Immunology Basics Quiz

Immune System

• The immune system defends against pathogens and other harmful substances.
• The two main categories of the immune system are innate and adaptive defenses.
• Innate defenses are nonspecific and respond quickly, while adaptive defenses are specific, take longer to respond, and work in tandem with innate defenses.

Innate Defenses

• The first line of defense includes intact skin and mucous membranes, which prevent the entry of microorganisms.
• The second line of defense includes antimicrobial proteins, phagocytes, and other cells. These defenses inhibit the spread of invaders and are characterized by inflammation, which is a critical mechanism.

Adaptive Defenses

• The third line of defense is the adaptive (specific) defense system, which launches an attack against specific foreign substances.

Surface Barriers

• The skin and mucous membranes, along with their secretions, form the first line of defense.
• Keratin in the skin acts as a physical barrier, resistant to weak acids, bases, and bacteria.
• Mucosae provide similar mechanical barriers.

Epithelial Chemical Barriers

• Epithelial membranes produce chemicals that destroy microorganisms.
• Skin acidity (pH 3-5) inhibits bacterial growth.
• Sebum contains chemicals toxic to bacteria.
• Stomach mucosae secrete hydrochloric acid and protein-digesting enzymes.
• Saliva and lacrimal fluid contain lysozyme.
• Mucus traps microorganisms in the digestive and respiratory systems.

Respiratory Tract Mucosae

• Mucus-coated hairs in the nose trap inhaled particles.
• The mucosa of the upper respiratory tract is ciliated, with cilia sweeping dust and bacteria away.

Internal Defenses: Cells and Chemicals

• The body uses nonspecific cellular and chemical defenses.
• Phagocytes and natural killer (NK) cells are involved, along with antimicrobial proteins, and inflammatory responses.
• Harmful substances have unique surface carbohydrates that aid in identification by internal defenses.

Phagocytes

• Macrophages are the main phagocytic cells. Free macrophages wander, while fixed macrophages reside in specific organs like the liver (Kupffer cells) and brain (microglia).
• Neutrophils become phagocytic when encountering infectious material.
• Eosinophils are weakly phagocytic against parasitic worms.
• Mast cells bind and ingest a diverse range of bacteria.

Mechanism of Phagocytosis

• The process involves engulfing and destroying microorganisms.

Natural Killer (NK) Cells

• NK cells lyse and kill cancer cells and virus-infected cells.
• They are a distinct group of large granular lymphocytes.
• They respond nonspecifically and release perforins and other cytolytic chemicals.
• They secrete chemicals enhancing the inflammatory response.

Inflammation: Tissue Response to Injury

• Inflammation is triggered when body tissues are injured.
• It prevents the spread of damaging agents, disposes of cell debris and pathogens, and prepares for repair.
• The four cardinal signs of acute inflammation are redness, heat, swelling, and pain.

Inflammatory Response

• The response begins with the release of inflammatory chemicals into the extracellular fluid.
• These mediators (kinins, prostaglandins, complement, cytokines) are released by injured tissue, phagocytes, lymphocytes, and mast cells.
• They cause blood vessels to dilate.

Inflammatory Response: Increased Permeability

• Inflammatory chemicals increase the permeability of local capillaries.
• Exudate (fluid containing proteins, clotting factors, and antibodies) seeps into tissue spaces, causing local edema (swelling) and contributing to pain.

Inflammatory Response: Benefits of Edema

• The surge of protein-rich fluids into tissue spaces (edema) dilutes harmful substances.
• It brings in oxygen and nutrients needed for repair.
• It allows entry of clotting proteins that prevent the spread of bacteria.

Inflammatory Response: Phases

• There are four main phases of inflammation.
• Leukocytosis: neutrophils are released from bone marrow in response to leukocytosis-inducing factors.
• Margination: neutrophils cling to the walls of capillaries in the injured area.
• Diapedesis: neutrophils squeeze through capillary walls and start phagocytosis.
• Chemotaxis: inflammatory chemicals attract neutrophils to the injury site.

Anti-Microbial Proteins

• These proteins enhance innate defenses.
• They attack microorganisms directly and hinder their reproduction.
• Important antimicrobial proteins include interferon and complement proteins.

Interferon (IFN)

• IFN synthesis is activated by a host cell's viral invasion.
• IFN molecules leave the infected cell and enter neighboring cells.
• IFN stimulates the neighboring cells to activate genes for PKR, an antiviral protein.
• PKR nonspecifically blocks viral reproduction in neighboring cells.

Interferon Family

• Interferons are a family of proteins with slightly different physiological effects.
• Lymphocytes secrete gamma (γ) interferon, while most other WBCs secrete alpha (α) interferon.
• Fibroblasts secrete beta (β) interferon.
• Interferons also activate macrophages and mobilize NK cells.
• FDA-approved alpha IFN is used as an antiviral drug (hepatitis C) and against genital warts.

Complement (Proteins)

• 20 or so proteins circulate in the inactive form in the blood.
• They include C1 through C9, factors B, D, and P, and regulatory proteins.
• Complement provides a major mechanism for destroying foreign substances.

Complement: Functions

• It amplifies all aspects of the inflammatory response.
• It kills bacteria and certain cells (our cells are immune)
• It enhances the effectiveness of both nonspecific and specific defenses.

Fever

• Fever (abnormally high body temperature) is a response to invading microorganisms.
• The body's thermostat is reset upwards by pyrogens, chemicals secreted by leukocytes and macrophages exposed to foreign substances.

Fever: Benefits and Risks

• High fevers can denature enzymes and be dangerous.
• Moderate fever can be beneficial by sequestering iron and zinc (needed by microorganisms) and increasing metabolic rate for tissue repair.

Adaptive Immunity

• A specific defense mechanism that uses lymphocytes, antigen-presenting cells (APCs), and specific molecules to identify and destroy non-self particles.
• Relies on cells' ability to:
  • Recognize foreign substances (antigens) by binding to them.
  • Communicate with each other to mount a response specific to those antigens.

Humoral Immunity Response

• Antigen challenge: The first encounter between an antigen and a naive immunocompetent cell.
• Occurs in the spleen or other lymphoid organs.
• If the lymphocyte is a B cell, the antigen provokes a humoral immune response, leading to the production of antibodies against the challenger.

Clonal Selection

• Stimulated B cell growth forms clones bearing the same antigen-specific receptors.
• A naive, immunocompetent B cell is activated when antigens bind to its surface receptors and cross-link adjacent receptors.
• Antigen binding is followed by receptor-mediated endocytosis of the cross-linked antigen-receptor complexes.

Fate of the Clones

• Most clone cells become antibody-secreting plasma cells.
• Plasma cells secrete specific antibody at a rate of 2000 molecules per second.
• Clones that do not become plasma cells become memory cells that can mount an immediate response to subsequent exposures of the same antigen.

Immunological Memory

• Primary immune response: Cellular differentiation and proliferation occur on the first exposure to a specific antigen.
  • Lag period: 3 to 6 days after antigen challenge.
  • Peak levels of plasma antibody: Achieved in 10 days.
  • Antibody levels then decline.
• Secondary immune response: Re-exposure to the same antigen.
  • Sensitized memory cells respond within hours.
  • Antibody levels peak in 2 to 3 days at much higher levels than in the primary response.
  • Antibodies bind with greater affinity and their levels in the blood can remain high for weeks to months.

Active Humoral Immunity

• B cells encounter antigens and produce antibodies against them.
  • Naturally acquired: Response to a bacterial or viral infection.
  • Artificially acquired: Response to a vaccine of dead or attenuated pathogens.
• Vaccines: Spare us the symptoms of disease and their weakened antigens provide antigenic determinants that are immunogenic and reactive.

Passive Humoral Immunity

• Differs from active immunity in the antibody source and the degree of protection.
  • B cells are not challenged by antigens.
  • Immunological memory does not occur.
  • Protection ends when antigens naturally degrade in the body.
  • Naturally acquired: From the mother to her fetus via the placenta.
  • Artificially acquired: From the injection of serum, such as gamma globulin.

Antibodies

• Also called immunoglobulins.
  • Constitute the gamma globulin portion of blood proteins.
  • Are soluble proteins secreted by activated B cells and plasma cells in response to an antigen.
  • Are capable of binding specifically with that antigen.
• There are five classes of antibodies: IgD, IgM, IgG, IgA, and IgE.

Classes of Antibodies

• IgD: Monomer attached to the surface of B cells, important in B cell activation.
• IgM: Pentamer released by plasma cells during the primary immune response.
• IgG: Monomer that is the most abundant and diverse antibody in primary and secondary response; crosses the placenta and confers passive immunity.
• IgA: Dimer that helps prevent attachment of pathogens to epithelial cell surfaces.
• IgE: Monomer that binds to mast cells and basophils, causing histamine release when activated.

Basic Antibody Structure

• Consists of four looping polypeptide chains linked together with disulfide bonds.
  • Two identical heavy (H) chains and two identical light (L) chains.
• The four chains bound together form an antibody monomer.
• Each chain has a variable (V) region at one end and a constant (C) region at the other.
• Variable regions of the heavy and light chains combine to form the antigen-binding site.

Antibody Structure

• Antibodies responding to different antigens have different V regions but the C region is the same for all antibodies in a given class.
• C regions form the stem of the Y-shaped antibody and:
  • Determine the class of the antibody.
  • Serve common functions in all antibodies.
  • Dictate the cells and chemicals that the antibody can bind to.
  • Determine how the antibody class will function in elimination of antigens.

Antibody Targets

• Antibodies themselves do not destroy antigen; they inactivate and tag it for destruction.
• All antibodies form an antigen-antibody (immune) complex.
• Defensive mechanisms used by antibodies are neutralization, agglutination, precipitation, and complement fixation.

Complement Fixation and Activation

• Complement fixation is the main mechanism used against cellular antigens.
• Antibodies bound to cells change shape and expose complement binding sites.
• This triggers complement fixation and cell lysis.
• Complement activation:
  • Enhances the inflammatory response.
  • Uses a positive feedback cycle to promote phagocytosis.
  • Enlists more and more defensive elements.

Other Mechanisms of Antibody Action

• Neutralization: Antibodies bind to and block specific sites on viruses or exotoxins, thus preventing these antigens from binding to receptors on tissue cells.
• Agglutination: Antibodies bind the same determinant on more than one antigen.
  • Makes antigen-antibody complexes that are cross-linked into large lattices.
  • Cell-bound antigens are cross-linked, causing clumping (agglutination).
• Precipitation: Soluble molecules are cross-linked into large insoluble complexes.

Monoclonal Antibodies

• Commercially prepared antibodies are used:
  • To provide passive immunity.
  • In research, clinical testing, and treatment of certain cancers.
• Monoclonal antibodies are pure antibody preparations:
  • Specific for a single antigenic determinant.
  • Produced from descendents of a single cell.

Cell-Mediated Immune Response

• Since antibodies are useless against intracellular antigens, cell-mediated immunity is needed.
• Two major populations of T cells mediate cellular immunity:
  • CD4 cells (T4 cells): Primarily helper T cells (TH).
  • CD8 cells (T8 cells): Cytotoxic T cells (TC) that destroy cells harboring foreign antigens.
• Other types of T cells are:
  • Suppressor T cells (TS).
  • Memory T cells.

Importance of Humoral Response

• Soluble antibodies:
  • The simplest ammunition of the immune response.
  • Interact in extracellular environments such as body secretions, tissue fluid, blood, and lymph.

Importance of Cellular Response

• T cells recognize and respond only to processed fragments of antigen displayed on the surface of body cells.
• T cells are best suited for cell-to-cell interactions and target:
  • Cells infected with viruses, bacteria, or intracellular parasites.
  • Abnormal or cancerous cells.
  • Cells of infused or transplanted foreign tissue.

Antigen Recognition and MHC Restriction

• Immunocompetent T cells are activated when the V regions of their surface receptors bind to a recognized antigen.
• T cells must simultaneously recognize:
  • Nonself (the antigen).
  • Self (a MHC protein of a body cell).

MHC Proteins

• Both types of MHC proteins are important to T cell activation.
• Class I MHC proteins:
  • Always recognized by CD8 T cells.
  • Display peptides from endogenous antigens.

Class I MHC Proteins

• Endogenous antigens are:
  • Degraded by proteases and enter the endoplasmic reticulum.
  • Transported via TAP (transporter associated with antigen processing).
  • Loaded onto class I MHC molecules.
  • Displayed on the cell surface in association with a class I MHC molecule.

Class II MHC Proteins

• Class II MHC proteins are found only on mature B cells, some T cells, and antigen-presenting cells (APCs).
• A phagosome containing pathogens (with exogenous antigens) merges with a lysosome.
• Invariant protein prevents class II MHC proteins from binding to peptides in the endoplasmic reticulum.

Class II MHC Proteins

• Class II MHC proteins migrate into the phagosomes where the antigen is degraded and the invariant chain is removed for peptide loading.
• Loaded Class II MHC molecules then migrate to the cell membrane and display antigenic peptides for recognition by CD4 cells.

T Cell Activation: Step One - Antigen Binding

• Step one in T cell activation is antigen binding.

T Cell Activation: Step Two - Co-Stimulation

• Before a T cell can undergo clonal expansion, it must recognize one or more co-stimulatory signals.
• This recognition may require binding to other surface receptors on an APC.
  • Macrophages produce surface B7 proteins when nonspecific defenses are mobilized.
  • B7 binding with the CD28 receptor on the surface of T cells is a crucial co-stimulatory signal.
• Other co-stimulatory signals include cytokines and interleukin 1 and 2.

T Cell Activation: Step Two - Co-Stimulation

• Depending on receptor type, co-stimulators can cause T cells to complete their activation or abort activation.
• Without co-stimulation, T cells:
  • Become tolerant to that antigen.
  • Are unable to divide.
  • Do not secrete cytokines.

T Cell Activation: Step Two - Co-Stimulation

• T cells that are activated:
  • Enlarge, proliferate, and form clones.
  • Differentiate and perform functions according to their T cell class.

Cytokines

• Mediators involved in cellular immunity, including hormonelike glycoproteins released by activated T cells and macrophages.
• Some are co-stimulators of T cells and T cell proliferation.
• Interleukin 1 (IL-1) released by macrophages co-stimulates bound T cells to:
  • Release interleukin 2 (IL-2).

Cytokines

• IL-2 is a key growth factor, which sets up a positive feedback cycle that encourages activated T cells to divide.
  • It is used therapeutically to enhance the body’s defenses against cancer.
• Other cytokines amplify and regulate immune and nonspecific responses.

Cytokines

• Examples include:
  • Perforin and lymphotoxin - cell toxins.
  • Gamma interferon - enhances the killing power of macrophages.
  • Inflammatory factors.

Helper T Cells (TH)

• Regulatory cells that play a central role in the immune response.
• Once primed by APC presentation of antigen, they:
  • Chemically or directly stimulate proliferation of other T cells.
  • Stimulate B cells that have already become bound to antigen.
• Without TH, there is no immune response.

Helper T Cells (TH)

• TH cells interact directly with B cells that have antigen fragments on their surfaces bound to MHC II receptors.
• TH cells stimulate B cells to divide more rapidly and begin antibody formation.
• B cells may be activated without TH cells by binding to T cell–independent antigens.
• Most antigens, however, require TH co-stimulation to activate B cells.
• Cytokines released by TH amplify nonspecific defenses.

Cytotoxic T Cell (Tc)

• TC cells, or killer T cells, are the only T cells that can directly attack and kill other cells.
• They circulate throughout the body in search of body cells that display the antigen to which they have been sensitized.
• Their targets include:
  • Virus-infected cells.
  • Cells with intracellular bacteria or parasites.
  • Cancer cells.
  • Foreign cells from blood transfusions or transplants.

Cytotoxic T Cells

• Bind to self-antiself complexes on all body cells.
• Infected or abnormal cells can be destroyed as long as appropriate antigen and co-stimulatory stimuli (e.g., IL-2) are present.
• Natural killer cells (NK) activate their killing machinery when they bind to MICA receptors.
• MICA receptor: MHC-related cell surface protein found on stressed or infected cells.

Mechanisms of Tc Action

• In some cases, TC cells:
  • Bind to the target cell and release perforin into its membrane.
    • In the presence of Ca2+, perforin causes cell lysis by creating transmembrane pores.
• Other TC cells induce cell death by:
  • Secreting lymphotoxin, which fragments the target cell’s DNA.
  • Secreting gamma interferon, which stimulates phagocytosis by macrophages.

Other T Cells

• Suppressor T cells (TS): Regulatory cells that release cytokines, which suppress the activity of both T cells and B cells.
• Gamma delta T cells (Tgd): 10% of all T cells found in the intestines that are triggered by binding to MICA receptors.

Organ Transplants

• The four major types of grafts are:
  • Autografts: Graft transplanted from one site on the body to another in the same person.
  • Isografts: Grafts between identical twins.
  • Allografts: Transplants between individuals that are not identical twins, but belong to the same species.
  • Xenografts: Grafts taken from another animal species.

Prevention of Rejection

• Prevention of tissue rejection is accomplished by using immunosuppressive drugs.
• However, these drugs depress the patient’s immune system so it cannot fight off foreign agents.

Immunodeficiencies

• Congenital and acquired conditions in which the function or production of immune cells, phagocytes, or complement is abnormal.
  • SCID (severe combined immunodeficiency) syndromes: Genetic defects that produce:
    • A 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.

Acquired Immunodeficiencies

• Hodgkin’s disease: Cancer of the lymph nodes 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 (CD4) cells.
  • Characterized by severe weight loss, night sweats, and swollen lymph nodes.
  • Opportunistic infections occur, including pneumocystis pneumonia and Kaposi’s sarcoma.

Test your knowledge on the fundamental concepts of immunology, including innate and adaptive immunity, the role of phagocytes, and the mechanisms of T cell activation. This quiz also covers the key differences between humoral and cell-mediated immunity, as well as the significance of inflammation and fever in immune responses.