Immunity

Chapter 23

Smallpox Vaccine

• Before vaccines, smallpox had up to 50% death rates• Now smallpox is practically eradicated

Immunity

• Body’s ability to resist and combat diseases• Depends on mechanisms that recognize

proteins as self or nonself• Antigen– Any molecule the body recognizes as nonself and

provokes an immune response

Evolution of Defenses

• Innate immunity– Preset responses to nonself cues– Complement, phagocytes

• Adaptive immunity– Prepares defenses to specific pathogens

encountered during an individual’s lifetime– Cytokines, lymphocytes

Adaptive and Innate Immunity

Three Lines of Defense

• Physical barriers– exclude pathogens

• Innate immunity– begins as soon as antigen is detected

• Adaptive immunity– forms cells that fight infection and prevent

later infection

White Blood Cells

• Form in bone marrow• Participate in adaptive and innate responses• Release cytokines and other cell-to-cell

signaling molecules

Chemical Weapons

neutrophil eosinophil

mast cellbasophil

White Blood Cells

T lymphocyteB lymphocyteNK cell

White Blood Cells

dendritic cell macrophage

White Blood Cells

Surface Barriers

• Physical barriers– Intact skin

• Mechanical barriers– Mucus, cilia, flushing

• Chemical barriers – Protective secretions, low pH, lysozyme

Cilia in Airways

Bacterial Invaders

Table 23-3, p.385

Innate Immune Response

• Phagocytosis• Complement• Fever• Acute inflammation

Complement

• Many types of circulating proteins • Activated by binding to antigen– Triggers reactions that activate more complement

• Attract phagocytic cells

Membrane Attack Complexes

antibody activatedcomplement

bacterial pathogen

lipid bilayer of pathogen

Activation Cascade reactions

Formation of attack complexes

Lysis of target

one membrane attack complex (cutaway view)

hole in the plasma membrane of an unlucky baterium

Fig. 23-6, p.388

lipid bilayer of one kind of pathogen

Acute Inflammation

• Nonspecific response to foreign invasion, tissue damage

• Destroys invaders, removes debris• Symptoms are redness, swelling, warmth,

and pain

Inflammation

• Mast cells release histamine• Capillaries dilate and leak• Complement proteins attack bacteria• White cells attack invaders and clean up

a Bacteria invade atissue and directly kill cells or releasemetabolic productsthat damage tissue.

b Mast cells in tissue releasehistamines, which then triggerarteriole vasodilation (henceredness and warmth) as well asincreased capillary permeability.

c Fluid and plasmaproteins leak out ofcapillaries; localizededema (tissue swelling) and pain result.

d Complementproteins attackbacteria. Clottingfactors wall offinflamed area.

e Neutrophils, macrophages, engulf invaders and debris.Some macrophage secretions kill targets,attract more lymphocytes, and call for fever.

Fig. 23-7, p.388

Fever

• Temperature up to 39°C (102°F)• Enhances immunity, increases rates of enzyme

and phagocyte activity• Accelerates tissue repair

Features of Adaptive Immunity

• Self/nonself recognition • Specificity• Diversity • Memory

Antigens

• “Nonself” markers on foreign agents and altered body cells such as tumors

• Trigger division of B and T cells

Memory and Effector Cells

• When a B or T cell is stimulated to divide, it produces 2 cell types

• Memory cells: set aside for future use • Effector cells: engage and destroy the current

threat

Key Components of Immune Response

• MHC markers• Antigen-presenting cells• T cells• B cells • Natural killer (NK) cells

antigen fragments

MHC molecule

antigen–MHC complex

Formation of Antigen–MHC

Complex

fragments of engulfed antigen

MHC markerthat the cell already made

antigen-MHC complex displayed at surface of plasma membrane

Fig. 23-9, p.390

Antibody-MediatedImmune Response

naive B cells+

antigen+

complement

Cell-MediatedImmune Response

antigen-presenting cells

naive helper T cells

effectorhelper T cells

+memory

helper T cells

naivecytotoxic T cells

effector cytotoxic T cells+

memory cytotoxic cells

activatedB cells

effector B cells+

memory B cells

Fig. 23-10, p.390

Key Interactions

Antigen Interception

• Antigen-presenting T cells are trapped in lymph nodes

• Macrophages, dendritic cells, and B cells bind, process and present antigen

Fig. 23-11a, p.391

TONSILS

RIGHT LYMPHATIC DUCT

THYMUS GLAND

THORACIC DUCT

SPLEEN

SOME OF THE LYMPH VESSELS

SOME OF THE LYMPH NODES

BONE MARROW

Fig. 23-11b, p.391

arrays of lymphocytes

valve (prevents backflow)

Antigen Receptors

• Antibodies– Synthesized by B cells– Bind to one specific antigen

• Mark pathogen for destruction by

phagocytes and complement proteins

Antibody Structure

• Consists of four polypeptide chains

• Parts of each chain are variable; provide antigen specificity

antigen binding site

constant region

variable region

variable region(dark green)of heavy chain

binding site for antigen

variable region of light chain

constant region (bright green) of heavy chain, that includes a hinged region

Fig. 23-12a, p.392

binding site for antigen

antigen on bacterial cell(not to scale)

binding site on one kind of antibody molecule for a specific antigen

Fig. 23-12b, p.392

Fig. 23-12c, p.392

antigen on virus particle

binding site on anotherkind of antibody moleculeFor a different antigen

Immunoglobins (Igs)

• Five classes of antibodies– IgG– IgA– IgE– IgM– IgD

a As a B cell matures, different segments of antibody-coding genes recombine at random into a final gene sequence.

b The final sequence is transcribed into mRNA.

c Processing yields a mature mRNA transcript (e.g., introns excised, exons spliced).

d mRNA is translated into one of the polypeptide chains of an antibody molecule.

Stepped Art

Fig. 23-13, p.393

Antigen Receptor Diversity

Antibody-Mediated Immune Response

• B cell responds to one particular extracellular pathogen or toxin

• Activated B cell forms clones that differentiate into effector and memory cells

• Effector B cells secrete antibodies that tag antigens for destruction

Antibody-Mediated Response

antigen

Antigen binds only to antibody specific to it on a naive B cell.

clonalpopulationof effectorB cells

Effector B cells secrete antibodies.

Fig. 23-15a, p.395

B Cell Division

First exposure to antigen provokes aprimary immune response.

Anotherexposure to the same antigenprovokes secondaryresponse.

effector cells memory cells

naive B cell

effector cells memory cells

Fig. 23-15b, p.395

B Cell Differentiation

Fig. 23-15c, p.395

Secondary Immune Response

Cell-Mediated Immune Response

• Cytotoxic T cells target altered body cells that evade antibody-mediated immune response

• Antigen-presenting dendritic cells activate helper T cells

Fig. 23-16, p.396

Cell-Mediated Immune Response

• Helper T cells secrete cytokines– Induce formation of cytotoxic T cells– Proliferate NK cells – Enhance macrophage activity

• Destroy infected or altered cells

cytotoxic T-cell

tumor cell

Cell-Mediated Immune Response

Immunization

• Process that induces immunity• Active immunization:– Vaccination with antigen– Long-lasting immunity

• Passive immunization:– Purified antibody is injected– Protection is short lived

Allergies

• Immune reaction to harmless proteins (allergens)

• IgE binds to mast cells, causing inflammatory response

• Histamine release causes symptoms

Anaphylactic Shock

• Life-threatening allergic reaction• Caused by histamine released by many mast

cells• Airways constrict• Blood pressure drops as fluid leaks out of

capillaries

Autoimmune Disorders

• Failure of immune system to distinguish between self and nonself– produces antibodies against self

• Graves’ disease • Multiple sclerosis

Deficient Immune Responses

• Primary immune deficiencies– Present from birth

• Secondary immune deficiencies– Acquired by exposure to agent such as HIV

HIV Replication

reversetranscriptase

core proteins(two layers)

integrase

viral RNAenters cell

reversetranscriptionof viral RNA

host cell

viral DNA

viral genes are integrated

into the host DNADNA is

transcribed

viral RNAviral

proteins

budding

viral RNA

lipid envelopewith proteins

viral coatproteins

c The viral DNA becomes integrated into host cell’s DNA.a viral RNA

enters a T cell.

b Viral DNA forms by reverse transcription of viral RNA.

f Virus particles that bud from the infected cell may attack a new one.

d DNA, including the viral genes, is transcribed

viral DNA

Viral RNAviral

proteins

viral RNA

viral enzyme (reverse transcriptase)

25-30m

e Some transcripts are new viral RNA, others are translated into proteins. Both self-assemble as new virus particles.

Fig. 23-20, p.396

nucleus

HIV Infection

• HIV infects immune system cells– Macrophages, dendritic cells, helper T cells

• T cells are killed• Cytokine IL-4 is released• Immune system destroys itself• Secondary infections and tumors cause death

Table 23-4, p.399

HIV Transmission

• Virus transmitted by– Sex– Infected mothers– Shared needles

• Not transmitted by causal contact

Treatment

• No cure • AZT and other drugs slow disease and

increase life span• Traditional vaccines do not work• Researchers continue to work