BIOL2260 - Immune System

Immune system components

Cellular and molecular structures, not organs like other systems

Immunity

The goal of the immune system; protection from harm

Pathogens

Infectious agents that can damage or kill a host

Bacteria

Single-celled prokaryotes that lack a nucleus, nuclear envelope, and organelles, and are enclosed by a cell wall

Viruses

Pieces of DNA or RNA in a capsid (protein shell) that must enter a cell to reproduce (obligate intracellular parasites)

Fungi

Eukaryotes with a plasma membrane and cell wall that include mold, yeast, and multicellular fungi that produce spores; release proteolytic enzymes that induce inflammation

Protozoans

Eukaryotes without a cell wall; are called parasites when they cause disease

Parasitic worms

Nonmicroscopic multicellular parasites that take nourishment from host they reside in

Prions

Fragments of infectious proteins that cause damage in nervous tissue; are neither viruses nor bacteria

Immune response

Collective term for all physiological processes of the immune system components

Innate immune response

Provides the first and general/nonspecific response; immune response we are born with

Adaptive immune response

Provides a specific, custom-made response that takes days to respond fully; must have encountered the attacking pathogen to engage

Branches of adaptive immunity

1. Cell-mediated immunity

2. Antibody-mediated immunity

Cell-mediated immunity

Does not rely on antibodies; involves T-lymphocytes reacting directly with antigens

Antibody-mediated immunity

Involves B-lymphocytes, plasma cells, and antibodies to neutralize or eliminate pathogens

Nonspecific internal defenses

-Selected immune cells

-Antimicrobial proteins

-Inflammation

-Fever

The two types of immunity differ based on

-Cells involved

-Specificity of cell response (what antibody attacks each cell)

-Mechanisms of eliminating harmful substances

-Amount of time for response

First line of defense

Skin and mucous membranes (keep pathogens out)

Second line of defense

Internal processes such as activities of immune cells (neutrophils, macrophages, etc.), chemicals (interferons and complement), and physiological processes (inflammation and fever)

Leukocytes

WBCs that are formed in the red bone marrow

Cytokines

Small proteins that regulate immune activity; produced by both the innate and adaptive immune cells and act as chemical messengers released from one immune cell that bind to the receptors of the target cell

Effects of cytokines

-Regulates cell-to-cell communication

-Controlling the development and behavior of immune cells

-Regulating immatory response

Autocrine cytokines

Act on the cell that released it

Paracrine cytokines

Act on locall cells (no not circulate through blood)

Endocrine cytokines

Act on distant cells after circulating through blood

Antigens

Unique molecule on the surface of a pathogen that bind to a component of the adaptive immune system, which trigger immune responses to produce antibodies; lymphocytes must distinguish between foreign and self-antigens

Examples of antigens

-Antigens on the capsid of a virus

-Antigens of cell walls of bacteria

-Tumor antigens of cancer cells

Immunogen

An antigen that produces an immune response

Haptens

A small molecule that is too small to cause an immune response, but becomes antigens when attached to a host molecule

Phagocytosis

Engulfing unwanted substances that is performed by dendritic cells, macrophages, and neutrophils, in which all three present antigens to B cells

Respiratory burst

Production of reactive oxygen-containing molecules that help destroy pathogens

Chemotactic chemicals

Chemicals released by basophils and mast cells that attract immune cells and promote inflammation

Histamine

Increases vasodilation and capillary permeability

Heparin

Acts as an anticoagulant

Eisosanoids

Released from the plasma membranes of basophils and mast cells that increase inflammation

Natural killer (NK) cells

Lymphocytes that destroy unhealthy (e.g., viral- and bacterial-infected cells, tumor cells, etc.) by releasing chemicals and perform immune surveillance

Perforin

Creates a transmembrane pore

Granzymes

Enters pores created by perforin and causes apoptosis

Eosinophil immune response

-Attack parasitic worms

-Degranulate, release enzymes and other toxic substances via forming transmembrane pores in parasites

-Participate in immune responses of allergy and asthma

-Engage in phagocytosis of antigen-antibody complexes

Pattern recognition receptors

Receptors on microbe's cell surface that bind to cells of the innate immune system

Antimicrobial proteins

Function against microbes

Interferons

A class of cytokines that nonspecifically interferes with the spread of intracellular parasites

IFN-alpha and IFN-beta

Bind to neighboring cells and prevent their infection, inhibits synthesis of viral proteins, and stimulates NK cells to destroy virus-infected cells; produced by leukocytes and virus-infected cells

IFN-gamma

Stimulates macrophages to destroy virus-infected cells; produced by T-lymphocytes and NK cells

Complement system

Group of over 30 plasma proteins that help antibodies to fight infections by attaching to the surface of a pathogen enters; made by the liver and circulate in blood

Classical pathway of complement

Help antibodies by attaching to antibodies of foreign substances

Alternative pathway of complement

Helps and binds to polysaccharides of bacterial or fungal cell wall

Lectin pathway of complement

Lectin protein binds to carbohydrates on some microbes and complement attaches to lectin

Inflammation

An immediate local, nonspecific response of vascularization tissue to injury or infection; major response of innate immune system

Events of inflammation

1. Release of chemicals by pathogens, basophils, and neutrophils such as histamine, leukotrienes, prostaglandins, and chemotactic factors

2. Released chemicals cause vasodilation and capillary permeability; cells increase leukocyte attachment

3. Recruitment of leukocytes

Cell-adhesion molecules (CAMs)

Increased endothelial expression of molecules for leukocyte adhesion

5 cardinal signs of inflammation

1. Redness

2. Heat

3. Swelling

4. Pain

5. Loss of function

Redness (rubor)

Increased blood flow due to vasodilation

Heat (calor)

Increased blood flow and increased metabolic activity within the area

Swelling (tumor)

Increase in fluid loss from capillaries

Pain (dolor)

Stimulation of pain receptors due to compression from extra fluid and chemical irritants

Loss of function (functio laesa)

From pain and swelling in severe cases

Margination

The physical adhesion of leukocytes to endothelial CAMs

Diapedesis

Cells escape BV

Chemotaxis

Leukocytes migrate towards chemicals released from damaged, dead, or pathogenix cells

Acute and chronic inflammation

Acute inflammation usually lasts 8-10 days

Chronic inflammation has detrimental effects

Inflammatory time frame

Inflammation slows after 72hr as macrophages eat bacteria, damaged host cells, and dying neutrophils

Blood clotting

-Seal microbes out by having plasma proteins arrive to the injury site

-Plasma proteins include antibodies, complement, clotting proteins, and kinins

-Leukocytes release cytokines that stimulate leukopoiesis in bone marrow

Pyrogens

Fever-inducing molecules released by macrophages

Fluid at injury site

Higher percentage of fluid is taken up by the lymphatic system to monitor contents of blood and prevent spread of infection

Pyrexia

Abnormal body temperature elevation (fever); 2F or more than normal; results from the release of pyrogens

Benefits of fever

-Inhibits reproduction of bacteria and viruses

-Promotes interferon activity

-Increases activity of adaptive immunity

-Accelerates tissue repair

-Increases CAMs on endothelium of capillaries in lymph nodes, as well as additional immune cells migrating out of cells

-Recommneded to leave a low fever untreated

Events of fever

1. Onset

2. Stadium

3. Defervescence

Onset

Temperature begins to rise; hypothalamus stimulates constriction of dermal BV (blood moves towards core) and shivering of skeletal muscle generates heat

Stadium

Elevated temperature is maintained; metabolic rate increases to promote elimination of harmful substances

Defervescence

Time when temperature returns to normal; hypothalamus stimulates to release heat (e.g., vasodilation of skin BV, sweating)

CD4

Protein receptor located on helper T-cells

CD8

Protein receptor located on cytotoxic T-cells

BCR

Protein receptor (antibody) located on B-cells

Events in the life of a lymphocyte

1. Formation and selection

2. Activation

3. Effector response

Formation and selection

Lymphocytes become able to recognize one specific foreign antigen; occurs in primary lymphoid structures

Activation

Migration to secondary lymphoid structures

Effector response

Lymphocytes are first exposed to antigen and become activated; replicate to form identical lymphocytes

Helper T-cells

T-lymphocytes that regulate cells of the adaptive and innate immune systems; release cytokines

Cytotoxic T-cells

Destroy unhealthy cells by apoptosis

Memory T-cells

Persist in the body after an infection to provide long-term protection against future exposures to the same pathogen

Plasma cells

Produce antibodies

B cells

Sense the need for antibodies and stimulate plasma cells (matured B cells) to produce them

Neutralization

An antibody physically covers the area the pathogen uses to enter the cell and makes it ineffective in establishing infection

Agglutination

An antigen-antibody complex is formed and antibodies link to multiple pathogens forming clots

Precipatition

An antibody cross-links circulating antigens, becomes insoluble, precipitates out of body fluids, and gets phagocytized

Classes of immunoglobulins

1. IgG

2. IgM

3. IgA

4. IgD

5. IgE

IgG

Most common immunoglobulin (75-85%) in blood and other bodily liquids that can participate in all types of antibody actions; only immunoglobulin that can cross the placenta

IgM

Found mostly in blood and has a pentamer structure that is effective at agglutination and binding complement; responsible for rejection of mismatched tranfusions

IgA

-Found in areas exposed to the external environment and is composed of two antibody molecules

-Produced in mucus, saliva, tears, and breastmilk, and protects the respiratory and GI tracts

-Prevents pathogens adhering to and penetrating epithelium via agglutination

IgD

Functions as a B-cell receptor to identify and regulate immature lymphocytes ready for activation; found on the surface of B-cells and in serum

IgE

Activated in response to parasites and allergic reactions, which attracts eosinophils and release of products from basophils and mast cells

Immunological memory

Results from formation of a long-lived army of lymphocytes after exposure to a specific antigen

Primary response

The first time the immune system encounters a specific pathogen and is slow at producing antibodies; no detectable antibodies for 3-6 days and IgM and IgG produced within 1-2 weeks

Secondary response

The second time the timmune system encounters a specific pathogen and produces antibodies much more quickly

Lag phase

The period of little or no antibody production; longer in primary response and shorter in secondary phase

Antibody titer

Concentration of antibody that can measure the development of antibodies; initial exposure can be via active infection or vaccine

Vaccines

Contain weakened or dead pathogens to stimulate the immune system to develop memory B-cells; may provide lifelong immunity or require a booster shot

Herd immunity

Resistance of members within a population to a disease due to a high proportion (~83-94%) of people who are immune to the disease, so that the number of infectible people are low

Active immunity

Results from a direct encounter with the pathogen where memory cells against the specific pathogen are formed