Immune System - Lecture Notes

Infectious agents

• Can damage or kill a host

• Pathogenic agents are one that cause harm

Five major categories

1. Bacteria

2. Viruses

3. Fungi

4. Protozoans

5. Multicellular parasites

Bacteria

• Single-celled prokaryotes, some harmless, others virulent (e.g., Clostridium tetani, Streptococcus)

• Small (1 to 2 µm) cell with both a membrane and a cell wall

• •Varied types: spherical (cocci), rodlike (bacilli), or coiled (spirilla)

• Virulent bacteria may have a pili, capsule, or release toxins or damaging enzymes

Viruses

• Non-living DNA or RNA in a protein shell

• They are not cells - they are much smaller, about one-hundredth of a micrometer

• Obligate intracellular parasite

  • Must enter host cells to reproduce (e.g., cold, Ebola, chickenpox)

  • Infected cells make copies of nucleic acid and capsid (shell)

  • Virus or immune response may kill the host cell

Fungi

• Eukaryotic cells with membrane and cell wall

• Include molds, yeasts, multicellular fungi that produce spores

• Release proteolytic enzymes inducing inflammation

  • Can cause superficial (ringworms) or internal infections (histoplamosis)

  • Can infect mucosal linings (for example, vaginal yeast infections)

Protozoans

• Eukaryotic cells without cell walls

• Intracellular and extracellular parasites

• Disease examples: malaria and trichomonoiasis

Multicellular parasites

• Non-microscopic

• Takes nourishment from host they live in

• For example: tapeworm

Prions

• Fragments of infectious proteins

• Neither cells nor viruses

• Causes disease in nervous tissue

• Example: Variant Creutzfeldt-Jakob disease (“mad cow disease”)

  • Can be spread from cows to humans by consuming infected meat

Which pathogen must enter a cell to replicate? Which type of pathogen is composed of prokaryotic cells?

Viruses; bacteria

Leukocytes (white blood cells)

• Formed in the red bone marrow, including:

  • Granulocytes: neutrophils, eosinophils, basophils

  • Monocytes: Become macrophages when they leave blood and enter tissues

  • Lymphocytes: B-lymphocytes, T-lymphocytes, NK (natural killer) cells

Immune cells and their locations

• Structures that house immune system cells

• Most leukocytes are in body tissues (instead of blood)

Secondary Lymphoid Structures

T- and B-lymphocytes, macrophages, dendritic cells, and NK cells housed in lymph nodes, spleen, tonsils, MALT, lymphoid nodules

Select Organs

• House macrophages

• May be permanent residents of the organ, or migrating macrophages

  • Some permanent ones named for location (for example, alveolar macrophages)

Epithelial layers of skin and mucosal membranes

• House dendritic cells

• These dendritic cells are usually derived from monocytes

• Engulf pathogens and migrate into lymph

Connective Tissue

• Houses mast cells

  • Typically in close proximity to small blood vessels

• Abundant in dermis and mucosa of respiratory, GI, and urogenital tracts

• Also found in connective tissue of organs (example, endomysium of muscle)

Primary Location of Immune Cells

Cytokines

• Small proteins that regulate immune activity,

• Produced by cells of both innate and adaptive immune system

• Chemical messengers release from one cell that bind to receptors of target cells

  • Can act on cell that released it (autocrine); on local cells (paracrine); or on distant cells after circulating through blood (endocrine)

  • Have short half-life

Cytokines Effects

• Signaling cells (including non-immune cells, for example, neurons)

• Controlling development and behavior of immune cells

• Regulating inflammatory response

• Destroying cells

Two types of immunity differ based on

• Cells involved

• Specificity of cell response

• Mechanisms of eliminating harmful substances

• Amount of time for response

Although innate and adaptive immunities are distinct, they work together in body defense

Innate Immunity

• Present at birth

• Protect against variety of different substances (non-specific)

  • No prior exposure to substance necessary

• Includes barriers of skin and mucosal membranes, non-specific cellular and molecular internal defenses

• Respond immediately to potentially harmful agents

Characteristics of Innate Immunity

• Prevents entry of potentially harmful substances

• Responds nonspecifically to harmful substances

• First line of defense is skin and mucosal membranes

• Second line of defense involves internal processes

  • Activities of neutrophils, macrophages, dendritic cells, eosinophils, basophils, and NK cells

  • Chemicals such as interferon and complement

  • Physiological processes such as inflammation and fever

First line of defense

• Skin: Physical barrier with antimicrobial secretions (epidermis and dermis)

  • Secretions from sweat glands and sebaceous glands (Dermicidin, lysozyme, sebum, defensins)

• Mucous Membranes: Trap pathogens, produce mucus, and release antimicrobial substances (Defensins, lysozymes, IgA)

  • Respiratory tract contains cilia to help remove trapped microbes; the GI tract utilizes saliva and stomach acid to kill ingested microbes

Adaptive immunity

• Acquired/specific immunity

• Response to antigen involves specific T- and B-lymphocytes

  • A particular cell responds to one specific foreign substance but not another

• Takes several days to be effective

Commensal microflora (normal microflora)

• Microorganisms that reside on body surfaces (for example, skin, GI tract)

  • Nonpathogenic

  • Interfere with attachment of potentially pathogenic organisms

Second Line of Defense: Nonspecific Internal Defenses

• Should pathogens pass the first line of defense, the second line of defense (nonspecific internal defenses) is initiated

• Nonspecific internal defenses include

  • Selected immune cells

  • Antimicrobial proteins

  • Inflammation

  • Fever

Second line of defense

• Phagocytic Cells: Neutrophils, macrophages, and dendritic cells engulf pathogens

• Proinflammatory Cells: Basophils and mast cells release histamine and heparin

• Apoptosis-Initiating Cells: NK cells destroy virus-infected and cancer cells

• Parasite-Destroying Cells: Eosinophils release cytotoxins against parasites

Neutrophils and Macrophages (Nonspecific)

Destroy engulfed particles

• Intake vesicles fuse with lysosomes, forming a phagolysosome

• Digestive enzymes break down the unwanted substances

• Respiratory burst produces reactive oxygen-containing molecules that help destroy the microbes

• Degraded residue is released by exocytosis

Dendritic Cells (Nonspecific)

Destroy particles and then present fragments

• Antigens are presented on dendritic cell surface T-lymphocytes

• Necessary for initiating adaptive immunity

• Macrophages can also perform antigen presentation

Basophils (Nonspecific)

• Pro-inflammatory chemical-secreting cells; promote inflammation

• Basophils circulate in the blood

Mast Cells (Nonspecific)

• Reside in connective tissue, mucosa, internal organs

• They release granules containing chemicals

  • Chemicals increase movement of fluid from blood to injured tissue

  • They serve as chemotaxis chemicals - they attract immune cells

  • Histamine increases vasodilation and capillary permeability

  • Heparin acts as an anticoagulant

• Eicosanoids released from their plasma membrane also increase inflammation

Natural Killer (NK) Cells (Nonspecific)

• Destroy unhealthy/unwanted cells

• Formed in bone marrow, circulate in blood and accumulate in secondary lymphoid structures

  • Perform immune surveillance - patrols body, detect unhealthy cells

• Destroy virus-infected cells, bacteria-infected cells, tumor cells, cells of transplanted tissue

NK Cells Cytotoxic Chemicals

• They release cytotoxic chemicals to kill bacteria

  • Perforin creates a transmembrane pore in unwanted cell

  • Granzymes enter pore and cause apoptosis of cell

    • Apoptosis is cell death that cause shriveling rather than lysis

Eosinophils (Nonspecific)

• Attack multicellular parasites

• Degranulate, release enzymes and other toxic substances

  • Can release proteins that form transmembrane pores in parasite’s cells

• Participate in immune responses of allergy and asthma

• Engage in phagocytosis of antigen-antibody complexes

• Cells of innate immune system recognize microbes as foreign because of receptors

  • Pattern recognition receptors (toll-like receptors) on cell surface bind to patterns on microbe surface

Antimicrobial Proteins

are molecules that function against microbes

Antimicrobial proteins: Interferons

• Class of cytokines that prevent viral spread

• IFN-α and IFN-β  produced by leukocytes and virus-infected cells

  • Bind to neighboring cells and prevent their infection

    • Triggers synthesis of enzymes that destroys viral nucleic acids, and inhibit synthesis of viral proteins

  • Stimulate NK cells

• IFN-g produce by T-lymphocytes and NK cells

  • Stimulates macrophages

Antimicrobial proteins: Complement System

• Enhances inflammation, opsonization, cytolysis

• Over 30 plasma proteins that work along with antibodies

• Identified with letter “C” and number (example: C2)

• Synthesized by liver, continuously released in inactive form

  • Activation occurs by enzyme cascade

• Complement activation follows pathogen entry:

  • Classical and alternative pathway

• Especially potent against bacterial infections

Complement System: Classical Pathway

Antibody attaches to foreign substance, then complement binds to antibody

Complement System: Alternative Pathway

Complement binds to polysaccharides of bacterial or fungal cell wall

Effects of activated Complement: Inflammation

• Enhanced by complement

• Activates mast cells and basophils

• Attracts neutrophils and macrophages

Effects of activated Complement: Opsonization

Effects of activated Complement:

Effects of activated Complement: