Chapter 16-19  Immunology

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I.          This material is not covered in a formal exam, though it will be covered on a quiz (or two) and some may be needed on the final exam.

II.         Main Concept of Immunology

            A.        The human body possesses two types of immunity

1.         Innate Immunity:  A nonspecific system that is present at birth for rapid response, first-line and second lines of defense

2.         Adaptive Immunity: A system utilizing specific recognition of microbes as the last line of defense.

III.       Innate Immunity: Nonspecific Defenses

            A.        First Line of Defense

                        1.         Skin and Mucous Membranes

a.         As we discussed in the last section, any pathogens that are not directly injected into a human have to pass through the skin and/or mucous layers as their portal of entry.

b.         In addition to the physical barrier presented by these systems, a number specific physical mechanisms are also at work.

            i.          Saliva

            ii.          Cilia

            iii.         Lacrimal apparatus

            iv.         Defecation and vomiting

            v.         genitor-urinary secretions

c.         The first line of defense has a number of chemical systems used to supplement the integrity of the physical barriers.

            i.          sebum – skin oil

            ii.          perspiration – lysozyme

            iii.         gastric juice

                        2.         Normal Microbiota – competition against other organisms.

            B.         Second Line of Defense

                        1.         Formed Elements of Blood

A.        When blood separates the clear top layer is called plasma, this layer contains the formed elements (cells and cell fragments) of the blood.

B.         Leukocytes – white blood cells

1.         Granulocytes – possess large numbers of granules in the cytoplasm.

2.         Agranulocytes – possess granules that are invisible to the light microscope.

                                    C.        Granulocytes are broken down to four classes

1.         Neutrophil (polymorphonucleur cells) – highly phagocytic and motile, able to exit the blood and enter tissues to attack infections.

2.         Basophil – release histamine and activated in allergic responses.

3.         Eosinophils – Discharge large amounts of toxic compounds in response to parasites.

                                                4.         Dendritic Cells – involved in adaptive response

                                    D.        Agranulocytes

                                                1.         Monocytes – immature phagocytic cells

2.         Macrophage – when monocytes migrate into the tissues they mature into phagocytic cells

3.         Lymphocytes –

            a.         T-cells – adaptive immunity

            b.         B-cells – adaptive immunity

c.         Natural Killer Cells (NK) – respond to foreign cells by releasing toxic chemicals

                        2.         Phagocytic cells eat and digest pathogens (bacteria in particular).

1.         Some bacteria (Listeria, Mycobacteria, etc.) can survive phagocytosis and live inside phagocytic cells.

2.         Phagocytic cells kill pathogens with a variety of compounds, especially superoxide compounds

3.         Some organisms use a thick capsule to prevent phagocytosis (i.e. Bacillus anthracis and Streptococcus pneumoniae)

            C.        Inflammation

1.         Damage induces the release of histamines, kinins, prostogladins, and leukotrienes that signal cell damage.

2.         Blood Clots form (Platlets)

3.         Abscess starts to form (pus – dead cells and body fluid)

4.         Margination – phagocytes migrate to and stick to the endothelium

5.         Emigration – phagocytes migrate into the damaged tissue

6.         Phagocytosis of pathogens

            D.        Antimicrobial Substances

                        1.         Complement – lyses pathogens and promotes phagocytosis

                        2.         Interferon – protects uninfected cells from viruses

                        3.         Transferrins – sequester iron

                        4.         Antimicrobial Peptides – lyses bacteria

IV.       Adaptive Immunity: Specific Defenses

            A.        The adaptive immune system is divided into two systems

                        1.         Humoral Immunity – immunity mediated by antibodies

                        2.         Cellular Immunity – immunity mediated by specialized cells

B.         Adaptive immunity was discovered due to experiments designed to find a function for two organs, the thymus in humans (T Cells) and the Bursa of Fabricius (B Cells)

C.        Antigens and Antibodies

            1.         Antigens are either proteins or large polysaccharides

            2.         Antigens cause the adaptive immune system to respond.

3.         Antibodies, or Immunoglobulins, are proteins produced in the immune system that can bind to antigens

            D.        B Cells and Humoral Immunity

                        1.         B Cells produce antibodies

2.         At anytime in a person’s body there are a large number of B cells with unique antibodies (estimates are as high as 10¹⁵).

3.         Antigens trigger the proliferation of those B cells whose antibodies respond to them.

4.         Proliferations can be T-cell dependent or T-cell independent

5.         During proliferation a small subset of B-cells mature into long-lived memory cells, allowing for rapid response to later infections.

6.         The majority of proliferated cells mature into antibody factories called plasma cells.

            E.         Antigen/Antibody Binding

                        1.         Binding of antibodies to targets cause a variety of responses

                                    a.         Agglutination

                                    b.         Opsonization

                                    c.         Neutralization

                                    d.         Complement

                                    e.         Antibody-dependent cell-mediated cytotoxicity

            F.         T-Cells and Cellular Immunity

                        1.         Populations of T-Cells

                                    a.         Helper T-Cells: activate other immune responses

b.         Cytotoxic T-Cells: cells capable of directly killing other cells, most commonly those that are virally infected.

            G.        Antigen Presentation

1.         Macrophage and Dendritic cells can process pathogens and display fragments of them (antigens) to the immune system. 

2.         When these cells operate in this role, they are classified as antigen presenting cells (APC)

H.        Immunological Memory – the proliferated B-cells and allow for rapid responses to a second exposure.

I.          Types of adaptive immunity

1.         Naturally Acquired Active Immunity – immunity developed from surviving an infection.

2.         Naturally Acquired Passive Immunity – the natural transfer of antibodies from mother to child.

3.         Artificially Acquired Active Immunity – vaccination

4.         Artificially Acquired Passive Immunity – passage by the injections of antibodies

V.        Practical Applications of Immunology

A.        Vaccine – a suspension of organisms or fractions of organisms that is used to induce immunity.

B.         Vaccination works by inducing a subacute immune response that promotes immunological memory.

C.        Types of Vaccines

1.         Attenuated Whole-Agent Vaccine – living, but weakened, microbe.  Typically these vaccines promote long-term and highly effective immunities.  This is common in viruses, such as measles, mumps, and rubella.

2.         Inactivated Whole-Agent Vaccine – Using whole, but killed, microbes (i.e. rabies)

3.         Toxoids – inactivated toxins (i.e. anthrax, tetanus, and diphtheria) which produce immunity by neutralizing the active exotoxins, though these vaccines are typically shorter effective time ranges.

4.         Subunit Vaccines – Modern vaccines utilizing only antigenic components (acellular vaccines).

5.         Conjugated Vaccines – Mixing a poor antigen (capsular polysaccharides) with a strong antigen (i.e. Diptheria toxoid) to promote a stronger immunological memory.

6.         Nucleic Acid Vaccine (DNA Vaccine) – Naked DNA injected into a muscle that produces momentary production of protein that leads to an immune response.

D.        Monoclonal Antibodies – artificially produced antibodies that target a specific antigen.

VI.       Disorders of the Immune System

A.        Hypersensitivity – an antigenic response beyond that is which considered normal.

            1.         Type I (Anaphylactic) Reaction –

a.         Often occur between 2 and 30 minutes after a person sensitized to an antigen is reexposed to that antigen.

b.         Can be fatal

c.         Triggered by massive degranulation of Basophils and Mast Cells

                        2.         Type II (Cytotoxic) Reaction –

                                    a.         Triggering of the complement cascade to lyses cells

                                    b.         Transfusion reactions

                        3.         Type III (Immune Complex) Reaction –

                                    a.         Complexes of circulating antibodies and antigens

                                    b.         Can cause damage to kidneys

                        4.         Type IV (Delayed Cell-Mediated) Reactions –

                                    a.         Caused by T-cells

                                    b.         Occurs after a while, in sensitized individuals

                                    c.         Poison Ivy

            B.         Autoimmune Disease – The immune system attacks the host’s own cells

                        1.         Relatively Rare, affecting about 5% of the population

2.         Autoimmunity results from breaking of tolerance, the ability of the host to weed out self-reactive immune cells.

3.         Cytotoxic Autoimmune Reactions – those governed by antibodies

a.         Graves’ disease – antibodies that trigger the continual release of thyroid hormones.

b.         Myasthenia gravis – antibodies that destroy the acetylocholine receptors and leads to progressive muscle weakness.

4.         Immune Complex Autoimmune Reactions – governed by antibody complexes.

a.         Systemic Lupus Erythematosus – complex disease that destroys various organs due to complex formation.

                        5.         Cell-Mediated Autoimmune Reactions – governed by T-cells

a.         Hashimoto’s Thyroiditis – autoimmune destruction of the thyroid gland resulting in the long term in death due to complete shutdown of the body’s metabolism (easily correctable)

b.         Type I Diabetes – autoimmune destruction of the pancreas.

            C.        Immunodeficiencies – absence of part or all the immune system.

D.        AIDS – Acquired Immune Deficiency Syndrome – a disease caused by advanced HIV infection

1.         HIV infects a subclass of immune cells (T-Helper Cells) which handicaps the immune system.

    2.         AIDS results in recurrent infections from those pathogens that need the T-Helper Cells (fungal a prominent example).

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