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Figure 43.0 Specialized lymphocytes attacking a cancer cell

The Body’s Defense: The Immune System

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A lymphocyte: They display specificity for an antigen

There are:

B lymphocytes or cells and T lymphocytes or cells

They display:

Specificity

Diversity

Memory

Can distinguish self from nonself

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Figure 43.1 An overview of the body's defenses

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Nonspecific Defenses

1. Skin

a) Oil and sweat glands keep pH about 3-5 and this prevents bacteria from inhabiting the area.

b) Lysozyme: an example of a protein that digests bacterial cell walls.

Found in eyes, upper respiratory tract.

2. Mucous

a) traps bacteria in respir. tract

b) action of cilia

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3. Action of neutrophils

a) phagocytes

b) exhibit a chemotaxis: attracted by chemicals released by damaged cells

4. Monocytes

a) develop into macrophages that will engulf bacteria

b) attracted to the polysaccharides on the bacteria’s surface.

c) engulfed into a vacuole and then nitric oxide (NO) will destroy it.

5. Natural Killer Cells

a) attack virus-infected cells and cause the cells to lyse

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Figure 43.3 Phagocytosis by a macrophage

Bacteria are the rod-shaped structures

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Figure 43.3x Macrophage

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The Importance of the Lymph Nodes

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The Inflammatory Response

Pyrogens

Complement system: bunches of proteins

Interferons: released by virus-infected cells

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Figure 43.6 Clonal selection

Selected B cell makes clones

Antigen receptors are actually mem-brane antibodies or immunoglobulins

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Immune Response: Know this well

Primary Immune Response

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Figure 43.10 An overview of the immune responses (Layer 2)

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Figure 43.8 The development B and T Cells or lymphocytes

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Figure 43.9 The interaction of T cells with MHC molecules

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Major Histocompatibility Complex (MHC)

1. There are genes that code for two types of distinguishing glycoproteins on a cell’s surface:

a) Class I MHC

b) Class II MHC

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2. The Role of the MHC Glycoproteins

a) Antigen Presentation

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Figure 43.10 An overview of the immune responses (Layer 4)

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Figure 43.11 The central role of helper T cells: a closer look

CD4: Helper T cell surface protein: binds to the presented antigen fragment of the APC

Upon activation by the APC, the TH cells will make many clones and also produce memory TH cells.

Once activated, a macrophage will make IL-1 which helps to make IL-2 which stimulates TH cells to divide as well as the production of B cells

TH cells: involved in both cell mediated and humoral responses.

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Figure 43.12a The functioning of cytotoxic T cells

MHC I Glycoprotein: all nucleated cells

Tumor Cells: present tumor antigens to Tc cells so the body can fight against tumors

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Figure 43.12b A cytotoxic T cell has lysed a cancer cell

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Figure 43.13 Humoral response to a T-dependent antigen (Layer 3)

B cells can be stimulated by TH cells to make antibodies.

This is a T- dependent antigen.

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Figure 43.10 An overview of the immune responses (Layer 2)

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Figure 43.11 The central role of helper T cells: a closer look

CD4: Helper T cell surface protein: binds to the presented antigen fragment of the APC

Upon activation by the APC, the TH cells will make many clones and also produce memory TH cells.

Once activated, a macrophage will make IL-1 which helps to make IL-2 which stimulates TH cells to divide as well as the production of B cells

TH cells: involved in both cell mediated and humoral responses.

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Epitopes (antigenic determinants)

Epitopes: small portion of an antigen to which the

antibody binds.

Epitope A

Epitope BEpitope C

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Figure 43.15a,b The structure of a typical antibody molecule

Fig. 43-13

DNA of undifferentiated B cell

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DNA of differentiated B cell

pre-mRNA

mRNA

Light-chain polypeptide

Variableregion

Constantregion

Translation

B cell

B cell receptor

RNA processing

Transcription

DNA deleted between randomly selected V and Jsegments

Functional gene

V37 V38 V39 V40 J1 J2 J3 J4 CJ5 Intron

V37 V38 V39 CJ5 Intron

V39 CJ5 Intron

V39 CJ5 Poly-A tailCap

CV

VV

V

V

C C

C C

2

3

4

Recombinase acts randomly to combine any one of the J gene segments with any one of the V gene segments.

40V x 5J x 1C = 200 different ways.

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Figure 43.15c Antibody molecule

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Table 43.1 The Five Classes of Immunoglobulins

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Figure 43.16 Effector mechanisms of humoral immunity

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Figure 43.17 The classical complement pathway, resulting in lysis of a target cell

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Types of Immunity

1. Active Immunity

a) naturally acquired after an infection (chicken pox)

b) acquired by an immunization (vaccination)

c) person demonstrates the secondary response

2. Passive Immunity

a) antibodies acquired from another person

b) antibodies are passed from a mother’s breast milk to nursing child while the child’s immune system is

developing.

c) a rabies bitten person can receive antibodies from those vaccinated against rabies

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Allergic Reactions

1. An allergen causes a specific kind of antibody IgE to be released from plasma cells and instead of binding to the allergen (pollen) they bind to mast cells that are present in connective tissue (ligaments, tendons, etc).

2. This causes the mast cells to release histamine

3. Histamine causes blood vessels to dilate and also increases their permeability so lots of fluid leaks out.

4. Antihistamine

5. Anaphylactic shock: allergic response is one of huge release of histamine and so much blood goes to periphery that blood pressure drops.

(bee stings, food allergies (peanuts)

Person takes a shot of epinephrine.

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Figure 43.18 Mast cells, IgE, and the allergic response

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Figure 43.x4 Alternaria spores, a cause of allergies in humans

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Figure 43.19 A T cell infected with HIV

T cell

Viruses: small blue dots

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Figure 43.19x2 HIV budding

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Figure 43.19x2a T cell infected with HIV

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Figure 43.20 The stages of HIV infection

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HIV MOLECULAR BIOLOGY

1. Retrovirus

2. Several strains of HIV

3. Binding and Entry

a) RNA has 9 different genes encoding 15 proteins.

b) Entry requires the fusion of the viral envelope with the host cell membrane.

c) The viral envelope interacts with specfic cell surface receptors.

d) gp120 is on the viral surface binds to the CD4 receptors on the T cells.

e) gp41

4. Virus attacks cells with CD4 receptors on TH cells(immune system cells)

5. Role of TH cells? Stimulates the immune system; they bind to MHC II APC’s which stimulates both cell mediated immunity and antibody secretion from plasma cells

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6. HIV binds to probably several proteins: CD4 receptor, a fusin protein which allows for the envelope of the virus to join with the T cell and another receptor CCR5 which is on

macrophages.7. CXCR4 binds to T-cells in later stages of the disease.

8. In up to 13% of individualos of northern Eurpean descent, a naturally occurring deletion of 32 base pairs in the CCR5 gene results in a mutant CCR5 receptor that never reaches the cell surface.

a) Individuals homozygous for this mutation (1-2% of Caucasian population) are almost completely resistant to HIV infection.

9. Binding of gp120 and CD4 produces changes in gp41, it springs open and grabs the lipid bilayer of the target cell. This promotes fusion.

10. Detection for HIV antibodies: 1-12 months after exposure/infection.