2. Study of body’s protective and defensive
mechanisms against foreign substances
Discriminate self vs. non self
Eliminate non-self (infectious agents)
IMMUNOLOGY
3. 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
Immune System
4. 1. Provides defense mechanism.
2. Identification and destruction of
abnormal cells.
Two (2) Important Roles of the
Immune System
6. Non-specific Specific
Natural Acquired
1st/ 2nd line 3rd line
Memory- NO Memory- YES
Rxn time- RAPID Rxn time- SLOW
CELLULAR: CELLULAR:
◦ Phagocytes, mø, ◦ Specific B (plasma cells)
monocytes, NK cells, & T cells
Mast cells ◦ APCs
HUMORAL: HUMORAL:
◦ Complement (Alternate) ◦ Abs
◦ Cytokines ◦ Complement (Classic)
◦ Cytokines
Innate Adaptive
7.
8. Mechanical Defenses
1.) Skin
A. Epidermis: Thin outer layer of epithelial tissue.
Contains Langerhans cells, dead cells, and
keratin (waterproof).
B. Dermis: Thick inner layer of connective tissue.
Infections are rare in intact skin. Exceptions:
Hookworms can penetrate intact skin
Dermatophytes: “Skin loving” fungi
First Line of Defense:
Skin and Mucous Membranes
9. • Mechanical Defenses
2.) Mucous Membranes:
Lines gastrointestinal, genitourinary, and respiratory tracts.
Two layers:
◦ Outer epithelial
◦ inner connective layer.
◦ Epithelial layer secretes mucus which maintains moist
surfaces.
◦ Although they inhibit microbial entry, they offer less
protection than skin.
◦ Several microorganisms are capable of penetrating mucous
membranes:
Papillomavirus
Treponema pallidum
Enteroinvasive E. coli
Entamoeba histolytica
First Line of Defense:
Skin and Mucous Membranes
10. I. Mechanical Defenses
3. Lacrimal apparatus: Continual washing and blinking
prevents microbes from settling on the eye surface.
4. Saliva: Washes microbes from teeth and mouth
mucous membranes.
5. Mucus: Thick secretion that traps many microbes.
6. Nose Hair: Coated with mucus filter dust, pollen,
and microbes.
7. Ciliary Escalator: Cilia on mucous membranes of
lower respiratory tract move upwards towards throat
at 1-3 cm/hour.
First Line of Defense:
Skin and Mucous Membranes
11. I. Mechanical Defenses
8. Coughing and sneezing: Expel foreign
objects.
9. Epiglottis: Covers larynx during
swallowing.
10. Urination: Cleanses urethra.
11. Vaginal Secretions: Remove microbes
from genital tract.
First Line of Defense:
Skin and Mucous Membranes
12. ◦ Sebum: Oily substance produced by sebaceous
glands that forms a protective layer over skin.
Contains unsaturated fatty acids which inhibit growth
of certain pathogenic bacteria and fungi.
◦ pH: Low, skin pH usually between 3 and 5. Caused
by lactic acid and fatty acids.
◦ Perspiration: Produced by sweat glands. Contains
lysozyme and acids.
◦ Lysozyme: Enzyme that breaks down gram-positive
cell walls. Found in nasal secretions, saliva, and
tears.
B. Chemical Defenses:
13. ◦ Gastric Juice: Mixture of hydrochloric acid,
enzymes, and mucus. pH between 1.2 to 3
kills many microbes and destroys most toxins.
Many enteric bacteria are protected by food
particles.
Helicobacter pylori neutralizes stomach acid and
can grow in the stomach, causing gastritis and
ulcers.
◦ Transferrins: Iron-binding proteins in blood
which inhibit bacterial growth by reducing
available iron.
B. Chemical Defenses
14. 1. Phagocytosis:
◦ Derived from the Greek words “Eat and cell”.
◦ Phagocytosis is carried out by white blood cells:
macrophages, neutrophils, and occasionally
eosinophils.
◦ Neutrophils predominate early in infection.
◦ Wandering macrophages: Originate from
monocytes that leave blood and enter infected
tissue, and develop into phagocytic cells.
◦ Fixed Macrophages (Histiocytes): Located in
liver, nervous system, lungs, lymph nodes, bone
marrow, and several other tissues.
II. Second Line of Defense
16. These cells have enzymatic constituents in
their granules to oxidize, kill, digest,
and destroy particulate material that
they ingest.
Professional Phagocytic cells
17. 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 Langerhan’s cells
G. Spleen Spleenic macrophages
H. Connective tissue Histiocytes
I. Bone Osteoclast
J. Peyer’s patches
K. Tonsils
1.) Mononuclear phagocytes
(formerly RES)
20. A. Neutrophils (most aggressive
phagocyte)
B. Eosinophils (antiparasitic phagocyte)
C. Basophils (secretory cells)
2. Polymorphonuclear leukocytes
(PMNs)
21. 1. Chemotaxis: Phagocytes are chemically
attracted to site of infection.
2. Adherence: Phagocyte plasma membrane
attaches to surface of pathogen or foreign
material.
Adherence can be inhibited by capsules (S.
pneumoniae) or M protein (S. pyogenes).
Opsonization: Coating process with opsonins that
facilitates attachment.
◦ Opsonins include antibodies and complement
proteins
Stages of Phagocytosis
22. 3. Ingestion: Plasma membrane of phagocytes
extends projections (pseudopods) which engulf
the microbe. Microbe is enclosed in a sac called
phagosome.
4. Digestion: Inside the cell, phagosome fuses
with lysosome to form a phagolysosome.
Lysosomal enzymes kill most bacteria within 30
minutes and include:
Lysozyme: Destroys cell wall peptidoglycan
Lipases and Proteases
RNAses and DNAses
After digestion, residual body with undigestable
material is discharged.
Stages of Phagocytosis
(Continued)
24. Triggered by tissue damage due to
infection, heat, wound, etc.
Four Major Symptoms of Inflammation:
1. Redness
2. Pain
3. Heat
4. Swelling
May also observe:
5. Loss of function
2. Inflammation
25. 1. Destroy and remove pathogens
2. If destruction is not possible, to limit
effects by confining the pathogen and its
products.
3. Repair and replace tissue damaged by
pathogen and its products.
Functions of Inflammation
26. I. Complement System: Large group of serum proteins that
participate in the lysis of foreign cells, inflammation, and
phagocytosis.
Three mechanisms of complement activation:
1. Classical Pathway: Initiated by an immune reaction of
antibodies.
2. Alternative Pathway: Initiated by direct interaction of
complement proteins with microbial polysaccharides.
Both pathways cleave a complement protein called C3,
which triggers a series of events.
3. Lectin pathway
Antimicrobial Substances:
27. Antiviral proteins that interfere with viral
multiplication.
◦ Small proteins (15,000 to 30,000 kDa)
◦ Heat stable and resistant to low pH
◦ Important in acute and short term infections.
◦ Have no effect on infected cells.
◦ Host specific, but not virus specific.
Interferon alpha and beta: Produced by virus
infected cells and diffuse to neighboring cells.
Cause uninfected cells to produce antiviral
proteins (AVPs).
Interferon gamma: Produced by lymphocytes.
Causes neutrophils to kill bacteria.
II. INTERFERONS
28. LGL / Null cells
Lack T cell receptor, CD3 proteins, and
surface IgM & IgD
Thymus are not required for development
Activity not enhance by prior exposure
Associated w/ ADCC
CD56 & CD16
NK cells
29. 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
Functions of NK cells
31. Antigen – Antibody reaction
Cells:
◦ B cells
◦ T cells
Adaptive Immunity
32. Antigens molecules that react w/ Abs
compound that does not
necessarily elicit an immune response
Immunogens molecules that induce an
immune response
at least 2 antigenic
determinant
Antigens & Immunogens
33. 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.
Two properties of Antigens:
34. CARRIER PORTION
◦ The bigger part that is responsible for the MW
of antigen
EPITOPE/ ANTIGENIC DETERMINANT
◦ Determines specificity of antigen, therefore, an
antigen w/out epitope is said to be nonspecific.
Parts of Ag:
35. 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)
Haptens
36. A molecule that when coupled to a
hapten, renders hapten immunogenic.
E.g:
◦ Albumin
◦ Globulin
◦ Synthetic polypeptides
CARRIER
37. Foreignness
Molecular size
Chemical-Structural Complexity
Antigenic Determinants (Epitopes)
Features of molecules that
determine immunogenicity
40. are the sites for generation and early
maturation of lymphocytes (B and T
cells)
Central/ Primary
41. Hematopoeisis
◦ RBC
◦ Platelets
◦ Monocytes
◦ Granulocytes
Lymphopoeisis
◦ B cells
◦ T cell precursors
NK cells
Dendritic cells
Mast cells
A. Bone Marrow (Bursa of Fabricus
equivalent)
42. Maturation & Differentiation of T cells
B. Thymus
43. T & B cells Central L.T. Migrate
Peripheral L.T. Respond to foreign
antigens
trap antigens
are the sites for initiation of most
immune response
provide signals for recirculation of
lymphocytes
Secondary/ Peripheral
44. Major antigen-trapping sites of the body
Filters foreign substances from the
tissue fluids and lymph
Central organ for lymphocyte traffic and
circulation
A. Lymph nodes
45. PARTS:
◦ CORTEX (Germinal center) B cells
◦ PARACORTEX (Juxtamedullary) T cells
Lymph Nodes
46. Filters foreign substance from the blood
Critical line versus blood borne infections
Eliminates dead worn-out RBCs
B. Spleen
47. White pulp
◦ Marginal zone
◦ Germinal center
◦ PALS (mostly T cells)
◦ Primary follicles (mostly B cells)
Spleen
49. 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
BALT
52. Bone Marrow
lymphocytes
.. . .. .
. . …
natural killer
(NK) cell
Postnatal life
53. T CELLS
◦ Pre T cell Immature (thymocyte) Mature T
cell Lymphokines
B CELLS
◦ Pro B cell Pre B cell Immature Mature B
cell Plasma cells Abs
HEMATOPOESIS
54. 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 sheep’s RBC
forming rosette.
T cells
55. 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
Subsets of T cells
56. 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
B cells
57. Comparison of T & B cells
Feature T cells B cells
Antigen receptors Yes Yes
IgM on surface No Yes
CD3 proteins on surface Yes No
Clonal expansion after contact w/ Yes Yes
specific antigen
Immunoglobulin synthesis No Yes
Regulator of Antibody synthesis Yes No
IL-2, IL-4, IL-5 & Gamma interferon Yes No
synthesis
Effector of CMI Yes No
Maturation in Thymus Yes No
Maturation in Bursa or its equivalent No Yes
58. Soluble mediators that serves as the
language for cell communication.
Either immune / non-immune
CYTOKINES/ LYMPHOKINES
59. 1. Interleukins
IL-1 T cell activation factor (MØ)
IL-2 Activates Tc cell
IL-3 Stimulates hematopoietic cells
IL-4 Activates B cell
IL-5 Activates eosinophils
IL-6 Activates B cell
IL-7 Differentiation and Maturation of T & B cell
IL-8 Activates Neutrophils
IL-9 Proliferation of T cells, thymocytes, mast cells
IL-10 Inhibition of cytokine synthesis
IL-11 Regulates hematopoiesis
IL-12 Activates NK cells
60. INF α augments NK cell activity
INF β identical to IL-6
INF major mØ activator
antagonistic to IL-4
augments NK cell activity
2. Interferons
64. Globulin proteins (immunoglobulins) that
react specifically w/ the antigen that
stimulated their production
20% of the protein in the blood plasma
Gamma globulins
Glycoproteins
Part of the adaptive immune response
(humoral immunity)
Antibodies
65. 1. Alloantibody
- produced after exposure to genetically
different or non-self antigens of same
species
2. Autoantibody
- produced in response to self antigen
Types:
67. Pepsin
◦ One large F(ab)2 fragment
◦ LMW peptides
Papain
◦ Two (2) Fab fragments
◦ One (1) Fc
Ig tx:
68. 5 classes/ Isotypes (constant heavy
chain)
◦ IgG: gamma heavy chain
◦ IgA: alpha heavy chain
◦ IgM: mu heavy chain
◦ IgE: epsilon heavy chain
◦ IgD: Delta heavy chain
Major Ig Classes
69. Property IgG IgA IgM IgE IgD
A. Physiologic
% of total Ig in Serum 75 15 9 0.004 0.2
Catabolic rate(1/2 life) 18-23 5-6.5 5-6 2.3 2.8
MW 150 170/ 400 900 190 180
Structure Monomer Mono/di Mono/penta Mono Mono
B. Biological + +2 +4 - -
Agglutinating Capacity
Complement fixing + - +4 - -
ADCC + - - - -
Mediation of allergic - - - +4 -
Response
Placental transport + - - - -
Present in external + +4 ± +2 -
secretion
Receptor on B cell - - + - ?
Opsonization + - - - -
Polymeric form J chain - + + - -
Subclasses 4 2 - - -
70. Four subclasses: IgG1, IgG2, IgG3 & IgG4
Monomer
Highest concentration in plasma
Transported across the placenta
Activates complement
Opsonizes
Main Ab in the secondary immune response
Mediates Antibody-dependent cellular
cytotoxicity (ADCC)
1. IgG
72. Two subclasses: IgA1 & IgA2
Monomer/ Dimer
Main Ig in external secretions such as milk,
tears, saliva & respiratory & intestinal mucus
Protects mucosal surfaces
Major protective factor in colostrum
It is present in the secretion as dimer w/ a J
(joining) chain & secretory piece. J chain is made
by B or plasma cell; Secretory piece made by
epithelial cell
2. IgA (Secretory)
74. Produced in the primary response
Pentamer: serum (held by J chains)
Monomer: Ag receptor on B-cell surface
1st antibody that an infant makes
Most efficient at activating complement
Highest agglutinating capacity
3. IgM
79. Antigenic (amino acid) differences in their
constant heavy regions
Heavy chain isotypes: 9
Total isotypes: 18
Isotypes
80. additional antigenic features of Ig that
vary among individuals
Results from the substitution of only one
or two amino acids in the constant
regions (usually) of heavy or light
chains
No biological significance
Allotypes
81. Antigenic determinants formed by the
specific amino acids in the hypervariable
region
Individual, unique differences between
antibodies of different antigen binding
specificities
Individually specific to each Ig
molecule
Idiotype
83. 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)
Complement
87. Complement Regulatory
Proteins
Protein Regulatory Functions
C1 INH Binds to C1, thereby preventing it from initiating
complement activation
Properdin Stabilizes the alternative pathway C convertase
C4bp Accelerates dissociation of C3 convertase (CP)
DAF Accelerates the dissociation of both C3 convertase
Factor I Cleaves and inactivates C3b and C4b
AI Proteolytically cleaves anaphylotoxins
MIRL/HRF/ S- Inhibits MAC formation
protein
88.
89. Plateau
Log
Lag
Decline
4 Phases of Ab response
