The Human Immune System

Human Immune System

Innate Immunity Adaptive Immunity (A.K.A. Non-Specific Immunity) (A.K.A. Specific Immunity) 1. Membrane Barriers A. Dry (Cutaneous) B. Wet (Mucous) Humoral Imm. Cell Mediated Imm. 2. Antimicrobial Cellular Defenses B-Lymphocytes T-Lymphocytes A. Macrophages Mature into A. T4 (Helper) Lymphs B. Natural Killer Cells B. T8 (Cytotoxic killer) Lymphs 3. Antimicrobial Proteins Plasma Cells C. TSuppressor Lymphs A. Interferon that synthesize B. Complement Antibodies 4. Inflammation 5. Fever

The Human Immune System

• Unlike our other organ systems, this one is composed of trillions of individual cells circulating throughout the body

• Many of these cells are associated with the lymph nodes, thymus and spleen

Definitions:

• Immunity = Resistance to disease

– Innate Immunity – Responds to any substance that is non-self, altered-self, or missing self

• You are born with these defenses in place

– Adaptive Immunity – a highly specific response targeted against a particular foreign invader or altered-self cell

• Your body will synthesize or activate these defenses if required by the environment

• Both systems require appropriate genes

Innate Body Defenses

1. Membrane barriers – skin and mucosae

2. Antimicrobial cells

3. Inflammation

4. Antimicrobial proteins

5. Fever

Innate Body Defenses

1. Membrane Barriers - Body’s 1rst Line of Defense

– Skin and Mucosae• Cutaneous (Dry membranes)

– Skin – highly keratinized and acidic– Sebum – toxic to bacteria

• Mucous (Wet membranes)– Vaginal secretions – acidic (Lactobacillus)– Stomach – gastric juice is pH ~2– Saliva and lacrimal fluid - lysozyme– Sticky mucus traps – in digestive and resp. tract

2. Non-Specific Antimicrobial Cells

• Phagocytes– All macrophages = “large eater”cells– Classified by tissue in which they are found

• Kupffer cells – liver• Langerhans cells – epidermis of skin• Microglial cells – brain• Monocytes – blood• Neutrophils - blood

Phagocytes in the Blood

Neutrophils

Monocytes

Job Description of Neutrophils

• 1rst to respond to invasion• React within 1 hour of invasion• Some granules are lysosomes• Some granules contain “defensins” –

– Antibiotic like proteins• Neutrophils self-destruct when used

• Respiratory burst H2O2

Job Description of Monocytes

• Arrive at invasion site within 8-12 hours

• Janitorial duty• Initially are small and

sluggish• Become very active

phagocytes• Phagosome + lysosome phagolysosome• Act as antigen presenting

cells (APC’s)

3. Inflammation

• Pavementing• Diapedesis• Chemotaxis• Pus• Abscess• Infectious granuloma

4 Cardinal Signs of Inflammation

• Heat - histamine• Redness - histamine• Swelling - histamine• Pain - prostaglandins

Inflammation - Body’s 2nd line of defense

– Prevents spread of damaging agents

– Disposes of cell debris and pathogens

– Sets the stage for the healing process

– Brings in large quantities of • O2

• Nutrients• Fighter cells &

proteins

Non-Specific Antimicrobial Cells , cont.:Natural Killer Cell

• Not a phagocyte• Release chemicals

onto surface of non-self or altered-self cell– Synthesize and

release perforin– Cause holes to form in

cell membrane– May be used in future

to fight cancers

4. Antimicrobial Proteins

• Complement System– A collection of proteins dissolved in the blood

until activated– Enhances effects of the inflammatory process– 2 pathways:

• Classical• Alternate• Both pathways have a common terminal pathway• Make Membrane Attack Complex (MAC)

Complement/ Formation of MAC

MAC = Membrane Attack Complex

• Causes– Cell lysis– Promotes

phagocytosis– Enhances

inflammation– Causes opsonization

of target cell

Interferons

• When cells are infected by viruses, they release small proteins called interferons before they die

• Interferons’ job is to inhibit viral replication in neighboring cells

• Inhibit synthesis of mRNA and DNA, thereby preventing synthesis of viral particles

• Are not target specific, but are host specific

• Also activate macrophages and NK cells

Interferons, cont.

• Have been used clinically to treat viral infections and viral induced cancers– Resistant herpes infections– Viral induced cancers such as

• Kaposi’s sarcoma• Hepatitis C• Hairy cell leukemia

– Other viral infections such as AIDS

• Currently made using genetic engineering

5. Fever

• Normal TB = 98.6o F (?o C?)

• Regulated by __________?

• Pyrogens – secreted by macrophages

Raise TB

• Fever metabolic rate– Causes liver & spleen to sequester Fe & Zn

Adaptive Body Defenses• The Adaptive Immune System =

Body’s 3rd line of defense

• Major difference between Innate and Adaptive immune systems – – Adaptive Immune System is:

• Target specific• Systemic• Challenge sensitive• It has memory

2 Divisions in Adaptive Immune System

• Humoral mediated immunity

• Cell mediated immunity

2 Divisions in Adaptive Immune System

Humoral Mediated Immunity• Proteins that circulate in

body fluids– Blood – Lymph– Sweat, tears, saliva, breast

milk

• Proteins selectively bind to specific target molecules

Cell Mediated Immunity• Cells attacking other, specific

cells• Can act directly by lysing

cells, or• Act indirectly

– by releasing chemicals that increase inflammatory response or activate other macrophages/ lymphocytes

Definitions:

Antibody• Immunoglobulins (proteins)

secreted by B- lymphocytes that have matured into plasma cells

These two molecules form an antigen/ antibody complex

Antigen• Usually a protein

• Very large (M.W. >10,000 AMU’s)

• Very complex • Foreign to blood & other body

proteins

Why plastics are not good antigens

Are large molecules, BUT

• Are composed of simple, highly repeating hydrocarbon units

• Can be used in body– Prostheses– Stints– Wraps

Teflon

Haptens

• Small organic molecules that can become antigenic if they bind to carrier proteins in the body

• Example: penicillin, urushiol (poison ivy toxin)

Humoral Mediated Immunity

• Draw blood– Serum– Buffy coat– Packed red cells

• Electrophoresis of serum and

globulins

B-Lymphocytes Regulate Humoral Mediated Immunity

Plasma cell

Lymphocytes

Globulins = Immunoglobulins = Antibodies

Antibodies Are Immunoglobulins

• 2 light chains• 2 heavy chains

• Constant Regions – Fc– Crystallizable fragment

• Variable Regions - Fab– Antigen binding site– Binds with antigen determinant

site on antigen

The 5 Classes of Immunoglobulins

• IgG – most plentiful in body fluids; protects fetuses

• IgE – causes allergic reactions; hypersensitivity reactions; used against parasites

• IgA – found in body secretions such as sweat and breast milk

• IgM, IgD – are secreted during first stage of initial infection by a pathogen

5 Ways That Antibodies Render Antigens Harmless

B-Lymphocytes Regulate Humoral Mediated Immunity

• “B” stands for Bursa of Fabricius - or Bone Marrow

• Mature into plasma cells that secrete

antibodies

B-Lymphocytes Regulate Humoral Mediated Immunity

Plasma cell

Lymphocytes

B-Lymphocyte Clonal Selection

• Note only 1 kind of B-lymph is activated by a particular antigen– Called “Clonal Selection”

• Most B lymphs mature into plasma cells, which secrete antibodies

• Note that Memory cells are also made

• Memory cells impart immunity

Primary and Secondary Response to Infection

Memory Cells Impart Immunity

Primary Response

• Primary Response = – The first time you are infected by a microbe– The first time you are vaccinated– Initial high concentrations of IgM/ IgD– Followed by in IgG

Secondary Response

Requires prior exposure to specific antigens – a very rapid release of high antibody concentration– Active Immunity – Requires presence of

memory cells• Naturally acquired and artificially acquired

– Must have had disease or been vaccinated

– Passive Immunity – Based only on the presence of antibodies

• Naturally acquired and artificially acquired– Breast fed baby or administration of globulins

• A short-term response

Phases of Sickness

Incubation

Prodromium

Acute phase

Convalescence

Vaccines

• Clinical immunization programs

• All vaccines work by eliciting the production of memory cells

• Vaccination from Latin word for “cow” (“vacca”)

• Vaccines are made from dead or weakened organisms (or viruses) or purified products from them

Cell Mediated Immunity

The Development of

T-Lymphocytes

2 Basic Kinds of T-Lymphocytes

• T4 Lymphocytes

– AKA Thelper lymphs

– Tsuppressor lymphs (?)

• T8 Lymphocytes

– Tcytotoxic killer lymphs

– Tsupressor lymphs (?)

• MHC Class II Markers T4 lymphs

– MHC II markers are found on:• Macrophages (APC’S)• B lymphocytes

• MHC Class I Markers T8 lymphs

– MHC I markers are found on:• All nucleated cells in the body

• System depends upon bonding by coreceptor proteins and antigen specific Tcell receptors

CD8 coreceptor bonds T8 cells to all nucleated cells of body via MHC class I markers

CD4 coreceptor bonds T4 cells to all cells bearing MHC class II markers (macrophages, B lymphs)

The Role of Thelper Lymphocytes in the Cell-Mediated Immune Response

T4 Cells Secrete IL1 and IL2Activate Other Components of the Immune

System

The Molecular Structure of HIV

Symptoms of AIDS – Opportunistic Infections/ rare cancers

Kaposi’s sarcoma Candidiasis

Cachexia = body wasting

The Face

of

AIDS

AIDS is a Pandemic

Treatment of AIDS

• It pays to start therapy early

• HAART= Highly Aggressive AntiRetroviral Therapy

• The use of HAART has reduced the AIDS mortality rate in the U.S.

• Medication holidays

Designing HIV vaccines

Autoimmunity• Definition

– Autoimmune Diseases: Examples• Systemic Lupus Erythematosis (SLE)• Type I Diabetes (Juvenile Onset)• Grave’s Disease• Multiple Sclerosis

• Why we are not autoimmune– Clonal Deletion

• (Supported by tissue and organ transplants to embryos)

– Clonal Anergy • (Supported by sudden development of

autoimmunity)