The Human Immune System
Jul 30, 2015
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
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)
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)
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• 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
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
B-Lymphocytes Regulate Humoral Mediated Immunity
• “B” stands for Bursa of Fabricius - or Bone Marrow
• Mature into plasma cells that secrete
antibodies
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 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
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
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)
• 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
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)