Week 9 Exam 3 Flashcards
immunology
- study of the body’s 2nd and 3rd lines of defense
- study of the body’s response to infectious agents
- study of allergies and cancer
- immunity:
- immune function:
- wbcs:
-immunity: ability to ward off disease. it is carried out by a network of cells and fluids in every tissue and organ
-healthy immune system will:
provide surveillance
recognize foreign material
destroy entities deemed to be foreign
-WBCs:
recognize body cells: self
differentiate them from foreign material: non-self
-ability to evaluate macromolecules as self or non self is central to the functioning of the IS
-autoimmune disorders are the result of the body attacking its self
Lymphatic system & lymph
- made up of lymphatic vessels
- lymphatic vessels:conduct flow of lymph fluid to/from lymphatic tissues/organs/cells
- lymph: colorless water liquid made from fluid leaked from blood vessels
- lymph carries microbes to lymph nodes, where lymphocytes & macrophages destroy pathogens
Whole blood contains:
- plasma: water containing electrolytes, dissolved gasses, nutrients and proteins
- RBCs: carry oxygen
- WBCs: part of immune response
- platelets: stop bleeding at wounds
Hematopoiesis
whole blood production
defensive component of blood
- eosinophil
- leukocytes & neutrophils
- lymphocytes
- leukocytes: defensive blood cells
- lab tests show the type of infection
- increased level of eosinophil: allergies or parasite
- increased level of leukocytes & neutrophils: bacteria
- increased level of lymphocytes: virus
resistance:
susceptibility:
resistance: ability to ward off diseases
susceptibility: lack of resistance to a disease
- humans do not have natural resistance to all pathogens
innate immunity
natural immunity: nonspecific that protects against any pathogen
First, second, third line of defense
- first: physical barriers- skin, hair, cilia, mucus membrane, mucus & chemical secretions, digestive enzymes in mouth, and stomach acid
- second: internal defenses- inflammatory response, complement proteins, phagocytic cells, and natural killer (NK) cells
- third: adaptive immunity (specific resistance & uses a specialized type of cells (T&B)) - antibodies and the humoral immune system, cell-medicated immune system, and memory response
first line of defense
- skin & mucus membrane (chemical and physical barriers)
(chemical factors can inhibit microbial growth or destroy them) - human microbiome
skin layers & chemicals
- antimicrobial peptides
- perspiration
- sebum
- epidermis: multiple layers of tightly packed cells; few pathogens can penetrate from a cut; shedding of dead skin removes microorganisms; contains dendritic cells (phagocytize pathogens)
- dermis: collagen fibers help skin resist abrasions
- antimicrobial peptides: 20-50 amino acids secreted by dermal cells(inhibit growth of microorganisms)
- perspiration: secreted by sweat glands. contains salt, lysosome, & dermicidins (antimicrobial proteins)
- sebum: secreted by sebaceous glands to keep skin flexible & lowers pH
mucus membranes & layers
- epithelium
- deeper connective
-line all body cavities open to environment
two layers:
-epithelium: made of epithelial cells tightly packed to prevent entry of pathogens; shedding of epithelial cells carries away microbes; dendritic cells below this layer phagocytize cells; goblet & ciliated columnar cells remove invaders
-deeper connective: layer supports the epithelium
other physical barriers:
- lacrimal apparatus:
- saliva:
- urine:
- lacrimal apparatus: washes eyes with tears
- saliva: washes microbes off teeth
- urine: cleanses urethra and flows out
barrier loss
- loss of immunity or absence of normal immunity
- patients w/ severe burns, blockages in salivary glands, tear ducts, intestines, and urinary tracts
- First LOD alone is not sufficient protection
normal microbiota/microbial antagonism
-makes it hard for pathogens to complete their normal activities
normal microbiota:
-consume nutrients
-create an unfavorable environment(pH, waste products)
-stimulate bodys 2nd LOD
-promote overall health by providing vitamins
antimicrobial secretions
- gastroferritin
- transferrin
- stomach acid digests/inhibits microorganisms
- gastroferritin (stomach) & transferrin (blood) hide/take away iron which microorganisms need
- bile inhibits growth of most microorganisms
Second line of defense
- when pathogens penetrate the skin or mucus membrane
- important factors in 2nd LOD: plasma, WBCs, neutrophils & macrophages, and eosinophils
- carries out these processes: fever, inflammation, phagocytosis, and chemical defenses (antimicrobial protiens)
phagocytes & two types
-cells that ingest/engulf microbes or particles of a cell
types:
-neutrophils: act early, recruited by inflammation, component of pus
-macrophages: present in tissues
we can distinguish they type of macrophage by its location (spleen, bone marrow, alveolar, knupffer cells, dendritic cells, brain)
process of phagocytosis
- chemotaxis: uses pseudopods to move towards microorganisms
- adherence: binding complementary chemicals on the surface of the cell wall
- ingestion: pseudopod fuse to form a food vesicle called, phagosome
- maturation: lysosome fuses w/ phagosome to form, phagolysosome which contains digestive chemical
- killing: the digestive chemicals have reactive forms of oxygen & acidic pH of the phagolysosome which kills the microorganisms
- elimination: remnants of microorganism are released by exocytoxins
microbial evasion of phagocytosis
- capsule makes microorganisms slippery and inhibit adherence: Streptococcus pneumoniae
- leukocidins prevent phagosome-lysosome fusion: S. arueus
- Lyse phagocytes by membrane attack complex: Listeria mobocytogenes
- escape phagosome: Shigella
- survive in phagolysosome: Coxiella burnettil
signs of inflammation
-redness
-heat
-swelling
-pain
redness & heat reduced by histamine & kinin, allow for: vasodilation
swelling & pain mediated by: prostaglandin & leukotriene, when cause increased permeability
inflammation
- destroys agents or limits their effectiveness
- repairs or replaces damaged tissues
- dilation caused by histamine & kinin
- increased permeability of blood vessels is mediated by prostaglandin & leukotriene
- neutrophils arrive first, then monocytes
- tissue repair occurs when extra nutrients & oxygen are delivered
fever
- body temp. at 37c
- pyrogens/cytokines trigger hypothalamus to increase body temp. by releasing prostaglandins
- fever is protective
- enhance effect of interferon, inhibits growth of microbes, enhance innate or adaptive immune processes
interferons: INFs
-proteins released by host cells (lymphocytes & macrophages) to inhibit viral replication and bacterial pathogens
types of INFs
- Type 1: INF-α (epithelium & leukocytes) & INF-β (tribroblasts) cause cells to produce antiviral proteins
- Type 2:INF-γ produced by lymphocytes that causes neutrophils & macrophages to phagocytize bacteria
complement
serum proteins produced by the liver, when activated, results in lysis of foreign cells
complement activation:
- opsonization: enhances phagocytosis by promoting attachment
- cytolysis: membrane attack complex leads to cytolysis
- inflammation: activated complement proteins bind to mass cells which release histamine to cause inflammation
complement inactivation
proteins bind and break down activated complement proteins
nonphagocytic killing
- eosinophils: attach to surface of parasitic helminths and secrete toxins that weaken or kill the parasites; release mitochondrial DNA and potions that kill bacteria
- natural killer lymphocytes: secrete toxins onto surface of cells infected w/ tumors or viruses
- neutrophils: (inolved in phagocytosis) produce chemicals that kill nearby invaders; generate extracellular fibers that bind and kill bacteria, this is called NETs
- neutrophil extracellular traps NETs
nonspecific chemical defenses
- trigger a response and recruit more immune system helpers
- toll-like receptors: in membrane of phagocytic cells (host cells); bind Pathogen-Associated molecular Patterns PAMPs; when they are bound: apoptosis, secrete inflammatory mediators, stimulate adaptive immune response
- NOD proteins: in cytosol; bind PAMPs; trigger inflammation and apoptosis, mutation in NOD genes are associated w/ immune deficiency diseases like IBS or chromes disease
adaptive immunity
- body recognizes & defends against pathogens/invaders and their products
- lymphocytes (B & T cells) mediate these actions
- specific:
- inducible:
- clonal:
- unresponsive to self:
- memory:
- specific: only acts against one molecular shape
- inducible: activated when pathogen is present
- clonal: form many generations of cells when induced
- unresponsive to self: immune responses do not attack self
- memory: responds more quickly to pathogens that have previously encountered
antigens
portions (whole bacteria or part of a single molecule) of cells & viruses that begin the immune response
- lymphocytes & antibodies bind to epitopes to trigger adaptive immune response
- epitopes: binding site of an antigen
types of antigens
- exogenous antigens:
- endogenous antigens:
- autoantigens
- exogenous antigens: (outside of cell wall or secreted) toxins, secretions, components of cell wall, pili, & flagella
- endogenous antigens: protozoa, fungi, bacteria & viruses that replicate inside a cell
- autoantigens: self-antigens from normal cellular processes
Immunological development
1: lymphocyte development & clonal deletion (B & T cells mature and remove autoantigens)
2: presentation of antigens & clonal selection (B & T cells bind to antigens and replicate the selected)
3: challenge B & T cells
4: -T-lymphocyte response: cell mediated
- B-lymphocyte response: creates antibodies
where are lymphocytes
- b-lymphocyte
- t-lymphocyte
- lymphocytes are made by hematopoiesis from blood stem cells in bone marrow
- B-lymphocytes: mature in bone marrow, involved in humoral immune response; activated into plasma cells which release antibodies
- T-lymphocytes: mature in the thymus, involved in cell mediated immune response; acts against intracellular pathogens; produces cytokines which results in the elimination of pathogens
T-lymphocyte
- act against internal pathogens in cell-mediated immune response
- make up 70-85% of lymphocytes
- maturation in thymus & produces T cell receptor TCR to be placed on each cells cytoplasmic membrane. TCR binds to etiopope of antigen
- antigen presenting cells: dendritic cells engulf & degrade microbes to display T cells
cell-mediated immune response
1 antigen presentation 2 helper T cell differentiation 3 clonal expansion 4 self-stimulation 5 -cytotoxix T cells killing (CD4): perforin-granzyme OR CD95 OR -activates B cells (CD8)
perforin-granzyme cytotoxic pathway
- perforin-granzyme: vesicles in cytoplasm of cytotoxic T cells
- vesicles fuse w/ cytoplasmic membrane to exit T cell & enter infected cell
- perforins create pores/channels in infected cell
- granzyme enters channel and activates apoptosis
- apoptosis: programed cell death
CD95 cytotoxic pathway
- present in membrane of animal cells
- cytotoxic T cells binds to CD95 w/ receptor proteins (CD95L)
- triggers apoptosis
memory T cells
- contacts an epitope-MHC 1; produces cytotoxic T cell clone
- do not kill
- if second exposure to pathogen w/ specific epitope, cell mediated immune response is more effective and quicker
T cell regulation
sends signals to cytotoxic T cells to start or stop immune response
B cell
- spleen, lymph nodes, and MALT
- small % of lymphocytes
- function: secrete antibodies
- each B cell has the same and several copies of BCR
- contains 4 polypeptide chains, 2 heavy and 2 light, linked by covalent bonds between sulfur atoms
antibodies
- immunoglobulins
- secreted by plasma cells
- have antigen binding sites that are identical to BCR sites
antibody binding to epitope leads to:
- inflammation
- activate complement
- opsonization
- direct killing
- neutralization
- agglutination
- antibody dependent cytotoxicity
classes of antibodies
- IgM:
- IgG:
- IgA:
- IgE:
- IgD
- IgM: 1st produced, pentamer, agglutinates microbes
- IgG: most common & long lasting, 80% Ig in serum, monomer, crosses placenta (protect developing child)
- IgA: body secretions(tears), dimer
- IgE: response to parasitic & allergies infections, monomer
- IgD: unknown function, monomer
how are antibodies produced
- T-independent antigens: no helper T cells needed
- T-dependent antigens: helper T cells activates the B cells
memory b cells
- made: during B cell proliferation
- dont secrete antibodies. their BCR s identical to epitope
- cells persist over 20 years & can initiate antibody production
Types of adaptive immunity
- naturally acquired active: you are infected; antibodies are made as a result
- naturally acquired passive: maternal antibodies acquired
- artificially acquired active: vaccine introduces antibodies & causes B cell activation
- artificially acquired passive: immunotherapy where antibodies are injected (antisera or antitoxins); used when toxins and pathogens are so deadly active immune response in inadequate
- vaccination:
- herd immunity:
- vaccination: use of antigens or antibodies to provide some immunity; (produces a primary immune response, leads to formation of antibodies and memory cells, produces a rapid and intense secondary response)
- herd immunity: immunity in most of the population; outbreaks are sporadic due to lack of susceptible individuals
types of artificial immunity
first vaccine
- active immunization: patient mounts an immune response
- passive immunization: patient acquires antibodies
- Jener used Cowpox against Smallpox 1796
attenuated vaccine
- use of pathogen with reduced virulence (attenuated pathogen)
- results in strong immune response and mild symptoms
- may result in contact immunity
inactivated vaccine and three types
- whole agent:
- subunit:
- conjugated:
- whole agent: deactivated whole microorganism (many antigens)
- subunit: part of microorganisms (not as many antigens)
- conjugated: proteins (strong antigens) conjugated to carbs (weak antigens)
- booster might be required for full immunity
toxoid vaccine
- chemically or thermally modified toxins that stimulate immune response
- require multiple doses b/c toxins contain few antigens
recombinant gene technology
delete gene from pathogen producing ani irreversibly weaker microbe
- produce large quantities of antigens
- genetically altered bacteria or viruses may express the antigen as a vaccine
adjuvants
chemicals added to vaccines to improve effectiveness
- enhances immunogenicity
- improve innate immuunity
- most common in US: alumis (aluminum salt)
vaccine Saftey
-safest and most effective in children
-complications:
fever, allergies, local reactions
