• Chapter 43 ~ The Body’s Defenses

T CELLS.htm

Overview• Three cooperative lines of defense• Defense against pathogens from food, air, water as

well as cancerous cells• Nonspecific: (innate)

– First Line: external– Second Line: internal

• Inflammation signals its action has been activated

• Specific: Third Line (acquired)– Immune System– Simultaneous with Second Line of Defense

Lines of Defense

I NONSPECIFIC DEFENSES

• .

First Line of defense• External

– Prevents entry of microbes

• Skin– Physical barrier

• Mucous membranes-trap; ciliated epithelial cells sweep out mucus and trapped particulate – Trachea

• Secretions: Chemical defenses:• Oil and sweat glands create a low pH (skin 3-5)• Normal flora help maintain this low pH• Saliva, tears, mucous secretions contain antimicrobial proteins–

for example lysozymes• Stomach pH—exception is Hepatitis A virus

Second Line of Defense

• First line broken….

• 1.Phagocytic white blood cells (leukocytes)

• 2.Antimicrobial proteins

• 3. Natural Killer Cells

• 4. The Inflammatory response

1. Types of Phagocytic White Blood Cells• Neutrophils 60-70% WBCs;Enter infected cellsAttracted by chemicals released by infected cell engulf and destroy microbes inside infected tissue. Short life span—few days• Monocytes 5% WBCs Develop into macrophages Large; Long lived, use pseudopodia Digest microbeSome migrate; some strategically fixed—such as spleen,

lymph nodes and tissue

• Eosinophils 1.5% WBCs; destroy large parasitic invaders (parasitic

worms)Position themselves against invader-discharge enzymes

• Natural killer (NK) cells• Don’t attack microbe directly• destroy virus-infected body cells & abnormal cells• Not phagocytes• Attack-cause cell lysis

• 2. Antimicrobial Proteins• 1. Complement Proteins—lysis results

• 2. Interferons-• Produced by virus-infected cells• Inhibit viral replication and activate natural killer cells• secreted by virus infected cells—limit cell-to-cell infection• Reproduced by recombinant DNA—being tested for treatment of

viral infections and cancer

Other Nonspecific Defenses

The Inflammatory Response

• Occurs upon damage to tissue– Physical injury– Microorganism entry

3.The Inflammatory Response (localized)• Tissue injury; release of chemical signals~ • most

common is histamine (basophils & mast cells): • Causing Vasodilation and increased permeability; • Prostaglandins released from WBC and damaged tissues

– This increases blood flow to injury

– Enhances delivery of clotting elements &more phagocyte( cells release chemokines attracts) :

• The Vasodilation and increased flow of blood causes characteristic reddening.

4- Phagocytosis of pathogens~neutrophils arrive first, followed by macrophagesMacrophages destroy as well as clean up (pus) •

Systemic Responses to more severe infection

Meningitis, appendicitisFever & Pyrogens: leukocyte-released molecules (pyrogens) increase body

temperature—sets body’s thermostat at higher temp.

High Temp: inhibits microbe growth; facilitate phagocytosis; speed up tissue repair

Septic ShockOverwhelming systemic responseHigh fever & low blood pressure Most common cause of death in U.S. non-coronary critical care

units

II SPECIFIC IMMUNITY

• .

Specific Immunity—Acquired Immunity

• Lymphocytes provide specific defense (special kinds of leukocytes)– B cells and T cells

• The Innate and acquired defenses interact---Helper T cells coordinate.

• Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms); usually a protein.

• Antibodies: circulating antigen-binding immunoglobulin, produced by B cells

• Antigen receptors: plasma membrane receptors on B and T cells

• Ended here Friday

APC- Antigen Presenting Cells

• Macrophages and B-Cells

• Display internalized antigens to Th cells.

• Lymphocyctes• Develop from Pluripotent stem

cellsin bone marrow or liver of fetus.• Display specificity for a particular epitope (binding site) on an

antigen.• Recognize self from non-self cells

• 2 main types:– 1. B Cells – 2. T Cells (thymus)

• B-Cells

--mature in bone marrow– Secrete antibodies (immunoglobulins)

– Recognize intact antigens (on whole microbes found while patrolling body fluids—blood/lymph)

– Humoral Response

– Also have membrane antibodies on surface

– APC-present antigens to Th, then they are activated and proliferate

– -----------------------------------------------

T-Cells• mature in thymus• don’t secrete antibodies• 2 types

• cytoxic (killer) -T Cells– Function in Cell-Mediated Immunity– Infected cells, cancerous, foreign cells– Receptors for Class I MHC– CD8 protein enhances binding to Th cell for activation.

Helper T-Cells

• Usually needed to activate B Cells & their proliferation– T-Dependent antigens

Have receptors for class II MHC proteins

CD4 protein enhances Th cell binding to B-cell in the humoral response.

Function in both types of immune responses:

1. Humoral (free invaders in body fluids)

2. Cell-Mediated (infected, defective, foreign cell)

MHC• Major histocompatability complex

– Glycoproteins embedded in plasma membranes.– “self-markers”; Most polymorphic genes known

– 2 main classes:• Class I MHC: located on all nucleated cells

• Class II MHC: specialized cells: macrophages & B cells.• Function in antigen presentation-bind to antigen &

facilitate antigen binding to a T cell.

Clonal selection- page 905Antigens interact with specific lymphocytes, inducing

immune responses and immunological memory

• Clonal selection: antigen-driven cloning of lymphocytes

• Antigen binds to receptor• “Selected” cell proliferates.• 2 “clones” of cells are produced.• 1.Effector cells: short-lived cells

that combat the antigen.• 2. Memory cells: long-lived cells

that bear receptors for the antigen.

• “Each antigen, by binding to specific receptors, selectively activates a tiny fraction of cells from the body’s diverse pool of lymphocytes; this relatively small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating the antigen.”

Induction of Immune Responses• Primary immune response: lymphocyte proliferation and differentiation the

1st time the body is exposed to an antigen.takes 10-17 days for max response.

During this time, selected B- cells generate antibody producing effector cells (clonal selection) called Plasma cells:

And Selected T-cells will produce effector T cells (no antibodies)• Secondary immune response: immune response if the individual is exposed

to the same antigen at some later time~ Immunological memory• Faster, more intense, longer than Primary

2 Types of immune responses• Humoral immunity• B cell activation• Production of antibodies• Microbes circulating in blood

and lymph (body fluids)• Defend against free bacteria,

toxins, and viruses in body fluids.

• Cell-mediated immunity• Tc cell activation• Binds to and/or lyses cells• Defend against cells infected

with bacteria, viruses, fungi, protozoa, and parasites; nonself cells, cancer.

Helper T cells—bring on the calvary• Function in both humoral (antibody production) & cell-mediated immunity• Activated by antigen presenting cells (APCs) bearing the class MHCII molecule• CD4 (Th surface protein), enhances activation, as does

Interlukin 1 (IL-1) .• Once activated, it proliferates, clone forms, Interlukin II (IL-2)further stimulates and helps

activate B-cells and Tc• Cytokines secreted (stimulate other lymphocytes): a) interleukin-2 (IL-2):

activates B cells and cytotoxic T cells b) interleukin-1 (IL-1): activates helper T cell to produce IL-2

Cell-mediated Immunity:cytotoxic T cells• Destroy cells infected by intracellular pathogens and cancer cells• Infected cell displays antigen (pieces of pathogen) on its….• Class I MHC molecules • Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC)• TC cell releases perforin, a protein that forms pores in the target cell membrane; cell lysis and pathogen

exposure to circulating antibodies

Antibody Structure & Function• Globular serum proteins

• Epitope: region on antigen surface recognized by antibodies

• 2 heavy chains and 2 light chains joined by disulfide bridges

• 2 Antigen-binding sites (variable region)

5 classes of Immunoglobins• IgM: 1st to circulate; First to respond to

infection. indicates current infection; too large to cross placenta

• IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement

• IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration

• IgD: do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells

• IgE: very large; small quantity; releases histamines-allergic reaction

Abnormal immune function• Allergies (anaphylactic shock): hypersensitive responses to environmental antigens

(allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine

• Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus

• Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.

Antibody-mediated Antigen Disposal• Neutralization (opsonization): antibody binds to and blocks antigen activity• Agglutination: antigen (and microbe) clumping• Precipitation: cross-linking of soluble antigens (proteins)• Complement fixation: activation of 20 serum proteins, through

cascading action, lyse viruses and pathogenic cells.– MAC attack

Immunity in Health & Disease• Active: naturally acquired : conferred

immunity by recovering from disease

• Active: artificially acquired: immunization and vaccination;

produces a primary response & memory

• Passive immunity: transfer of immunity (antibodies) from one individual to another.

• Short term—weeks to months

natural: mother to fetus via breast milk

artificial: rabies antibodies

• ABO blood groups (antigen presence)

• Rh factor (blood cell antigen); Rh- mother vs. an Rh+ fetus (inherited from father). IgG

..\..\videos

• NOVA Online Surviving AIDS See HIV in Action.mht NOVA Online Surviving AIDS Fighting Back.mht