells and trigger cell death
by apoptosis
 ADCC (Antibody-Dependent Cell-mediated Cytotoxicity)
o Another effector action of NK is the destruction of cells
coated with IgG, via Fc receptors (FcyRIII or CD16)
 Receptors for activation and inhibition
o Balance between the signals generated by these receptors
determines NK activation
o The inhibitory receptors recognize the self MHC class I
molecules, expressed on the surface of all nucleated cells
o In general, there is dominance of inhibitory receptors,
preventing lysis of host’s normal cells that express MHC
class I
o Infected cells, especially by virus, and tumor cells often
have low expression of MHC class I proteins, becoming
vulnerable to the action of NK
o The tumoricidal capacity of NK is increased by cytokines,
such as interferons and interleukins (IL-2 and IL-12)
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Explanation of Picture on Lower Left: (Based on lecture)
On the picture above (A), it is the action of NK cell on a normal cell. It will have
2 “handshake-like” interaction. First, the activation receptor binds with the
surface-molecule of the cell, and the Second, the inhibition receptor will look
for MHC Class I. Remember that MHC Class I is found in all nucleated cells. If
both receptors have interactions, there will be no enzyme released
On the picture below (B), it is the action of NK cell on a sick cell. As you can
see there is no MHC Class I in the sick cell, therefore there will be no
interaction on the inhibition receptor of the NK cell which will then lead to
releasing of enzymes (perforins & granzymes) that will kill the sick cell
MAST CELLS
 Derived from CD34+ hematopoietic progenitors in bone marrow and
in general, are not found in the circulation
 They are stationary
 They have surface receptors of high affinity, FcεRI, bound to IgE
molecules and are activated by multivalent antigen recognition by
IgE
o Together with basophils, it produces a Type I
Hypersensitivty reaction via FcεRI activation
 Stimuli such as products of complement activation, basic substances,
including some animals’ poisons, certain neuropeptides, and several
physical agents (mechanical trauma, heat, and cold) can activate
mast cells independently of IgE binding
 The binding of bacterial components to TLRs 1, 2, 4 and 6 and other
specific receptors such as CD48, also activates mast cells, leading to
mediators’ release
 After the stimulus, degranulation and release of preformed
mediators (vasoactive amines, proteases, heparin, IL-4, TNF-α, and
GMCSF) occur, followed by release of newly formed mediators
(platelet activating factor, arachidonic acid derivatives, and a series
of cytokines)
 Effects:
o Induces inflammatory cell migration (neutrophils and
macrophages)
o Increased vascular permeability
o Mucus secretion
o Increase GIT motility
o Increase bronchoconstriction
BASOPHILS
 They are circulating
 Are granulocytes derived from precursors in the bone marrow, where
they mature and make up less than 1% of peripheral blood leukocytes
 While not normally present in tissues, they can be recruited to
inflammatory site together with eosinophils
 The granules found in basophils have mediators similar to those of
mast cells
 Basophils also express FcεRI, bind IgE, and are activated by IgE-
antigen complexes and may contribute to immediate
hypersensitivity reactions (Type I Hypersensitivity)
EOSINOPHILS
 Granulocytes and eosinophils are important infection-fighting cells.
And their anti-parasitic action (helminths) is one of the most
powerful and effective
 They are also important in allergic reactions and asthma
 Eosinophils develop in the bone marrow, producing and storing
various proteolytic granules before leaving the marrow
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Eosinophils continued….. In Cognitive phase- the immune system would first determine what belongs
 After maturation, they circulate through the bloodstream in small to the body (self) and what does not belong to the body (nonself)
amounts and can be found in greater numbers in mucosal regions In Activation phase- if the antigen is nonself, there will be activation
 Eosinophils are recruited to sites of parasitic infections by antibody- In Effector phase- here, elimination happens. For example, a chicken pox
dependent cell-mediated cytotoxicity (ADCC), with FcεRI receptor virus would be recognized by the specific antibodies for chicken pox so that if
there will be a binding of receptors, the immune system will stimulate the
participation
memory cells that had a previous encounter with the chicken pox virus, and
o Adhere to pathogens coated with IgE (or IgA) and release
activation occurs. Elimination happens when the memory cells form
their granular content after FcεRI receptors bind to IgE antibodies against the virus to kill it
bound to target antigen
o Production of variety of cytokines such as IL 1, 2, 3, 4, 5,
CARDINAL FEATURES AND PHASES OF THE IMMUNE RESPONSE
6, 8, 13, and TNF-α, and release proinflammatory lipid 1. Specificity
mediators such as leukotrienes (LTC4, LTD4, LTE4) and o Immune responses are specific for distinct antigen
prostaglandins (PGE2) o An epitope or determinant is that part of the antigen that
o Elastase enzymes and the growth factor TGF-ß, growth is specifically recognized by antibodies
factor derived from platelets (PDGF), and endothelial o Epitopes could be polysaccharides or complete proteins
vessel growth factor (VEGF) contributes to tissue 2. Diversity
remodeling o The total number of antigenic specificities of the
 Major Basic Protein lymphocyte is large
o Presents toxicity to parasites o The immune system can discriminate at least 109 antigenic
o Induces degranulation of mast cells and basophils determinants or epitopes
o Activates the synthesis of remodeling factors by epithelial o This is due to variability in the structures of the antigen-
cells binding sites of lymphocyte receptors for antigens
 Eosinophil has cationic protein and neurotoxin are ribonuclease with 3. Memory
antiviral properties o Exposure of the immune system to a foreign antigen
 Eosinophils also producing ROS (Reactive oxygen species). enhances its ability to respond again to that antigen
Peroxidase forms ROS and NO, promoting oxidative stress in target- o Secondary immune responses are usually more rapid and
cell and causing cell death by apoptosis and necrosis larger
4. Self-limitation
Note: Eosinophils, Mast Cells & Basophils have receptors that bind to the FC o All normal immune responses wane with time after
portion of immunoglobulins but the eosinophils is the one that commands antigen stimulation
both the basophil and mast cells to release their mediators o This results from the elimination of the stimulus for
lymphocyte activation since the immune response
Eosinophils releases major basic protein for the mast cells and basophils to
functions to eliminate the antigen
start releasing their mediators
5. Discrimination of self from non-self
o The ability to distinguish between foreign antigens and
PHASES OF IMMUNE RESPONSE
self-antigens
1. Cognitive Phase
o Tolerance is immunologic unresponsiveness
o Consists of the binding of foreign antigens to specific
o Autoimmune diseases are due to abnormalities in the
receptors on mature lymphocytes that exist prior to
maintenance of self-tolerance
antigenic stimulation
2. Activation Phase
o It is the sequence of events induced in lymphocytes as a
REFERENCES
consequence of specific antigen recognition
o Lymphocytes undergo two major changes:  Biochemistry Manual (2018)
a) Lymphocyte proliferation – leads to  Dr. Echavez Recordings
amplification of the protective response
b) Lymphocytes differentiation – antigen-
recognizing B lymphocytes differentiate into
cells that activate phagocytes to kill
intracellular microbes
o Some TLs directly lyse cells that are producing foreign
antigens such as viral proteins
o Helper T cells promote this process of activation
3. Effector Phase
o The stage at which lymphocytes (effector cells) that were
specifically activated by antigens perform the functions
that lead to the elimination of the antigen
o This also involves the participation of non-lymphoid cells
such as neutrophils and substances such as complement
and cytokines

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“Strength In Knowledge” BESHYWAP 7