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Eastern University Nicanor Reyes Medical Foundation

Microbiology Basic Immunology

Mary Joyce M. Saborrido-Teoxon, M.D.

IMMUNOLOGY
Study of bodys protective and defensive mechanisms against
foreign substances
Discriminate self vs. non self
Antigen-antibody reaction
Eliminate non-self (infectious agents)

Immune System
Collection of organs, tissues, cells and soluble factors that allow
individuals to defend against harmful agents such as viruses,
bacteria, fungi, parasitic organisms, and tumor cells

Two (2) Important Roles of the Immune System:
1. Provides defense mechanism.
2. Identification and destruction of abnormal cells.

HISTORY
Louis Pasteur father of immunology; actually the one who discovered
the rabies vaccine
Edward Jenner discovered small pox vaccine from cowpox

Innate vs. Adaptive

First Line of Defense

a. Physiologic Barriers
Skin
Hookworms can penetrate skin
Tinea corporis
Dermatophytes
b. Chemica Barriers
Lysozymes: chemical barrier/enzyme that dissolves some bacterial
cell wall
Gastric pH of the stomach
c. Biologic Barrier
Nomal flora (Lactobacillus acidophilus)

Second Line of Defense
Phagocytes: effective only for extracellular pathogens
Anti-microbial proteins and inflammatory response

ThirdLine of Defense
Lymphocytes: can kill intracellular pathogens; memory cells

Acquired Immunity: Active vs. Passive
Active actively producing antibody after an exposure to an antigen;
life-long protection
Passive antibody from other source; immediate but short term
protection
Natural naturally made; cant be produce by humans
Artificial immunoglobulins; commercially availabe
Passive Immunity
Natural
Artificial
Placental transfer of IgG
Antibodies
or
immunoglobulins
Colostral transfer of IgA

Immune cells


Active Immunity
Natural
Artificial
exposure to sub-clinical
Vaccination
infections

Professional Phagocytic cells
These cells have enzymatic constituents in their granules to oxidize,
kill, digest, and destroy particulate material that they ingest.
nd
Part of 2 line of defense

1. Mononuclear phagocytes (formerly RES)
A. Monocytes (in the blood)
B. Tissue Macrophages
a. Liver Kupffer cells
b. Lungs Alveolar macrophages/ Dust cells
c. Kidney Mesangial macrophages
d. CNS Microglial cells
e. Lymph nodes Dendritic cells
f. Skin Langerhans cells

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g. Spleen Spleenic macrophages

h. Connective tissue Histiocytes

i. Bone Osteoclast
j. Peyers pathches
k. Tonsils

Functions of M
a. Phagocytosis
Ingestion & killing of microbes
Mostly for extracellular pathogens
STEPS:
Chemotaxis (C5a,LTB4,IL-8,N-formyl methionine)
Diapedesis
Adherence
Engulfment/ Opsonins (C3b, IgG)
Phagosome formation
Fusion
Digestion/Destruction

b. Antigen Presentation
Presentation of antigen in association with class II MHC
proteins to CD4 = helper T cells
APCs:
M
B cells
Langerhans cells
Dendritic cells

c. Cytokine Production
Synthesis and release of cytokines such as IL-1 & TNF, and
chemokines such as IL-8

2. Polymorphonuclear leukocytes (PMNs)
a. Neutrophils (most aggressive phagocyte)
b. Eosinophils (antiparasitic phagocyte)
c. Basophils (secretory cells)

NK cells
LGL / Null cells
Lack T cell receptor, CD3 proteins, and surface IgM & IgD
Thymus are not required for development

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Activity not enhance by prior exposure

Associated w/ ADCC
CD56 & CD16

Functions of NK cells
Kill virus-infected/ Cancer cells
Killing
Non-specific
Not dependent on foreign antigen presentation by class I or II
MHC proteins
Activated by the failure of a cell to present self antigen
Produce perforins & granzymes, w/c cause apoptosis of target
cell

Adaptive Immunity
Antigen Antibody reaction
Cells:
B cells
T cells

Antigens & Immunogens
Antigens
molecules that react w/ Abs
compound that does not necessarily elicit an immune response

Immunogens
molecules that induce an immune response (antibody)
at least 2 antigenic determinant
*All immunogens are antigens, but not all antigens are immunogens.

Two properties of Antigens:
Immunogenecity: ability to induce specific immune response
resulting to formation of antibodies or immune lymphocytes
Antigenecity/ Specificity: the ability to react specifically with the
antibody or cell that caused it to be produced

Parts of AG:
Carrier portion
The bigger part that is responsible for the MW of antigen
>10000 dalton more immunogenic
Epitome/ Antigenic determinant
Determines specificity of antigen, therefore, an antigen w/out
epitope is said to be nonspecific.
Reactive sites (Ab/ TCR)

HAPTENS
Molecule that is not immunogenic by itself but can react w/ specific
antibody
Incomplete Ag
Small molecules (<10,000D)
univalent
HMW nucleic acids
Drugs (e.g. Penicillin)
Cathechol (plant oak)

 CARRIER
A molecule that when coupled to a hapten, renders hapten
immunogenic.
E.g:
Albumin
Globulin
Synthetic polypeptides

Features of molecules that determine immunogenicity
Foreignness
Molecular size
Chemical-Structural Complexity
Antigenic Determinants (Epitopes)

Lymphoid System
A.
Primary/ Central

B.

T & B cells Central L.T. Migrate Peripheral L.T.

Respond to foreign antigens

Flow of lymph

are the sites for generation and early maturation of lymphocytes
(B and T cells)
a. Bone Marrow (Bursa of Fabricus equivalent)
Hematopoeisis
RBC
Platelets
Monocytes
Granulocytes
Lymphopoeisis
B cells
T cell precursors
NK cells
Dendritic cells
Mast cells
b. Thymus
Maturation & Differentiation of T cells

Secondary/ Peripheral

To thoracic
duct

a. Lymph nodes
Major antigen-trapping sites of the body
Filters foreign substances from the tissue fluids and lymph
Central organ for lymphocyte traffic and circulation
PARTS:
CORTEX (Germinal center) B cells
PARACORTEX (Juxtamedullary) T cells

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b. Spleen
Filters foreign substance from the blood
Critical line versus blood borne infections
Eliminates dead worn-out RBCs
2 pulps Red pulp and
White pulp
Marginal zone
Germinal center
PALS (mostly T cells)
Primary follicles (mostly B cells)

Subsets of T cells
1. T helper cell (CD4 marker)
Recognize Ag in association w/ MHC class II
Collaborate w/ B cells to produce Abs
Th1/Th2
2. T cytotoxic cell (CD8 marker)
Has killer function
3. T effector cell
Also called as TdTh cell
Responsible for delayed type of HPS
4. T suppressor cell (CD8 marker)
Involved in presenting autoimmunity activated by Ag

Mucosa-associated Lymphoid Tissue (MALT)
GUT-associated lymphoid tissue (GALT)
Bronchus-associated lymphoid tissue (BALT)

BALT
L.T. beneath the respiratory mucosa and the aggregates of nodular
lymphatic tissues called Tonsils.
Tonsils nodular aggregates of B cells & diffuse areas that contain
mostly of T cells
for airborne and alimentary tract pathogens

T cells
Responsible for foreign antigen recognition or cellular immune
response, which include:
rejection in organ transplantation
regulation of antibody production
secretion of soluble mediators
It has the ability to bind with sheeps RBC forming rosette.

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B cells
Have shorter life span (5-7 days)
Precursors, regulators, and effectors of immunity.
May transform or differentiate into plasma cell to produce
immune antibodies.
CD19, CD20, CD21, CD22, CD35

Comparison of T & B cells

Complement
Composed of several proteins found in human serum (other animal
serum)
Synthesize in the liver (main)
Heat labile (inactivated by heating serum at 56 C for 30 mins)
3 Pathways:
Classic (activated by Ag-Ab(IgM & IgG only!); for IgM w/
1pentameric structure and IgG w/ 2 monomeric structure)
Alternative
Lectin
CLASSIC

LECTIN

Ag-Ab

C1 q, r,s

ALTERNATIVE
Microbial
surface

MBP

MASP

C3

C2

C4

C4b2a/ C4b2b
( C3 Convertase)

C3bBb
(C3 Convertase)

C3

C4b2a3b/ c4b2b3b
(C5 Convertase)

C3bBb3b
(C5 Convertase)

C5

C5bC6C7C8C9
(Membrane Attack
Complex)

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Classic
Activator: Ag-Ab(IgM & IgG only!); for IgM w/ 1pentameric
structure and IgG w/ 2 monomeric structure
st
1 complement protein will be activated C1, usually attached
to the FC portion of Ab is C1q.
C1r surrounds C1q and C1s.
C1s is the most active portion stimulating C4.
C4 will then be cleaved into two (C4a & C4b).
C4a will serve as the anaphylatoxin (assoc. w/
hypersensitivity reaction resulting to increase vascular
permeability stimulating swelling and inflammation).
C4b is the active part and will continue the process.
After C4 activation, C2 will be activated by C1s also.
C2 will be then cleaved into C2a and C2b.
Either C2a or C2b will bind to C4b to become C3
convertase that will activate C3.
C3 will then be cleaved into C3a and C3b.
C3a (anaphylatoxin) and C3b is the active portion that will
have a separate action as the opsonin or can bind to C3
convertase forming C5 convertase that would then
activate C5.
C5 will be cleaved into C5a that will act as the
anaphylatoxin/chemotaxin and C5b will be the active portion
and will stimulate C6C7C8C9 (Membrane attack complex).

Lectin
Activator: MBP (found in the cell wall of gram + bacteria); doesnt
involve Ab, also called as Antibody Independent Complement
Pathway
No C1 activated, but MASP (Mannose Associated Serine Protease)
will act as C1 that will activate C4 and so on

Alternate
Activator: Microbial surfaces
Also Antibody Independent, alternate or shortcut, bypassing C1,
C4, and C2. Automatically activates C3 that will split into C3a
(anaphylatoxin) and C3b (active portion).
Factor B, a unique component produced only in this pathway that
will be cleaved into Ba (no biologic significance) and Bb will attach
to C3b producing C3 convertase activating C3.
C3 will be cleaved to C3a (anaphylatoxin) and C3b will bind to C3
convertase of alternative pathway producing C5 convertase that
will then stimulate C5.
C5 will be cleaved into C5a (anaphylatoxin) and C5b stimulate
C6C7C8C9 (MAC).

Functions of complement:
Anaphylatoxins C3a, 4a, 5a
Chemoattractants- C5a, LTB4, IL-8, bacterial products
Opsonins C3b, IgG
Bacterial cell lysis C5b, 6, 7, 8, 9

Complement Regulatory Proteins

Complement Deficiencies
C1sINH Hereditary Angioedema
C2 Increased incidence of Connective tissue d/o (SLE)
C1/C4/C2 Opsonization not efficient (LAD)
C3 Increased susceptibility to pyogenic infection
C5-8 Recurrent Neisseria infection

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