lesson 11 adaptive immunity “specific immunity” march 31,2015

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Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

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Page 1: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Lesson 11Adaptive Immunity“Specific Immunity”

March 31,2015

Page 2: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Immunity Review

• Innate Immunity: defenses against any pathogen– Skin– Phagocytes– Inflammation– Fever

• Adaptive Immunity: induced resistance to a specific pathogen– Humoral (antibodies)– Cell-mediated

Page 3: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Extracellular antigens

A B cell binds to the antigen for which it is specific. A T-dependent B cell requires cooperation with a T helper (TH) cell.

The B cell, often with stimulation by cytokines from a TH cell, differentiates into a plasma cell. Some B cells become memory cells.

Plasma cells proliferate and produce antibodies against the antigen.

Intracellular antigens are expressed on the surface of an APC, a cell infected by a virus, a bacterium, or a parasite.

A T cell binds to MHC–antigen complexes on the surface of the infected cell, activating the T cell (with its cytokine receptors).

Activation of macrophage (enhanced phagocytic activity).

The CD8+T cell becomes a cytotoxic T lymphocyte (CTL) able to induce apoptosis of the target cell.

B cell

Plasma cell

T cell

TH cell

Cytotoxic T lymphocyte

CytokinesCytokines

Lysed target cell

Cytokines activate macrophage.

Cytokines from the TH cell transform B cells into antibody-producing plasma cells.

Cytokines activate T helper (TH) cell.

Memory cell

Some T and B cells differentiate into memory cells that respond rapidly to any secondary encounter with an antigen.

Humoral (antibody-mediated) immune system Cellular (cell-mediated) immune systemControl of freely circulating pathogens Control of intracellular pathogens

Figure 17.20 The dual nature of the adaptive immune system.

Page 4: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Dual Nature of Adaptive Immunity

• Main components of Adaptive Immunity are T cells and B cells

• The fetal liver serves as the source of both T and B cells early in development and in bone marrow in adulthood– T cells develop in thymus in adults– B cells develop in the red bone marrow in adults

Page 5: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Stem cells develop in bone marrow or in fetal liver

Stem cell(diverges intotwo cell lines)

Red bone marrow of adults

Differentiate to B cells in adult red bone marrow

B cell

Thymus

Differentiate toT cells in thymus

T cell

Migrate to lymphoid tissue such as spleen, but especially lymph nodes

Figure 17.8 Differentiation of T cells and B cells.

Page 6: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Dual Nature of Adaptive Immunity

• Humoral Immunity– Due to antibodies – B cells mature in the bone marrow

• Name derived from chickens: bursa of Fabricius – Bursa is an organ found in chickens that when removed results in

the abrogation in antibody production

Page 7: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Dual Nature of Adaptive Immunity

• Cellular Immunity – Due to T cell activation– T cells mature in the thymus

1. Stimulate the production macrophages and other phagocytes2. Activate B-cells into becoming plasma cells3. Activate Cytotoxic T-Lymphocytes

Page 8: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

The Nature of Antigens• Antigen (Ag): a substance that causes the body to

produce specific antibodies or sensitized T cells “foreign molecules”– Microbial cell wall components, proteins, capsules,

flagella, toxins, viral coats– Non-microbial agents such as blood cell surface molecules

can serve as antigens• Organ rejection

– Antibodies (Ab) interact with epitopes, or antigenic determinants which are specific regions on the antigen

– Hapten: antigens that are too small to stimulate a immune response. Require carrier molecules

Page 9: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Binding sites

Epitopes (antigenic determinants) on antigen

Antibody A

Antigens:componentsof cell wall

Antibody B

Bacterial cell

Figure 17.1 Epitopes (antigenic determinants).

Page 10: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Hapten molecules

Carrier molecule

Hapten-carrier conjugate

Figure 17.2 Haptens.

Page 11: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

The Nature of Antibodies

• Globular proteins called Immunoglobulins

• Antigen-binding sites (ABS) are parts of the antibody that binds the epitope

• Valence refers to the number of antigen binding sites on an antibody– Two binding sites are bivalent (most common)– One binding site is monovalent

Page 12: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.3ab The structure of a typical antibody molecule.

Antigen-binding site

Heavy chainLight chain

Hingeregion

Antibody molecule

Enlarged antigen-binding site bound to an epitope

Fc (stem) region

Epitope(antigenic

determinant)

Antigen

Antigen-binding site

Page 13: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

IgG Antibodies

• Monomer• 80% of serum antibodies• Fixes complement• Found in blood, lymph, and

intestine• Cross placenta (passive

immunity)• Enhance phagocytosis;

neutralize toxins and viruses; protect fetus and newborn

• Half-life = 23 days

Page 14: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

IgM Antibodies

• Pentamer• 5–10% of serum

antibodies• Fixes complement• In blood, in lymph, and

on B cells• Agglutinate microbes;

first Ab produced in response to infection

• Half-life = 5 days

Disulfide Bond

J-Chain

Page 15: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

IgA Antibodies

• Dimer• 10–15% of serum

antibodies• In secretions• Mucosal protection• Secretory Component

protects Ab from degradation

• Most abundant antibody in the body

• Half-life = 6 days

J-Chain

Secretory Component

Page 16: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

• Monomer

• 0.2% of serum antibodies

• In blood, in lymph, and on B cells

• On B cells, initiate adaptive response

• Half-life = 3 days

IgD Antibodies

Page 17: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

• Monomer

• 0.002% of serum antibodies

• On mast cells, on basophils, and in blood

• Allergic reactions; lysis of parasitic worms

• Attracts complement and phagocytic cells

• Half-life = 2 days

IgE Antibodies

Page 18: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

• B-cells, when activated, become either plasma cells (Ab producers) or memory cells (responsible for enhanced secondary response)

• B-cells are capable of producing multiple Abs (IgM, IgG, IgA) with the same antigenic determinants (class switching)

• Major histocompatibility complex (MHC) expressed on mammalian cells are responsible for antigenic determinants– Molecules containing glycoproteins– Found on Antigen-presenting cells (APC) and lymphocytes– Presents antigen on the surface of the B cell

Activation of B Cells

Page 19: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

• T-dependent antigens– Ag presented with (self) MHC to TH cell

• Distinguishes (self) from antigen to prevent antibody production against host cells

– Lupus, Type I diabetes, and rheumatoid arthritis– TH cell produces cytokines that activate the B cell

• T-independent antigens– Antigens stimulate B cells directly to make Abs– Antigens are characterized by repeating subunits that bind multiple B

cell receptors• Polysaccharides• Lipopolysaccharides

Page 20: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.4 Activation of B cells to produce antibodies.

Extracellularantigens

Ag fragment MHC class II with Ag fragment

B cell

Immunoglobulin receptorscoatingB cell surface

B cell

B cell

Immunoglobulin receptors on B cell surface recognize and attach to antigen, which is then internalized and processed. Within the B cell a fragment of the antigen combines with MHC class II.

MHC class II–antigen-fragment complex is displayed on B cell surface.

Receptor on the T helper cell(TH) recognizes complex ofMHC class II and antigenfragment and is activated—producing cytokines, whichactivate the B cell. The TH cellhas been previously activated byan antigen displayed on adendritic cell (see Figure 17.10).

B cell is activated by cytokines and begins clonal expansion. Some of the progeny become antibody-producing plasma cells.

MHC class II with Ag fragment displayed on surface

TH cell

Cytokines

Plasma cell

Antibodies

Page 21: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.6 T-independent antigens.

Polysaccharide(T-independent antigen)

Epitopes

B cell receptors

Page 22: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.5 Clonal selection and differentiation of B cells.Stem cell

B cells

Antigen

Some B cells proliferate into long-lived memory cells, which at a later date can be stimulated to become antibody-producing plasma cells. See Figure 17.17.

Memory cells

B cell III complexes with its specific antigen and proliferates.

Other B cells proliferate into antibody-producing plasma cells.

Plasma cells

Plasma cells secrete antibodies into circulation.

Antigens in circulation now attached to circulating antibodies

Cardiovascular system

I II III IV

Stem cells differentiate into mature B cells, each bearing surface immunoglobulins against a specific antigen.

Page 23: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Activation of B Cells

• Clonal Deletion eliminates harmful B cells– MHC molecules that contain self-antigens– Process in which the immune system does not attack

an antigen is called immune tolerance• Gestational immune tolerance protects a baby from the

immune system of the parent– Produces cytokines to inhibit immune system detection

(neurokinin B)– Do not contain receptors that bind cytotoxic Tcells

Page 24: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Antigen-Antibody Binding

• Affinity—is the strength of a bond b/w antigen and antibody– Antibodies recognize the shape of an antigen– Better the fit b/w the antigen’s shape and Ab the

stronger the affinity– Abs are highly specific (discern minor differences

in antigens)

Page 25: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Results of Antigen–Antibody Binding

1. Agglutination2. Opsonization3. Activation of complement4. Antibody-dependent cell-mediated

cytotoxicity5. Neutralization

Page 26: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.7 The results of antigen–antibody binding.PROCTECTIVE MECHANISM OF

BINDING ANTIBODIES TO ANTIGENS

Activation of complement(see also Figure 16.9)

Agglutination(see also Figure 18.5)

Opsonization(see also Figure 16.9)

Antibody-dependentcell-mediated cytotoxicity

(see also Figure 17.16)

Neutralization(see also Figure 18.9)

Reduces number of infectious units to be dealt with

Coating antigen with antibody enhances phagocytosis

Phagocyte

Bacteria

Causes inflammation andcell lysis

Bacterium Lysis

Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells

EpitopesEosinophil

Perforin and lytic enzymes

Large target cell (parasite)

Blocks adhesion of bacteria and viruses to mucosa

Bacterium

Virus

Blocks attachment of toxin

Toxin

Complement

Page 27: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Cells and Cellular Immunity

• T cells are derived from stem cells of bone marrow

• These stem cells migrate to the thymus where they mature into T cells– Thymic selection eliminates many immature T cells

• Similar to clonal deletion of B cells. Weed out cells that would otherwise attack “self”

• Mainly responsible for clearance of intracellular bacteria

Page 28: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Table 17.2 Principal Cells That Function in Cell-Mediated Immunity

Page 29: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Cells and Cellular Immunity

• T cells require antigen-presenting cells (APCs) to become activated

• T cells respond to Ag by T-cell receptors (TCRs)– Similar to antibodies on the surface of B cells

• Pathogens entering the gastrointestinal or respiratory tracts pass through: – M (microfold) cells over– Peyer’s patches (secondary lymphoid organs), which contain APCs

• T cells are characterized by glycoproteins on surface– CD4—bind to MHC II molecules (found on lymphocytes)– CD8—bind to MHC I molecules (present on all nucleated cells)

Page 30: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.9 M cells.

Antigen M cell

Microvilli on epithelial cell

TH cell

Pocket

B cells

Macrophage Epithelial cell(b) M cells facilitate contact between the antigens passing through

the intestinal tract and cells of the body’s immune system.

M cell on Peyer’s patch. Notethe tips of the closely packedmicrovilli on the surroundingepithelial cells.

(a)

Page 31: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Cell Classification

• Certain glycoproteins on the surface of T cells help distinguish different classes of T cells– Clusters of Differentiation (CD)– Responsible for the adhesion of T cells to

receptors– Cells containing CD4 are called CD4+ cells and cells

containing CD8 are called CD8+ cells

Page 32: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Helper Cells

• CD4+ or TH cells– TCRs recognize Ags and MHC II on APC– TLRs are a costimulatory signal on APC and TH

– TH cells produce cytokines and differentiate into:• TH1cells

• TH2 cells

• TH17 cells

• TFH cells• Memory cells

Page 33: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Helper Cells

– TH1 produce IFN-gwhich activates cells related to cell-mediated immunity, macrophages, and Abs

– TH2 activate eosinophils and B cells to produce IgE

– TH17 stimulate the innate immune system

– TFH stimulate B cells to produce plasma cells and are involved in class switching

Page 34: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.11 Lineage of effector T helper cell classes and pathogens targeted.

Antibodies

B cell

Recruits neutrophils; provides protection against extracellular bacteria and fungi

Extracellularbacteria

Fungi

TH1 cells

TH2 cells

TH17 cells

IL-17

IL-4

IFN-g

Cell-mediated immunity; controlof intracellular pathogens, delayed hypersensitivity reactions (page 535); stimulates macrophages.

Important in allergic responses, especially by production of IgE

Stimulates activity of eosinophils to control extracellular parasites such as helminths (see ADCC, page 495).

Neutrophil

Mast cellBasophilEosinophil

Macrophage

TH1 cells

TH2 cells

TH17 cells

Intracellular bacteria and protozoa

TH cell

Helminth

Page 35: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.10 Activation of CD4+T helper cells.

APC (dendritic cell)

Antigen

Costimulatory molecule, (required to activate T cells that have not previously encountered antigen)

Microorganism carrying antigens

Antigen fragment (short peptides)

TH cell receptor (TCR)

Complex of MHC class II molecule and antigen

fragment

A receptor (TCR) on the surface of the CD4+T helper cell (TH cell) binds to the MHC–antigen complex. If this includes a Toll-like receptor, the APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines.

The cytokines cause the TH cell (which recognizes a dendritic cell that is producing costimulatory molecules) to become activated.

Cytokines

T helper cell

An APC encounters and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC.

Page 36: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Cytotoxic Cells

• CD8+ or TC cells

• Target cells are self-cells carrying endogenous antigens

• Activated into cytotoxic T lymphocytes (CTLs)– CTLs recognize Ag + MHC I– Induce apoptosis in target cell

• CTL releases perforin and granzymes

Page 37: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.12 Killing of virus-infected target cell by cytotoxic T lymphocyte.

Processed antigen

MHC class I

Virus-infected cell (example of endogenous antigen) Virus-infected cell Cytotoxic T lymphocyte (CTL)

T cell receptors

Infected target cell is lysed

A normal cell will not trigger a response by a cytotoxic T lymphocyte (CTL), but a virus-infected cell (shown here) or a cancer cell produces abnormal endogenous antigens.

The abnormal antigen is presented on the cell surface in association with MHC class I molecules. CD8+T cells with receptors for the antigen are transformed into CTLs.

The CTL induces destruction of the virus-infected cell by apoptosis.

Processed antigen presented withMHC class I

CTL

Page 38: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.13 Apoptosis.

Page 39: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

T Regulatory Cells

• Treg cells CD4 and CD25 on surface

• Suppress T cells against self

Page 40: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Antigen-Presenting Cells

• Digest antigen

• Ag fragments on APC surface with MHC– B cells– Dendritic Cells– Activated Macrophages

Page 41: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.14 A dendritic cell.

Page 42: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.15 Activated macrophages.

Activated macrophages

Resting (inactive)macrophage

Page 43: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

• Granular leukocytes destroy cells that don’t express MHC I

• Kill virus-infected and tumor cells

• Attacks parasites

Natural Killer (NK) Cells

Page 44: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

ADCC

• Antibody-dependent cell-mediated cytotoxicity

Page 45: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.16a Antibody-dependent cell-mediated cytotoxicity (ADCC).

Organisms, such as many parasites, that are too large for ingestion by phagocytic cells must be attacked externally.

Cytotoxic cytokines

Lytic enzymesPerforin enzymes

KEY

Macrophage

Fc region

Large parasite

Eosinophil

Extracellular damage

Epitope

Antibody

(a)

Page 46: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.16b Antibody-dependent cell-mediated cytotoxicity (ADCC).

Eosinophils adhering to the larval stage of a parasitic fluke.

Fluke

Eosinophils

Page 47: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Cytokines

• Chemical messengers– Allows for communication between cells

• Overproduction leads to cytokine storm

Page 48: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Cytokines

Cytokine Representative Activity

Interleukin-1 (IL-1) Stimulates TH cells in presence of antigens; attracts phagocytes

Interleukin-2 (IL-2) Proliferation of antigen-stimulated CD4+ T helper cells, proliferation and differentiation of B cells; activation of CD8+ T cells and NK cells

Interleukin-12 (IL-12) Inhibits humoral immunity; activates TH1 cellular immunity

Page 49: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Cytokines

Cytokine Representative Activity

Chemokines Induce the migration of leukocytes

TNF-α Promotes inflammation

Hematopoietic cytokines

Influence differentiation of blood stem cells

IFN- and IFN- Response to viral infection; interfere with protein synthesis

IFN- Stimulates macrophage activity

Page 50: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Immunological Memory

• Antibody titer is the amount of Ab in serum

• Primary response occurs after initial contact with Ag

• Secondary (memory) response occurs after second exposure

Page 51: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Figure 17.17 The primary and secondary immune responses to an antigen.

IgG

IgM

Initial exposure to antigen

Second exposure to antigen

Time (days)

Antib

ody

titer

in s

erum

Page 52: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Types of Adaptive Immunity

• Naturally acquired active immunity– Resulting from infection

• Naturally acquired passive immunity– Transplacental or via colostrum

• Artificially acquired active immunity– Injection of Ag (vaccination)

• Artificially acquired passive immunity– Injection of Ab

Page 53: Lesson 11 Adaptive Immunity “Specific Immunity” March 31,2015

Terminology of Adaptive Immunity

• Serology: the study of reactions between antibodies and antigens

• Antiserum: the generic term for serum because it contains Ab

• Globulins: serum proteins• Immunoglobulins: antibodies • Gamma () globulin: serum fraction containing

Ab