Applications of immunology Flashcards
Vaccines vs. Variolation
- Vaccines:
suspension of organisms or fractions of organisms that induce immunity
most desirable way of disease control
Variolations:
inoculation of smallpox into the skin
early vaccinatons (1796)
Principles of vaccinations
- provokes immune response
- produce a rapid, intense secondary response
- herd immunity
Types of vaccines
- Live attenuated
- Inactivated killed
- Subunit
- Toxiod
Live attenuated vaccine
- 1 or 2 dose for LIFELONG immunity
- contains live weakened microorganisms w/ reduced virulence
- cell cultured, embryonated egg, live animal
- mimics actual infection
- no boosters needed
- replicated in the body
-RISK
- might mutate to be pathogenic
- weakened/ immunocompromised people can get infection
Inactivated killed vaccine
- whole microbe thats been killed
- grown in a lab
- pathogen cant replicate
- requires repeated dosage or boosters
- humoral antibody immunity
Subunit vaccine
- consist of antigenic fragments
- genetically modified
- recombination vaccine
- Hepatitis b vaccine is made from modified yeast
- reduces the need for viral host cells to grow viruses for vaccines
- Virus-like particle vaccines
- resembles intact viruses but without the genetic information - Conjugates vaccines
- used in to treat disease in young children with poor immune response to capsular polysaccharides - Nucleic acid (DNA) vaccine
-injected naked DNA produce protein antigens
- Protein antigens are carried to the red bone marrow to stimulate humoral and cellular immunity
Toxoids
- inactivated toxins
- targets harmful substances made by bacteria
- ex. tetanus toxiod, diptheria toxoid
Adjuvants
- Chemicals used to improve vaccines usefulness
- improve innate immunity
- Only Alum and Lipid A are approved in the US
Sensitivity vs specificity
Sensitivity: is a test that reactive if the specimen is a true positive
Specificity: is a test that will not reactive if the specimen is a true negative
Monoclonal antibodies
- Hybridoma (mabs)
- infused antibody-producing B cells w/ a cancer cell
- allows the growth of identical antibody molecules (B cells)
- Immortal
- highly specific
- Used in human therapy and diagonistic tools- made often from mouse cells
- infused antibody-producing B cells w/ a cancer cell
Types of monoclonal antibodies
- Murine monoclonal
- made form mouse (-omab) - Chimeric
- mouse and human (-ximab - Humanized
- mostly human but with some mouse antigens- binding sites (-zumab) - Fully human
- made from human genes in a mouse (-umab)
Agglutination
- Clumping of cells
- measures concentration of serum antibody (titer)
Indirect passive agglutination
- antibodies react with soluble antigen adhering to particles or vice versa
Direct agglutination
- detects antibodies against large cellular antigens
- more antibodies @ start = more dilutions needed
Neutralization reaction
- Antigen- antibody reaction with harmful effects of an exotoxin or virus
- Viral hemagglutination inhibition test is used to subtype viruses
- antitoxins combined with exotoxins cause neutralization
Completment - fixation reactions
- used to detect very small amounts of antibodies
- ## a group of serum protein
Enzyme-Linked Immunosorbent Assay (ELIZA)
Direct
-1 antibody is used
- detects antigens
- adding substrate for linked enzymes and a color is produced
- Used for drug test
Indirect
- 2 antibodies are used
- detects antibodies
- used for
Selective toxicity
selectively finding and destroying pathogens w/o damaging the host
Superinfetion
overgrowth of normal microbiota that is resitant to antibiotics
Tetracycline
Largest broad spectrum antibody
Antimicrobial drugs that inhibit cell wall synthesis
- Penicillins
- Cephalosporins
- Bacitracin
- Vancomycin
Antimicrobial drugs that inhibit protein sythesis
- Without proteins microbes can grow
- Chloramphenicol
- Erythromycin
-tetracyline - Streptomycin
Antimicrobial drugs that inhibit nucleic acid replication and transcription
- Quinolones
- Rifampin
Antimicrobial drugs that injure the plasma membrane
- Polymyxin B
- usually a topical treatment
Antimicrobial drugs that inhibits metabolite synthesis
- Sulfanilamide
- Trimethoprim
- interferes with critical pathways
Penicillin
- inhibits the cell wall by preventing the synthesis of peptidoglycan
- contains B-lactam rings
Natural- Penicillin G: injected
- Penicillin V: oral
- Narrow spectrum
- Penicillin G: injected
Semisynthetic Penicillins
- Contain chemically added side chains to make it resistant to penicillinases
Inhibiting protein synthesis
- Targets 70s bacterial ribosomes
Chloramphenicol
Inhibits protein synthesis
- inhibits peptide bond formation
- cant make protein
Synthesized chemically - Broad spectrum
- suppress bone marrow and affect blood cell formation
Aminoglycoside
Inhibits protein synthesis
- causes misshaping of proteins
- shapes of 30S and 70S - Causes audiotory damage
- Secondary infections
- Streptomycin
- Neomycin
- Gentamicin
Tetracyclines
Inhibits protein synthesis
- Interferes with tRNA attachments
- Broad spectrum
- can suppress normal intestinal microbiota
Macrolides
Inhibits protein synthesis
-Plugs the exit tunnel of growing peptides
- Narrow spectrum
Injury of plasma membrane
- Lipoproteins
- Polymyxin
- Topical, bactericidal
- effective against gram neg.
- Daptomycin- used for skin infections
- attacks bacterial cell membrane
-Polypeptide antibiotics change plasma membrane permeability
- Polymyxin
Inhibit nucleic acid synthsis
- Interferes with DNA replication and transcription
-Rifamycin- inhibits mRNA synthesis
- penetrates tissue
Quinolone and Fluoroquinolones - Nalidixic acid
- synthetic
- inhibits DNA gyrase
- Norfloxacin- Broad spectrum non-toxic
Inhibits essential metabolites
- Stops synthesis of folic acid
- Needed for synthesizing nucleic acids and proteins
-competetitvly binds with the enzyme for para-aminobenzoic- para-aminobenzoic (PABA) produces folic acid
Antifungal drugs
- interurrps the synthesis of ergosterol
- makes the membrane excessively permeable - Polynese
- Amphoterincin: toxic to the kidneys
Azoles - Imidazoles: treats cutaneous mycoses
- Triazole: treats systemic fungal infections
Allylamines - azole- resistant infections
- Amphoterincin: toxic to the kidneys
Echinocandins
-antifungal drug that inhibits cells wallF
Flucytosine
- antifungal drug that interferes with RNA synthesis
Antivirals for treating HIV/AIDS
-Nucleoside analog (zidovudine)
-Nucleotide analog (tenofovir)
- Non-nucleoside inhibitors (nevirapine)
- Protease inhibitiors (atazanavir)
- Intergrase inhibitors (raltegravir)
- Entry inhibitors (miracviroc)
- Fusion inhibitors (enfuvirtide)
Resistance to antimicrobial drugs
-Persister cells
- microbes with genetic characteristics allowing them to survive when exposed to antibiotics
- Superbugs
- bacteria that are resistant to a large number of antibiotic
Resistant genes
- Spread horizonataly among bacteria on plasmids or transposones
- via conjunction or transduction
Mechanisms of Resistance
- Prevention of penetration to the target site within the microbe
- enyzmatic destruction or inactivation of drug
- Rapid efflux or antibiotic
- Alteration of drugs target site
Hypersensitivity
- Antigenic response beyond normal
- Sensitivized by pervious exposure
Type 1 Hypersensitivity ( Anaphyactic)
- occurs minutes after a person is reexsposed to that antigen
- IgE antibodies
- Exposed to mast cells and basophils
- Histamines: increase blood capillaries permability
- Leukocytes: cause prolonged contraction of smooth muscle
- Prostaglandins: increases muscle secretion and affects smooth muscle
Type 1 Hypersensitivity ( Anaphyactic) PT.2
- Systemic anaphylactic shock
- sensitized by antigen then reexposed
- may result in death or circulatory collapse- Treated with EPINEPHRINE
- blood vessels dialate
- Treated with EPINEPHRINE
Localized anaphylaxis
- Ingestion or inhalation of antigen
- Hives, hay fever, asthma
- Treated with antihistamines
Type 2 Hypersensitivity II (Cytotoxins)
- IgG and IgA
- ABO blood group system
- Cellular damage can occurs in 5-8 hours by macrophage and other antibodies
- Transfusion reactions
- A antigens, B antigens or both
- Type O has no. antigens
Blood types
Cytotoxic reaction
- AB is universal acceptor
- O is universal donor
- Type A is anti B
- Type B is anti A
- Type O is anti A & B
Rh blood group
Cytotoxic reaction
- Rh factor antigens are found on RBC s of 85% of the population
- Rh+ blood given to an Rh recipient will stimulate anti Rh antibodies
- Hemolytic disease of newborns
- Rh- mother with Rh+ fetus will cause the mother to produce anti Rh antibodies
- Damages fetus RBCs
- Rh- mother with Rh+ fetus will cause the mother to produce anti Rh antibodies
Drug induced cytotoxic reaction
- Thrombocytopenic purpura
- Platelets + Drugs= antigenic complex
- Antibodies + Complement = destroyed platelets
-Agranulocytosis
- Drug- induces immune destruction of granulocytes - Hymolytic anemia
- Drug-induces immune destruction of RBCs
Type III (immune complex) reaction
- antibodies form against soluble antigens in the serum
- on the cell or tissue surface
- immune complex
- IgG
- removed rapidly by phagocytosis
- Activates complement and cause inflammation
- Glomerulonephritis
- inflammatory damage to the kidney due to immune complexes as a result of infection
- Attacks the body
- lupus
Type IV (delayed cell- mediated) reaction
- Caused by T cells
- Reexposure to antigens cause memory cells to release destructive cytokines
- Delayed because it takes time for Tcells and macrophages to migrate near foreign antigens
- ex: transplant rejection
- Foreign antigens bind to tissues cells and are phagocytied by macrophages
- Skin Test
- Posion ivy, latex ect.
- response mediated by cells
interluken cells
Autoimmune Diseases
- Lose of self-tolerance
- the abitlity to distingish between self and non-self
- immune system response to self antigens causing damage to organs
- Cytoyoxic
- Immune complex
- Cell mediated
Cytotoxic
autoimmune
- antibodies react with cell surface antigens
- Multiple Sclerosis
- Neruo disease
- T cells and macrophages attack the myelin sheath of nerve cells
- causes: compromises nerve impulses and lead to scarring
- Graves disease
- Thyroid gland produces excessive amounts of hormones
- Usually the production of hormones are from the brain
- Causes: Budged eyes, sweating, trembling - Myasthenia Gravis
- Antibodies coat acetylcholines receptors
- Causes: muscles fail to receive nerve signals
- Result in: collapse lung b/c the muscle tissue cant receive signals
Immune complex
autoimmune
- Systemic lups
- immune complexes form in kidney glomeruli
- Rheumatoid arthritis
- Immune complexes formed in the joints
- IgG and IgM and complexes are depositied in the joints - severe damage to the cartilage and bones of joints
- Immune complexes formed in the joints
Cell mediated
Autoimmune
- T cells attack tissues
- Insulin dependent diabetes
- T cells attack insulin secreting cells
-Psoriasis and Psoriasis arththritis - Disease of the skin
- treated with immunesuppressants that target T cells
- T cells attack insulin secreting cells
Reactions related to human leukocyte antigen complex
- Histocompatibility antigens
- self antigens on cell surfaces - Major histocompatibility antigens (MHC)
- Genes encoding histocompatibility - Human leukocyte antigens (HLA)
- major histocompatibility antigens in human
- some are related to specific diseases
Reactions to Transplants
- transplant may attack Tcells, macrophages and complement-fixing antibodies
- Privileged sites and tissues
- SITES
- areas of the body that dont elicit immune response
- TISSUE
- area of the body or tissue that dont elicit immune response
EX of site and tissue: heart valve and cornea transplants
- area of the body or tissue that dont elicit immune response
- SITES
Stem cells
- master cells that can generate many different cell types
- Embryonic stem cells
- from blastocysts
- used to regenerate tissue and organs
- Pluripotent can regenerate all types of cells
- from blastocysts
- Adult stem cells
- adult tissues that have differentiated
Bone marrow transplants
- For those who lack Tcells and B cells which are vital for immunity
- Increases RBCs in recipient
Grafts
- transfer of tissue from one body part to another
- for burn victims or plastic surgery ect.
- Auto graph: one’s own tissue
- Isograft: identical twin
- Allograft: from another person
- Xenotransplant: from nonhuman tissue
- Graft vs host
- bone marrow contains immunocompetent cells
Cancer Cells
- removed by immune surveillance
- cancer cells have tumor assoicated antigens that are marked as nonself
- Limitations
- non antigenic epitotes to target
- tumor cells reproduce rapidly
- tumor become invisible to the immune system
- latent metastasis
- Cells become cancerous after undergoing transformation w/o control
Immunotherapy for cancer
- Endotoxins from bacteria to stimulate TNF to interdere with the blood supply of cancers
- Vaccines
- Feline lekemia, cervical cancer, and liver cancer
- Monoclonal antibodies
- breast cancer: herciptin
- immunotoxins targets and kills tumors w/o damaging host cells
Immunodeficiencies
- Absence of sufficient immune response
- Congenital immunodeficiencies
- defective or missing gene
Aquired immunotherapy - developed during someones life
- from drugs, cancers or infections
- defective or missing gene
(AIDS) Acquired Immunodeficiency disease
- virus destroys CD4+ cells
- allows cancer & bacterias, virus , fungi protazoan to cause HIV infection
- orignated in the Congo
- Genus: Lentivirus
- Retrovirus
- reverse transcription enzymes
- phospholipid envelope
- gp12 glycoprotien spike - 2 identical RNA strands
Pathogenicity of HIV
- Virus fuses and enter the cell via receptor mediated endocyotsis
- spreads by dendritic cell and macrophages the contact w/ lymphoid organs cause the activation of T-helper cells
- once virus is inside the cell RNA is transcribed into DNA w/ reverse transcription
- virus undergoes rapid antigenic changes at a high rate of mutation
Subtypes of HIV
- HIV-1
- Related to infecting chimpanzees and gorillas
- Group M 90% - HIV-2
- Related to infecting monkeys and sooty mangabeys
- less pathogenic than HIV-1
Stages of HIV
- Phase 1
- asymptomatic or lymphadenopthaty
- Phase 2
- CD4+ T cell decline steadily
- only a few symptoms
- CD4+ T cell decline steadily
- Phase 3
- AIDS develops
- CD4+ count is below 200 cells
Resistance to HIV infection
- strong and effective immune response initially’
- Once HIV is in the latently infected CD4+ T cells the infection is impossible to clear
HIV Transmission
- Survies 6hr outside of cell
- can survive 1.5 day inside a cell
- sex, breast milk, needles, organ transplants ad blood transfusion
Preventing and treating AIDS
- Use of condoms
- limited sexual partners
- uses sterile needles
- medication
- fusion and cell entry inhibitors
- reverse transcription inhibitors
- nucleoside
- Tenofovir and emtricitabrine
- nucleoside
- Antiretroviral thearpy
- minimizes survival of resistant strains
-Intergrase inhibitors - Intergrase inhibitor
- prevents the production of genetic information getting into the host cells
- minimizes survival of resistant strains
drugs that inhibit the life cycle of HIV
- Fusion and entry inhibitors
- Enfuvirirde
- Maraviroc
Reverse Transcription
- Tenofovir
- Emtricitabine - Integrase inhibiots
- Raltgravir
