Chapter 22

Essentials of Immunology

Cells and Organs of the Immune System

• Immunity: the ability of higher organisms to resist infection.

• Blood: made up of cells, plasma, and platelets.• Lymph: blood - RBCs.• Blood cells include: erythrocytes (RBCs) and

leukocytes (WBCs).• Plasma: liquid portion (54%) of blood, includes

electrolytes and proteins, such as fibrinogen clotting. Plasma - clotting agents = serum.

Cells and Organs of the Immune System (cont.)

• Platelets: cell fragments derived from the megakaryocyte cell, aid in clotting.

• Blood is pumped by the heart arteries capillaries veins back to heart.

• Lymph may leave the capillaries and circulate through the lymphatic system to the tissues.

• Lymph is drained from the tissues into the lymph nodes.

• Lymph nodes filter out microorganisms and antigens and may become infected by the organisms they are trying to filter out.

Cells and Organs of the Immune System (cont.)

• Leukocytes: macrophages, lymphocytes, and other polymorphonuclear cells, etc.

• Macrophages: found in tissues and lymph nodes, act as filters for the lymph.

• Lymphocytes: involved in the specific immune response, found in lymph nodes and spleen (filter for the blood), can be divided into T cells and B cells.

• T cells: originate in bone marrow, mature in the thymus

• B cells: originate and mature in bone marrow.

Lines of Defense

• The body’s 1st line of defense: physical and chemical barriers.

• 2nd line of defense: nonspecific immunity.

• 3rd line of defense: specific immunity.

Nonspecific Immunity

• Nonspecific immunity: the body’s innate ability to resist infection.

• Mediated by Phagocytes: cells that engulf, digest, and destroy most pathogens. Some phagocytes can acts as Antigen-Presenting Cells (APCs) in order to activate the specific immune response.

• Phagocytes contain lysosomes - what are these and what do they do?

• Polymorphonuclear phagocytes (PMNs), ex. neutrophils, contain large #’s of lysosomes.

Nonspecific Immunity (cont.)

• Macrophages: can ingest and destroy most pathogens and antigens and can cooperate with lymphocytes by acting as APCs.

• Monocyte: circulating precursor to macrophage.

• Macrophage: mature form that is fixed to tissue surfaces.

Nonspecific Immunity (cont.)

• Some pathogens have developed mechanisms for neutralizing the effects of toxic phagocyte products (ex. Staph. aureus, M. tuberculosis), for killing the phagocyte (ex. Staph. aureus, Strep. pyogenes), or for avoiding phagocytosis (Strep. pyogenes, Strep. pneumoniae).

• Hosts can combat these pathogens by mechanisms such as opsonization - production of antibodies to cell surface molecules on the pathogens to reverse the protective mechanisms developed by the pathogens.

The Specific Immune Response

• Specific Immunity: acquired ability to recognize and destroy an individual pathogen or its products.

• Mediated by Lymphocytes, Antibodies.

• APCs present antigens (Ag) from pathogens to T cells, which recognize the Ag through T cell receptors (TCRs).

• There are 3 types of T cells: cytotoxic T cells, T helper cells, and T suppressor cells.

The Specific Immune Response (cont.)

• Cytotoxic T cells directly attack and destroy APCs.• T suppressor cells regulate the attack.• T helper cells help indirectly by secreting cytokines

that activate other cells to destroy APCs and by stimulating B cells.

• B cells are stimulated by cytokines to produce antibodies (neutralize or destroy the Ag) and memory cells to guard against future attack by this pathogen.

The Specific Immune Response (cont.)

• 2 types of specific immunity: cell-mediated immunity and humoral (antibody-mediated) immunity.

• Cell-mediated immunity: kills pathogens and pathogen-infected host cells.

• Humoral immunity: effective against viruses and bacteria in blood or lymph or against soluble pathogen products, ex. toxins.

The Specific Immune Response (cont.)

• Nonspecific immune response: nonspecifically challenges any invading microbe.

• Specific immune response: tailored specifically to the invading organism and takes a few days to develop.

• Immunologic memory allows the host to specifically resist reinfection by previously encountered pathogens. We take advantage of this by vaccinations with live attenuated, killed, or subunits of pathogens.

• Tolerance is the acquired inability to make an immune response to certain antigens, ex. self antigens.

Immunogens and Antigens

• Antigens (Ag): react with either Ab or antigen-spec. T cell receptors (TCRs).

• Immunogens: substances that induce an immune response. Most Ag are immunogens.

Intrinsic Features of Immunogens• Immunogens share common properties: size, complexity, form.

• Haptens: small mw Ag that bind to Ab, but don’t induce an immune response unless coupled with a carrier, ex. sugars, amino acids. Most immunogens = 10,000+ mw.

• Complexity: complex, nonrepeating polymers (proteins, complex carbs.) are effective immunogens, whereas things composed of repeating monomers (nucleic acids, lipids) are not.

• Physical form: complex macromolecules in insoluble or aggregated form are better immunogens than the same molecules in soluble form.

Extrinsic Features of Immunogens

• Dose of the immunogen: 10g - 1 g generally required for an immune response, above or below this range can suppress immune response and cause tolerance.

• Route of administration: parenteral (outside GI) routes (ex. injection) generally more effective than topical or oral administration.

• Foreign nature of immunogen with respect to host: most important feature of an immunogen since the immune system is designed to recognize and eliminate only foreign (nonself) Ag.

T cell Receptor (TCR)

• Each T cell has thousands of copies of the same TCR on its surface.

• TCRs consist of variable and constant domains.

• The immune system can generate TCRs that will bind nearly every known peptide Ag.

• TCRs can only recognize and bind an Ag if it is presented to it by APCs.

Major Histocompatibility Complex (MHC) proteins

• MHCs = Human Leukocyte Antigens (HLAs) and are important in major donor organs for recipients.

• MHCs = antigen-presenting molecules that interact with Ag and TCR.

• MHC Class I: found on the surfaces of all nucleated cells.• MHC Class II: found only on the surface of B cells,

macrophages, and other APCs.• There are several hundred different MHC genes in

humans, which is the main reason why tissues transplanted from one individual to another seldom match and may be rejected as foreign.

Ag Presentation

• CD4 = coreceptor (in addition to TCR) for T helper cells.• CD8 = coreceptor (“) for cytotoxic T cells.• If any cell gets infected with foreign Ag, it will present

some of that Ag, using its MHC I, to cytotoxic T cells. Cytotoxic T cells will bind to the MHC I + Ag with their TCR and CD8 molecules and will release cytoxins to kill the target cell and cytokines to alert other immune cells.

• If a phagocyte ingests foreign Ag, it will present some of that Ag, with its MHC II, to T helper cells. T helper cells will bind to the MHC II + Ag with their TCR + CD4 molecules and will release cytokines to alert other immune cells.

Cytotoxic T cells

• Cytotoxic T cells kill any cell displaying foreign Ag.

• Cytotoxic T cells degranulate when this interaction occurs. The granules contain perforin and other enzymes that cause apoptosis, or programmed cell death.

• Cytotoxic T cells remain unaffected.• Degranulation occurs only at the contact surface

between the two cells.

Natural Killer Cells

• NK cells recognize that lack of appropriate MHC I proteins.

• Tumor cells and virus-infected cells are the main targets of NK cells.

• NK cells kill target cells with the same chemicals as those used by cytotoxic T cells.

• NK cells can destroy cells lacking appropriate MHC I without previous exposure to foreign Ag.

T Helper Cells

• T helper 1 cells activate macrophages.• T helper 2 cells interact with B cells and stimulate

Ab production.• Macrophages kill some foreign cells by

themselves, but need to be activated by (cytokines, etc.) T helper 1 cells to kill others that neutralize the initial efforts of phagocytes.

• B cells act as APCs, maintaining Ab on their surfaces without releasing them, until they are activated by T helper 2 cells to release the Ab.

Immunoglobulins (Ab)

• Ab are composed of light chains and heavy chains, constant and variable domains.

• IgG: 80% of all serum Ig• IgM: 10% of all serum Ig, also present on the surface of B

cells, binds Ag to B cells.• IgA: present in body secretions, ex. saliva, tears, breast

milk, mucus secretions.• IgE: rare Ig (1/50,000 serum Igs), but important in

mediation of immediate-type hypersensitivities (allergies).• IgD: low conc. in serum, abundant on surface of B cells,

binds Ag to B cells.

Complement

• Complement: proteins, many with enzymatic activity, that are present in the serum and activated by Ag-Ab complexes.

• Complement protein 1 (C1) is activated by Ag-Ab binding, which causes a cascade of complement protein interactions.

• Complement is activated by Ag binding to IgG or IgM only.• Complement can cause inflammation.• Several complement proteins cause lysis of bacterial cells.• Complement proteins can also enhance phagocyte

recognition and destruction of Ag by opsonization. Phagocytes have Ab and complement receptors on their surfaces.

Immunization to Prevent Disease

• The purposeful artificial induction of specific immunity to infectious diseases is a major contribution of microbiology to the treatment and prevention of infectious diseases.

Ways that humans and animals can acquire immunity to a disease

• 1. Natural active immunity: individual may acquire infection and develop immunity.

• 2. Artificial active immunity: individual may be exposed to an Ag to induce formation of Ab

• 3. Artifical passive immunity: individual may receive injections of an antiserum derived from another individual who has previously formed Ab against the Ag in question.

• 4. Natural passive immunity: newborns have maternal IgG in their blood for several months after birth.

New Immunization Strategies

• See Table 22.4 for diseases and types of vaccines used, ex. toxoid, killed bacteria, attenuated strains.

• Synthetic peptides (ex. for foot and mouth disease) and genetically engineered virus vaccines (ex. vaccinia virus smallpox) can be produced and used as vaccines. The requirement is that the vaccine contain an known epitope to the infectious agent, ex. Hepatitis B.

• DNA vaccines: DNA in a plasmid vector is injected into an animal the protein is produced within the animal the animal responds to the foreign protein effective vaccination results.

Hypersensitivity• Hypersensitivity: inappropriate immune responses that result in host

damage. • Immediate hypersensitivity rxn.: occur within min. after exposure to

Ag (allergen) = allergies, can be mild anaphylaxis. IgE and mast cells are involved histamine and serotonin are released.

• Delayed-type hypersensitivity: T helper 1 cells involved, can result in contact dermatitis due to poison ivy, jewelry, cosmetics, certain chemicals, and can illicit rxns. to microbes, ex. M. tuberculosis.

• SuperAg: proteins produced by bacteria and viruses that cause massive stimulation of immune cells, resulting in host damage, ex. S. aureus, Strep. pyogenes.