Innate = Defenses against any pathogen; present at birth; good against pathogen; no memory
Adaptive = Defenses against or resistance to a specific pathogen; specific reaction to a pathogen; acquired through exposure; memory response
Toll-Like Receptors
Receptors on macrophages that recognize pathogens by looking for PAMPs (Pathogen Associated Molecular Patterns - peptidoglycan, endotoxin, flagella protein, double stranded RNA)
Components of 1st Line of Defense
Physical = skin (sebum), epidermis (consists of tightly packed cells with Keratin), mucous membranes (mucous traps microbes), ciliary escalator (microbes trapped in mucous are transported from lungs), lacrimal apparatus (washes eye), saliva (washes off microbe), urine (flows out), vaginal secretions (flows out)
Chemical = fungistatic fatty acid in sebum, low pH of skin, lysozyme in perspiration, tears, saliva, & urine, low pH of gastric juice, low pH of vaginal secretions
2nd Line of Defense
Blood consists of plasma & formed elements (RBCs, WBCs, T cells, B cells, & Platelets)
WBCs
2 Types:
1. Granulocytes
Neutrophils - phagocytosis
Basophils - histamine, allergies, inflammation
Eosinophils - kills parasites, allergies
2. Agranulocytes
Monocytes (Macrophages) - phagocytosis
Dendritic Cells - phagocytosis, present antigen to adaptive immune cells, bridge to 3rd line of defense
Chemotaxis = Chemotactic chemicals produced (chemokines) along a gradient causing movement of phagocytes to microbes - movement toward a chemical signal
Adherence = Attachment of phagocyte's membrane to microbe; opsonization (coating of microbe by antibodies or complement); toll-like receptors cause activation of phagocyte to release cytokines
Ingestion = Pseudopods engulf microbes & fuse together forming phagosome; pH is lowered inside the phagosome
Digestion = Phagosome fuses with lysozome creating the phagolysozome; lysozome degrades peptidoglycan while other enzymes break down other cell components; after microbe is digested, vesicle becomes a residual body & expels waste outside the cell; also presents antigens to the 3rd line of defense
Ways Microbes Evade Phagocytosis
Inhibit Adherence = M protein, capsules
Kill Phagocytes; = Leukocidins
Lyse Phagocytes = Membrane attack complex
Escape Phagosome
Prevent Phagosome-Lysozome Fusion
Survive in Phagolysozome
Inflammation
Body's response to cell damage characterized by redness, heat, pain, swelling
Vasodilation = increased permeability of blood vessels; release of acute phase proteins (histamines, kinins, prostaglandins, leukotrienes) causes increased leakiness of vessels to allow migration of leukocytes to site of damage; blood clots can form around abcess to prevent dissemination of infection
Phagocyte Migration & Phagocytosis = phagocytes normally flow with blood through vessels; can adhere loosely & then bind tightly when stimulated; then follow chemokine gradient & can squeeze through endothelial cells to move into tissues; adhere to microbes & phagocytose them
Tissue Repair = final stage; new cells are produced by the supporting tissues and/or the functioning tissue; can be abnormal if fibroblasts are activated to produce scar tissue
Complement
Complement System = defensive system consisting of over 30 proteins produced by the liver and found circulating in blood serum and within tissues throughout the body
Complements the cells of the immune system in destroying microbes; not adaptable and does not change over the course of a person's lifetime (belongs to the innate immune system)
What Complement Activation Leads To
Inactive C3 splits into activated C3a and C3b.
C3b binds to the surface of a microbe, and receptors on phagocytes attach to the C3b. Thus C3b enhances phagocytosis by coating a microbe, opsonization promotes attachment of a phagocyte to a microbe.
C3b also initiates a series of reactions that result in cytolysis.
The transmembrane channels of the MAC result in cytolysis.
C3a and C5a bind to mast cells and cause them to release histamine and other chemicals that increase blood vessel permeability during inflammation. C5a also functions as a very powerful chemotactic factor that attracts phagocytes to the site of an infection.
Complement Pathways
Classical = Initiated when antibodies bind to antigens
Alternative = Does not involve antibodies; activated by contact between certain complement proteins and a pathogen
Lectin = When macrophages ingest bacteria, viruses, and other foreign matter by phagocytosis, they release cytokins that stimulate the liver to produce lectins, proteins that bind to carbs
Interferon
Class of similar antiviral proteins produced by certain animal cells, such as lymphocytes and macrophages, after viral stimulation; interferes with viral multiplication
Types of Interferon
Alpha & Beta Interferon = produced by virus-infected host; induces uninfected cells to produce antiviral proteins that prevent viral replication
Gamma Interferon = produced by lymphocytes; induces neutrophils and macrophages to kill bacteria; causes macrophages to produce nitric oxide that appears to kill bacteria as well as tumor cells by inhibiting ATP production
Antimicrobial Peptides
Inhibit cell wall synthesis; form pores in plasma membranes, resulting in lysis; destroy DNA and RNA
Produced by nearly all plants and animals, and bacterial resistance to AMPs has not yet been seen
B Cells & T Cells
B Cells = type of WBC; differentiates into andtibody-secreting plasma cells and memory cells; recognize antigens and make specific antibodies against them
T Cells = type of WBC; develops from a stem cell processed in the thymus gland that is responsible for cell-mediated immunity; contact with an antigen complementary to a TCR can cause certain types of T cells to proliferate and secrete cytokines rather than antibodies
Antibodies
Globulin proteins aka immunoglobulins (Ig); made in response to an antigen
Structure = antibody monomer has 4 protein chains joined by disulfide links and other bonds to form a Y-shaped molecule; the two sections located at the ends of the y's arms are called variable regions
Classes of Antibodies
IgG = enhances phagocytosis; neutralizes toxins and viruses; protects fetus and newborn
IgM = especially effective against microorganisms and agglutinating antigens; first antibodies produced in response to initial infection
IgA = localized protection of mucosal surfaces
IgD = serum function not known; presence on B cells functions in initiation of immune response
IgE = allergic reactions; possibly lysis of parasitic worms
MHC (Major Histocompatibility Complex) Molecules
Collection of genes that encode molecules of genetically diverse glycoproteins that are found on the plasma membranes of mammalian nucleated cells
Identifies the host and its use here prevents the immune system from making antibodies that would be harmful to the host
5 Processes That Occur Following Binding of Antibody to Antigen
Agglutination = antibodies cause antigens to clump together
Opsonization = the antigen, such as a bacterium, is coated with antibodies that enhance its ingestion and lysis by phagocytic cells
Neutralization = IgG antibodies inactivate microbes by blocking their attachment to host cells and neutralize toxins in a similar manner
Activation of Complement System = triggered by either IgG or IgM antibodies which llyses the microbe, which then attracts phagocytes and other defensive immune system cells to the area
Antibody-Dependent Cell-Mediated Cytotoxicity = resembles opsonization in that the target organism becomes coated with antibodies; however, destruction of the target cell is by immune system cells that remain external to the target
Classes of T Cells
Helper T Cell = coordinates and regulates the immune response by secreting interleukins; regulate other t cells, b cells, leukocytes (macrophages and granulocytes); can recognize an antigen presented on the surface of a macrophage
Cytotoxic T Cell = destroys infected cells as well as pathogens by releasing destructive compounds that will kill the pathogen; secretes toxins and digestive enzymes as well
Supressor T Cell = inhibit and regulate the immune response
Natural Killer Cell = can attack cancer and some pathogens
Types of Professional Antigen-Presenting Cells
Dendritic Cells = present all types of antigens, but present viral antigens efficiently
Macrophages = present bacterial antigens well
B Cells = present peptides of soluble protein antigens, such as protein toxins, that they have internalized via their antigen receptors
NK Cells
Not immunologically specific; they do not need to be stimulated by an antigen
They first contact the target cell and determine whether it expresses MHC class I self-antigens; if it does not they kill the target cell
Cytokines
A small protein released from human cells that regulates the immune response; directly or indirectly may induce fever, pain, or T cell proliferation
Immunological Memory
The capacity of the body's immune system to remember an encounter with an antigen due to the production of circulating antibodies and expanded clones of long-lived B and T cells during the primary response
Ensures that subsequent infections with the same pathogen will provoke a faster, stronger, longer secondary immune response
4 Types of Acquired Immunity
Naturally Acquired Active Immunity = develops when a person is exposed to antigens, becomes ill, and then recovers. One acquired, immunity is lifelong for some diseases
Naturally Acquired Passive Immunity = involves the natural transfer of antibodies from mother to her infant. Antibodies in a pregnant woman cross the placenta to her fetus
Artificially Acquired Active Immunity = result of vaccination; introduces vaccines into the body
Artificially Acquired Passive Immunity = involves the injection of antibodies (rather than antigens) into the body. These antibodies come from an animal or person who is already immune to the disease
Vaccines
A suspension of organism or fractions of organisms that is used to induce immunity
Live Attenuated Vaccines = includes a live virus that has mutated so that it has reduced ability to grow in human cells and is no longer pathogenic to humans
Inactivated Killed Vaccines = Includes virus particles that have been treated with formalin, heat, or irradation so that they are no longer able to replicate
Subunit Vaccines = use only those antigenic fragments of a microorganism that best stimulate an immune response
Conjugated Vaccines = involves attachment of a polysaccharide to a protein
Nucleic Acid (DNA) Vaccines = plasmids of "naked" DNA injected into muscle results in the production of the protein antigen encoded in the DNA; the protein antigens are carried to the red bone marrow and stimulate both humoral and cellular immunity
Monoclonal Antibodies
Antibodies that recognize a single, specific epitope of an antigen of interest
When a hybridoma is grown in culture, its genetically identical cells continue to produce the type of antibody characteristic of the ancestral B cell
Useful because they are uniform, highly specific, and they can be produced readily in large amounts
Precipitation & Agglutination Reactions
Precipitation Reactions = involve the reaction of soluble antigens with IgG or IgM andtibodies to form large, interlocking molecular aggregates called lattices; used in precipitin ring test and immunodiffusion tests
Agglutination Reactions = involve either eithe particulate andtigens or soluble antigens adhering to particles; these antigens can be linked together by antibodies to form visible aggregates; used in direct agglutination tests and indirect agglutination tests
Neutralization Reactions
Antigen-antibody reaction in which the harmful effects of a bacterial exotoxin or a virus are blocked by specific antibodies
Complement-Fixation Reactions
Antibodies that do not produce a visible reaction, such as precipitation or agglutination, can be demonstrated by the fixing of complement during the antigen-antibody reaction
Indirect Vs. Direct ELISAs
Indirect = detects antibodies in a patient's sample rather than an antigen such as a drug; antigen is adsorbed to well, patient serum is added and complementary antibody binds to antigen, enzyme-linked anti-HISG is added and binds to bound antibody, enzyme's substrate is added and reaction produces a product that causes a visible color change
Direct = tests to detect the presence of drugs in urine; antibody is adsorbed to well, patient sample is added and complementary antigen binds to antibody, enzyme-linked antibody specific for test antigen is added and binds to antigen, forming sandwich, enzyme's substrate is added, and reaction produces a product that causes a visible color change
Hypersensitivity
Refers to an antigenic response beyond that which is considered normal; aka allergy
Hypersensitivity responses occur in individuals who have been sensitized by previous exposure to an antigen; aka allergen
Type 1 (Anaphylactic) = IgE binds to mast cells or basophils; causes degranulation of mast cell or basophil and release of reactive substances such as histamine - anaphylactic shock from drug injections and insect venom; common allergic conditions such as hay fever or asthma
Type 2 (Cytotoxic) = antigen causes formation of IgM and IgG antibodies that bind to target cell; when combined with action of complement, destroys target cell - transfusions reactions, Rh incompatibility
Type 3 (Immune Complex) = antibodies and antigens form complexes that cause damaging inflammation - arthus reactions, serum sickness
Type 4 (Delayed Cell-Mediated, or Delayed Hypersensitivity) = antigens activate Tc that kill target cell
HLA Typing
Used to identify and compare HLAs (human leukocyte antigen)
Certain HLAs are related to an increased susceptibility to specific diseases
Medical application of HLA typing is to identify such susceptibility and in transplant surgery
Autoimmunity
Condition in which one's own immune system cannot discriminate between foreign and self antigens
Transplant Rejection
Specific immunological eradication of a graft
Hyperacute Rejection = preexisting antibodies in recipient, Ag-Ab complex, mismatched blood groups
Acute Rejection = due to difference in MHC I and II alleles, happens in 10 - 14 days and is cell-mediated,
Chronic Rejection = due to difference in minor histocompatibility antigens, slow progressive (months to years), both humoral and cellular immunity
Graft Vs Host Rejection = lymphocytes in a graft attacking the recipient, if immunocompromised
Types of Transplants
Privileged Sites and Privileged Tissue
Stem Cells
Grafts
Bone Marrow Transplants
How Cancer Cells Escape Detection By The Immune System
Some cancer cells can produce proteins that shut down the immune system in the area around the tumor
Some cancers occur in places that the immune system has a hard time getting to such as the brain
Immunodeficiencies (Congenital Vs. Acquired)
Congenital = the inability, due to an individual's genotype, to produce specific antibodies or T cells
Acquired = the inability, obtained during the life of an individual, to produce specific antibodies or T cells, due to drugs or disease
HIV Infection
Retrovirus that has two identical strands of RNA, the enzyme reverse transcriptase, and an envelope of phospholipid
Spread by dendritic cells that cary it to the lymphoid organs where it contacts cells of the immune system; viral DNA becomes integrated into the chromosomal DNA of the host cell
Cell Types Infected by HIV & How This Affects The Immune System
T Cells
Causes the immune system to shut down
Sties, Pimples, Carbuncles, Folliculitis
Causative Agent = S. aureus
Identifying Characteristic = Localized infection, with or without pus
Impetigo
Causative Agent = S. aureus
Identifying Characteristic = Highly contagious, vesicular rash; passed through direct contact
Toxemia - Scalded Skin Syndrome
Causative Agent = S. aureus
Identifying Characteristic = Staph toxins enter blood stream; results in fever, rash, and shock
Erysipelas
Causative Agent = S. pyogenes
Identifying Characteristic = Reddish patches on skin or mucous membranes with fever
Necrotizing Fasciitis
Causative Agent = S.pyogenes; MRSA
Identifying Characteristic = Bacteria invade tissue and destroy it
Identifying Characteristic = Yeast infection; thrush; commonly found in immunosuppressed
Scabies
Causative Agent = Mites Sarcoptes scabiei
Identifying Characteristic = Burrow under skin; papules and itching
Pediculosis
Causative Agent = Pediculus humanis (lice)
Identifying Characteristic = Itchiness due to sensitization to louse saliva
Conjunctivitis
Causative Agent = Hemophilus influenzae (bacteria); can be viral too
Identifying Characteristic = Inflammation of the conjunctiva of the eye; aka pink eye
Trachomatis
Causative Agent = Chlamydia trachomatis
Identifying Characteristic = G- coccoid; swelling and pus; birth canal or wrimming; Trachoma - scar
Opthalmia Neonatorum
Causative Agent = Neisseria gonorrhoeae
Identifying Characteristic = Acquired during birth; acute infection with pus; blindness; newborns tx with antibiotics
Herpetic Keratitis
Causative Agent = HSV-1
Identifying Characteristic = Inflammation of cornea
Ameobic Keratitis
Causative Agent = Acanthamoeba
Identifying Characteristic = Fresh water, usually in contact lens wearers who make own saline
Urethritis
Causative Agent = Opportunistic G- bacteria
Identifying Characteristic = Inflammation of the urethra
Cystitis
Causative Agent = E. coli, Staphylococcus saprophyticus
Identifying Characteristic = Inflammation of the bladder
Ureteritis
Causative Agent = Opportunistic G- bacteria
Identifying Characteristic = Inflammation of the ureters
Pyelonephritis
Causative Agent = E. coli
Identifying Characteristic = Inflammation of the kidneys
Leptospirosis
Causative Agent = Leptospira interrogans
Identifying Characteristic = Transmitted by urine contaminated water from animals (dogs, rats); causes fever, chills, and can lead to liver and kidney issues
Gonorrhea
Causative Agent = Neisseria gonorrhoeae
Identifying Characteristic = Attaches to mucosal cells using fimbriae; results in painful urination and pus discharge in men; can cause blindness if passed to infant during birth
Nongonococcal Urethritis (NGU)
Causative Agent = Chlamydia trachomatis
Identifying Characteristic = Inflammation of urethra; chlamydia most common STI; mild symptoms; also causes blindness in infants
Pelvic Inflammatory Disease
Causative Agent = N. gonorrhoeae; C. trachomatis
Identifying Characteristic = Bacterial infection of the female pelvic organs; can result in blockage of uterine tubes and sterility
Syphillis
Causative Agent = Treponema pallidum
Identifying Characteristic = Spirochete; not grown in media; has 4 distinct stages = primary - sore at site of infection, secondary - rash on skin and mucous membranes, latency - can last years, tertiary - presence of gummas (skin lesions); also affect cardiovascular and nervous systems
Lymphogranuloma Venereum
Causative Agent = C. trachomatis
Identifying Characteristic = Disease of tropics; initial lesion and then blockage of lymphatic system leading to swollen genitals
Bacterial Vaginosis
Causative Agent = Gardenella vaginalis
Identifying Characteristic = Infection of the vagina (no inflammation); diagnosis based on increased pH; fishy odor and presence of clue cells (vaginal epithelial cells coated with bacteria)
Genital Herpes
Causative Agent = Herpes Simplex Virus type II (also HSV-1)
Identifying Characteristic = Fluid filled vesicles on genitals; virus goes latent in nerve cells; virus can cause recurrent lesions upon reactivation
Genital Warts
Causative Agent = HPV
Identifying Characteristic = 1/4 of women infected; linked with cervical cancer; causes wart like growths on genitals in females; asymptomatic in males
Candidiasis (Yeast Infection)
Causative Agent = Candida albicans
Identifying Characteristic = Lesions in vagina with itching and irritation; treated with OTC medications
Trichomoniasis
Causative Agent = Trichomonas vaginalis
Identifying Characteristic = Protozoan infection of vagina; raises pH
Toll-like receptors are proteins that bind to what?
Pathogen-associated molecular patterns
The lacrimal apparatus is considered what type of factor in the 1st line of defense?
Physical
What component is found in tears, saliva, and perspiration that is harmful to bacteria?
Lysozyme
The primary phagocyte in the blood is which cell?
Neutrophils
Monocytes mature into what cells?
Macrophages
The coating of microbes with serum proteins is known as
Opsonization
Bacteria can prevent the formation of what to escape phagocytosis?
Phagolysosome
Inflammation results in blood vessel permeability and diapedesis of immune cells
True
Activation of C3 results in which of the following?
Opsonization and cell lysis
Which interferon is important in activation of immune cells and antigen presentation?
IFN-gamma
Lymphocytes that mature in the bone marrow are called
B cells
Lymphocytes that mature in the thymus are called
T cells
B and T cells that react strongly to self antigen are eliminated during the selection process
True
The part of the antibody molecule that binds to antigen is part of the variable region
True
IgM is a class of antibodies that can form pentamers
True
The T cell receptor recognizes free antigen that is present in the serum and tissues
False
CD4+ T cells recognize antigen presented using __ on which cells?
MHC II---antigen presenting cells
Cytotoxic T cells lyse target cells or induce apoptosis using the molecules
Perforin and Granzyme
The secondary response is due to the presence of memory cells and occurs at a faster rate than the primary response
True
The immunity developed after infection is called naturally acquired active immunity
True
Name the 5 mechanisms for pathogen destruction/inactivation that results from the binding of antibodies to antigens