The Immune System: Innate and Adaptive Body Defenses: Part B

The Immune System: Innate and Adaptive Body Defenses: Part B

ADAPTIVE DEFENSES Adaptive immune response

Is specific Is systemic Has memory

Two separate overlapping arms1. Humoral (antibody-mediated) immunity2. Cellular (cell-mediated) immunity

ANTIGENS

Substances that can mobilize the adaptive defenses and provoke an immune response

Most are large, complex molecules not normally found in the body (nonself)

COMPLETE VS. INCOMPLETE ANTIGENS

Important functional properties Immunogenicity: ability

to stimulate proliferation of specific lymphocytes and antibodies

Reactivity: ability to react with products of activated lymphocytes and antibodies released

Examples: foreign protein, polysaccharides, lipids, and nucleic acids

Called Haptens Small molecules (peptides,

nucleotides, and hormones) Not immunogenic by

themselves Are immunogenic when

attached to body proteins Cause the immune system

to mount a harmful attack Examples: poison ivy,

animal dander, detergents, and cosmetics

Complete Antigens Incomplete Antigens

ANTIGENIC DETERMINANTS

Certain parts of an entire antigen that are immunogenic

Antibodies and lymphocyte receptors bind to them

Most naturally occurring antigens have numerous antigenic determinants that Mobilize several different lymphocyte

populations Form different kinds of antibodies against it

Large, chemically simple molecules (e.g., plastics) have little or no immunogenicity

Figure 20.7

Antigenic determinantsAntigen-bindingsitesAntibody A

Antibody BAntibody C

Antigen

SELF-ANTIGENS: MHC PROTEINS

Protein molecules (self-antigens) on the surface of cells

Antigenic to others in transfusions or grafts Example: MHC proteins

Coded for by genes of the major histocompatibility complex (MHC) and are unique to an individual

Class I MHC are found on all body cells Class II MHC are found only on certain cells that

act in immune response In the MHC is a groove where the cell displays a

peptide usually from broken down cellular proteins ***this peptide CAN come from fragments of foreign antigens

CELLS OF THE ADAPTIVE IMMUNE SYSTEM

Two types of lymphocytes B lymphocytes (B cells)—humoral immunity T lymphocytes (T cells)—cell-mediated immunity

Antigen-presenting cells (APCs) Do not respond to specific antigens Play essential auxiliary roles in immunity

LYMPHOCYTES

Originate in red bone marrow B cells mature in the red bone marrow T cells mature in the thymus

When mature, they have Immunocompetence; they are able to recognize

and bind to a specific antigen Self-tolerance – unresponsive to self antigens

Naive (unexposed) B and T cells are exported to lymph nodes, spleen, and other lymphoid organs

Figure 20.8

1

2

3

Red bone marrow: site of lymphocyte origin

Secondary lymphoid organs: site ofantigen encounter, and activation to becomeeffector and memory B or T cells

Primary lymphoid organs: site ofdevelopment of immunocompetence as B orT cells

Lymphocytes destined to become T cellsmigrate (in blood) to the thymus and develop immunocompetence there. B cells develop immunocompetence in red bone marrow.

Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. They “seed” the lymph nodes, spleen, and other lymphoid tissues where they encounter their antigen.

Antigen-activated immunocompetent lymphocytes (effector cells and memory cells) circulate continuously in the bloodstream and lymph and throughout the lymphoid organs of the body.

Redbone marrow

Bone marrow

Thymus

Lymph nodes,spleen, and otherlymphoid tissues

Immaturelymphocytes

Adaptive defenses Humoral immunityCellular immunity

T CELLS T cells mature in the thymus under negative

and positive selection pressures Positive selection

Selects T cells capable of binding to self-MHC proteins (MHC restriction)

Negative selection Prompts apoptosis of T cells that bind to self-antigens

displayed by self-MHC Ensures self-tolerance

Figure 20.9

Adaptive defensesPositive selection: T cells must recognize self major histocompatibility proteins (self-MHC).

Antigen-presentingthymic cell

Failure to recognize self-MHC results in apoptosis (death by cell suicide).

Recognizing self-MHC results inMHC restriction—survivors are restricted to recognizing antigen on self-MHC. Survivors proceedto negative selection.

Recognizing self-antigen results in apoptosis. This eliminates self-reactive T cells that could cause autoimmune diseases.

Failure to recognize (bind tightly to) self-antigen results in survival and continued maturation.

MHCSelf-antigen

T cell receptor

DevelopingT cell

Cellular immunity

Negative selection: T cells must not recognize self-antigens.

B CELLS

B cells mature in red bone marrow Self-reactive B cells

Are eliminated by apoptosis (clonal deletion) or Undergo receptor editing – rearrangement of

their receptors Are inactivated (anergy) if they escape from the

bone marrow

ANTIGEN RECEPTOR DIVERSITY

Lymphocytes make up to a billion different types of antigen receptors Coded for by ~25,000 genes Gene segments are shuffled by somatic

recombination Genes determine which foreign substances

the immune system will recognize and resist NOT the antigen!!!!

ANTIGEN-PRESENTING CELLS (APCS)

Engulf antigens Present fragments of antigens to be

recognized by T cells Major types

Dendritic cells in connective tissues and epidermis

Macrophages in connective tissues and lymphoid organs

B cells

Figure 20.10

MACROPHAGES AND DENDRITIC CELLS

Present antigens and activate T cellsMacrophages mostly remain fixed in the

lymphoid organsDendritic cells internalize pathogens and

enter lymphatics to present the antigens to T cells in lymphoid organs

Activated T cells release chemicals thatProd macrophages to become insatiable

phagocytes and to secrete bactericidal chemicals

ADAPTIVE IMMUNITY: SUMMARY

Uses lymphocytes, APCs, and specific molecules to identify and destroy nonself substances

Depends upon the ability of its cells to Recognize antigens by binding to them Communicate with one another so that the whole

system mounts a specific response

HUMORAL IMMUNITY RESPONSE

Antigen challenge First encounter between an antigen and a naive

immunocompetent lymphocyte Usually occurs in the spleen or a lymph node

If the lymphocyte is a B cell The antigen provokes a humoral immune

response Antibodies are produced

CLONAL SELECTION

1. B cell is activated when antigens bind to its surface receptors and cross-link them

2. Receptor-mediated endocytosis of cross-linked antigen-receptor complexes occurs

3. Stimulated B cell grows to form a clone of identical cells bearing the same antigen-specific receptors(T helper cells are usually required to help B cells achieve full activation)

FATE OF THE CLONES

Most clone cells become plasma cells secrete specific antibodies at the rate of 2000

molecules per second for four to five days Secreted antibodies

Circulate in blood or lymph Bind to free antigens Mark the antigens for destruction

Clone cells that do not become plasma cells become memory cells Provide immunological memory Mount an immediate response to future

exposures of the same antigen

FATE OF THE CLONES

Clone cells that do not become plasma cells become memory cells Provide immunological memory Mount an immediate response to future

exposures of the same antigen Memory cells allow the secondary immune

response to be faster, more prolonged and more effective than primary immune response. (antibodies can peak in 2-3 days instead of the nearly 10 days in first response lag time)

Figure 20.11 (1 of 2)

Primary response(initial encounterwith antigen)

Antigen bindingto a receptor on aspecific B lymphocyte (B lymphocytes with non-complementary receptors remain inactive)

Proliferation toform a cloneActivated B cells

Plasma cells(effector B cells)Secretedantibodymolecules

Memory B cell—primed to respond to same antigen

Adaptive defenses Humoral immunity

Antigen

IMMUNOLOGICAL MEMORY

Primary immune response Occurs on the first exposure to a specific

antigen Lag period: three to six days Peak levels of plasma antibody are reached in 10

days Antibody levels then decline

Figure 20.13

PassiveActive

Humoralimmunity

Artificiallyacquired

Injection ofimmune serum (gamma globulin)

Naturallyacquired

Antibodiespass from mother tofetus via placenta; or to infant in her milk

Artificiallyacquired

Vaccine;dead or attenuated pathogens

Naturallyacquired

Infection;contact with pathogen

ANTIBODIES

Immunoglobulins—gamma globulin portion of blood

Proteins secreted by plasma cells Capable of binding specifically with antigen

detected by B cells

BASIC ANTIBODY STRUCTURE

T-or Y-shaped monomer of four looping linked polypeptide chains

Two identical heavy (H) chains and two identical light (L) chains

Variable (V) regions of each arm combine to form two identical antigen-binding sites

Constant (C) region of stem determines The antibody class (IgM, IgA, IgD, IgG, or IgE) The cells and chemicals that the antibody can

bind to How the antibody class functions in antigen

elimination

Figure 20.14a

Antigen-bindingsite

Stemregion

Hingeregion

Light chainconstant regionDisulfide bond

Light chainvariable region

Heavy chainconstant region

Heavy chainvariable region

(a)

ANTIBODIES: TYPE/ LOCATION/ FUNCTION/ UNIQUE TRAITS

Type of Antibody

Location Function/ traits

IgD Always attached to B cell Activates B cells

IgM Can be attached to B cells or free in blood plasma

Largest antibody (actually huge compared to rest) / first Ig released in

primary response

IgG 75-85% of all antibodies in blood

Most abundant in blood plasma, can cross placental barrier so IgG is passive

immunity to fetus

IgA Secretions such as saliva, tears, intestinal juice, milk

Secretory IgA because bathes body surfaces/ important first defense

IgE Mucosal lining of respiratory and GI tracts/ tonsils

Troublemaker antibodies involved in allergies

CLASSES OF ANTIBODIES IgM

A pentamer; first antibody released Potent agglutinating agent Readily fixes and activates complement

IgA (secretory IgA) Monomer or dimer; in mucus and other

secretions Helps prevent entry of pathogens

Table 20.3

CLASSES OF ANTIBODIES

IgD Monomer attached to the surface of B cells Functions as a B cell receptor

IgG Monomer; 75–85% of antibodies in plasma From secondary and late primary responses Crosses the placental barrier

IgE Monomer active in some allergies and parasitic

infections Causes mast cells and basophils to release

histamine

Table 20.3

GENERATING ANTIBODY DIVERSITY

Billions of antibodies result from somatic recombination of gene segments

Hypervariable regions of some genes increase antibody variation through somatic mutations

Each plasma cell can switch the type of H chain produced, making an antibody of a different class

ANTIBODY TARGETS

Antibodies inactivate and tag antigens Form antigen-antibody (immune) complexes

Defensive mechanisms used by antibodies PLAN= precipitation/ lysis by complement/

agglutination/ neutralization Neutralization and agglutination (the two most

important) Precipitation is similar to agglutination Complement fixation we have discussed earlier

and is the chief antibody defense against cellular antigens such as bacteria/ foreign red blood cells

NEUTRALIZATION

Simplest mechanism Antibodies block specific sites on viruses or

bacterial exotoxins Prevent these antigens from binding to

receptors on tissue cells Antigen-antibody complexes undergo

phagocytosis

AGGLUTINATION

Antibodies bind the same determinant on more than one cell-bound antigen

Cross-linked antigen-antibody complexes agglutinate Example: clumping of mismatched blood cells

PRECIPITATION

Soluble molecules are cross-linked Complexes precipitate and are subject to

phagocytosis

COMPLEMENT FIXATION AND ACTIVATION

Main antibody defense against cellular antigens

Several antibodies bind close together on a cellular antigen

Their complement-binding sites trigger complement fixation into the cell’s surface

Complement triggers cell lysis Activated complement functions

Amplifies the inflammatory response Opsonization Enlists more and more defensive elements

Figure 20.15

Inactivates by

Antigen Antibody

Fixes and activates

Enhances Enhances Leads to

Phagocytosis

Chemotaxis

Histaminerelease

Inflammation Cell lysis

Agglutination(cell-bound antigens)

Precipitation(soluble antigens)

Neutralization(masks dangerousparts of bacterial

exotoxins; viruses)

Complement

Antigen-antibodycomplex

Adaptive defenses Humoral immunity

CELL-MEDIATED IMMUNE RESPONSE

As opposed to Humoral Immune Response where the antibodies attach to obvious antigens and mark them for destruction, cell-mediated immune response finds the hidden pathogens and then directly attacks.

T cells provide defense against intracellular antigens Two types of surface receptors of T cells

T cell antigen receptors (MHC) Cell differentiation glycoproteins

CD4 or CD8 Play a role in T cell interactions with other cells

CELL-MEDIATED IMMUNE RESPONSE

Major types of T cells CD4 cells become helper T cells (TH) when

activated CD8 cells become cytotoxic T cells (TC) that

destroy cells harboring foreign antigens Other types of T cells

Regulatory T cells (TREG) Memory T cells

Figure 20.16

Maturation

CD4cell

T cellreceptor

T cellreceptor

CD4

Helper T cells(or regulatory T cells)

Cytotoxic T cells

APC(dendritic cell)

APC(dendritic cell)

Activation Activation

Memorycells

CD8cell

CD8

Lymphoidtissues andorgans

Blood plasma

Thymus

Class I MHCprotein

Class II MHCprotein

Effectorcells

Adaptive defenses Cellular immunity

Immaturelymphocyte

Red bone marrow

COMPARISON OF HUMORAL AND CELL-MEDIATED RESPONSE

Antibodies of the humoral response The simplest ammunition of the immune

response Targets

Bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph)

T cells of the cell-mediated response Recognize and respond only to processed

fragments of antigen displayed on the surface of body cells

Targets Body cells infected by viruses or bacteria Abnormal or cancerous cells Cells of infused or transplanted foreign tissue

MONOCLONAL ANTIBODIES

Commercially prepared pure antibody Produced by hybridomas

Cell hybrids: fusion of a tumor cell and a B cell Proliferate indefinitely and have the ability to

produce a single type of antibody Used in research, clinical testing, and cancer

treatment Attach to cancer cells and induce immune

response Also used to treat rheumatoid arthritis, Crohn’s

disease, ulcerative colitis, prevention of kidney transplant rejections, and severe allergic asthma

ANTIGEN RECOGNITION

Immunocompetent T cells are activated when their surface receptors bind to a recognized antigen (nonself)

T cells must simultaneously recognize Nonself (the antigen) Self (an MHC protein of a body cell)

MHC PROTEINS

Two types of MHC proteins are important to T cell activation Class I MHC proteins - displayed by all cells

except RBCs Class II MHC proteins – displayed by APCs

(dendritic cells, macrophages and B cells) Both types are synthesized at the ER and

bind to peptide fragments

CLASS I MHC PROTEINS

Bind with fragment of a protein synthesized in the cell (endogenous antigen)

Endogenous antigen is a self-antigen in a normal cell; a nonself antigen in an infected or abnormal cell

Informs cytotoxic T cells of the presence of microorganisms hiding in cells (cytotoxic T cells ignore displayed self-antigens)

Figure 20.17a

Cytoplasm of any tissue cell

Transportprotein(ATPase)

Endogenous antigen—self-protein or foreign(viral or cancer) protein

Endogenousantigen is degradedby protease.

Endogenous antigenpeptides enter ER viatransport protein.

Extracellular fluid

(a) Endogenous antigens are processed and displayed on class I MHC of all cells.

Antigenic peptidePlasma membrane of a tissue cell

Cisternae ofendoplasmicreticulum (ER)

Endogenousantigen peptide isloaded onto classI MHC protein.

Loaded MHC proteinmigrates in vesicle tothe plasma membrane,where it displays theantigenic peptide.

12

3

4

CLASS II MHC PROTEINS

Bind with fragments of exogenous antigens that have been engulfed and broken down in a phagolysosome

Recognized by helper T cells

Figure 20.17b

Cytoplasm of APC

Lysosome

Class II MHCis exportedfrom ER in avesicle.

Vesicle fuses withphagolysosome. Invariantchain is removed, andantigen is loaded.

Vesicle withloaded MHCmigrates to theplasmamembrane.

Class II MHC issynthesized in ER.

Phagosome mergeswith lysosome, forminga phagolysosome;antigen is degraded.

Phagosome

Cisternae ofendoplasmicreticulum (ER)

Invariant chain prevents class II MHC from bindingto peptides in the ER.

Extracellularantigen (bacterium)is phagocytized.

Extracellular fluid

(b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs).

Plasma membrane of APCExtracellularantigen

Antigenic peptide

1a

1b

2a

2b

3

4

T CELL ACTIVATION

Remember immunocompetent T cells are considered “naïve” until activated

APCs (most often a dendritic cell) migrate to lymph nodes and other lymphoid tissues to present their antigens to T cells

T cell activation is a two-step process1. Antigen binding2. Co-stimulation

Figure 20.16

Maturation

CD4cell

T cellreceptor

T cellreceptor

CD4

Helper T cells(or regulatory T cells)

Cytotoxic T cells

APC(dendritic cell)

APC(dendritic cell)

Activation Activation

Memorycells

CD8cell

CD8

Lymphoidtissues andorgans

Blood plasma

Thymus

Class I MHCprotein

Class II MHCprotein

Effectorcells


Immaturelymphocyte

Red bone marrow

T CELL ACTIVATION: ANTIGEN BINDING

CD4 and CD8 cells bind to different classes of MHC proteins (MHC restriction)

CD4 cells bind to antigen linked to class II MHC proteins of APCs

CD8 cells are activated by antigen fragments linked to class I MHC of APCs


Dendritic cells are able to obtain other cells’ endogenous antigens by Engulfing dying virus-infected or tumor cells Importing antigens through temporary gap

junctions with infected cells Dendritic cells then display the endogenous

antigens on both class I and class II MHCs


TCR that recognizes the nonself-self complex is linked to multiple intracellular signaling pathways

Other T cell surface proteins are involved in antigen binding (e.g., CD4 and CD8 help maintain coupling during antigen recognition)

Antigen binding stimulates the T cell, but co-stimulation is required before proliferation can occur

Figure 20.18

1 Dendritic cell engulfs an exogenous antigen, processes it, and displays its fragments on class II MHC protein.

2 ImmunocompetentCD4 cell recognizes antigen-MHC complex. Both TCR and CD4 protein bind to antigen-MHC complex.

3 CD4 cells are activated,proliferate (clone), and become memory and effector cells.

Viral antigen

Dendriticcell

Class lI MHCproteindisplayingprocessedviral antigenCD4 protein

Immunocom-petent CD4T cell

ActivatedhelperT cells

Helper Tmemory cell

T cell receptor(TCR)

Cloneformation


T CELL ACTIVATION: CO-STIMULATION

Requires T cell binding to other surface receptors on an APCDendritic cells and macrophages produce

surface B7 proteins when innate defenses are mobilized

B7 binding with a CD28 receptor on a T cell is a crucial co-stimulatory signal

Cytokines (interleukin 1 and 2 from APCs or T cells) trigger proliferation and differentiation of activated T cell

T CELL ACTIVATION: CO-STIMULATION

T cells that are co-stimulated are activated Produce cytokines Enlarge, proliferate, and form clones Differentiate and perform functions according to their

T cell class

Without co-stimulation, anergy occurs T cells

Become tolerant to that antigen Are unable to divide Do not secrete cytokines

T CELL ACTIVATION: CO-STIMULATION Primary T cell response peaks within a week T cell apoptosis occurs between days 7 and

30 Effector activity wanes as the amount of

antigen declines Benefit of apoptosis: activated T cells are a

hazard Memory T cells remain and mediate

secondary responses

CYTOKINES Mediate cell development, differentiation, and

responses in the immune system Include interleukins and interferons Interleukin 1 (IL-1) released by macrophages co-

stimulates bound T cells to Release interleukin 2 (IL-2) Synthesize more IL-2 receptors

IL-2 is a key growth factor, acting on cells that release it and other T cells Encourages activated T cells to divide rapidly Used therapeutically to treat melanoma and kidney

cancers Other cytokines amplify and regulate innate and

adaptive responses

ROLES OF HELPER T(TH) CELLS

Play a central role in the adaptive immune response

Once primed by APC presentation of antigen, theyHelp activate T and B cells Induce T and B cell proliferationActivate macrophages and recruit other

immune cells Without TH, there is no immune response

HELPER T CELLS

Interact directly with B cells displaying antigen fragments bound to MHC II receptors

Stimulate B cells to divide more rapidly and begin antibody formation; results in faster response and more antibodies produced

B cells may be activated without TH cells by binding to T cell–independent antigens, but this activation is weak and short-lived compared to TH activation

Most antigens require TH co-stimulation to activate B cells

Figure 20.19a

(a)B cell (being activated)

MHC II proteinof B cell displayingprocessed antigen

IL- 4 and othercytokines

Helper T cellCD4 protein

T cell receptor (TCR)

Activated helperT cell 1

2

TH cell binds with the self-nonself complexes of a B cell that has encountered its antigen and is displaying it on MHC II on its surface.

TH cell releases interleukins as co-stimulatory signals to complete B cell activation.

TH cell help in humoral immunity

HELPER T CELLS

Cause dendritic cells to express co-stimulatory molecules required for CD8 cell activation

Figure 20.19b

Class II MHCprotein

Class IMHC protein

APC (dendritic cell)

IL-2

CD4 protein

CD8 T cell

Helper T cell

CD8protein

(b)

1

2

Previously activated TH cell binds dendritic cell.

TH cell stimulates dendritic cell to express co-stimulatory molecules (not shown) needed to activate CD8 cell.

3 Dendritic cell can now activate CD8 cell with the help of interleukin 2 secreted by TH cell.

TH cell help in cell-mediated immunity

ROLES OF CYTOTOXIC T(TC) CELLS

Directly attack and kill other cells Activated TC cells circulate in blood and

lymph and lymphoid organs in search of body cells displaying antigen they recognize

Targets Virus-infected cells Cells with intracellular bacteria or parasites Cancer cells Foreign cells (transfusions or transplants)

CYTOTOXIC T CELLS

Bind to a self-nonself complex Can destroy all infected or abnormal cells Lethal hit

Tc cell releases perforins and granzymes by exocytosis

Perforins create pores through which granzymes enter the target cell

Granzymes stimulate apoptosis In some cases, TC cell binds with a Fas

receptor on the target cell, and stimulates apoptosis

Figure 20.20a

1 TC binds tightly tothe target cell when it identifies foreign antigen on MHC I proteins.

3 Perforin molecules insert into the target cell membrane, polymerize, and form transmembrane pores (cylindrical holes) similar to those produced by complement activation.4 Granzymes enter the

target cell via the pores. Once inside, these proteases degrade cellular contents, stimulating apoptosis.

5 The TC detaches and searches for another prey.

(a) A mechanism of target cell killing by TC cells.

2 TC releases perforin and granzyme molecules from its granules by exocytosis.

CytotoxicT cell (TC)

Targetcell

Perforin

TC cellmembrane

Targetcellmembrane

Perforinpore

Granzymes

Granule


NATURAL KILLER CELLS

Recognize other signs of abnormality Lack of class I MHC Antibody coating a target cell Different surface marker on stressed cells

Use the same key mechanisms as Tc cells for killing their target cells

REGULATORY T (TREG) CELLS

Dampen the immune response by direct contact or by inhibitory cytokines

Important in preventing autoimmune reactions

Figure 20.21

Ag-infectedbody cell engulfedby dendritic cell

Becomes

ActivatesActivates

Induceco-stimulation

Free Agsmay directlyactivate B cell

NaïveCD4T cells

Activated to cloneand give rise to

NaïveCD8T cells

Antigen-activated B cells

Activated to cloneand give rise to

Cytokines stimulate

ActivatedcytotoxicT cells

Memoryhelper T cells

ActivatedhelperT cells

Memorycytotoxic T cells

Together the nonspecific killersand cytotoxic T cells mount a

physical attack on the Ag

Nonspecific killers(macrophages andNK cells of innateimmunity)

Circulating lgs along withcomplement mount a chemical attack on the Ag

Antibodies (Igs)

Secrete

Plasma cells(effector B cells)

MemoryB cells

Clone andgive rise to

InhibitsInhibits

Antigen (Ag) intruder

Innate defenses

Surfacebarriers

Internaldefenses

Adaptive defenses

Triggers

Ag-presenting cell(APC) presentsself-Ag complex

Cell-mediatedimmunity

Humoralimmunity

ORGAN TRANSPLANTS

Four varieties Autografts: from one body site to another in the

same person Isografts: between identical twins Allografts: between individuals who are not

identical twins Xenografts: from another animal species

PREVENTION OF REJECTION

Depends on the similarity of the tissues Patient is treated with immunosuppressive

therapy Corticosteroid drugs to suppress inflammation Antiproliferative drugs Immunosuppressant drugs

Many of these have severe side effects

IMMUNODEFICIENCIES

Congenital and acquired conditions that cause immune cells, phagocytes, or complement to behave abnormally

SEVERE COMBINED IMMUNODEFICIENCY (SCID) SYNDROME Genetic defect Marked deficit in B and T cells Abnormalities in interleukin receptors Defective adenosine deaminase (ADA)

enzyme Metabolites lethal to T cells accumulate

SCID is fatal if untreated; treatment is with bone marrow transplants

“bubble boy” disease

HODGKIN’S DISEASE

An acquired immunodeficiency Cancer of the B cells Leads to immunodeficiency by depressing

lymph node cells

ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

Cripples the immune system by interfering with the activity of helper T cells

Characterized by severe weight loss, night sweats, and swollen lymph nodes

Opportunistic infections occur, including pneumocystis pneumonia and Kaposi’s sarcoma


Caused by human immunodeficiency virus (HIV) transmitted via body fluids—blood, semen, and vaginal secretions

HIV enters the body viaBlood transfusionsBlood-contaminated needlesSexual intercourse and oral sex

HIVDestroys TH cellsDepresses cell-mediated immunity


HIV multiplies in lymph nodes throughout the asymptomatic period

Symptoms appear in a few months to 10 years

HIV-coated glycoprotein complex attaches to the CD4 receptor

HIV enters the cell and uses reverse transcriptase to produce DNA from viral RNA

The DNA copy (a provirus) directs the host cell to make viral RNA and proteins, enabling the virus to reproduce


HIV reverse transcriptase produces frequent transcription errors; high mutation rate and resistance to drugs

Treatment with antiviral drugs Reverse transcriptase inhibitors (AZT)

Protease inhibitors (saquinavir and ritonavir) New Fusion inhibitors that block HIV’s entry to

helper T cells

AUTOIMMUNE DISEASES

Immune system loses the ability to distinguish self from foreign

Production of autoantibodies (antibodies that attach to body’s own tissues) and sensitized TC cells that destroy body tissues

Examples include multiple sclerosis, myasthenia gravis, Graves’ disease, type I diabetes mellitus, systemic lupus erythematosus (SLE), glomerulonephritis, and rheumatoid arthritis

MECHANISMS OF AUTOIMMUNE DISEASES

1. Foreign antigens may resemble self-antigens Antibodies against the foreign antigen may

cross-react with self-antigen Example streptococcal infection antibodies can

attack heart muscle as well…rheumatic fever

2. New self-antigens may appear, generated by Gene mutations Changes in self-antigens by hapten attachment

or as a result of infectious damage Trauma can stimulate novel self-antigens

previously not shown (for example hidden behind blood-brain barrier)

HYPERSENSITIVITIES

Immune responses to a perceived (otherwise harmless) threat

Causes tissue damage Different types are distinguished by

Their time courseWhether antibodies or T cells are involved

Antibodies cause immediate and subacute hypersensitivities

T cells cause delayed hypersensitivity

IMMEDIATE HYPERSENSITIVITY

Acute (type I) hypersensitivities (allergies) begin in seconds after contact with allergen

Initial contact is asymptomatic but sensitizes the person

Reaction may be local or systemic The mechanism involves IL-4 secreted by T

cells IL-4 stimulates B cells to produce IgE IgE binds to mast cells and basophils,

resulting in a flood of histamine release and inducing the inflammatory response

ANAPHYLACTIC SHOCK

Systemic response to allergen that directly enters the bloodExample: bee sting, spider bite

Basophils and mast cells are enlisted throughout the body

Systemic histamine releases may causeConstriction of bronchioles Sudden vasodilation and fluid loss from the

bloodstreamHypotensive shock and death

Treatment: epinephrine

SUBACUTE HYPERSENSITIVITIES

Caused by IgM and IgG transferred via blood plasma or serum

Slow onset (1–3 hours) and long duration (10–15 hours)

Cytotoxic (type II) reactionsAntibodies bind to antigens on specific

body cells, stimulating phagocytosis and complement-mediated lysis of the cellular antigens

Example: mismatched blood transfusion reaction

SUBACUTE HYPERSENSITIVITIES Immune complex (type III) hypersensitivity

Usually long term exposure Antigens are widely distributed through the body

or blood Insoluble antigen-antibody complexes form Complexes cannot be cleared from a particular

area of the body Intense inflammation, local cell lysis, and death

may result Example: systemic lupus erythematosus (SLE)

DELAYED HYPERSENSITIVITIES (TYPE IV)

Slow onset (one to three days) Mechanism depends on helper T cells Cytokine-activated macrophages and

cytotoxic T cells cause damage Example: allergic contact dermatitis

Poison ivy Nickel in jewelry Cosmetic or deodorant allergies

Documents

The Immune System: Innate and Adaptive Body Defenses: Part B