Specific Host Defense Mechanisms

Lecture 6

Specific Host Defense Mechanisms

NORBEL A. TABO, RM, SM

Learning Objectives 1. 2. 3. 4. 5. 6. 7. 8.

Define immunology. Differentiate humoral and cell-mediated immunity. Outline the steps involved in the processing of Tindependent and T-dependent antigens. Identify the two primary functions of the immune system. Identify and describe the five immunoglobulin classes. List the type of cells that are killed by NK cells. Distinguish between active acquired and passive acquired immunity. 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 (Nonspecific) Humoral Immunity

Adaptive (Specific) Cell-Mediated 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 antibodies. 

stimulate

the

production

of

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 2. 3. 4. 5.

tolerance is inadequate Alloantigens – cell surface markers of one individual that are antigens to another of that same species Heterophilic antigens – molecules from unrelated species that bear similar antigenic determinants Superantigens – potent T cell stimulators, provoke an overwhelming response 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 II MHC molecule

class III MHC genes

class I MHC genes

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 0

(BCG)

P

(HepB)

P1

1

2

3

4

5

6

7

P2

8

9

10

Years 11

12

14

16

18

20

P3

P1

P2

P3

B1

(OPV/IPV)

P1

P2

P3

B1

(Measles)

24

3

4

5

6

7

13

P4

(DTP)

B2

Td B2

P

HiB

P1

P2

PCV

P1

P2

RV

P1

P3 P3

B1

PPV

P2

Influenza

P1

P2

Varicella

P1

MMR

P1

HepA

P1

Legend:

22

P

Primary Dose

B

Booster Dose

C

Catch-up immunization

Td

Booster Tetanus Diphtheria

()

Covered by EPI

P2 P2

C P2

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 ! ! !