Immunity

Impacts, IssuesFrankie’s Last Wish

Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers – including the one that killed Frankie McCullogh

A. Integrated Responses to Threats

1. Immunity - the capacity to resist and combat infection by pathogens such as viruses, bacteria, and fungi

2. Proteins in eukaryotic cell membranes have unique patterns (antigens) that the body recognizes as self & cells of multicelled eukaryotes have receptors that recognize nonself cues (anitgens) on or in pathogens, and trigger defense responses

B. Three Lines of Defense

1. Physical, chemical, and mechanical barriers - keep pathogens outside the body

Chemical Weapons of Immunity

Vertebrate Surface Barriers

B. Three Lines of Defense

1. Physical, chemical, and mechanical barriers - keep pathogens outside the body

2. Innate immunitya. General responses destroy invaders inside the body

before they become established

b. Complement: Proteins that destroy microorganisms or flag them for phagocytosis

Animation: Innate defenses

videos_animations/innate_defenses_m.html

B. Three Lines of Defense

1. Physical, chemical, and mechanical barriers - keep pathogens outside the body

2. Innate immunitya. General responses destroy invaders inside the body

before they become established

b. Complement: Proteins that destroy microorganisms or flag them for phagocytosis

3. Adaptive immunityc. system of defenses that specifically targets billions

of different antigens an individual may encounter during its lifetime

d. Huge populations of white blood cells form to target and remember a specific antigen

Comparing Innate and Active Immunity

White Blood Cells

C. Innate Immune Responses

Innate immune mechanisms nonspecifically eliminate pathogens that invade internal tissues before they become established• Phagocytes• Complement• Inflammation• Fever

1. Phagocytes

(Macrophages)a. Large phagocytes that patrol interstitial fluid and

engulf and digest pathogens

b. Secrete cytokines when receptors bind to antigen

c. Cytokines attract more macrophages, neutrophils, and dendritic cells to infection site

2. Complement proteins become activated when they encounter antigena. Cascading enzyme reactions concentrate

activated complement at infection site

b. Complement attracts phagocytes to infection site and tags pathogens for destruction

c. Forms attack complexes that puncture bacteria

d. Helps mediate active immunity

Complement Attack Complexes

Animation: Complement proteins

videos_animations/membrane_attack.html

3. Inflammationa. A local response to tissue damage

characterized by redness, warmth, swelling and pain, triggered by activated complement and cytokines

b. Mast cells release histamine, increasing capillary permeability

c. Phagocytes and plasma proteins leak out, attack invaders, form clots, and clean up debris

Fig. 38-8, p. 665

A Bacteria invade a tissue and release toxins or metabolic products that damage tissue.

B Mast cells in tissue release histamine, which widens arterioles (causing redness and warmth) and increases capillary permeability.

C Fluid and plasma proteins leak out of capillaries; localized edema (tissue swelling) and pain result.

D Complement proteins attack bacteria. Clotting factors also wall off inflamed area.

E Neutrophils and macrophages engulf invaders and debris. Macrophage secretions kill bacteria, attract more lymphocytes, and initiate fever.

Stepped Art

4. Fevera. A temporary rise in body temperature – above

the normal 37°C (98.6°F) – that often occurs in response to infection

b. Cytokines stimulate brain cells to release prostaglandins, which act on the hypothalamus

c. Fever enhances the immune response by speeding up metabolism and phagocyte activity

d. Fever over 40.6°C (105°F) can be dangerous

D. Overview of Adaptive Immunity

1. Vertebrate adaptive immunity adapts to different antigens it encounters during its lifetime

2. Lymphocytes and phagocytes interact to effect four defining characteristics: Self/nonself recognition, specificity, diversity, and memory

3. First Step – The Antigen Alert

a. Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis - all descendent cells recognize the same antigen

b. T cells do not recognize an antigen unless it is presented by an antigen-presenting cell - macrophages, B cells, and dendritic cells digest particles and display antigen-MHC complexes

c. Cell Types

i. Effector cells - differentiated lymphocytes (B and T cells) that act at once to fight infection

ii. Memory cells - long-lived B and T cells reserved for future encounters with the same antigen

cell engulfs an antigen-bearing particle

Fig. 38-9b, p. 666

antigen–MHC complexes become displayed on

cell surfaceendocytic vesicle forms

MHC markers bind fragments of particle

particle is digested into bits

lysosome fuses with endocytic vesicle

Stepped Art

4. Two Arms of Adaptive Immunity

a. Antibody-mediated immune response - B cells produce antibodies that bind to specific antigen particles in blood or interstitial fluid

b. Cell-mediated immune response - Cytotoxic T cells and NK cells detect and destroy infected or altered body cells

Interactions Between Antibody-Mediated and Cell-Mediated Responses

5. Intercepting and Clearing Out Antigen

a. After engulfing antigen-bearing particles, dendritic cells or macrophages migrate to lymph nodes, where T cells bind and initiate responses

b. During an infection, lymph nodes swell due to accumulation of T cells

c. Antibody-antigen complexes bound by complement are cleared by the liver and spleen

The Lymphatic System

E. Antibodies and Other Antigen Receptors

1. Antigen receptors on B and T cells have the potential to recognize billions of different antigens

2. Antibodya. Y-shaped antigen receptor (protein), made only

by B cells, that binds only to the antigen that prompted its synthesis

b. Activates complement, facilitates phagocytosis, or neutralizes pathogens or toxins

Antibody Structure

3. Making Antigen Receptors

a. Genes that encode antigen receptors occur in several segments on different chromosomes

b. Different versions are randomly spliced together during B or T cell differentiation, producing about 2.5 billion different combinations

c. T cells mature in the thymus, which stimulates production of MHC and T cell receptors

Antigen Receptor Diversity

F. The Antibody-Mediated Immune Response

1. Antigen activates naïve B cells and dendritic cells

2. Naïve T cell binds to APC and differentiates into effector and memory helper T cells

3. Helper T cells bind antigen-MHC complexes on activated B cell and secrete cytokines

4. B cell differentiates into effector B cells, which produce antibodies targeting a specific antigen, and memory B cells

Fig. 38-14, p. 670

Stepped Art

A

naive B cell

B cell

complement

A The B cell receptors on a naïve B cell bind to a specific antigen on the surface of a bacterium

dendritic cell

B

bacterium

antigen- presenting dendritic

cell

B The dendritic cell engulfs the same kind of bacterium that the B cell encountered.

D cytokines

D Antigen receptors of one of the effector helper T cells bind antigen-MHC complexes on the B cell.

E

memory B cell

effector B cell

E The cytokines induce the B cell to divide, giving rise to many identical B cells.

FF The effector B cells begin making and secreting huge numbers of IgA, IgG, or IgE.

C The antigen-MHC complexes on the antigen-presenting cell are recognized by antigen receptors on a naïve T cell.

naive T cell

effector helper T

cell

memory helper T cell

C

5. Clonal Selection and Memory Cells

a. Only B cells with receptors that bind antigen divide (clone) and differentiate into effector and memory B cells

b. First exposure (primary response) produces memory B and T cells; secondary response is stronger and faster

Clonal Selection and Memory Cells

Primary and Secondary Immune Response

G. The Cell-Mediated Response

1. Dendritic cell ingests altered body cell, displays antigen-MHC complexes, migrates to lymph node

2. Naïve helper T and cytotoxic T cells bind to APC

3. Activated helper T divides and differentiates into memory and effector cells; cytokines signal division of activated cytotoxic T cells

4. Cytotoxic T cells circulate and touch-kill altered body cells

Fig. 38-17, p. 672

Stepped Art

dendritic cell

A

antigen- presenting dendritic

cell

A A dendritic cell engulfs a virus-infected cell.

naive cytotoxic

T cell

C

activated cytotoxic

T cell

C Receptors on a naïve cytotoxic T cell bind to the antigen-MHC complexes on the surface of the dendritic cell.

D

cytokines

memory cytotoxic

T cell

effector cytotoxic

T cell

D The activated cytotoxic T cell recognizes cytokines secreted by the effector helper T cells as signals to divide.

E E The new cytotoxic T cells circulate through the body.

B

effector helper T

cell

memory helper T

cell

B Receptors on a naïve helper T cell bind to antigen-MHC complexes on the dendritic cell.

naive helper T

cell

Cytotoxic T Cells

Animation: Cell mediated response

videos_animations/cell_mediated_vid.html

5. Natural Killer Cells

a. Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division

b. Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers

H. Allergies

1. An immune response to a typically harmless substance (allergen)

2. First exposure stimulates production of IgE, which becomes anchored to mast cells and basophil

3. Later exposure stimulates secretion of histamine and cytokines that initiate inflammation

4. Anaphylactic shock is a severe and potentially fatal allergic reaction

Allergies: Annoying or Life-Threatening

ABC video: Food Allergy Increase

videos_animations/Food_Allergy_Increase.html

I. Vaccines

1. Immunization - the administration of an antigen-bearing vaccine designed to elicit immunity to a specific disease

2. Vaccine (active immunization) - a preparation containing an antigen that elicits a primary immune response

3. Passive immunization - administration of antibodies; no immune response

Smallpox Vaccine

Edward Jenner created the first vaccine against smallpox, which has now been eradicated

Recommended Immunizations

J. Immunity Gone Wrong

Misdirected or compromised immunity is sometimes the result of mutation or environmental factors

The outcome is often severe or lethal

1. Autoimmune Disorders

a. Sometimes lymphocytes and antibodies fail to discriminate between self and nonself

b. Autoimmune responsei. An immune response that is misdirected

against the person’s own tissues

ii. Rheumatoid arthritis, Graves’ disease, multiple sclerosis

2. Immunodeficiency

a. In immunodeficiency, the immune response is insufficient to protect a person from disease

b. Primary immune deficiencies are present at birth - SCIDs, ADA

c. Secondary immune deficiency results from exposure to an outside agent, such as a virus - AIDS

3. Gene Therapy

Primary immunodeficiency is the result of mutation; Cindy Cutshwall was successfully treated for ADA, a type of severe combined immunodeficiency (SCID), using gene therapy

Video: Gene therapy

videos_animations/gene_therapy.html

K. AIDS Revisited—Immunity Lost

1. Acquired immune deficiency syndrome (AIDS) a. A group of disorders resulting from a failure of

the immune system due to HIV infection

b. Includes rare cancers and infections caused by normally harmless microorganisms

2. Human immunodeficiency virus (HIV) - a retrovirus that attacks specific cells of the immune system, including helper T cells

T Cells and AIDS

Global HIV and AIDS Cases

3. Transmission and Treatment

a. Common modes of HIV transmission - unprotected sex, mother to child, shared syringes

b. HIV testing - antibodies are found in blood, saliva or urine

c. Drugs - there is no cure; protease inhibitors and reverse transcriptase inhibitors can slow its progress

4. Prevention

a. Vaccines - experimental vaccines are mostly ineffective or risky; the virus’ high mutation rate is an obstacle

b. Education - the best option for preventing the spread of HIV is teaching people how to avoid being infected

5. The Global AIDS Program

The global battle continues; researchers are using several strategies to develop an HIV vaccine

Video: HPV vaccine

videos_animations/csHPV_Vaccine.html