review 4th exam periottt
Leukocytosis
increase in the number of white blood cells
mechanisms for recognition of microbe by phagocyte:
Opsonin-independent (nonopsonic) recognition `\ Opsonin-dependent (opsonic) recognition
What are phagocytes?
Survey tissues, discover microbes, particulate matter, and injured/dead cells Ingest via phagocytosis kill eliminate or present (macrophage or DC)
14.4 Microbiota-Host Communications
Microbiota communicate to host with chemicals and vibrations -Three-way "discussion" --Quorum sensing --Microbial products influence host gene expression --Host molecules affect microbes
How are antibodies synthesized in the lab?
Monoclonal antibodies -Epitope-specific Ab -Produced by a single Ab-producing B-cell clone (hybridoma) Polyclonal antibody -Ab isotypes against many different epitopes
What are stem cells?
-Undifferentiated cells -Blood stem cells (hematopoietic) maintained in red bone marrow
Secondary antibody response is the basis of immunization:
After B-cell activation memory cells are generated When memory B cells encounter Ag again they quickly trigger a robust secondary Ab response
Vaccines of the Future?
A blast of helium fires tiny gold pellets carrying harmless snippets of a pathogen's DNA into the skin. The DNA infiltrates the nucleus of the skin and muscle cells. The DNA forces the cell to produce pathogen proteins, triggering the immune system. Although a promising technology, no commercial DNA vaccines are yet available.
The hygiene hypothesis postulates that the increase in asthma is caused by what?
A decrease in microbiota diversity
What do we call a substance that is too small to be recognized by the immune system on its own but can stimulate an immune response if it is bound to a larger molecule?
A hapten
Vaccines induce herd immunity:
A. Two infected and contagious people can rapidly spread disease throughout an uninfected population. B. Immunizing only a few healthy people in a population does not slow the spread of disease among the unvaccinated (greater than 90% in the example still get ill), but doing so will protect those who were vaccinated. C. Vaccinating a large fraction of the population, however, will prevent most of those unvaccinated (75% in the example) from encountering sick and contagious individuals.
Why can it be more difficult to treat infections in the brain than in other locations?
Antibiotics can be blocked by the blood-brain barrier.
Mechanisms of NK Cell activation
Antibody-dependent cell-mediated cytotoxicity (ADCC) Loss of MHC-I
Richard, who is blood group B, was undergoing surgery after a car accident and accidentally received a transfusion with type A blood. Within hours, Richard experienced chills and lowered blood pressure. His urine turned red with blood. All these symptoms indicate an ABO blood group incompatibility. Red blood cells that contain the ---antigen are destroyed (lysed) by anti-A antibodies when transfused into a type B person.
B
What type of cell would you expect to interact with the receptor being shown in this diagram?
B cells
What are memory B cells?
B cells primed to become plasma cells if activated again in the future
Vaccination most prominent in childhood but adults need vaccinations as well:
Boost an older immunization (tetanus, pertussis) Protect against "adult" infections such as pneumonia, shingles Provide special protection in people with certain medical conditions
What is the result of the activation of the complement system?
C3b functions as an opsonin C3a & C5a induce inflammation C5b + C6 + C7 + C8 + C9 cause cell lysis (MAC)
Can microbiota be pathogenic?
Cavities and periodontitis -Streptococcus mutans and S. salivarius form a glycocalyx that firmly adheres them to oral surfaces and each other Dental procedures -Bacteria may enter blood (bacteremia) heart, grow vegetations Sx of subacute bacterial endocarditis Dysbiosis (fluctuations within normal flora) -Antibiotics -Loss of antagonism
Which of the following body compartments are sterile in healthy individuals?
Cerebrospinal fluid Heart Blood
Toxoid vaccines
Chemically or thermally modified toxins used to stimulate active immunity Stimulates Ab-mediated immunity More boosters needed
What factors influence antigenicity (immunogenicity)?
Contribution of biological system -Genetic Factors -Age -Activity -Nutrition -Trauma
Type IV Hypersensitivity
Delayed, cell-mediated immune reactions Examples: allergic contact dermatitis, TB hypersensitivity, some autoimmune diseases, transplantation rejection
15.5 Interferon
Describe antimicrobial function of interferons (IFNs): IFN-α and IFN-β -Induce cells to produce antiviral proteins IFN-γ -Proinflammatory cytokine; stimulates phagocytic activity of macrophages and PMNs
Autoimmune Diseases
Determined by genetics, influenced by gender Results from loss of self-tolerance -Autoantibodies or T cell mediated -May be systemic or organ specific > 80 recognized autoimmune diseases -Affect 5 - 8% of US population -Women account for ~75% of autoimmune disease -Biological basis remains a mystery
An example of a primary immunodeficiency is________________.
DiGeorge syndrome
What do granzymes do?
Granzymes stimulate cell death in infected cells.
Which of the processes below are parts of the humoral immune response, and which are parts of the cell-mediated immune response? Indicate your answer by dragging the labels to the appropriate bins.
HUMORAL IMMUNITY -The production of memory B-cells -The production of plasma cells -Activation of B-cells -Killing most types of bacteria Cell-Mediated Immunity -Cytokine activation of machrophages -The activation of killer T-cells -Killing virally infected cells
Microbiota May influence obesity in two major ways:
Harvesting of energy from ingested foods Triggering of intestinal inflammation
Jamal is vaccinated against varicella, also known as chicken pox, as a young child. If he has subsequent exposure to the varicella virus as an adult, what would you expect to occur?
His titer levels of IgG would be much higher than they were after vaccination.
Ranges of fever:
Low grade: 37.7-38.3°C (100-101°F) Moderate: 38.8-39.4°C (102-103°F) High: 40.0-41.1°C (104-106°F)`\
Explain how pathogens may be killed extracellularly:
Neutrophils produce reactive oxygen and nitrogen species, and antimicrobial peptides --Neutrophil extracellular traps (NETs) - bind to and kill bacteria
Mature T cells are naïve until activated by Ag presentation
Require MHC recognition Once activated proliferate into effector cells and memory cells All produce cytokines with a spectrum of biological effects
Intracellular Digestion and killing:
Respiratory burst - toxic oxygen products kill microbes
Natural Killer (NK) Cells
Role in innate immunity -Target viral infected cells, abnormal cells, parasites -Activated by interferons and cytokines Kill by secreting: -Perforins -Granzymes
What are the cardinal signs of inflammation?
Rubor/erythema - red Tumor/edema - swelling Dolor - pain Calor - heat Loss of function Other signs of inflammation: -Ulcer -Pus -Abscess (Boil, pimple, stye, etc.) -Granuloma (chronic inflammation)
Hemolytic disease of the newborn
Sensitization Rhogam (anti Rh Ab)
17.5 Tools of Immunology
Serology: study of serum and its contents Agglutination = Cross-linking principle -Measures insoluble antigen on whole cell -Identification of bacterial pathogens -Blood typing - Antibody-antigen interaction = clumping (positive)
Routes of Administration
Subcutaneous Intramuscular Intradermal Oral, Nasal -Can stimulate IgA -Convenience
Cooperation Between Pathogen Recognition Receptors (PRRs)
TLRs and NLRs recognize & bind unique MAMPs
How do natural killer cells recognize their targets?
Target cells lack MHC I molecules.
Both MHC class I receptors and MHC class II receptors are synthesized on the rough ER. What keeps MHC class II receptors from binding to antigens while in the ER?
The MHC class II receptor has its binding site covered by a protein called the invariant chain. Until that is removed, it is unable to bind to any antigens.
Opsonization facilitates
phagocytosis
B Lymphocytes Plasma cells
Humoral immunity -B cells -Plasma cells - Antibodies
Describe the composition of blood:
-Blood cells suspended in plasma -Plasma = clear, yellowish fluid -Serum = plasma without clotting proteins --Used in immune testing & therapy
T Lymphocytes (T cells)
-Cell mediated immunity -Naïve cells differentiate into subsets --CD4 helper T cells (TH) ---Th1, Th2, Th17, Th22 --CD8 cytotoxic T cells (CTLs or TC) --T Reg
The Maternofetal (Placental) Barrier
-Placenta keeps fetus pathogen free by separating maternal and fetal circulation -Identify pathogens that may cross this barrier: TORCH
Mast Cells
-Prevalent in connective tissues -Contain inflammatory granules - histamine and heparin
Functions of immune system:
-Prevention of infection -Surveillance -Detection / recognition of foreign material -Destruction of entities deemed foreign / harmful
Dendritic Cells
-Professional antigen presenting cells -Regulate balance between immunity & tolerance
What do we know about the usefulness of probiotics?
-Treat diarrhea post antibiotics -Fecal transplants replace harmful bacteria with helpful bacteria as a treatment for inflammatory intestinal diseases
Gastrointestinal Tract Microbiota
10^9-10^11 bacteria / gram feces -Anaerobes/facultative anaerobes : aerobes (1000 : 1) Flora varies by section -Jejunum: Slightly alkaline from pancreas and gall bladder (bile) secretions -Ileum and cecum: Slightly acidic, less bile -Colon: Slightly acidic -Can be influenced by stress, diet, antibiotic
After allergen exposure, when do most severe reactions become apparent in individuals with type I hypersensitivity?
30 minutes after exposure
Epitope or antigenic determinant:
3D shape, region of antigen recognized by immune system
Differentiate the Ab Isotypes:
5 classes: IgG, IgA, IgM, IgD, IgE All have similar structure -Heavy and light chains are held together by disulfide bonds -Variable hinge regions -J chain on IgA and IgM
Which of the following blood types is considered to be the universal recipient?
AB
Leukopenia
Abnormally low white blood cell count
Which of the following is NOT one of the functions of the IgG class of antibodies?
Activating mast cells
17.6 Vaccines and Immunization
Active Immunization - Injecting antigen stimulating immune system -Induce primary immune response =Antigen-specific Ab and T cells made, memory B/T cells -If pathogen later enters body, secondary immune response will be immediate, powerful, and sustained Passive Immunization - Protective Ab are administered -Injection of immune globulin -Antitoxins -Breastfeeding
What is the role of inflammation in immunity?
Acute inflammatory response - generally develops quickly; short lived Mobilizes/attracts immune components to injury site Activates repair mechanisms and clears harmful substances ` Destroys microbes and blocks further invasion
Contrast advantages and disadvantages of fever:
Advantages -Increases IL-1 activity (WBC activation) -Produces interferon -Slows microbial growth -Inactivates microbial enzymes/toxins -Increases metabolism (20%) -Increases transferrins (decreases Fe availability) -Induces rest Disadvantages -Dehydration -Tachycardia -Acidosis -44-46°C fatal
Activation of cytotoxic T cells:
Ag presentation on MHC-I in secondary lymphoid tissues TCR is Ag specific CD8 on TC cell binds self MHC-I on target cell TH cell activated by Ag on MHC-II differentiation secretion IL-2 clonal expansion of TC IL-2 auto-stimulates TC Activated (effector) TC cells migrate to site of infection
Which of the following statements correctly describes immunogens?
All immunogens are antigens.
Where are lymphatic vessels located?
All over body, except avascular tissue Lymphatic capillaries and capillary beds Larger vessels parallel deep arteries
Which of the following would be two antibodies of different isotypes?
An IgG antibody and an IgA antibody that bind to the same antigen and were created by plasma cells that descended from the same activated B cell
Other Autoimmune Diseases
Autoimmune hemolytic anemia - antibodies to self RBCs Type I diabetes mellitus - destruction of islet of Langerhan's cells in the pancreas Celiac Disease -Gluten =A peptide present in wheat (includes semolina, triticale, etc), barley, and rye =Consumption triggers an autoimmune response ==Only autoimmune disease where the trigger is known, though onset is brought on by other factors Signs & Symptoms -Intestinal problems such as abdominal pain, bloating, constipation or diarrhea -Other seemingly unrelated issues: Malabsorbtion of nutrients can lead to a number of problems Treatment: strict gluten-free diet for life
16.4 Humoral Immunity: Primary and Secondary Antibody Responses
B cell development begins and ends in red bone marrow (hematopoiesis) -Hematopoietic stem cell lymphoid stem cell B cell -Development of tolerance to self (immune tolerance) =Removal of potentially harmful clones through clonal deletion =Autoimmune diseases may result from loss of immune tolerance or survival of "forbidden clones"
How are B cells able to respond to millions of different antigens?
B cells randomly rearrange immunoglobulin genes to make unique antigen-binding sites.
What are probiotics?
Bacteria used to populate/repopulate GI tract with "good" microbiota -Most commonly used probiotics contain species of Lactobacillus and Bifidobacterium
What is normal microbiota (microbiome)?
Bioburden -Bacteria, fungi, protozoa and viruses (virome) Two types: -Resident microbiota -Transient microbiota
What is adaptive/ acquired immunity?
Body's ability to recognize & defend itself against distinct invaders & their products (antigens) Humoral/Ab mediated - B cells / plasma cells Cell mediated - T cells
phagocytosis & intracellular killing:
Chemotaxis -Cytokines / chemokines Adherence -TLRs attach to PAMPs -TLRs induce cytokines that regulate intensity & duration of immune responses Ingestion Phagosome Phagolysosome Killing Exocytosis or presentation on MHC-II
Derek, a 16-year-old high school chess prodigy, was rushed by his parents to the St. Michael's emergency department in Toronto, Canada. The staff found Derek very confused and disoriented. His parents said that Derek had complained of a sore throat a few days earlier but over the last 24 hours developed a very high fever and a severe headache. When examined, Derek had a stiff neck and many reddish spots, called petechiae, over his body. The attending physician performed a lumbar puncture, in which a needle is inserted into the spinal column between two lower back vertebrae to remove cerebrospinal fluid (CSF). Normally clear, Derek's CSF was cloudy, looking like dilute milk. The physician diagnosed meningitis. A few hours later, the hospital laboratory reported that the CSF contained Gram-negative diplococci, and a rapid test indicated Neisseria meningitidis. The doctor was not surprised, because this was Derek's third bout with meningitis caused by this organism. The other infections occurred when Derek was 9 and 13 years old. After this last episode, the physician suspected that Derek might have a genetic deficiency in one of his blood complement components. The laboratory confirmed that Derek's blood had a deficiency in complement factor C8. Derek's deficiency affects which of the following complement pathways?
Classical
Which of the following occurs after a B cell binds to an epitope?
Clonal expansion of the activated B cell occurs.
What factors influence antigenicity (immunogenicity)?
Contribution of immunogen -Foreignness -Size of dose (threshold dose) -Size of Ag -Chemical composition -Physical form - -Degradability
Type I Hypersensitivity
Diagnosis IgE against specific allergen - -ImmunoCAP -Skin tests Treatment -Avoid allergen -Medication - Antihistamines, Corticosteroids (Cortisone, prednisone), Epinephrine (Epi pen) -Immunotherapy (allergy shots)
What are the main functions of the lymphatic system?
Drain excess interstitial fluid to circulatory system Transport white blood cells, dietary lipids & lipid soluble vitamins -Lacteals Immunity
Type II - Cytotoxic Reactions
Due to IgG & IgM - complement fixing Ab Examples: ABO/Rh incompatibility, Transfusion Reactions, Erythroblastosis fetalis
Secondary Immunodeficiency Diseases
Due to drugs, cancer, radiation, malnutrition, HIV and other infections, stress, trauma
Microbiome ‒ Double Sided
Enterotoxins produced by some Gram-negative pathogens damage the host small intestine and cause diarrhea --Enterotoxins may also protect against colorectal cancer by activating membrane Ca2+ channels in intestinal epithelial cells Increasing Ca2+ transport turns on an antiproliferative pathway that slows cell division -Altered gut microbiome associated with risk for: -Crohn's disease -Diabetes -Heart disease -Asthma -Autism, Moods, Schizophrenia -Obesity
Enzyme-Linked Immunosorbent Assay (ELISA)
Enzyme-linked Ab converts colorless substrate to a colored product Can detect antibody or antigen -Direct - detect Ag in serum with enzyme conjugated Ab -Indirect - detect Ab in serum with known Ag -Sandwich - Capture antibody =Ag from serum sample and secondary Ab =Enzyme-conjugated Ab
What treatment options are available for hypersensitive patients who experience edema, low blood pressure, cardiovascular collapse, and severe breathing difficulties after a bee sting?
Epinephrine
14.3 Keeping Microbiota in Their Place
Epithelial barriers held together by tight junctions between cells -Series of molecules that attach to cytoskeleton -Regulated: only open/close in response to various signals
Is the Microbiome an Organ System?
Evidence human microbiota is an organ system: -10X more microbial cells than human cells -100X more microbial genes than human genes -Contained in separate defined areas of body by tight junctions -Changes or harm to microbiota may profoundly impact host -Microbiota is inherited (at least initially) from the mother
The construction of antibodies uses light and heavy "chains" that are held together through covalent bonds. Considering the most critical areas of antibodies for immunity, according to the figure, which of the following is the specific region on an antibody that binds antigens?
F(ab)
Which of the following is Derek unable to do as a result of this deficiency?
Form pores in the membranes of bacteria in the blood
Chronic Inflammation
From persistent inflammation Permanent tissue damage Causes of chronic inflammation: -Chronic infection and/or Intracellular pathogens (i.e. M. tuberculosis) -Continual stimulation basic inflammatory response -Nonliving, irritant material (i.e. splinters, asbestos, surgical implants, etc.)
Describe the structure of immunoglobulins:
Glycoproteins Four polypeptide chains connected by disulfide bonds Two functionally distinct fragments: -FAb fragment: =Variable regions of heavy & light chains =Hypervariable region: Site on Ab where epitope binds -Fc fragment: = Involved in binding to various cells, Ab & molecules of immune system (complement) =Determines isotype
14.2 Benefits and Risks of a Microbiome
Human microbiota is often beneficial (mutualism): -Digest food Ferment unused energy substrates -Synthesize compounds (such as vitamins) -Produce hormones to direct host to store fats Microbial antagonism --Maintain homeostasis of microbiota --Inhibit colonization by pathogens --Compete for attachment sites, food --Synthesize antimicrobial compounds -Regulate development of the gut -Train/enhance immune system --Produce immunomodulins that modify secretion of cytokines
14.5 Natural Biological Control of Microbiota
Hygiene hypothesis - changes in human behavior has led to loss of microbiota diversity -Overuse of antimicrobials -Dietary changes -Cesarean birth -Absence of breast-feeding Loss of diversity impacts homeostasis -Greater enabling of pathogenic species -Increased risk of inflammatory diseases --Asthma, allergies, etc.
Which of the following cytokines must be present to continue a cell-mediated, cytotoxic T-cell response?
IL-2
Identify each of the following as part of innate immunity, adaptive immunity, or both.
INATE IMMUNITY mast cells basophils complement ADAPTIVE IMMUNITY T cells lymphocytes antibodies BOTH leukocytes macrophages
Which antibody class is most commonly associated with allergies?
IgE
Which class of antibody is capable of crossing the placenta to give passive immunity to the fetus?
IgG
Which class of antibody is the first to be detected in the early stages of an adaptive immune response?
IgM
Type III Hypersensitivity
Immune complex reactions Examples: Arthrus reaction, Hypersensitivity pneumonitis, Glomerulonephritis, Rheumatoid arthritis, Systemic lupus erythematosus
How are antibodies used to identify pathogens?
Immunofluorescence - Stain sample with Ab linked to fluorophore -Examine with UV microscope -Rapidly identifies organisms that are difficult to grow
How can the use of antibiotics alter the microbiota of the vagina?
It allows the increased growth of Candida, a normal component of the vaginal microbiota.
Which statement accurately describes the classical pathway of complement activation?
It links the innate immunity of complement with adaptive immunity.
Requirements of an Effective Vaccine
It should - not harm the person being vaccinated stimulate B-cell and T-cell responses result in long-term memory not require many boosters protect against the natural pathogen
Some viruses have the ability to evade the immune system by blocking the cell's ability to display antigens in MHC class I receptors. How would the loss of MHC class I receptors affect the immune system's response?
It would prevent cytotoxic T cells from recognizing the cell as infected.
Explain how pathogens may be killed extracellularly:
Killing by eosinophils -Attack parasitic helminthes by attaching to surface -Secrete toxins (major basic protein) that weakens or kills helminthes -Eosinophilia may be indicative of helminth infestation
Type I (Immediate) Hypersensitivity
Localized or systemic reaction -Results from release of inflammatory molecules -Commonly called "allergy" Reaction depends on portal of entry: -Foods may be allergens causing diarrhea or other GI Sx -Local dermatitis may produce rash or urticaria (hives) -Atopic dermatitis (eczema) -Small inhaled allergens may reach lungs and cause asthma
Lower Respiratory Tract
Lungs originally thought to be sterile -Contributes to lung mucosal immunity Mucus produced by ciliated epithelium -Mucociliary escalator -If damaged increased colonization by pathogens --Biofilms interfere with lung function
Endogenous Ag Processing & Presentation - MHC I
MHC I binds to Ag peptides that originate in cytoplasm and present antigen to CD8+ T cells
Exogenous Ag Processing & Presentation - MHC II
MHC II binds to Ag fragments that come from outside cell and present to CD4+ T helper cells APC's = macrophages, dendritic cells and B-cells
There are two types of major histocompatibility complexes (MHCs): class I and class II. Which characteristics below describe MHC class I and which describe MHC class II?
MHC class I -Interact with CD8 -Found on all nucleated cells -Antigens come from the ER -Displays endogenous antigen -Present antigen to cytotoxic T cells MHC class II -Interact with CD4 -Found only on APCs -Antigens come from the lysosomes -Displays exogenous antigen -Present antigen to helper T cells
This diagram shows the creation of what type of receptor?
MHC class II
What is the function of MHC class II receptors?
MHC class II receptors display antigens to helper T cells.
Rank the following leukocytes from most to least common in healthy blood.
MOST COMMON Neutrophils Lymphocytes Monocytes Eosinophils Basophils LEAST COMMON
Type III hypersensitivity involves the formation of antigen-antibody complexes. Which immune cells normally engulf and clear these complexes?
Macrophages
How do cells differentiate self from non-self?
Major histocompatibility complex (MHC): - -Human leukocyte antigen (HLA) complex -Group of genes on chromosome 6 -Important in determining histocompatibility All cells have unique surface markers: MHC-I MHC-II MHC-III
In the secondary response, the IgG levels rise much faster than they did during the first antibody response. Why is this?
Memory B cells are present for the secondary response. Those cells are much easier to activate than the naive B cells; therefore, the response occurs much more quickly and on a larger scale.
Which of the following support(s) the classification of the microbiome as an organ system?
Microbes contribute to functions such as digestion. Portions of the microbiome are inherited from one's mother. Defects in the microbiome are associated with disease states.
Characterize the humoral immune response:
Mounted against exogenous pathogens B cells primarily in spleen, lymph nodes & MALT BCR binds Ag Activated B cells -Clonal selection/activation: one antibody, one epitope -B cells differentiate into Ab-producing plasma cells and memory cells
Autoimmunity: Type IV Hypersensitivity
Multiple Sclerosis: Antibodies to myelin sheaths surrounding insulated neurons
Complement Deficiencies
Mutation(s) in complement protein genes -Other aspects of humoral and cell-mediated immunity likely intact Patients more susceptible to infection -Especially bacterial infection =S. pneumoniae, S. pyogenes, H. influenzae, and N. meningitidis Treatment involves plasma -Contains complement and antibodies
Autoimmunity: Type II Hypersensitivity
Myasthenia Gravis -Antibodies made to acetylcholine receptor interfere with ACh signaling at nerve synapse -Muscle weakness, paralysis Grave's disease -Antibodies to TSH receptor are stimulatory -Hyperthyroidism results in weight loss, nervousness, tremor & exophthalmos (edema behind eyes) Hashimoto's -Hypothyroidism; fatigue -Gluten free diet
List the four categories of acquired immunity:
Natural immunity: is acquired through the normal life experiences of a human and is not induces through medical means. -Active immunity-is the consequence of a person developing his or her own immune response to a microbe (Infection) -Passive immunity-is the consequence of one person receiving preformed immunity made by another person. (Maternal antibody) Artificial immunity: is that produced purposefully through medical procedures (also called immunization) -Active immunity- is the consequence of a person developing his or her own immune response to a microbe. (Vaccination) -Passive immunity-the consequence of one person receiving preformed immunity made by another person. (Immune globulin therapy)
What is a fever (pyrexia)?
Nearly universal sign of infection -Pyrogens trigger hypothalamus to increase core body temp ==Exogenous: =Products of pathogens, endotoxins =Blood products, vaccines, injectable solutions ==Endogenous: =Cytokines - Ex: IL-1 & TNF -May also be associated with allergies, cancer, & other illnesses
How do Ab eliminate/ inactivate their targets?
Neutralization Opsonization Oxidation Agglutination (Immune complexes) Complement activation ADCC
There is a second, delayed spike of IgM in the secondary response. Why might this be occurring?
New naive B cells have been able to activate and produce a new primary response.
Severe combined immunodeficiency (SCIDs)
No humoral or cell mediated immunity -By 6 months of age, most SCID infants develop recurrent infections -Treatment is bone marrow transplant or IVIG Why must IVIG must be given every 1-3 months?
Fatima is the third child of Moroccan consanguineous healthy parents (cousins of first degree). From birth, she has suffered from numerous infections, including varicella pneumonia, disseminated candidiasis, enterovirus encephalitis, and E. coli meningitis. When she was 3 years old, she underwent an extensive immunological workup to identify the cause of these recurring illnesses. Her white blood cell counts were in the normal range, as were her neutrophil and total lymphocyte counts. However, her total IgG, IgA, and IgM antibody levels were extremely low. This extreme IgG deficiency was the likely cause of her failure to fend off infections. However, the team of physicians treating Fatima still did not know the cause of the antibody deficiency. More tests were ordered to examine key protein surface markers on B cells (IgD), TH0 cells (CD4), TC cells (CD8), and APCs (MHC I and MHC II classes). Her B cell numbers were normal, but her T cells were low, especially the CD4 set. The surprise came when the laboratory reported an absence of MHC class II proteins on her APC cells. The presence of MHC class I proteins, however, was quite normal. The physicians now understood the problem, but the cure would be risky. Fatima had a genetic disorder called bare lymphocyte syndrome. Fatima is missing her MHC class II proteins. Where should these receptors be found?
On macrophages, dendritic cells, and B cells
Explain how lymph is transported:
One-way system - "All vessels lead to heart" Extracellular spaces and reticular tissues--> Lymphatic capillaries --> vessels --> nodes trunks --> ducts--> subclavian vein
Negative effects of microbiota:
Opportunistic pathogens -Failure of host immunodefenses -Introduction into unusual location
Subunit vaccines
Part of organism
Which of the following statements describes the appearance of a plasma cell?
Plasma cells have much more endoplasmic reticulum than naive B cells to support the increased need for protein synthesis.
T-cell education and deletion occurs in thymus:
Positive selection ensures MHC restriction by testing ability of TCR to recognize self MHC Negative selection tests for self tolerance -If T cell binds too strongly or binds self-MHC that isn't presenting Ag, or presenting self-Ag, it will fail negative selection apoptosis -T cell should only weakly bind to self-MHC presenting foreign Ag Regulatory T cells (Tregs) block activation of harmful self-reactive lymphocytes -Tregs prevent autoimmune disease
Identify anatomical structures of the lymphatic system:
Primary lymphoid organs -Red bone marrow -Thymus Secondary lymphoid organs -Lymph nodes/vessels -Spleen -MALT --Tonsils/adenoids --Peyer's patches (GALT) --NALT --BALT -Appendix
Monitoring Ab Production Over Time:
Primary response -1st exposure to Ag -During latent period no Ab produced (Ag is concentrated in lymphoid tissues) -As plasma cells produce Ab, serum titer increases & then tapers off to a low level over weeks & months -IgM 1st followed by IgG Secondary or anamnestic response -Exposure to same Ag weeks, months, or even years later -Rate of Ab synthesis, peak titer, & length of Ab response is increased -IgG > than IgM
Exocytosis
Process by which a cell releases large amounts of material PMNs Macrophages & DCs undergo process called Ag presentation
What do we know about the safety of probiotics?
Quality concerns
Which of the cell types from the list below would NOT express MHC class I receptors?
Red blood cells
Autoimmunity: Type III Hypersensitivity
Rheumatoid arthritis -IgM against some IgG -Immune complexes deposited in joint =Joints begin to break down & become distorted -Trigger not well understood -Treated with anti-inflammatory drugs, immunosuppressive for some
15.7 Compare and contrast the complement pathways:
Serum proteins activated in a cascade results in lysis of foreign cell Complement can be activated in three ways: -Classical pathway -Alternate pathway -Lectin pathway
Describe lymphatic vessels:
Similar to veins but: -Thinner wall, more valves -Closed-ended -Pump lymph via muscle contraction
Combination vaccines
Simultaneous administration of antigens from several pathogens
15.2 Distinguish physical and chemical innate defenses:
Skin - Langerhans cells Hair Eyelashes Mucous membranes -Mucociliary escalator Washing or flushing: -Tears, saliva, urine, sweat
How do some pathogens evade the immune system?
Some viruses down-regulate MHC I or utilize a decoy MHC receptor Many pathogens alter their surface proteins through antigenic variation Some pathogens cause cell death of T cells Some block pro-inflammatory cytokines Intracellular pathogens hide from immune cells or avoid intracellular killing
Autoimmunity: Type III Hypersensitivity
Systemic lupus erythematosus -Autoantibodies against DNA result in immune complex formation -Many other autoantibodies can also occur =Against RBC, platelets, lymphocytes, muscle cells -Sometimes misdiagnosed Dx: blood test + signs/symptoms Tx -Immunosuppressive drugs reduces autoantibody formation -Corticosteroids reduce inflammation
Most of the proteins found in our bodies are proteins that are made by our own cells. Why don't T cells activate in response to self antigens?
T cells that bind to MHC molecules containing self antigens are killed in the thymus during T-cell education.
Contrast T-dependent and T-independent activation of B cells:
T-independent Ag -Ag stimulates B cell to make only IgM - -Weaker than TDEP response -Doesn't induce maturation response that leads to class switching -Poor memory induction to TIND Ag
Target is killed by TC cells
TC cells bind Ag presented on APC cells in lymph nodes Upon activation, TC leave lymph node and find host cells presenting same Ag TC cells kill infected/cancerous host cell
Which of the following regions of the fetus is generally colonized before birth?
The intestines
Once an antigen-presenting cell (APC) has processed antigens for the lymphocytes, it must travel through the body to find the B lymphocytes and T lymphocytes. Where do APCs travel to find waiting lymphocytes?
The lymph nodes
Zika is an emerging virus that has been linked to severe birth defects (e.g., microencephaly) in infants born to affected mothers. Imagine a situation where anti-Zika IgG, but not IgM, is detected in serological tests on both the mother and her newborn. How would these results be best interpreted?
The mother had a prior exposure to Zika, but so far, there is no sign of fetal infection.
How are antigens processed before binding to MHC class I molecules?
They are digested in the cytoplasm of the cell by the proteasome.
Type IV (Delayed or Cell-Mediated) Hypersensitivity
Tissue transplantation -Autograft -Isograft -Allograft -Xenograft Graft rejection Graft-versus-host disease
Attenuated (live) vaccines
Use pathogens with reduced virulence Strong immune response Contact immunity possible
Once bacteria are present in maternal blood, how common is the transfer to fetal systems?
Very few bacteria can pass through the placental membrane and endothelial cells to the fetus.
How do naïve lymphocytes recognize unique Ag?
We can synthesize 1011 different (unique) antibodies! -Variable region is Ag specific -TCR also exhibits specificity How does this happen? -Rearrangement of antibody genes (VDJ) -Random mutations -Generation of different codons during rearrangements
Link between Obesity and Dysbiosis
What causes obesity? -Genes, diet, and imbalance between energy intake and expenditure -Studies show connections between gut microbiota and obesity Landmark study from Jeffrey Gordon et al. demonstrated obesity in humans is clearly linked to their microbiomes -Study involved transplantation of microbiomes from monozygotic human twins into gnotobiotic mice
Inactivated (killed) vaccines
Whole agent vaccines & Subunit vaccines Both safer than live vaccines Fewer antigens available Adjuvants
Point-of-Care Rapid Diagnostics
Widely available - Immunochromatographic assay Advantages - Culturing not required -Immediately initiate specific antibiotic therapy Disadvantages - -No data on antibiotic sensitivity -Double or multiple infections more likely to be overlooked than in culture -False positive or negative results
Fatima's bone marrow is making the normal number of helper T cells. Why would the number of helper T cells in her blood be low?
Without MHC class II receptors, the helper T cells cannot proliferate in response to pathogens in the body.
Allergy shots can be helpful for reducing the signs and symptoms of seasonal allergies (to grass or tree pollen for example). What is the proposed mechanism for how allergy shots work?
`Delivery of small doses of allergens stimulates IgG production, which competitively inhibits IgE.
Neutropenia
a decreased number of neutrophils
A bee stings a 9-year-old boy walking with his mother at the zoo. Within minutes, the boy begins sweating and itching. His chest then starts to tighten and he has tremendous difficulty breathing. Terrified, he looks to his equally frightened mother for help. The 9-year-old boy in this case history must be allergic to bees and is experiencing ----, which is characterized by a rapid drop in blood pressure, constricted airways, and swelling of the epiglottis.
anaphylaxis
Rh incompatibility occurs in the first pregnancy when the Rh- mother makes --- to her Rh+ child.
anti -
Immunogen
antigen that elicits an immune response -"foreign agents" body recognizes as non-self -Induce an immune response -Usually are portions of bacterial cell, virus, fungi, or protozoa
What is hematopoiesis?
blood cell formation
Which of the following pairs of organs are both considered primary lymphoid organs?
bone marrow and thymus
Antigen (Ag):
can be bound by receptors on cells involved in adaptive immunity (self or non-self)
A mutant strain of C. difficile lacking the ability to produce --- would be expected to be significantly less virulent compared to the parent strain.
endospores
Formed Elements in Blood
erythrocytes (RBC), leukocytes, Thrombocytes (platelets)
Which of the following courses of therapy hold the most promise for long-term resolution of Marie's chronic diarrhea?
fecal transplant
Antipyretics
medications that reduce fever no aspirin for children and teens
An individual who has had tuberculosis in the past will have --- that can recognize the antigens. These cells will release a variety of cytokines that call polymorphonuclear leukocyte (PMN) cells to the site, leading to a large red welt on the patient's skin within 24 to 48 hours.
memory T cells
Three types of granulocytes
neutrophils, eosinophils, basophils
Marie was a 77-year-old woman who developed bacterial pneumonia one winter following a nasty bout with the flu. She was prescribed a 10-day course of clindamycin and was recovering well at home until she slipped on the icy sidewalk outside her house. Upon admission to the hospital with a broken hip, the physician reviewing her record noted she had also been suffering for several years with depression and type II diabetes. Later that week, Marie was transferred to a rehab facility where she began experiencing an upset stomach, pain in her lower abdomen and severe diarrhea. Tests of Marie's stool revealed an infection by Clostridioides difficile (formerly classified as Clostridium difficile). Both metronidazole and vancomycin were only temporarily successful in controlling the diarrhea, which returned following cessation of each course of treatment. Marie was most likely put at risk for C. difficile infection by a medication for which condition in her recent medical history?
pneumonia
Which of the following must an immature T cell do in order to survive and enter the periphery?
recognize "self" MHC molecules not react strongly with self proteins
Where does hematopoiesis occur?
red bone marrow
In the first stage of type I hypersensitivity reactions, IgE-coated mast cells are said to be (A) and now can hang around in the body waiting for another encounter with the allergen. In stage 2, degranulation occurs within (B) upon second exposure to an antigen.
sensitized, minutes
Hapten
small antigen
Archaea in the gut might also tilt metabolic balance toward obesity
About 50% of humans have significant numbers of methanogens, primarily Methanobrevibacter smithii
--
Activated TC cells bind to & kill target cell by inducing apoptosis TC cells kill by secreting perforin & granzymes apoptosis All nucleated cells have MHC I, & can be killed by TC cell
Put the steps of B-cell activation in the correct order from first to last.
FIRST Each B cell rearranges its DNA to create a unique B-cell receptor. B cells digest antigens that are bound to the antibodies on their surface. B cells display antigens in MHC class II receptors on the cell surface. B cells become activated by interacting with helper T cells. B cells undergo clonal selection. Antibodies released by plasma cells bind to antigen so they will be destroyed by other immune system cells. LAST
Distinguish physical and chemical innate defenses:
Sweat - salt Antimicrobial peptides / Defensins Fungistatic fatty acid in sebum Lysozyme in tears, saliva, milk and mucus Low pH -Skin (3-5) -HCl in gastric juice (1.2-3.0) -Vaginal secretions (3-5) - maintained by microbiota
Which of the following activities do normal intestinal flora perform to prevent infection by potential pathogens?
compete for attachment sites produce antimicrobial compounds compete for nutrients
Blood-brain barrier
Very tight junctions between endothelial cells of capillaries to brain
Lymph = Plasma-like liquid carried by lymphatic circulation
-Composed of: Water, dissolved salts, ~2-5% protein -Transports WBC, fats, cellular debris, and infectious agents that have gained access to tissue spaces
T cells respond to intracellular pathogens and abnormal body cells
Viruses, intracellular protozoa & bacteria, cancer cells, non-self cells
Granulocytes
-Irregularly-shaped nuclei with 2-5 lobes -Cytoplasm has granules with substances that kill microbes and enhance inflammation --Wright stain
Role of Microbiota in the Immune System
-MAMPs and PAMPs, PRR (immune cell) -Cytokines attract immune cells --Promote or inhibit inflammation --Can limit growth of microbiota
Agranulocytes
-Monocytes -Macrophages --Also a prof APC
The body's immune response to a microbe is really multiple responses to multiple small regions of that microbe. Each small region that is recognized by a specific component of the immune system is referred to as what?
An epitope
T-dependent Ag
Ag presented on MHC-II to TH cell TH cell produces cytokines that activate B cell All Ab types produced