The Body’s Defenses

Chapter 43

Nonspecific Defenses

• Animals need way to protect against disease.

• 3 lines of defense; 2 nonspecific (don’t distinguish) 1 is specific.

• 1st nonspecific disease - external (skin).

• 2nd internal (phagocytes)• 3rd immune system.• Microbe must get past 1st line

(mucous and skin) to get to 2nd line (inflammatory response).

http://www.humanillnesses.com/images/hdc_0001_0001_0_img0010.jpg

• Skin intact, act as barrier. Little bit of opening can allow pathogens to enter.

• All mucous membranes act as barriers.

• Mucous membranes secrete enzymes to fight off intruders.

• Cilia in respiratory tract help move trapped organisms out of system up trachea.

http://pediatrics.med.unc.edu/div/infectdi/pcd/images/cilia.jpg

• Tears contain lysozyme - enzyme that digests peptidoglycan cell walls of some bacteria.

• Acid in stomach acts as protection.

http://www.xenophilia.com/zb/zb0017/acidreflux.jpg

• If microbe gets past defenses, moves to 2nd line of defense - depends on phagocytosis - ingestion of invading organisms by certain types of white cells.

• Variety of proteins function in nonspecific defense by attacking microbes directly or impeding reproduction.

• Complement proteins - work together to create pore through bacterial membrane - causes cell to burst.

http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/19.03.jpg

• Phagocytes (neutrophils and macrophages) WBCs that non-specifically seek out, ingest infectious invaders through phagocytosis.

• Defense against infection - organisms that live in body.

• Microorganisms found in human body (digestive tract), like E. coli.

• Advantages to humans for having organisms in body.

• Compete with other infectious organisms for space.

http://biology.clc.uc.edu/fankhauser/Labs/Microbiology/Gram_Stain/Gram_stain_images/E._coli&yogurt_P1232898.JPG

• Taking antibiotics kills bad bacteria, also kills bacteria found in body naturally.

http://www.surgeryencyclopedia.com/images/gesu_01_img0021.jpg

Specific immunity

• Body also has specific immune responses - occurs when body is invaded by specific organisms, uses B and T cells (white blood cells) to recognize and destroy foreign invaders.

• B and T cells - lymphocytes.

http://www.biosci.ohiou.edu/virology/WestNile/akira'2.jpg

Self from non-self

• B and T cells tested to see if self-destruct while still developing.

• Potential problems removed leaving those who react to foreign invaders, not themselves.

• Prevents body from attacking itself and only attack foreign invaders.

http://www.sciencemuseum.org.uk/on-line/lifecycle/images/1-2-5-3-5-2-0-0-0-0-0.jpg

• Lymphocytes exhibit specificity - respond to specific antigens (foreign materials).

• B or T cell responds to specific antigen from pathogen.

• B cell response - humoral response; T cell - cellular response.

http://www.biologyreference.com/images/biol_03_img0247.jpg

• B cells respond to antigen by making antibodies - proteins (immunoglobulins) that recognize and bind to specific antigens.

• Antibodies relatively same in structure; 1 end - constant region, other end - variable region (part that differs)

http://www.biology.arizona.edu/immunology/tutorials/antibody/graphics/antibody.gif

• 5 different classes of antibodies that perform different immune functions.

• IgA, IgM, IgE, IgG, and IgD (determined by constant region).

• IgM 1st one expressed during infection; found on the surface of B cells (along with IgD).

http://www.alerchek.com/igm400sh.GIF

• IgG - largest class in body.• IgE - involved in allergic

reactions.• IgA secreted from body linings

like mucous membranes.

http://sprojects.mmi.mcgill.ca/immunology/IgA.JPG

• Antibodies must recognize huge range of potential antigens found in pathogens (bacteria, viruses) but not recognize proteins produced by organism.

• Antibodies - complex proteins assembled from multiple polypeptides joined by disulfide bridges between light and heavy chains.

http://chip.inflam.lu.se/a-antibodies.jpg

• Variable regions of antibodies bind antigens including portions of both light and heavy chains that fold together in complete antibody molecule.

• During development of B cell, immunoglobulin goes through specific recombination of genes; allows for limitless possible options; each B cell has unique expression.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Fig. 43.15

• Cells have same genomic information, not true in B cells.

• B cells that have immunoglobulins that recognize proteins produced by self are destroyed so that they won’t attack body.

http://www.aecom.yu.edu/aif/gallery/sem/b-cell-buds-virus_c2005AECO.gif

• Bacterial infection occurs, B cells that bind to bacterial antigens will replicate - produce 2 types of B cells: plasma cells and memory cells.

http://medinfo.ufl.edu/year1/histo/images/p27c.jpg

• Plasma cells - antibody production factories which produce and secrete large amounts of antibodies into blood until after they die.

• Antibody cleared after couple of days.

• Short lived but powerful responses.

http://gsm.utmck.edu/amyloid/images/plasmacells.jpg

• Memory cells do not express antibodies, stay in circulation for years with immunoglobulin expression for that bacteria on surface.

• If same (or related) pathogen invades again, memory cells recognize it and provide rapid response, replicating and producing new plasma cells.

http://student.ccbcmd.edu/courses/bio141/lecguide/unit5/humoral/clonal/images/u3fg8d.jpg

• Memory cells responsible for effectiveness of vaccines.

http://www.accessexcellence.org/AE/AEC/CC/images/making_vaccines.gif

• T cells play different role in specific response - 2 different types of T cells.

• Cytotoxic T cells kill cells infected by pathogen that T cell recognizes.

• Helper T cells coordinate immune response of other cells against specific antigens.

http://content.answers.com/main/content/wp/en-commons/thumb/2/2a/220px-Cytotoxic_T_cell.jpg

• T cells produce wide range of proteins with antigen specificity - not secreted.

• Expressed by T cell receptors found in membrane of T cells.

• Recognizes antigen on surface of other cells in specific context, not antigens in solution.

http://www.haverford.edu/biology/Punt/T%20cells%20in%20blood.jpg

• Antigen stimulation - T cell receptor must be presented to cell as part of complex of proteins - major histocompatibility complex (MPH) or human leukocyte antigens (HLA) - found in plasma membrane of cells.

• 2 types of MHC involved in T cell response, MHC Class I and MHC Class II.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Fig. 43.9

• MHC I present on surface of all cells; MHC II a present on immune cells (macrophages, B cells, T cells).

• MHC present antigen from inside cell at cell surface - T cells can recognize it.

• T cell receptor of cytotoxic T cell must recognize antigen presented in MHC I on surface of infected cell.

http://www.rbej.com/content/figures/1477-7827-1-93-2.jpg

• If this happens, cytotoxic T cell will replicate.

• Future interactions of cytotoxic T cells with infected cell will cause cytotoxic T cell to kill infected cell.

• T cells involved in response of B cells to antigen.

• Helper T cells needed for B cells to respond to antigen.

• Macrophages will digest antigen and present it in MHC Class II at cell surface.

• Helper T cells with T cell receptors that recognize antigen will be stimulated.

http://library.thinkquest.org/03oct/00520/gallery/photos/HelperTcellandBcell.jpg

• Replicate and stimulate B cells that respond to antigen to replicated into plasma cells.

• Many cytokines (proteins or peptides that stimulate other lymphocytes) secreted by helper T cells to communicate with other cells to coordinate immune system.

http://www.reliatech.de/bilder/test/DC-Kurt-1.jpg

• MHC variable in humans and need to match between donor and recipient in an organ transplant.

http://www.cartoonstock.com/lowres/epa1439l.jpg

• Major histocompatibility complex (MHC) is responsible for stimulating rejection of tissue grafts and organ transplants.

• Minimize rejection, attempts are made to match MCH of tissue donor and recipient as closely as possible.

http://www.mun.ca/biochem/courses/3107/images/Stryer/Stryer_F14-41.jpg

• Prior to transplant, recipient is typically treated with irradiation to eliminate recipient’s immune system, leaving little chance of graft rejection.

• Donated marrow, containing lymphocytes, may react against recipient, producing graft versus host reaction, unless well matched.

• Person must still take drugs to help not reject transplant that leave them open to disease and cancers.

• Bone marrow transplants - graft itself, rather than host, source of potential immune rejection.

http://neurobio.mcphu.edu/FischerWeb/images/bone%20marrow%20stromal%20cells.jpg

Immunity in health and disease

• Active immunity (chicken pox) result of individual’s immune system already exposed to disease - can be acquired naturally or by vaccination.

• Vaccinated person who encounters actual pathogen will have same quick secondary response based on memory cells as person who had disease.

http://www.bbc.co.uk/schools/gcsebitesize/img/biwhitebloodcell.jpg

• Immunity can be transferred passively.

• IgG antibodies passed via placenta, IgA antibodies passed in breastmilk.

• Passive immunity occurs when animal passes (through injection) their immunity to another.

http://www.aphis.usda.gov/lpa/pubs/images/vb_vaccination.gif

Abnormal immune function

• Abnormal immune function can result in anything from allergies to autoimmune disease.

• Allergies are abnormal reaction to allergens (environmental antigens).

http://www.fourpaws.org/images_subpagenav/images_donate/items_for_sale/allergies-detail.jpg

• Most common allergies - antibodies of IgE class.

• Hay fever occurs when plasma cells secrete IgE specific for pollen allergens.

• Widespread, more dangerous -anaphylactic shock, life-threatening reaction to injected or ingested allergens.

• Anaphylactic shock results when widespread mast cell degranulation triggers dilation of peripheral blood vessels, causes precipitous drop in blood pressure.

• Sometimes body loses tolerance for itself, starts attack on itself - causes autoimmune disease (i.e. rheumatoid arthritis)

• SCID (severe combined immunodeficiency) - function of both humoral and cell-mediated immune defense compromised.

http://www.lpch.org/photos/greystone/ei_0062.gif

AIDS

• 1981 - AIDS (acquired immunodeficiency syndrome) became well-known.

• HIV virus (human immunodeficiency virus) - retrovirus that causes AIDS.

• Mortality for AIDS - 100% - one of the most lethal pathogens.

• Once inside cell, HIV RNA reverse-transcribed - product DNA integrated into host genome.

• Significant loss in humoral and cell-mediated immunity.

• Decline in helper T cells primarily caused by direct mortality from HIV infection.

http://www.wellesley.edu/Chemistry/Chem101/hiv/maturhiv.gif