Defenses Against DiseaseCh. 43

From the Tiniest Things…• Everyday we are invaded by

bacteria, viruses, and non-self molecules

• Immune system natural protection against non-self substances

• 3 parts:1) Physical barriers skin, tight

junctions, mucus layers, acidic environments

2) Innate Immune system non-specific reaction to all non-self molecules

3) Adaptive Immune system specific reaction to reoccurring non-self molecules

The White Army• Leukocytes “white blood cells”, soldiers

protecting your body; patrol the blood and lymph

• 6 main types:1) Macrophage phagocyte (cell eater)

that consume infected cells, pathogens, and non-self molecules

2) Monocyte become macrophages during 2nd wave of protection

3) Neutrophil consumes pathogens and tissue debris

4) Eosinophil secret enzymes to kill parasites (too big for phagocytosis)

5) Basophil respond to allergens, secrete histamine and cause inflammation

The White Army: Lymphocytes• Lymphocytes Groups of

cells in innate and adaptive immunity– NK cells natural killer cells;

kill cells infected by viruses or cancerous cells

– B-Cells capture and present antigens from bacteria

– Plasma cells secrete antibodies

– Helper T-cells help activate other B-cells

– Cytotoxic T-cells kill infected cells

Innate Immunity: Nonspecific!• Recovery time: 7-10 days• Various steps that are

generally effective• Steps made to build adaptive

immunity for faster response time

• Reactions:1) Antimicrobial peptides

simplest response; pathogens interacting with inner lining of body trigger release of defenins (enzymes that destroy membranes)

Innate Immunity: Inflammation• Inflammation heat, pain,

and swelling in infected area– Local only at infection site;

caused by histamine– Systemic throughout the

body (fever); caused by pryrogens which cause the hypothalamus to turn up the heat

• Heat and swelling allow better macrophage attack at infection site and help phagocytosis

Innate Immunity: Inflammation• Steps:1) Infection occurs; macrophages

at site detect pathogens2) Cytokines and histamine are

released; inflammation starts and blood vessels dilate

3) Neutrophils and monocytes drawn towards site (chemokines) and pass through permeable blood vessels

4) Neutrophils consume bacteria and die in the process (pus)

5) Monocytes change to macrophages as 2nd wave attack

6) Infection clears up; inflammation stops

Innate Immunity: Complement Systemand Interferons

• Complement system 30 proteins that recognize and attach to pathogens

• Membrane attack complex after proteins attach; attack complexes bind to them and attack pathogen membranes– Enzymes will produce holes in plasma

membrane– Cell cannot maintain homeostasis with

ions freely flowing; Pathogen swells and lyses

• Interferons released by cells infected with a virus; help block viruses from attaching to new hosts– Activated RNA degrading enzymes to

stop all protein synthesis

Innate Immunity: Natural Killer Cells• NK cells target cells infected by

viruses/cancer• Identify infected cells by the

number of MHC (major histocompatibility complex) proteins on their surface– Normal cell high number– Infected/Cancer protein synthesis

inhibited so low number• Releases perforin to degrade holes

in cell’s membrane; cell swells and lyses

• Also secretes proteases (degrades proteins) into the cell which causes apoptosis

Adaptive Immunity: Specific Defense!• All methods in innate immunity

are generalized; but each attack on our system allows us to build a strong adaptive immunity

• Antigen non-self molecule that generates antibodies; can be any organic molecule but mostly large proteins

• Antigens are recognized by:1) B-cells come from bone

marrow; produce antibodies2) T-cells mainly in Thymus; can

help spread antigen info (helper T-cells) and kill infected cells (cytotoxic T-cells)

Adaptive Immunity: Two Ways to Play• Antibody-mediated (humoral)

B-cells change into plasma cells to release large amounts of antibodies

• Cell-mediated T-cells become active and kill infected cells

• Both methods follow the same pattern:

1) Antigen is recognized2) Lymphocytes are activated3) Antigen is removed from the

body4) Memory cells made to prepare

for future infections

Antibody-Mediated Immunity: Receptors• Antigens must be recognized first• B and T cells are covered with

thousands of receptors for antigens• B-cell receptors 2 heavy chains

(transmembrane) and 2 light chains; 2 variable regions on the end react to specific antigen(s)– 10 trillion B-cells with 100 million

different receptors• T-cell receptors 2 short chains

(transmembrane) with 1 variable region

• Variable region only reacts to small part of antigen (epitope), so one antigen can react to multiple receptors

Antibody-Mediated Immunity: Antibodies• Immunoglobulins (Ig) complex

molecules made of 2 heavy chains and 2 light chains; have a constant region and a variable region

• Classes:1) IgM B-cell receptors2) IgG most abundant; used after 2nd

infection3) IgA secreted in specific parts of the

body; block pathogens from binding to cells

4) IgE secreted by plasma cells; bind to basophils and mast cells to release histamine; allergic response

5) IgD works with IgM; still unclear of function

Antibody-Mediated Immunity: Lymphocyte Activation

1) Dendritic cell engulfs pathogen2) Lysosome degrades pathogen;

antigens are isolated3) Dendritic cell presents antigens

on its membrane through class II MHC proteins; now a APC (antigen-presenting cell)

4) Antigen presented to CD4+ T-cell; T-cell activated

5) Interleukins from T-cell promote rapid division; some cells become helper T-cells and activate more lymphocytes (effector T-cells)

Antibody-Mediated Immunity: Lymphocyte Activation

6) B-cells present antigens on their cell surface and link with helper T-cells; when matched the B-cell becomes activated7) B-cells divided rapidly. Some cells become plasma cells and some become memory B-cells8) Plasma cells secrete antibodies which bind to antigens; inhibits pathogens and make them easier to find for phagocytosis9) Memory B-cells stay in body to create a faster response if a second infection occurs

Antibody-Mediated Immunity: Cleaning Up• Antigens removed from

body two ways1) Neutralization antibodies

bind to antigens inhibiting them from infecting cells; filtered from body with time or consumed

2) Agglutination pathogens are stuck together by antibodies; unable to move

• Both methods result in increased phagocytosis by the complement system

Antibody-Mediated Immunity: Memory Cells• Immunological memory

built from memory B-cells and memory helper T-cells after primary immune response (3-14 days)

• Secondary Immune response less antigen is needed to react with immune system so reaction is faster; flood of IgG antibodies

• Related antigens can set off reaction of similar antibodies

Building Immunities• Active immunity you

build your own antibodies– Vaccination dead or weak

form of the pathogen gives your body the antigen needed to make the antibody but not the disease

• Passive immunity antibodies given directly– IgG mother to fetus– IgA breast milk– Weaker form because effect

only last a month

Cell-Mediated Immunity: Cytotoxic T-Cells• System best for viruses1) Pathogen antigens released from

infected cell2) B-cell picks up antigens to become an

APC3) APC and CD+8 T-cell link and

cytokines secreted by helper T-cell trigger response

4) CD+8 T-cell divides to make cytotoxic T-cells and memory cytotoxic T-cells

5) Cytotoxic T-cells find antigen on class I MHC proteins; bind to infected cell

6) Cytotoxic T-cell uses proteases and other enzymes to destroy infected cell

When Immune Systems Break• All systems set up an

immunological tolerance; base level of what is and is not “self”; set up as fetus

• Autoimmune reaction antibodies attack “self” molecules– Type I diabetes body kills own

beta cells; no insulin– Lupus body attacks blood cells,

platelets, mitochondria, etc…– Rheumatoid arthritis body attacks

connective tissue– Multiple sclerosis body attacks

myelin sheaths

Mild to Sever Reactions• Allergic reactions caused by antigens

that cause B-cells to release large amounts of IgE; react with mast and basophil cells which release histamine

• What does this result in?– Inflammation response

• Most effect eyes, nasal and air passage ways; also stimulate smooth muscle contractions and mucus production (allergies)

• Asthma restricted breathing; stopped with antihistamines

• Anaphylactic shock sever reaction that can result in death; stopped with epinephrine

Mild to Sever Reactions• Suggested Homework:– Test Your Knowledge

• Actual Homework:– Discuss the Concepts #1– Interpret the Data