Term
| 2 artificial methods to make an individual immune to a disease |
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Definition
active immunization
passive immunization |
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Term
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Definition
Vaccine - nontoxic antigens that are ingested, injected or inhaled to induce a specific defense response without having to go through the disease process:
- live attenuated
- killed
- toxoid
patient actively mounts an immune response |
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Term
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Definition
| transfer of antibodies formed by an immune individual or animal |
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Term
| Socioeconomic and political problems prevent many developing nations from receiving vaccines |
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Definition
Lack of financial incentives for pharmaceutical industry to develop and produce vaccines for diseases that affect developing countries
Inability to develop effective vaccines for some pathogens
Vaccine-associated risks discourage investment in developing new vaccines |
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Term
| 3 general types of vaccines: |
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Definition
Attenuated (live, weakened)
Killed (inactivated)
Toxoid |
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Term
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Definition
Modified live vaccines
Uses pathogens that are living but have reduced virulence so they don’t cause disease |
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Term
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Definition
| is a process of reducing virulence |
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Term
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Definition
raise them in tissue culture cells for which they aren’t adapted; continually passage them in tissue culture in the lab
they lose the ability to produce disease |
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Term
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Definition
culture under unusual conditions - continually passage in the lab
genetic manipulation |
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Term
| Contain replicating microbes that can stimulate a strong immune response in infected cells due to the large number of antigen molecules. |
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Definition
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Term
| Viral vaccines are recognized as |
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Definition
| endogenous antigens trigger a cell-mediated immune response dominated by TH1 and cytotoxic T cells |
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Term
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Definition
| Vaccinated individuals can infect those around them |
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Term
| Problems with Attenuated Vaccines |
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Definition
Attenuated microbes may retain enough virulence to cause disease
especially in immunosuppressed individuals
Pregnant women should not receive live vaccines due to the risk of the modified pathogen crossing the placenta
Modified viruses may occasionally revert to wild type or mutate to a virulent form |
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Term
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Definition
| deactivated whole microbes |
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Term
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Definition
| antigenic fragments of microbes |
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Term
| whole agent/subunit vaccines vs live vaccines |
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Definition
Both types are safer than live vaccines since they cannot replicate, revert, or mutate to a virulent form
When microbes are killed must not alter the antigens responsible for stimulating protective immunity |
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Term
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Definition
is commonly used to inactivate microbes
cross-links proteins and nucleic acids
Recognized as exogenous antigens
Stimulates a TH2 response that promotes antibody-mediated (rather than cell-mediated) immunity |
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Term
| Problems with Inactivated Vaccines |
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Definition
Do not stimulate herd immunity
Whole agent vaccines may stimulate a inflammatory response due to non-antigenic portions of the microbe |
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Term
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Definition
| microbes don’t reproduce and don’t provide many antigenic molecules to stimulate the immune response - thus require booster immunizations. |
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Term
| Incorporation of an adjuvant |
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Definition
substances that increase the antigenicity of the vaccine
- Work by trapping antigens and releasing them slowly - prolong exposure to the antigen
Alum (aluminum salt) |
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Term
| Making Inactivated Vaccines more Effective |
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Definition
Administration in high or multiple doses
may produce allergic reactions |
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Term
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Definition
Chemically or thermally modified toxins
Useful for some bacterial diseases:
- diphtheria, tetanus, pertussis
Stimulate antibody-mediated immunity
Require multiple doses because they possess few antigenic determinants |
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Term
| Modern Vaccine Technology |
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Definition
Research attempts to make vaccines that are more effective, cheaper, and safer
A variety of recombinant DNA techniques can be used to make improved vaccines |
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Term
| Problems associated with vaccination |
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Definition
Mild toxicity is the most common problem
Especially seen with whole agent vaccines that contain adjuvants
May cause pain at the injection site
Rare cases can cause fever high enough to induce seizures |
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Term
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Definition
| allergic reaction that may develop to a component of the vaccine |
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Term
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Definition
Attenuated viruses occasionally cause disease in healthy children or adults
Allegations that certain vaccines against childhood diseases cause or trigger autism, diabetes, and asthma
Research has not substantiated these allegations! |
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Term
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Definition
Administration of preformed antibodies to a patient
Used when protection against a recent infection or an ongoing disease is needed quickly
Serum from human or animal donors that have been infected with the disease or immunized against it
Serum used for passive immunizations is called antiserum |
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Term
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Definition
Contain antibodies against many antigens
not just the ones of interest!
Repeated injections of antisera collected from a different species can trigger allergic reactions
May be contaminated with viral pathogens
Antibodies are degraded quickly |
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Term
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Definition
| Many of these limitations have been overcome through the development of hybridomas |
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Term
| Vaccine administration: Eliminate shots! |
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Definition
Nasal inoculations
- Skin patch
- Edible vaccines
- Naked DNA vaccines |
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Term
| Multivalent/Heterologous vaccines |
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Definition
| Eliminate the need for multiple boosters by giving a single vaccine that protects against multiple pathogens. |
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Term
| Two types of defense systems |
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Definition
Nonspecific (Innate) defenses
Specific (Adaptive) mechanisms |
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Term
| Nonspecific (Innate) defenses |
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Definition
| always present, first line of defense, general protection mechanisms that attempt to stop pathogens from invading body |
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Term
| Specific (Adaptive) mechanisms |
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Definition
| take longer to develop, aimed against specific target on specific pathogen (produce antibodies) |
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Term
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Definition
| signaling proteins produced by cells of both defense systems, control and organize the response of both systems |
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Term
| Antibodies (specific defense proteins) |
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Definition
help phagocytes (non-specific defense) to ingest and kill bacteria.
Antibodies also activate complement proteins (non-specific defense) that have antimicrobial effects. |
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Term
| Both defense systems must be tightly controlled/regulated |
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Definition
destructive for humans and microbes - damage host tissues while fighting infection.
Fever, tissue damage, pus, pain often caused directly by cells of defense system harming tissues rather than action of invading organism |
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Term
| Nonspecific Defenses: Two Levels |
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Definition
First line - Prevent pathogens from entering body: Skin, mucous membranes, antimicrobial chemicals
- Second line - Operative when pathogens invade body: Cells (ex. phagocytes), antimicrobial bloodborne chemicals (complement, cytokines, interferons, defensins), and processes (inflammation, fever, etc) |
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Term
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Definition
| Responds against a specific type of pathogen |
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Term
| Non-Specific Host Defenses - (Innate Immunity) |
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Definition
Recognize common structures of invading microbes as "dangerous" to host - ex., LPS, peptidoglycan, LTA, certain polysaccharides
PAMPs (Pathogen Associated Molecular Patterns) = fairly invariant molecules made by pathogen not host, usually required by invading pathogen for survival or pathogenicity
Operate regardless of specific invader
Examples of nonspecific defenses
Skin, mucosal surfaces, mucin, phagocytic cells, complement, cytokines |
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Term
| First Line: Defenses of Skin |
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Definition
Chemical and physical barrier to microbial colonization – Intact skin effective barrier to invading microorganisms
Two layers: epidermis (outer) & dermis (inner)
Epidermis composed of dead keratinized cells that are continuously shed
Keratin - protective protein, hard to degrade by microbes
Acidic pH - oil from sebaceous glands in skin produce sebum, lowers skin pH to 3-5
Dry
Cells tightly packed
Hair follicles, sweat glands, sebaceous glands - natural breaches in skin can be used by some microbes to move past skin surface.
These breaches protected by lipids that are toxic to microbes, lysozyme that degrades peptidoglycan
Normal microbiota - Mainly G+, Staphylococcus epidermidis and Propionibacterium acnes |
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Term
| dendritic cells (non-specific) |
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Definition
| Microbes that get past dermis through cuts, burns, etc., encounter underlying immune cells - incl. dendritic cells (non-specific) that process invading pathogens and activate specific defense systems. |
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Term
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Definition
| oil secreted from sebaceous glands in skin, lowers skin pH to ~5 |
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Term
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Definition
secreted in sweat, breaks down peptidoglycan, most effective against G+ organisms.
- tears have highest concentration
- also present in blood & tissues |
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Term
| First Line: Defenses of Mucous Membranes |
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Definition
Line all body cavities that are open to the outside environment
gastrointestinal, respiratory & genitourinary tracts
Temp 37C, pH 7-7.4, bathed in fluids, ideal conditions for growth of many microbes. Unlike skin - surface cells of mucous membranes are alive |
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Term
| Like skin - Chemical and Physical barriers protect mucosal surfaces from invading microbes |
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Definition
Mucus, cilia, lysozyme, lactoferrin, defensins, constant shedding of mucosal cells, normal microbiota
sIgA (specific defense)
Surface cells continually shed
Fluid flow
Cells tightly packed |
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Term
| Like skin, have underlying population of immune cells, defense system called |
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Definition
MALT - Mucosa Associated Lymphoid Tissue:
Composed of both non-specific and specific defense cells - macrophages, dendritic cells, T cells, and B cells - produce sIgA antibody (specific defense) secreted into mucus. |
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Term
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Definition
Mucus (sticky glycoprotein matrix) traps microorganisms
Cilia, coughing, sneezing, fluid flow move mucus and trapped materials from host
Secretory IgA
(sIgA) in mucus - antibody (specific defense) that defends mucosal surfaces |
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Term
| Chemical Barriers - examples |
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Definition
Antimicrobial substances present in body fluids:
Sebum - oil from sebaceous glands of skin
Lysozyme – tears, perspiration, saliva and mucus
Stomach acid
Bile - intestinal detergent
Vaginal secretions – slightly acidic
Defensins - antibacterial peptides in mouth and intestine
Transferrins – iron-binding chemicals
inhibit bacterial growth by limiting the amount of available iron |
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Term
| Physical barriers - examples |
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Definition
Mucous (sticky) membranes – mucus & cilia
Secretions – tears, saliva, perspiration, etc. va
Flushing/fluid flow - eyes, urethra, vagina, GI tract, etc.
Urinary tract infections more common in individuals that are unable to empty bladder completely or frequently enough
Coughing, sneezing
Individuals with impaired lung cilia functions, like smokers, increased risk of respiratory infections
Shedding of cells - skin and mucosal surfaces
Tightly packed cells - skin and mucosal surfaces |
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Term
| Second Line: Non-Specific Defenders of Blood and Tissue Phagocytes and Cytoxic Cells |
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Definition
Defenses of skin and epithelial surfaces are effective in preventing pathogens from entering tissue and blood
BUT sometimes pathogens succeed in breaching these surfaces
- Microbes that succeed in entering tissues and blood encounter formidable force - Cellular defenses
- Phagocytic cells
- Cytotoxic cells - Natural Killer/NK cells
This non-specific defense system composed of:
Cells (especially phagocytes)
Antimicrobial chemicals (complement, interferons, cytokines)
Processes (inflammation, fever)
Many of these components are found in or originate in the blood |
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Term
| Cellular Defenses of Blood |
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Definition
Blood - consists of 2 parts
liquid (plasma) = noncellular portion of blood
solid (cells and cell fragments)
3 CELL TYPES |
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Term
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Definition
Erythrocytes – red blood cells (RBC's)
contain hemoglobin and carry oxygen
Leukocytes – white blood cells (WBC's)
participate in non-specific and specific defense mechanisms
Platelets - fragments of cells
important for blood clotting |
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Term
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Definition
| the process by which the division of stem cells in the bone marrow produces 3 cell types: erythrocytes, platelets and leukocytes |
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Term
| Leukocytes (WBCs) - Defend body against invaders |
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Definition
Two major divisions - based on their appearance in stained blood smears
Granulocytes
Agranulocytes |
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Term
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Definition
have a granular cytoplasm
irregularly shaped, lobed nuclei
Basophils
Eosinophils
Neutrophils - also called polymorphonuclear leukocytes (PMNs, polys) |
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Term
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Definition
lack granules and have round nuclei
Monocytes - leave blood and mature into macrophages
Lymphocytes (T cells and B cells) |
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Term
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Definition
Leukocytes produced in bone marrow and released into blood
Major defenders against pathogens
Some remain in blood, others can leave blood and migrate to tissues during infection
Some are phagocytic (ex. PMNs, monocytes, macrophages), and some are not
Includes members of specific (B cells and T cells) and non-specific (neutrophils, monocytes, macrophages, etc) immune defense systems |
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Term
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Definition
Basophils
Some remain in the bloodstream
others migrate to tissues (settle close to blood vessels and epithelium) to become mast cells
release histamine (vasodilator) during inflammation
Makes blood vessels leaky, helps PMNs, monocytes and NK cells leave blood and move to site of infection
not phagocytic
play a major role in allergic responses |
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Term
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Definition
released during allergic reactions
Can leave bloodstream
Can phagocytize pathogens, but not their normal method of attack
important in parasitic infections where they attach to surface of parasitic worm and secrete toxins onto its surface (extracellular killing)
may turn off inflammatory reactions by releasing antihistamine |
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Term
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Definition
Normally found in blood
mount the first nonspecific defense
phagocytic
60-70% of all WBC’s, most abundant but short-lived
Can enter tissues
guard skin and mucous membranes against invasion |
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Term
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Definition
Can leave blood and mature into macrophages in tissues
can be wandering - circulate in blood or wander through tissues |
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Term
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Definition
In tissues, macrophages can be “free” or “fixed” -
Free macrophages - found in most types of tissues where they migrate through them in search of invaders to ingest and destroy
Fixed macrophages - remain stationary and found in tissues that filter blood or lymph (lymphoid tissue)
Lymphatic system: lymph, lymphatic vessels, lymph nodes, tonsils, spleen, bone marrow, thymus |
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Term
| once established in an area can differentiate into macrophages |
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Definition
| (more actively phagocytic cells with greater destructive power). Linked with both non-specific and specific host defenses. |
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Term
| Lymphocytes (T cells and B cells) |
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Definition
circulate in the blood
Most involved in specific immunity, with exception of natural killer (NK) cells
Non-specific T cells
Not phagocytic - NK cells secrete toxic proteins into cells infected with viruses and other intracellular pathogens (extracellular killing)
Causes death of infected host cells
also important in destroying tumor cells
large numbers are found in lymphoid tissue
Lymphatic system: lymph, lymphatic vessels, lymph nodes, tonsils, spleen, bone marrow, thymus |
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Term
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Definition
Prevent excess build-up of fluid in tissues and recycle blood proteins (complement, cytokines, chemokines, etc)
Blood gives off more fluid than it can absorb - not readily reabsorbed by blood vessels - lymph system must do this
Macrophages in this system sterilize lymph before dumped back into circulatory system.
Also linked to specific immune defenses since contains B and T cells. |
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Term
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Definition
Mainly neutrophils, monocytes and macrophages
They are the scavengers of the body
Engulf foreign organisms and damaged cells
Found in blood, tissues, lymph nodes |
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Term
| The process of phagocytosis |
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Definition
is the process of ingesting and digesting foreign particles (dead cells and cellular debris AND invading microbes)
5 steps:
Chemotaxis
Adherence
Ingestion
Digestion
Elimination |
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Term
| Leukocyte (WBC) Deployment How phagocytes get to site of infection |
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Definition
Margination
leukocytes adhere to blood vessel walls (mediated by cell adhesion molecules)
Diapedesis
leukocytes squeeze between endothelial cells into tissue space
Chemotaxis
leukocytes are attracted to inflammatory chemicals (cytokines, complement, etc)
Phagocytosis |
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Term
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Definition
phagocytes find microbes by moving toward a higher concentration of an attractant substance(s)
both infectious agents and damaged tissues release chemical attractants (nonspecific) |
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Term
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Definition
released by phagocytes at the site of infection to attract more phagocytes, also activate phagocytes to be more destructive to microbes
Complement - attracts phagocytes to site of infection and activate them to be more destructive to microbes
M. tuberculosis - thought to escape phagocytosis by producing a lipid that prevents chemotaxis |
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Term
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Definition
attachment of phagocytic membrane (cellular receptors) to microbe
(Phagocytes can bind microbe directly to ingest, but this process is enhanced by complement binding in a process called opsonization) |
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Term
| some bacteria have capsules or other virulence factors that make attachment difficult |
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Definition
Strepococcus pneumoniae (capsule)
Staphylococcus aureus (capsule)
Hemophilus influenzae type b (capsule)
Neisseria meningiditis (capsule)
Streptococcus pyogenes (M protein) |
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Term
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Definition
the cell membrane surrounds the microbe and forms a phagosome or endocytic vacuole around microbe to bring inside cell, internal pH drops (acidic) inside vacuole
capsulated bacteria interfere with the ingestion of bacteria by phagocytes
such as pneumococci (i.e. S. pneumoniae) |
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Term
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Definition
lysosomes fuse with the phagosome to create a phagolysosome
during this fusion process, lysosomes release their toxic enzymes and proteins into the vacuole to help kill microbe (low pH of phagolysosome required to acitivate these proteins) |
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Term
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Definition
Degradative enzymes (proteases, lysozyme), defensins, toxic forms of oxygen and nitrogen used
this process is called degranulation since the lysosome granules disappear
Degradative enzymes digest microbes into small molecules
Some bacteria can prevent phagosome-lysosome fusion, ex. Salmonella typhimurium |
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Term
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Definition
The body's response to tissue damage from injury or infection
Combination of complement activation, cytokine release, phagocyte migration/activation, and production of vasodilators.
Does more good than harm (as long as response is acute and not chronic)
Characterized by 4 cardinal signs
Pyrexia – increase in local temperature
Erythema - redness
Edema – swelling
Pain |
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Term
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Definition
Vasodilation – increased blood flow
injured tissue causes mast cells and basophils to release histamine
Red blood cells leak into the area via damaged vessels
Cytokine release (from WBCs and damaged tissues)
increases capillary permeability
RBCs leak from blood vessels |
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Term
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Definition
injured tissue releases cytokines
promotes an increase in number of leukocytes in the blood
increase in capillary permeability means blood cells and tissue fluid are crowding into the area
once macrophages arrive they release tumor necrosis factor alpha (TNF-) which also causes vasodilation and edema
Pus - accumulated white cells (dead and alive) and tissue debris |
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Term
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Definition
-algia = pain
Injured tissue releases bradykinin
stimulates pain receptors, also a vasodilator
prostaglandins - cellular regulators connected with pain receptors also are mediators in inflammation
contract smooth muscle
intensify the effect of bradykinin
Swelling of tissues also puts pressure on nerves
NSAIDs – Non-steroidal anti-inflammatory drugs
ASPIRIN (acetyl salicylic acid) works directly on blocking prostaglandin synthesis
ACETAMINOPHEN (Tylenol) blocks pain receptors |
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Term
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Definition
a systemic increase in body temperature
pyrogens – substances that elicit fever
exogenous (exotoxins and endotoxins from pathogens)
endogenous (released from macrophages)
Interleukin-1 (IL-1) is the endogenous pyrogen that causes certain neurons in the hypothalamus to release prostaglandins which reset the thermostat to a higher temperature |
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Term
| Benefits: can augment the beneficial effects of inflammation: |
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Definition
1) can inhibit or slow growth of some pathogens
2) may inactivate some toxins
3) increase chemical reactions of the body, help immune system and tissue repair
Like inflammation, has unpleasant side effects:
Body aches, malaise, tiredness; if too high, can lead to death
ASPIRIN, ACETAMINOPHEN are both antipyretics |
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Term
| Molecular Defenses examples |
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Definition
Cytokines
signaling proteins produced by some mammalian cells in response to stimuli
Interferons
a group of proteins released by virus-infected cells
Complement system
a set of more than 20 proteins made in the liver
Acute Phase Response Proteins
Proteins made in liver in response to an acute illness |
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Term
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Definition
Proteins that act to mediate the inflammatory response to microbial antigens
Also participate in activating cells of the immune system
Attract and activate phagocytes
Produced by a number of human cell types, including monocytes, macrophages, lymphocytes, endothelial cells and epithelial cells. |
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Term
| Their release is triggered by interaction between cytokine producing cells and bacterial surfaces. |
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Definition
Can act as messengers because the cells whose activities they direct have receptors for them on their surface and bind them and cause the cell to respond to their presence.
Uncontrolled regulation can lead to septic shock |
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Term
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Definition
Group of proteins in blood that must be activated by pathogens to exert their effect. Produced by liver.
Activated by contact with bacterial surfaces (directly or indirectly):
invading bacteria OR interaction with antibodies bound to bacteria (or their surface fragments).
Important in inflammation and septic shock. |
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Term
| Can act by themselves OR help a specific immune response; they: |
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Definition
1) enhance phagocytosis by acting as opsonins (opsonization),
2) regulate inflammation and immune responses
3) lyse microbes (formation of MAC) |
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Term
| Pathways of complement activation |
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Definition
Alternate pathway - activated directly by pathogen surface molecules (non-specific)
Classical pathway - activated by antibodies binding to surface of pathogen (specific)
Another example of link between non-specific and specific host defense systems!
Regardless of how the pathways are activated, they produce the same key activated components (C3a, C3b, C5a, C5b) |
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Term
| Acute Phase Response Proteins |
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Definition
Inflammatory cytokines released during infection (IL-6) stimulate the liver to release extra anti-microbial proteins (called acute phase response proteins) into the blood - make it difficult for pathogens to multiply
Transferrin - iron binding protein/sequesters iron
Complement proteins
C-reactive protein and mannose-binding protein – bind to phospholipids and mannose sugars (carbohydrate chains) of the cell membranes of pathogens
act like opsonins - help ingestion of pathogens by phagocytes |
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