Lecture 6

Specific Host Defense

Mechanisms

NORBEL A. TABO, RM, SM

 Learning Objectives
1. Define immunology.
2. Differentiate humoral and cell-mediated immunity.
3. Outline the steps involved in the processing of T-
independent and T-dependent antigens.
4. Identify the two primary functions of the immune system.
5. Identify and describe the five immunoglobulin classes.
6. List the type of cells that are killed by NK cells.
7. Distinguish between active acquired and passive acquired
immunity.
8. Distinguish between natural passive acquired and artificial
passive acquired immunity.
Immunology
 Scientific study of the immune system and
immune responses
Terminologies
 Immunity
protection against infections
 Immune system
collection of cells and molecules that defend us against
microbes
 Immune deficiencies
infections
 Immune excesses
autoimmune diseases
Overview of the Immune System

Immune System

Innate Adaptive
(Nonspecific) (Specific)

Humoral Cell-Mediated
Immunity Immunity
Third Line of
Defense
 Humoral Immunity
 Always involves the production of antibodies.
Development of the Dual Lymphocyte
System
 Starting in the embryonic & fetal stages, stem
cells in the yolk sac, liver, and bone marrow
release immature lymphocytes into the
circulation
 These undifferentiated cells must mature to
be able to react to antigen
 Maturation occurs differently for B and T cells
B cell maturation
 Directed by bone marrow sites that harbor
stromal cells, which nurture the lymphocyte
stem cells & provide hormonal signals
 Millions of distinct B cells develop & home to
specific sites in the lymph nodes, spleen, and
GALT where they come into contact with
antigens throughout life
T cell maturation
 Maturation is directed by the thymus gland
and its hormones
 7 classes of T-cell receptors termed CD
cluster
 Mature T cells migrate to lymphoid organs
and occupy specific sites
Antigens
 Foreign organic substances that are large
enough to stimulate the production of
antibodies.
 Foreign cells & large complex molecules over
10,000 MW are most antigenic
 Foreign molecules less than 1,000 MW
(haptens) are not antigenic unless attached to
a larger carrier
 Antigenic determinant, epitope – small
molecular group that is recognized by
lymphocytes.
Special categories of antigens
1. Autoantigens – molecules on self tissues for which
tolerance is inadequate
2. Alloantigens – cell surface markers of one individual
that are antigens to another of that same species
3. Heterophilic antigens – molecules from unrelated
species that bear similar antigenic determinants
4. Superantigens – potent T cell stimulators, provoke
an overwhelming response
5. Allergen – antigen that provokes allergy
Processing of Antigens
 T-cell dependent antigens must be processed
by phagocytes called antigen presenting cells
(APC).
 An APC alters the antigen and attaches it to
its MHC receptor.
 Antigen presentation involves a direct
collaboration among an APC, a T helper cell
and an antigen-specific B or T cell.
 Interleukin -1 is secreted by APC to activate
TH cells
 Interleukin-2 is produced by TH to activate B &
other T cells
Antibody
 Proteins produced by lymphocytes in
response to the presence of an antigen
 Found in blood (circulating antibodies),
lymph, tears, saliva and colostrum (protective
antibodies)
Antigen-Antibody Reactions
 Opsonization
 Neutralization
 Agglutination
 Complement fixation
Immune Response
 Primary response
 after first exposure to an Ag, immune system
produces IgM and a gradual increase in Ab
titer
 Secondary response
 after second contact with the same Ag,
immune system produces a more rapid,
stronger response due to memory cells
Monoclonal antibodies
 single specificity antibodies formed by fusing
a mouse B cell with a cancer cell.
 used in diagnosis of disease, identification of
microbes and therapy
Viral Inactivation
Toxin Inactivation
Agglutination
 Cell-mediated Immunity
 Involves macrophages, helper T-cells, cytotoxic
T-cells, delayed hypersensitivity T-cells, natural
killer cells, killer cells and granulocytes
Lymphocytes
 Present in lymphoid organs and in blood

 Groups
• T-lymphocytes (grow up in thymus)
• B-lymphocytes (grow up in bone marrow)

 Each one has receptors for a specific antigen

• Recognize millions of different antigens
• Diversity generated by:
 rearrangement of antigen receptor genes

 different joining of the gene segments

• Gene rearrangement studies

T-Lymphocytes
 Live in blood, bone marrow, lymphoid tissues

 Two basic functions:

• kill stuff
• help other cells do their jobs
 T-cell receptor (TCR) complex recognizes antigens
• binds antigen
• sends signals to the T cell
 Antigens must be:
• displayed by other cells…
• …AND bound to an MHC receptor
The T-Cell Receptor
 APC

T-Cell
Receptor

T-Cell
Types of Lymphocytes
1. Helper T cells (TH cells)
• CD4+ (and CD8-)
• help B cells make antibodies
• help macrophages eat bugs
• decreased in patients with AIDS
1. Cytotoxic T cells (Tc cells)
• CD8+ (and CD4-)
• kill virus-infected cells and tumor cells
Types of Lymphocytes
3. Delayed hypersensitivity cells (TD)
 responsible for allergies occurring several
hours or days after contact
3. T suppressor cells (TS)
 limit the actions of other T cells and B cells
CD8+ T cells surrounding tumor
 class II MHC genes class III MHC genes class I MHC genes

class II MHC molecule class I MHC molecule

B-Lymphocytes
 Live in blood, bone marrow, lymphoid tissues

 Basic function: make antibodies

(immunoglobulins)
 B-cell receptor complex recognizes antigens
• binds antigen
• sends signals to T-cells
 Antigens can be free and circulating (don’t have
to be bound to MHCs or displayed by other cells
to be recognized!)
The B-Cell Receptor

B cell
The B-Cell Receptor
Lymphocytes (Natural Killer Cells)
 Belong to innate immunity arm

 No highly variable receptors like T and B

cells

 Main job: recognize and kill damaged or

infected cells

 Antigens do not have to be bound to

MHCs or displayed by other cells!
Natural killer cell
Natural killer cell (top) killing infected cell
Antigen-presenting cells
 Main job: catch antigens and display them to
lymphocytes

 Dendritic cells
• Have fine cytoplasmic projections
• Present all over body: skin, lymph nodes, organs
• Capture bug antigens, display to B and T cells

 Other APCs
• Macrophages eat bugs and present antigens to
T cells, which tell macrophages to kill bugs
• B cells present antigens to helper T cells, which
tell B cells to make antibodies
dendritic cells
Effector Cells
 These guys carry out the ultimate immune
system task: eliminate infection

 Types of effector cells

• NK cells
• Plasma cells
• T cells (both CD4+ and CD8+)
• Macrophages
• Other leukocytes (e.g., neutrophils)
Lymphoid tissues
 Lymphocytes grow up in primary organs, then
travel to secondary organs, searching for
antigens.
 Primary organs
• thymus
• bone marrow
 Secondary organs
• lymph nodes
• spleen
• mucosal and cutaneous lymphoid tissues
Cell-Mediated Immunity
Cytokines
 Polypeptides that do lots of different things:
• help leukocytes grow and differentiate
• activate T cells, B cells and macrophages
• help leukocytes communicate
• recruit neutrophils

 Made by lymphocytes and macrophages

 Examples: TNF, the interleukins, interferon γ

Acquired immunity
 Natural immunity
 acquired as part of normal life experiences
 Artificial immunity
 acquired through a medical procedure such as a
vaccine
 Active immunity
 results when a person is challenged with Ag that
stimulates production of Ab.
 It creates memory, takes time and is lasting
 Passive immunity
 preformed Ab are donated to an individual. It does
not create memory, acts immediately, and is short
term.
 Louis Pasteur

Edward Jenner

Who’s first in the concept of vaccination?

Oral Polio Vaccination
 Vaccines Months Years

0 1 2 3 4 5 6 7 8 9 10 11 12 14 16 18 20 22 24 3 4 5 6 7 13

(BCG) P

(HepB) P1 P2 P3 P4

(DTP) P1 P2 P3 B1 B2 Td

(OPV/IPV) P1 P2 P3 B1 B2

(Measles) P

HiB P1 P2 P3

PCV P1 P2 P3 B1 PPV

RV P1 P2

Influenza P1 P2

Varicella P1 P2

MMR P1 P2 C

HepA P1 P2

Legend: P Primary Dose

B Booster Dose
C Catch-up immunization
Td Booster Tetanus Diphtheria
() Covered by EPI
DOH, 2006
Types of vaccine
1. Attenuated vaccines
 BCG, most vaccines for viruses

1. Inactivated vaccines
 Salk vaccine for polio, rabies

1. Subunit vaccines
2. Conjugate vaccines
 Hib vaccine

1. Toxoid vaccines
 DPT

1. DNA vaccines
 Still in experimental phase
 THANK YOU
VERY MUCH ! ! !