IMMUNOLOGY & SEROLOGY: PRELIMINARIES o Variola Minor – mild form of smallpox

Romie Solacito, MLS3C (a.k.a. Alastrim, Cuban itch, cottonpox,

INTRODUCTION milkpox, whitepox).
Pathogens: Fungi, Parasite, Bacteria, Virus, Carcinogen,  The term “Smallpox” was first used in Europe in
& Pollution the 15th Century to distinguish first from the
Two Types of Immune System “greatpox”/syphilis – causative agent:
1. Innate/Natural – is the ability of the individual to Treponema pallidum subsp. pallidum.
resist infection by means of normally present  Variolation – exposure to a material coming
body functions; do not possess immunologic from a manifested material of infection/disease
memory or no prior exposure required. (example: “smallpox” lesion).
2. Adaptive/Acquired – is a type of resistance that  Chinese (A.D. 1500) – developed a custom of
is characterized by specificity for each individual inhaling powdered crust from smallpox lesion.
pathogen and the ability to remember a prior  1718, Lady Mary Wortly Montagu (wife of
exposure = increased response upon repeated British Ambassador to Turkey) – introduced
exposure; POSSESS IMMUNOLOGIC MEMORY variolation to Europe; inserting smallpox lesion
 Immunology – the study of a host’s reaction when under the skin.
foreign substance are introduced into the body; the  Further refinements did not occur until the late
medically related consequences that arise when 1700s – English doctor discovered a remarkable
these mechanisms either fail or respond in an relationship…
exaggerated form; eliminate non-self-components  Edward Jenner (1700s) – Introduce the Cross-
such as infectious agents Immunity. It is a phenomenon in which exposure
 Antigen – a foreign substance that induces such as to one agent produces protection against
immune response; Macromolecules that are capable another agents.
of eliciting formation of immunoglobulin or o Cowpox (mild in cow) and Smallpox has
sensitized cells in an immunocompetent host. the same antigenic structure.
 Immunogens – Any substance that can induce an  May 14, 1796, Inoculated matter from “cowpox”
immune response; all immunogens are antigen, but lesion to an 8-year-old boy, James Phipps. The
all antigens are not immunogen.
boy developed cowpox infection (mild form) –
 Immunological Tolerance – the failure to mount an
the next day the boy gets better.
immune response to an antigen. This is the failure (a
 July 1796 – Jenner inoculated with matter from
good thing to attack the body’s own protein and
fresh smallpox lesion – no disease developed.
other antigens).
 Vaccination – from the Latin word “vacca”
 Immunity – condition being resistant to infection.
means “cow”. Injection of cellular material to
induce immunity. Cowpox – causative agent:
SIGNIFICANT MILESTONES
Cowpox virus (member of Orthopoxvirus);
 Thucydides – described a phenomenon where
Naturally a disease of cows
individual who recovered from a certain diseases
 Louis Pasteur (Father of Immunology) –
rarely contracted with the same disease again.
Attenuation, achieve by heating. To change; to
weaken = antigen.
Role of “Smallpox - Variola” in the development of
o Develop vaccines against:
Immunology
 Chicken Cholera
 Rabies
 Smallpox- caused by two virus variants:
 Anthrax – causative agent: Bacillus
o Variola Major – serious form of smallpox
anthracis.
 Variolation & Vaccination – these two
procedures were successful in decreasing
 smallpox mortality. World Health Organization o Innate Immunity – natural and non-specific
declared its totality eradication in 1979. o Adaptive Immunity – acquired and specific
IMMUNE SYSTEM: INNATE
Cellular Immunity vs. Humoral Immunity o Refers primarily to anatomical, humoral and cellular
defense that function in the early stages of host
 Elie Metchnikoff (1880-1900) – phagocytosis “eating defense in response to foreign substances.
cells”; macrophage and microphage (Cellular o Block or limit access to the body (i.e. physical
Immunity) barriers)
o Phagocytosis – a process of which a cell o Innate activation of immune mechanism (humoral
“leukocytes” is capable of engulfing or “eating” and cellular)
another cells o DO NOT POSSESS IMMUNOLOGIC MEMORY
 Emil Von Behring & Shibasaburo Kitasato (1890) – o Non Adaptive – no prior exposure required; response
antibodies (Humoral Immunity), protective factors in does not change with subsequent exposure.
the blood and other body fluids. From Plasma Cells o Non Specific – Same for all foreign substance to
from B-Cells, Specific factor; acts only to a certain which one is exposed.
antigen. Innate Immunity influenced by the following factors:
 Almoth Wright – Cellular & Humoral Immunity Nutrition
Age
CELLULAR IMMUNITY V HUMORAL IMMUNITY Fatigue
Stress
 Cellular Immunity – Immune Cells: Genetic determinants
o White Blood Cells (BENML) Innate mechanism includes:
o Dendritic Cells  External – 1st line of defense.
o NK Cells a. Anatomical barrier
o Mast Cells b. Resident flora
 Basophil – histamine c. Physiological factors
 Eosinophil – parasitic reaction  Internal – 2nd line of defense.
 Neutrophil – bacteria reaction a. Humoral factors
 Monocyte & Leukocyte – virus & fungi b. Cells
 Humoral Immunity – Immune response involving EXTERNAL DEFENSE
antibodies (Ab). I. Anatomical Barrier
THE IMMUNE SYSTEM a. Skin – keratinization and constant renewal of
 It is composed of wide array of cells, soluble the skin’s epithelial cells assist in the protective
molecules, & tissues with the following function of the skin.
characteristics: i. Staphylococcus epidermidis – releases
o Specificity Phenol Soluble Modulin acts as Antimicrobial
o Memory Peptide that fight other organism.
o Mobility b. Secretions
o Replicability i. Mucus – adhering the nose and nasopharynx
o Cooperation between different cells or cellular ii. Sebum – consists of lactic and fatty acids
products maintain the pH (3-5) of the skin inhibits the
 T-Cells – use for the antigen presentation, the one growth of microorganisms.
who releases lymphokines. c. Earwax – protect auditory canal from infection;
 Primary Role: Surveillance and destruction of targets the gram positive organism.
substances that are foreign to the body (tolerance). i. Lysosomes – attack cell wall of microbes,
 Two Categories of Immune System: especially gram positive bacteria; it digest
 the β (1-4) glycosidic bond between NAM b. Complement System – Series of Serum Protein
and NAG. in immediate inflammation.
d. Saliva, Tears, Mucous Secretions – wash away c. Cytokines – substances release as messengers
potential invaders and also contain for general.
antibacterial and antiviral substances. II. Cellular Factors
e. Cilia – hair like protrusions of the epithelial cell a. White Blood Cells: Neutrophil, Eosinophil,
membranes; the synchronous movement of Basophil, Lymphocyte, and Monocyte
cilia propels mucus – entrapped INFLAMMATION
microorganisms from these tracts.  The overall reaction of the body to injury or invasion
f. Elimination of liquid and substances by certain infectious agent.
i. Urination 1. 1st Objective: localize and eradicate irritant and
ii. Defecation repair the surrounding tissue.
iii. Coughing 2. Stages:
iv. Sneezing  Vascular Response
g. Acidity – vaginal (lactic acid) pH 5; stomach  Cellular Response
(hydrochloric acid) pH 1 (H. pylori can survive).  Resolution and Repair
II. Resident Flora – non-pathogenic organisms in some  Five Cardinal Signs of Inflammation
parts of the body. Lactobacillus acidophilus 1. Heat/Calor
III. Physical Factors: 2. Redness/Rubor
a. Body temperature 3. Pain/Dolor
b. Oxygen tension 4. Swelling/Tumor
c. Hormonal imbalance 5. Loss of Function/Fuctio Laessa
d. Age  Cause of Chemical mediator, histamine
INTERNAL DEFENSE STAGES OF INFLAMMATION
I. Humoral Factors I. Vascular Response
a. Acute Phase Reactants a. Vasodilation – 1st immune response; increases
blood flow to injured site (Hyperemia –
 Redness/Rubor); increases capillary permeability Acute Phase Reactant
(Plasma leakage to tissue – Tumor and Dolor).  Group of glycoproteins associated with acute phase
II. Cellular Response response
a. Chemotaxin – chemical messenger for  Rise at different rates and in varying levels in
chemotaxis response to injury
b. Neutrophils – used for acute inflammation  Increased shortly after trauma
c. Monocytes – transform into macrophage if they  Initiated and sustained with pro-inflammatory
are in tissues; used for chronic inflammation; cytokines
Antigenic Presenting Cell; APR: Synthesis
i. secretes monokines – calls the other  Synthesized rapidly in response to tissue injury
monocytes  Produced primarily by hepatocytes within 12-24hr in
d. IL -1 response to tissue injury.
o Hypothalamic Fever  Elevated 2 to 5 fold in certain diseases.
o Increase in APRs  Stimulated by the following cytokines:
o Stimulates T-cells to produce IL-2; T-cells  Interleukin-1β (IL-1β), interleukin-6 (IL-6), and
induces T-cell proliferation. tumor necrosis factor-alpha (TNF-α)
ACUTE PHASE REACTANTS  Strenuous exercise – can trigger release of APRs
Biomarkers of inflammation C–Reactive Protein (CRP)
 Elevated – Erythrocytes Sedimentation Rates –  Trace constituent of serum
screening for inflammation  Synthesized in the liver (stimulated by IL-6)
o Principles: measures the rate of Red Blood Cells  Discovered by Tillet and Francis (1930)
to settle down at the bottom.  Originally defined by its calcium dependent
 Elevated – White Blood Cells precipitation with the C-polysaccharide of
 Abnormal Serum Protein Electrophoresis – Pneumococcus
polyclonal gammopathy (low concentration of  Useful indicator of disease states
Albumin and high concentration of Gamma).  Physiologic role – binds to phosphocholine
 Elevated Acute Phase Reactants – Two Types: (SUBSTRATE: common constituent of microbial
membrane)
o Positive Acute Phase Reactant – increase during
 Activate the complement cascade
inflammation (i.e. C-RP, Mannose Binding
 Outstanding Characteristics:
Protein, Serum Amyloid A)
o Appears in sera of individuals in response to a
o Negative Acute Phase Reactant – decrease
variety of inflammatory conditions
during inflammation (i.e. Albumin, Transferrin, o Dramatic increase in concentration
and Antithrombin) o Disappears when inflammation subsides
o Appears rapidly after the onset of disease
o May increase 1000x its normal amount
o The fastest responding and most sensitive
indicator of inflammation
o Increases faster than ESR in responding to
inflammation
o Leukocyte count may remain within normal
limits despite infection
 Properties:
o MW = 118 - 120,000 daltons
o Sedimentation rate = 6.5
o Electrophoretic mobility = gamma region
 o Composed of 5 identical subunits approximately damage and in preventing the loss of iron by urinary
21,500 – 23,500 Da each linked in the form of a excretion.
cyclic pentamer  Provide protection against oxidative damage
o 100% protein with amino acids similar to mediated by free hemoglobin, a powerful oxidizing
immunoglobulins agent that can generate peroxides and hydroxyl
o CRP requires Calcium radicals
o Physical properties Fibrinogen
o Thermo-labile (destroyed at 70oC for 30  Accumulates at site of injury
minutes)  Converted to fibrin; Hastens wound healing process;
o Does not cross the placenta Stimulates fibroblast proliferation and growth
o Elevation of CRP above normal Ceruloplasmin (Copper Transporting Protein)
o Indicates tissue damage and/or inflammation  The liver normally takes copper from the
 Current & Potential Uses: bloodstream and puts it into ceruloplasmin proteins.
o The first to increase in presence of active  The ceruloplasmin is then released into blood
inflammation plasma.
 Onset: 4-6 hours  Ceruloplasmin carries copper around your body to
 Peak levels: 48 hours (M: 1.5 mg/L; F: 2.5 the tissues that need it.
mg/L) α-2 macroglobulin
 Half-life: 19 hours  Inhibitor of proteinases involved in inflammatory
 Decrease after postoperative day/recovery reactions.
period
 Can be used to correlate with (ESR, WBC COMPLEMENT SYSTEM
count, SPE)  Series of serum proteins that are normally present
Serum Amyloid A and whose overall function is mediation of
 Synthesized in the liver inflammation.
 Molecular weight of 11,685 daltons  Interacts in a specific way to enhance host defense
 Normal circulating levels are approximately 30ug/ml  First described by Paul Erlich
 Associated with HDL cholesterol
 Major role: promotes opsonisation & lysis of foreign
 Functions of Serum Amyloid A:
substance
o Helps in removing cholesterol from cholesterol-
 Heat–labile series of more than 30 soluble plasma
filled macrophages in tissue injury
proteins
o Involved in the cleaning up of the injured area.
o Some are enzymes or proteinases
o Facilitates recycling of cell membrane
o Major fraction of beta globulins
cholesterol and phospholipids for reuse in
 Part of the humoral component of the Innate
building membranes of new cells required during
immune system
acute inflammation
Alpha 1-antitrypsin o Participates in the INFLAMMATORY RESPONSE
Nomenclature
 Inhibits leukocyte proteases
 Comprises 90% of α1 – globulin band  Capital “C” and a “#” – Example: C1
 Prevents proteases from initiating tissue damage  Small letter after the number – Example: C4b
 Deficiency: Emphesymatous pulmonary disease; o Indicated that the protein is smaller portion of a
Juvenile hepatic disorders large precursor as a result of cleavage by
Haptoglobin protease
 MW – 100,000 daltons; α2 - electrophoretic o Larger – “b” except C2b
mobility; Irreversibly binds to free hemoglobin o Smaller – “a” except C2a
 Increase two – four folds Complement System
 Found in inflammatory processes; Plays an  There are 9 major complement components involve
important role in protecting the kidney from in the activation. Most are produced in the liver
 except C1 (produced by intestinal epithelial cell) and o C5a is released into the body fluids where it
Factor D (produced by adipose tissues) acts as an ANAPHYLATOXIN and
 Macrophages and Monocytes – additional sources of CHEMOTAXIN
C1, C2, C3, & C4 o C5b activates C6 and C7
 The rest of the components – acts as stabilizers and  SECOND MEMBRANE ATTACK UNITS: C6 and C7
control proteins and proteases o C6 binds to C5b thereby stabilizing it
 Jules Bordet – discovered Complement o This complex then attaches to cell surface
THREE COMPLEMENT PATHWAYS o C7 binds next, forming a trimolecular
1. Classical Pathway complex which allows insertion of C7 part of
 Recognition Unit – C1 molecule (C1q, C1r, and the C5b67 complex into the membrane of
C1s); Interlocking enzyme system; stabilized by the target cell.
Calcium Ions  FINAL MEMBRANE ATTACK UNITS: C8 and C9
 Requirement for activation o C8 binds to C7 and forms a small hole in the
o Antibody and antigen interaction membrane of the target cell
o Complement binds to CH2 domain o The pore formed by the binding of C5b678 is
o All IgM and IgG can fix complement small, capable of lysing RBCs but not
o Needs at least 2 monomers of IgG attached nucleated cells
to target cell o For lysis of nucleated cells to be achieved, C9
 First Activation Unit: C4 must bind to the complex
o C1s activates C4 Note: Anaphylatoxins – C4a, C3a, and C5a; Opsonins –
o C4 releases C4a and C4b (excess C3b); Most potent chemotaxin – C5a; C1 Inhibitor
o C4a plays no role in the complement cascade (C1INH) – dissociates C1r and C1a from C1q)
o C4b attaches to receptors on RBCs, bacterial  IgG3 – most efficient Ig that activates
cell membranes and other antigens complement
 SECOND ACTIVATION UNIT:  IgM – pentameric
o C1s also activates C2 after its interaction  Initiator – Antibody and antigen combination
with C4 recognition
o When combined with C4b, C2 releases C2a  Anaphylotoxins – increases vascular
and C2b permeability and can cause edema, swelling and
o C2a binds to C4b in the presence of inflammation.
MAGNESIUM (Mg++) to form C4b2a (C3  Opsonins – helps in coating foreign substance –
convertase) excess C3b
o C2b is labile and decays rapidly  Antibody – binds to epitope of cell membrane of
 THIRD ACTIVATION UNIT: C3 the antigen/microorganism.
o C3 is the most abundant complement  C3 – central molecule of Complement activation
component pathways. It is also the major constituent of the
o C3 converts splits C3 into C3a and C3b complement system and is present in the plasma
o C3b combines with C4b2a to form C4b2a3b at a concentration of 1200ug/mL
(C5 convertase)  Pivotal point for all three pathways – cleavage of
o Represents the most significant step in the C3 to C3b represents the most significant step in
entire process the entire process of complement activation
o C3b also serves as a powerful opsonin 2. Alternative Pathway or Properdin (Stabilizer)
 FIRST MEMBRANE ATTACK UNIT: C5  Lipopolysaccharide
o C5 convertase cleaves C5 into C5a and C5b  Bypasses C1, C4, & C2
 C3 – activates at slow rate by water and plasma
enzymes. Activated at slow rate celllysis due to
 increased water and permeability by osmotic 3. Mannose Binding Lectin (binds to Carbohydrates)
pressure plasma enzymes Pathway
 Factor D – cleaves Factor B  Initiated by microorganisms with mannose or
 C3b – binds to Factor B similar sugars in the cell wall or outer membrane
 Summary: aggregates of IgA, and IgG4; Yeast cell  MASP – Mannose binding Lectin Associated
wall or zymosan; LPS; bypasses C1, C4, and C2 Serine Protein
 MASP-1 activates MASP-2 that cleaves C4 and C2
 MLB – same to C1q

Complement Regulatory Proteins

1. C1 Inhibitors (C1INH) - Controls activity of C1; Binds
to C1 and can dislodge; Bound C1 to immunoglobulin
– C1 activation is halted
2. Factor I - Inhibitor of C4b – cleaves C4b to C4c and
C4d
3. C4 binding protein (C4BP) – destroys bound C4b and
can also displace C2a from the classical pathway C3
Convertase C4b2a
4. Inhibitors of C3 Convertase Formation - Factor I
inactivates C4b and C3b – converts C3b to iC3b;
requires Factor H as cofactor; Factor H and C4b
dissociates C3 Convertases of both classical and
alternative pathways
Regulation of MAC
 S Protein (Vitronectin) – binds the C5b-7 Complex,
thereby preventing its insertion in the cell
membrane forms C5b-9 complex
 Clusterin – also called Sp40 or apolipoprotein;  Gelatinase
prevents insertion of the C5b-7 complex into the cell  Plasminogen activator
membrane (similar function of S Protein)  Acid hydrolases
 Regulatory Proteins – species specific  Normally, half of the total neutrophil population is
Disease Component found in a marginating pool on blood vessel walls,
 C1 – Lupuslike Syndrome; Recurrent Infection while the rest circulate freely for approximately 6 to
 C2 – Lupuslike Syndrome; Atherosclerosis, 10 hours.
Recurrent Infection Eosinophils
 C3 – Glomerulonephritis; Severe Recurrent  12 to 15um in diameter, and they normally make up
Infection between 1 to 3% in non-allergic person
 C4 – Lupuslike Sundrome  Their number increases in an allergic reaction or in
 C5 to C8 – Neisseria infection; PID – pelvic; response to many parasite infections
Waterhouse Friedrichson  The nucleus is usually bilobed or ellipsoidal and is
 C9 – No know Disease often eccentrically located
 C1-INH – Hereditary Angioedema  Primary Granules
 Factor H & Factor I – Recurrent Pyogenic o Acid phosphatase
Infection o Arylsulfatase
IMMUNE CELLS – The second line of defense o Eosinophil-specific granules (Major basic
Cellular Defense Mechanism protein, Eosinophil cationic protein, Eosinophil
 Leukocytes or White Blood Cells in peripheral blood: peroxidase, Eosinophil-derived neurotoxin)
Neutrophil, Eosinophil, Basophil, Monocyte, and  These cells are capable of phagocytosis but are much
Lymphocyte. less efficient than neutrophils.
Neutrophil  Their most important role is neutralizing basophil
 Polymorphonuclear Neutrophilic (PMN) Leukocyte and mast cell products and killing certain parasites.
 Represents approximately 50 to 70 percent of the  Mechanism of Action – Parasite Killing
total peripheral white blood cells. o Does not recognize helminths directly, rather via
 These are around 10 to 15um in diameter, with a intermediary molecule, IgE antibody bound to
nucleus that has between two and five lobes. the helminth.
 They contain a large number of neutral staining o Has FcƐR
granules (pink), which are classified as primary, Basophil
secondary, and tertiary granules.  Less than 1 percent of all circulating leukocytes
o Primary Granules or Azurophilic Granules  The smallest of the granulocytes, they are between
 Myeloperoxidase 10 to 15um in diameter and contain coarse, densely
 Elastase – damage host tissue staining deep-bluish purple granules that often
 Proteinase 3 obscure the nucleus.
 Lysozyme – use to target bacteria cell  Constituents of these granules are histamine, a small
 Cathepsin G amount of heparin, and eosinophil chemotactic
 Defensins – increase membrane factor-A, all of which have an important function in
permeability inducing and maintaining immediate
o Secondary Granules hypersensitivity reactions.
 Collagenase  IgE, the immunoglobulin formed in allergic reactions,
 Lactoferrin – use for Iron binding binds readily to basophil cell membranes, and
 Lysozyme – use to target bacteria cell granules release their constituents when they
 Reduced nicotinamide adenine dinucleotide contact an antigen.
phosphate (NADPH) oxidase
o Tertiary Granules
Mast Cells ORGANS MACROPHAGE
 Resemble basophils, but they are connective tissue Liver Kupffer Cells
cells of mesenchymal origin. Lung Alveolar Macrophages
 Widely distributed throughout the body and are CNS Microglial
larger than basophils, with a small amount around Fat Preadipocytes
nucleus and more granules. Kidney Mesangial
 Long life span of between 9 and 18 months. Bone Osteoclast
 The enzyme content of the granules helps to Blood Monocyte
distinguish them from basophils, as they contain acid Bone Marrow Promonocyte + Monocytes
phosphatase, alkaline phosphatase, and protease. Lymph Node Lymph Node Macrophage
 Plays a role in hypersensitivity reaction by binding Spleen Splenic Macrophage
IgE, like basophil. Synovial Fluid Synovial A Cells
Monocytes Connective Tissue Histiocytes
 The largest cells in the peripheral blood, with a
diameter that can vary from 12 to 22um. Dendritic Cells
 One distinguishing feature is an irregularly folded or  Resembles nerve cell dendrites, their main function
horseshoe-shaped nucleus that occupies almost ½ of is to phagocytise antigen and present it to helper T-
the entire cell’s volume lymphocytes (lymphoid organs) to initiate the
 The abundant cytoplasm stains a dull grayish blue acquired immune response.
and has a ground-glass appearance due to the  They are the most potent phagocytic cell in the
presence of fine dust-like granules tissue.
 These granules are actually of two types, (1) contains PHAGOCYTOSIS
peroxidase, acid phosphatase, and arylsulfatase;  The reason why cells of the Innate Immune System
this indicates that these granules are similar to the are consider to provide non-specific immunity is due
lysosomes of neutrophils. (2) Contain Beta- to the nature of their receptors
gluconidase, lysozyme, and lipase, but no alkaline  The cells of the innate are able to recognize
phosphatase. destructive molecular structures that are
 Digestive vacuoles may also be observed in the synthesized by foreign pathogens.
cytoplasm Toll-Like Receptors
 They stay in peripheral blood for up to 70hours, and  Toll is a protein originally discovered in the fruit fly
then they migrate to the tissues and become known Drosophila, where it plays an important role in
as macrophages. antifungal immunity in the adult fly.
Macrophages  Very similar molecules as found on human
 All tissue macrophages arise from monocytes, which leukocytes, and some non-leukocyte cell types, and
can be thought of as macrophage precursors there are called Toll-Like Receptors
 As the monocyte matures into a macrophage, there  The highest concentration of these receptors occurs
is an increase in endoplasmic reticulum, lysosomes, on monocytes, macrophages, and neutrophils
and mitochondria  There are 11 slightly different TLRs in humans
 Unlike monocytes, macrophages contain no  Each of these receptor recognize a different
peroxidase. microbial product
 They functions include microbial killing, tumorcidal  Once a receptors binds to its, particular substance,
activity, intracellular parasite eradication, or ligand phagocytosis may be stimulated
phagocytosis secretion of cell mediators, and antigen  Thus, they play an important role in enhancing
presentation. natural immunity
 Macrophages have specific names according to their
particular tissue location
  Phagocytes have Toll Like Receptors – natural
receptors that detects pathogen product
 Primitive Pattern Recognition – recognizes
Carbohydrates and Lipids produced in
microorganism
 Steps of Phagocytosis
o Physical contact between the Leukocyte and the
foreign particle
o Formation of Phagosome
o Fusion with cytoplasmic granules to form a
Phagolysosome and
o Digest and release

Phagocytosis
 Direct Phagocytosis
o No need for opsonin
o Via Primitive Pattern Recognition Receptor
(PPRR) or Toll Like Receptor
o Engulfment
 Indirect Phagocytosis
o Enhanced by oposonization
o Via opsonins: Antibody, Complement, and CRP
o Cell Surface Receptor; RCR, Complement

 Physical contact occurs as neutrophils roll along until

they encounter the site of injury or infection
 They adhere to receptors on the Endothelial Cell
Wall of the blood vessels and penetrate through to
the tissue by means of Diapedesis
 The process is aided by Chemotaxis, where by cells
are attached to the site of inflammation by chemical
substance such as Soluble Bacterial Factors,
Complement, C-Reactive Protein.
Indirect Phagocytosis (L); Direct Phagocytosis (R)  Chemotaxis – a change in the direction of movement
 Oposonins – “to prepare for eating” and serum of a motile cell in response to a concentration
proteins that attached to a foreign substance and gradient of a specific chemical chemotaxins.
help prepare it for phagocytosis. o Positive – towards the stimulus
 Phagocytic cells have receptors for antibodies and o Negative – away from the stumulus
for complement components, which aid in contact  Chemotactic Factors: Antibodies, Complement
and in initiating ingestion. Fragments, Bacterial Factors, Chemotactic Cytokines
 (without these chemotactic factors cell motion is  Exocytosis – residual bodies containing indigestible
random) materials are excreted as waste
 Digestion Cytopepsis:
o 1st Mechanism LYMPHOID SYSTEM
 Granules in the phagocytic cytosol migrate –  The key cell involved in the immune response is the
fused with the phagosome to form lymphocyte. Lymphocytes represent between 20 and
phagolysosome 40% of the circulating leukocyte.
 Degranulation of neutrophil lead to releases  These cells are unique, because they arise from a
of: hematopoietic stem cell and they are further
1. Lactoferrin – binds Iron differentiated in the primary lymphoid organs.
2. Lysozyme – Target bacterial cell  Lymphocytes are segregated within the secondary
3. Defensin – increase membrane organs according to their particular functions. T-
permeability Lymphocytes are effector cells that serve a
4. Elastase – damage host tissues regulatory role and B-Lymphocytes produces
o 2nd Mechanism antibody.
 Activation of Enzymatic Complex, NADPH Primary Lymphoid Organs
oxidase, present in the phagosome  Bone Marrow
membrane via the Hexose monophosphate o All lymphocytes arise from pluripotential
pathway. hematopoetic stem cells that appears initially in
 Respiratory Burst: Oxygen Radicals the yolk sac of the developing embryo and are
1. O2 – highly toxic to microorganism later found in the fetal liver.
2. H2O2 – an important bactericidal agent, o Assumes this role when the infant is born
more stable than the others o Main source of hematopoietic stem cells, which
3. HOCl – hypochlorite radical, a powerful develop into erythrocytes, granulocytes,
oxidizing agent. monocytes, platelets, and lymphocytes
o Lymphocyte precursors are further developed in
the primary lymphoid organs.
o Functions as the center for antigen-independent
lymphopoiesis.
o In humans, B cell maturation takes place within
the bone marrow itself.
 Thymus
o T cells develop their identifying characteristics in
the thymus, which is a small, flat, bilobed organ
found in the thorax, or chest cavity, right below
the thyroid gland and overlying the heart.
o Diminishes in size, it is still capable of producing
T lymphocytes until at least the fifth or sixth
decade of life.
o Site of T Cell development; secretes Thymusin
(Facilitated proliferation and differentiation of
immature T Cells that migrates from the bone
marrow)
o Reticular structure of the Thymus (Capsule)
allows progenitor T-Lymphocyte from the bone
marrow to passes through.
 o Cortex – Immature (Bone Marrow Derived) T  Medullary T Cells, B Cells, and Macrophages
cells become thymocytes  Outer Cortex – outruns macrophages,
o Medulla – contains mature T-cells; only 5 – 10% and Bcells
of the maturing Lymphocytes survive and leave  Folicular dendritic cells are also present
the thymus. 90 – 95% die in the thymus.  Tonsil – respond to pathogens entering the
respiratory and alimentary tracts
Secondary Lymphoid Organs Other Organs
 Once differentiation occurs, Mature T and B  Appendix – an additional location of Lymphoid
lymphocytes are released from the Bone Marrow Tissue
and the thymus and migrate to secondary lymphoid  MALT – found in the GI, Respiratory and Urogenital
organs and become part of a recirculating pool.
 Main contact of cells with foreign antigen takes
place: Spleen - bloodstream, Lymph Node - tissues,
Mucosa – Associated Tissue (MALT), Peyer’s Patches,
Appendix, Tonsils
 Spleen
o The largest secondary lymphoid organ
o It is located in the upper-left quadrant of the
abdomen, just below the diaphragm and
surrounded by a thin connective tissue capsule.
o Large discriminating filter
o Splenic tissue can be divided into two main
types: Red Pulp (destroy old RBC) and White
Pulp (container B-cell that are not yet
stimulated by antigen).
o Responds First to intravenous particulate
antigens
o 50% B Lymphocyte and 30-40% T Lymphocyte
o Major site of Antibody production.
o Highly efficient organ - Contains Mature Naïve B
and T cells
 Lymph Nodes
o Small encapsulated structure
o Located along lymphatic ducts and serve as
central collecting points for lymph fluid from
adjacent tissues.
o Lymphoid filters: found throughout the body
o High Endothelial Venules – passage way of
lymphocytes from the blood stream.
o Secondary Follicles consist of antigen-
stimulated proliferating B cells contains Plasma
Cells and Memory Cells (activated form of B
Cells).
 Generation of B-cell memory is a primary
function of lymph nodes
 Paracortex – contains mostly T Cells and
some macrophages.