Immune System

AP Biology

Infectious Agents• The first conclusive

evidence that bacteria could cause disease was done by showing anthrax was caused by bacteria in the bloodstream through the independent work of:– Louis Pasteur

• also disproved spontaneous generation

– Robert Koch• Proposed a set of criteria

to determine whether a disease is caused by an infectious agent

Infectious agents (pathogens) include:

• Bacteria– Prokaryotic cells– Steptococcus, staphylococcus,

anthrax (bascillus)– Treated with antibiotics

• Viruses– Protein coat and nucleic acid– Influenza, HIV, common cold– Treated with vaccines

• Parasites– If your not the host, you’re a parasite– “Big fleas have little fleas upon their

backs to bite ‘em, Little fleas have lesser fleas and so on, ad infinitum”• Jonathon Swift

– Protzoans (unicellular) • plasmodia (malaria)

– Tapeworms (digestive tract)– Arthropods (fleas, ticks)– Fungi (mold, mildew, mushroom)– Treated with drugs that disrupt

metabolism

Nonspecific Defense

• 1st line of defense (external mechanisms)– Skin

• Acts as a barrier

– Mucus membranes• Line the digestive, respiratory, and genitourinary tracts• Trap microbes and move with cilia up throat to be swallowed

– Secretions (chemical defense) of skin/mucous membranes• Sebaceous (oil) and sweat glands

– Decrease pH of skin to 3-5 (not good for microbe growth)

• Saliva, Tears, Mucous– Contain lysozymes (digest cell walls of bacteria)

Nonspecific Defense• 2nd line of defense (internal mechanisms)

– White blood cells (spend most of their time in lymphatic system)• Neutrophils

– Attracted to damaged cells– Use phagocytosis to destroy foreign cell– Short-lived (few days)

• Monocytes (macrophages)– Large phagocytic cells– Long-lived (1-2 weeks)

• Eosinophils– Defend against large parasites (attach external wall/membrane)

• Natural killer (NK) cells– Destroy virus-infected body cells and potential cancer cells (attach membrane)

– Inflammatory response• Basophils or mast cells (WBC’s) release histamine• Chemokines – attract phagocytes• Pyrogens – set the body’s thermostat to a higher tempature

– Antimicrobial Proteins• Complement system – 20 serum proteins that lead to cell lysis• Interferons – released by virus-infected cells and inhibit viral reproduction

Inflammatory response to broken skin

1) Chemical signals (histamine or prostaglandins are released)

2) Capillaries dilate and become more permeable, clotting begins

3) Chemokines attract phagocytes

4) Pathogens are consumed and healing begins

5) Blood clotting closes the wound

Specific Defense (immune response)• 3rd line of defense (internal mechanisms)• Lymphocytes (other white blood cells)– Circulate through blood and lymph– Antigen recognition and response to

• Virus, bacteria, fungi, protozoan, pollen, transplanted tissues

– B lymphocytes (B cells)• Secrete antibodies• Humoral response (extracelluar pathogens)• Matures in bone marrow

– T lymphocytes (T cells)• Contain antigen receptors (similar to

antibodies)• Cell-mediated response (intracellular

pathogens)• Matures in thymus

Primary and Secondary Immune Response• 2nd exposure to the same pathogen results in a

much quicker, more numerous, and specific attack

Self vs. Nonself• B and T cell antigen receptors are tested for potential

self-reactivity while they mature– Lymphocytes with receptors that match molecules of the

body are rendered non-functional or destroyed by apoptosis

• Self-tolerance– No mature lymphocytes that react against self components

– Failure could lead to autoimmune disease• Multiple sclerosis

• Lupus

• Eczema

• Crohns disease

Major Histocompatibility Complex (MHC)• Set of genes that code for marker proteins

allowing the immune system to distinguish self from nonself= HLA (human leukocyte antigens)

• Must have a wide range of peptides:1)the MHC locus is polygenic2)MHC genes are highly polymorphic and numerous

alleles have been described3)MHC genes are codominantly expressedResult: each person is unique and this is why the body

rejects transplanted tissues/organsResult: adaptation that increases the likelihood that

some individuals will survive an epidemic

2 general classes of MHC molecules• Class I– Found on all nucleated cells and present peptides

to cytotoxic T cells (killer T cells)– Normal cells use Class I MHC molecules to

continually present self-peptides from protein turnover and defective ribosomal products

• Class II– Found on certain immune cells themselves:

macrophages, B cells and activated T cells, collectively known as antigen-presenting cells (APCs)• APC’s present foreign fragments to helper T cells which

stimulate an immune response

2 main types of T cells

• Cytotoxic T cells (killer T cells)– Antigen receptors bind to protein fragments on Class I

MHC molecules– Kill virus-infected cells

• Helper T cells– Antigen receptors bind to protein fragments on Class II

MHC molecules– Respond to APC’s (macrophages and B cells)– Send out signals to incite other cells to fight the pathogen

• Immune response depends on the ability of the MHC molecules to present a fragment of the pathogen

Immune Responses• Humoral immunity– B cell activation

• Produces antibodies– Defends against extracellular pathogens in body fluids

by binding to antigens and making them easier targets for phagocytes and complements (receptor proteins)

• Cell-mediated immunity– T cell activation– Defends against viruses and bacteria within infected

body cells and against fungi, protozoa and parasitic worms

– Destroy transplanted tissue and cancer cells … both perceived as “nonself”

• Cell signaling provides a network for these two systems to work together!

4 major attributes of immune responses

1) Specificity (complement system)

2) Diversity (genetic contribution)

3) Memory (B cells and T cells … 2nd exposure)

4) Self-tolerance (distinguish self from nonself)

Helper T cells function in both humoral and cell-mediated immunity

1) APC cell engulfs bacteria and transports part of it to the cell surface via a Class II MHC molecule

2) CD4 protein of T cell receptor enhances binding and activation of Helper T cell

3) IL-1 helps activate Helper T cell to produce IL-2 which serves to clone more Helper T cells

4) IL-2 activates cell-mediated and humoral immunity

• CD8 surface protein– Enhances interaction between virus-infected cells and

cytotoxic T cell by binding to Class I MHC molecule• Helps keep the 2 cells in contact while activation occurs

– Stimulated by IL-2 to become an active killer

1) Activation occurs (note: IL-2 not shown)2) Cytotoxic T cell discharges perforin molecules creating pores in the APC membrane3) Ions and water flow into the cell causing swelling and eventually lyses (bursts)

Note: now the virus has lost its place to reproduce and is exposed to circulating antibodies

• Notice the relevance of the Endomembrane System– Nucleus, ER, Golgi, Lysosome, Cell membrane

What is an antibody?• Globular serum proteins called

immunoglobulins (Igs) produced by B cells in response to an antigen

• 4 polypeptide chains (2 heavy, 2 light) shaped like a Y

• V = variable region; C = constant region

Antibodies bind to epitopes (part of antigens)

• Multiple antibodies can bind to the same antigen making microbes more easily identified and disposed

How do antibodies dispose of antigens?

Active vs. Passive Immunity

Active• Naturally acquired due to

previous infection

• Artificially acquired by immunization (vaccination)– Parts of inactivated or

weakened microbes that stimulate immune response and provide “memory”

• Long-term effect

Passive• Pregnant women to fetus

across the placenta

• Nursing mother to baby

• Injection of antibodies from animal already immune

• Short-term effect– Only lasts as long as the

antibodies last

– Few weeks to a few months

Connections• ABO blood groups– Type A = A-antigens– Type B = B-antigens– No memory … each exposure is the like the 1st time

• Rh factor (+/-)– Produces memory cells– Affects Rh(-) mother carrying an Rh(+) child– Especially affects next Rh(+) pregnancy as mothers own

immune system attacks the red blood cells of the fetus

• Allergies– immune response to substances generally not harmful

• Pollen, dust, perfume, bee stings, nuts, fish, studying (haha)

– Inflammatory response leads to sneezing, runny nose, tearing of eyes, smooth muscle contraction (restrict breathing)

– Combat with: antihistamines, epinephrine hormone (EPI pens)

Another Resource:

• http://www.examiner.com/wellness-in-birmingham/the-immune-system-how-it-works

• http://people.eku.edu/ritchisong/301notes4b.html