Immunology Exam 2

Yes, but they're largely protected by maternal IgG, so fetuses are unlikely to make their own unless they're infected IgM is the first antibody infants make in utero

Are fetuses capable of producing IgG? What's the first antibody made in utero?

Arthus Reaction (Localized) -Type III HS -if antigen is injected beneath the skin, it can form immune complexes with antibodies that have diffused from the blood into the connective tissue -complement gets activated and an inflammatory response ensues -appears as localized areas of redness and swelling

Arthus Reaction (Localized) -Type _______ HS -if antigen is injected beneath the _______, it can form immune complexes with antibodies that have diffused from the blood into the __________ __________ -complement gets activated and an inflammatory response ensues -appears as localized areas of redness and swelling

Local -common with inactivated vaccines -usually mild and self limiting -generally occur within a few hours of injection Systemic -common with whole cell or live attenuated vaccines Allergic -due to vaccine or vaccine component -rare -ex. people with egg allergies cannot receive the flu vaccine, which is made using eggs

Adverse Reactions and Extraneous Effects caused by Vaccination

Allergens -the majority of humans mount significant IgE responses only as a defense against parasites -after an individual is exposed to a parasite, the serum IgE levels increase and remain at high levels until the parasite is cleared -atopic person - have a genetic defect affecting the regulation of the IgE response -this allows non-parasitic antigens to stimulate inappropriate IgE production leading to tissue damaging Type I HS reactions -most allergic IgE responses occur on mucous membrane surfaces in response to allergens that enter the body by inhalation or ingestion

Allergens -the majority of humans mount significant _________ responses only as a defense against __________ -after an individual is exposed to a parasite, the serum IgE levels increase and remain at high levels until the parasite is cleared -atopic person - have a ___________ defect affecting the regulation of the IgE response -this allows non-parasitic antigens to stimulate inappropriate IgE production leading to tissue damaging __________ HS reactions -most allergic IgE responses occur on mucous membrane surfaces in response to allergens that enter the body by _____________ or ingestion

Attenuated (Weak) Vaccines -whole organism vaccines -most protect against viruses, except for TB and Oral Typhoid vaccines Oral Polio -RNA lacks proofreading, so oral polio vaccine could potentially revert back to active form, which is why this vaccine is no longer used Yellow Fever -no longer required in the U.S. Vaccinia -small pox vaccine -no longer given to public, but is administered to military to protect against biological warfare

Attenuated (Weak) Vaccines -whole organism vaccines -most protect against ________, except for TB and _______ _________ vaccines Oral Polio -RNA lacks ___________, so oral polio vaccine could potentially revert back to active form, which is why this vaccine is no longer used Yellow Fever -no longer required in the U.S. _____________ -small pox vaccine -no longer given to public, but is administered to military to protect against biological warfare

Attenuated Vaccines -organisms lose capacity to cause disease, but still grow/replicate in the host -mimics natural infection -as a general rule, the more similar a vaccine is to the natural disease, the better the immune response to the vaccine -live, attenuated vaccines better building memory responses than inactivated vaccines -immunocompromised individual can become sick from attentuated vaccine -grow organisms under abnormal conditions and select mutants -ex. mycobacterium bovis (BCG) is grown in bile for over 13 years

Attenuated Vaccines -organisms lose capacity to cause disease, but still __________ in the host -mimics _________ infection -as a general rule, the more _________ a vaccine is to the natural disease, the ________ the immune response to the vaccine -live, attenuated vaccines better building ___________ responses than inactivated vaccines -immunocompromised individual can become sick from attentuated vaccine -grow organisms under _____________ conditions and select mutants -ex. mycobacterium bovis (BCG) is grown in bile for over 13 years

Autosomal Recessive -rare -more commonly affects females -before 1950s, most patients died in childhood, making it difficult to pass the gene on X-Linked Recessive -more common -affects mostly men b/c they have only one copy of X chromosome

Autosomal Recessive vs X-Linked Recessive Immunodeficiencies

B Cell Deficiencies -usually characterized by recurrent bacterial infections with normal immunity to virus and fungal parasites -most common infections include staph. and strep. b/c antibody is critical for the opsonization and clearance of these organisms Examples -X linked agammaglobulinemia -X linked hyper IgM -selective IgA deficiency -common variable hypogammaglobulinemia -hypogammaglobulinemia of infancy

B Cell Deficiencies -usually characterized by recurrent __________ infections with __________ immunity to virus and fungal parasites -most common infections include _______ and _________ b/c antibody is critical for the ______________ and clearance of these organisms Examples -X linked agammaglobulinemia -X linked hyper IgM -selective _______ deficiency -common variable hypogammaglobulinemia -hypogammaglobulinemia of infancy

Bare Lymphocyte Syndrome -autosomal recessive mutation -T cell deficiency -mutation that prohibits the expression of class II MHC, therefore T Helper cells can't develop -mutations may also effect class I MHC, which would affect CD8 Tc cell development -presentation similar to DiGeorge's (SCID)

Bare Lymphocyte Syndrome -autosomal recessive mutation -T cell deficiency -mutation that prohibits the expression of ___________, therefore T Helper cells can't develop -mutations may also effect class I MHC, which would affect CD8 Tc cell development -presentation similar to _________________ (SCID)

Basic Characteristics of Hypersensitivity -first contact with allergen produces no symptoms, but the individual becomes sensitized -re-exposure to the same antigen (allergen) elicits a reaction -reaction is highly specific -re-exposure to the same allergen may increase and sometimes decrease the severity of the reaction (immunotherapy)

Basic Characteristics of Hypersensitivity -first contact with allergen produces _____ symptoms, but the individual becomes ___________ -____________ to the same antigen (allergen) elicits a reaction -reaction is highly ___________ -re-exposure to the same allergen may increase and sometimes __________ the severity of the reaction (immunotherapy)

No Only naive B and T cells can recognize HEV to reach the secondary lymphoid tissues Memory cells usually stay at sites where their specific antigen is likely to be present, like in the mucosa

Can memory cells recognize HEV?

Yes. Type I Hypersensitivities are caused by the binding of IgE to FcR on mast cells/basophils, which extends the half life of IgE to weeks or months, but not forever.

Can someone outgrow an allergy? Why or why not?

-no, small number of people will not be protected -not a problem if the majority of the population is immune (Herd Immunity)

Does vaccination work every time?

Chronic Granulomatous Disease (CGD) -mutation in one of four genes for NADPH Oxidase -X-linked -severe and recurrent infections with catalase positive organisms like Staph, Klebsiella, Serratia, Candida, Pseudomonas, and Aspergillus -catalase breaks down hydrogen peroxide, which is the killing factor from myelo-peroxidase -infections, if unresolved, lead to the formation of granulomas (response when macrophages can't kill something) -NBT tests for diagnosis -treated with antibiotics and IFN-gamma -bone marrow transplant is controversial but can cure CGD

Chronic Granulomatous Disease (CGD) -mutation in one of four genes for _________ __________ -X-linked -severe and recurrent infections with _________ positive organisms like Staph, Klebsiella, Serratia, Candida, ___________, and Aspergillus -catalase breaks down _________ ___________, which is the killing factor from myelo-peroxidase -infections, if unresolved, lead to the formation of ___________ (response when macrophages can't kill something) -________ tests for diagnosis -treated with antibiotics and IFN-gamma -_________ ________ transplant is controversial but can cure CGD

Cell Adhesion Molecules -selective gateways to the lymphoid organs -organize the traffic through secondary lymphoid tissue -CAMs on the lymphocytes recognize CAMs on endothelial cells -can be best observed via transmigration of activated or memory lymphocytes (and neutrophils) through the blood vessel walls into the tissues ex. CD18, selectins, CD34

Cell Adhesion Molecules -selective gateways to the __________ organs -organize the traffic through secondary lymphoid tissue -CAMs on the lymphocytes recognize CAMs on ____________ ___________ -can be best observed via _______________ of activated or memory lymphocytes (and neutrophils) through the blood vessel walls into the tissues ex. CD18, selectins, CD34

Chediak-Higashi -rare, autosomal recessive disorder -affects the synthesis and maintenance of storage granules in many cell types including neutrophils, melanocytes, monocytes, and NK cells -phagocytosed material is not delivered to the lysosomes because of a fusion defect -patients partially albino b/c the granules can't fuse together, which is necessary for phagocytes to work. Melanocytes are also granular and so are also unable to fuse together, affecting skin pigment -recurrent bacterial infections -no NK activity (increased incidence of lymphomas) -albinism b/c of affected melanocytes -lab diagnosis is a routine blood smear revealing giant granlues and neutropenia

Chediak-Higashi -rare, autosomal recessive disorder -affects the synthesis and maintenance of storage __________ in many cell types including __________, melanocytes, monocytes, and NK cells -phagocytosed material is not delivered to the ___________ because of a fusion defect -patients partially ________ b/c the granules can't fuse together, which is necessary for phagocytes to work. Melanocytes are also granular and so are also unable to fuse together, affecting skin pigment -recurrent __________ infections -no NK activity (increased incidence of _________) -albinism b/c of affected melanocytes -lab diagnosis is a routine blood smear revealing ________ __________and neutropenia

Combined Immunodeficiency Diseases -usually comprises defects in both the humoral and cell-mediated arms of the immune system -patients are susceptible to any type of pathogen, even those with low virulence -Severe Combined Immunodeficiency Disease: no B or T cells -In Wiskott-Aldrich Syndrome and Ataxia-Telangiectasia, B and T cells are still present, but not properly working

Combined Immunodeficiency Diseases -usually comprises defects in both the humoral and cell-mediated arms of the immune system -patients are susceptible to ________ type of pathogen, even those with low virulence -Severe Combined Immunodeficiency Disease: _________ or ___________ -In Wiskott-Aldrich Syndrome and Ataxia-Telangiectasia, B and T cells are still present, but not properly working

Common Allergens -generally small proteins -usually present in dried up particles -rehydrate upon inhalation and get presented by APCs to T Helper cells -leads to development of TH2 response and increased IgE

Common Allergens -generally _______ proteins -usually present in _______ up particles -rehydrate upon inhalation and get presented by ________ to T Helper cells -leads to development of _________ response and increased IgE

Common Variable Immunodeficiency -also called "late onset agammaglobulinemia" -heterogeneous disease -associated with increased incidence of autoimmunity -occurs in late teens and early 20s -antibody levels decrease with age -inadequate T cell:B cell signalling so that B cells can't differentiate into plasma cells -B cells can be found in the periphery, low antibody levels -patients present with recurrent bacterial infections

Common Variable Immunodeficiency -also called "late onset agammaglobulinemia" -heterogeneous disease -associated with increased incidence of _______________ -occurs in ________ and _________ -antibody levels ________ with age -inadequate T cell:B cell signalling so that B cells can't differentiate into _____________ cells -B cells can be found in the ___________, low antibody levels -patients present with recurrent bacterial infections

Complement Deficiencies -manifest similar to phagocytic deficiencies and antibody deficiencies -major sequelae associated with complement deficiencies include: -defects in opsonization -defects in lytic activity -defects in clearing immune complexes -complements prevent immune complexes from forming and aid in the clearing of immune complexes

Complement Deficiencies -manifest similar to phagocytic deficiencies and antibody deficiencies -major sequelae associated with complement deficiencies include: -defects in _____________ -defects in _______ activity -defects in clearing ________ ________ -complements prevent immune complexes from forming and aid in the clearing of immune complexes

Conjugate Polysaccharide Vaccines -polysaccharide conjugated to protein antigen -changes the immune response from T cell independent to T cell dependent -leads to increased immunogenicity in infants -antibody booster response to multiple doses of vaccine -ex. Hib vaccine (H. influenzae type B) and MCV4 vaccine (N. meningitidis)

Conjugate Polysaccharide Vaccines -polysaccharide conjugated to ________ antigen -changes the immune response from T cell independent to T cell _________ -leads to increased ___________ in infants -antibody booster response to multiple doses of vaccine -ex. ______ vaccine (H. influenzae type B) and ________ vaccine (N. meningitidis)

Cytotoxic -direct lysis of red blood cells -drugs, transfusion reactions, erythroblastosis fetalis, graft rejection Non-Cytotoxic -the cell or tissue is altered in function -Grave's Disease: antibodies bind to TSH receptor --> unregulated thyroid hormone production --> hyperthyroidism Myasthenia Gravis: antibodies bind to Ach receptors and block Ach binding

Cytotoxic vs Non-Cytotoxic Type II HS

The resistance to the spread of a contagious disease within a population that results if a sufficiently high proportion of individuals are immune to the disease, especially through vaccination.

Define Herd Immunity.

-immunization to elicit protective immunity and immunologic memory -immune system plays an active role -recommended childhood vaccines -boosters -vaccines for travelers and military

Describe artificial active immunity.

-injecting an individual with preformed antibodies -used to provide immediate protection to individuals who have been exposed to an infectious agent and are suspected of lacking immunity (like those who are not up to date with vaccinations or poisoning from spiders and snakes) -temporary immunity -does NOT activate the immune system of the recipient -no memory response -risks include the formation of immune complexes from different antibodies (like with two different IgGs) -ex. patients with Reactive varicella zoster are given hyper immune serum -ex. antiserum for rabies and tetanus

Describe artificial passive immunity. What are some of its risks?

Recovery from Disease Memory Formation

Describe natural active immunity.

-Placental Transfer -preformed antibodies transferred to a recipient -maternal antibodies protect the fetus against many pathogens -antibodies in the milk also protect breast fed infants -does NOT activate the immune system of the recipient

Describe natural passive immunity.

-Afferent Lymphatics (many; site of entry) -Efferent Lymphatics (only one; site of exodus) -post capillary venules -B cell areas (cortex) -T cell areas (para cortex) -germinal centers between the cortex and paracortex -medulla -vascularized tissue of lymph nodes is important in how WBCs leave the blood and enters the lymph nodes --> high endothelial venules (HEV)

Describe the basic anatomy of a lymph node.

-fetuses exclusively protected by maternal IgG -maternal IgG steadily depleted after birth -most immunodeficiencies not detected until 6 months of age, b/c this is when maternal IgG is almost completely depleted -at 12 months old, the percentage of infant antibodies is just a little more than half that of an adult, which is why children are sick so often

Describe the development of humoral immunity in infants.

Yes, but none in the periphery -Only humoral defect with no B cells -Increased risk of mucosal infections, viral infections, enterovirus infections, an infections from encapsulated bacteria

Do patients with X-linked agammaglobulinemia have pre-T cells present in their bone marrow?

Tetanus requires boosters, b/c antibody levels decline H. Influenzae B is rare in children under 2 and would not require boosters, b/c adults don't usually contract the disease

Do tetanus and H. Influenzae B vaccines require boosters?

-the first response in any tissue that's infected with a pathogen is to initiate the innate immune response (inflammation and phagocytosis) -eventually, the antigens arrive at the lymph nodes. If there's a lymphocyte specific to that antigen, an adaptive immune response is initiated -after the adaptive response is generated, we get effector B cells (plasma cells) and effector Tc cells -when the effector cells are made, they leave through the efferent lymphatics and are dumped back into circulation -wehn teh cells get dumped into circulation, they go back to the site of infection through chemotaxis for the effectors cells of the innate immune system to finish killing off the pathogen

Describe the diagram.

DiGeorge's Syndrome -autosomal dominant mutation -absence of a thymus -cardiovascular anomalies and characteristic facial features -reflects a failure of the 3rd and 4th pharyngeal pouches to develop between weeks 10-12 of gestation (development of aortic arch of heart) -recurrent infections with intracellular pathogens like Candida (chronic mucocutaneous candidiasis) and viruses -CD3, CD4, and CD8 negative

DiGeorge's Syndrome -autosomal dominant mutation -absence of a thymus -_____________ anomalies and characteristic facial features -reflects a failure of the 3rd and 4th __________ pouches to develop between weeks 10-12 of gestation (development of aortic arch of heart) -recurrent infections with intracellular pathogens like Candida (________ _______ ________) and _______ -CD3, CD4, and CD8 negative

Erythroblastosis Fetalis -Type II Hyper-Sensitivity -Rh- mother gives birth to an Rh+ fetus -transport of maternal IgG specific for Rh across the placenta -not much of a problem during the first pregnancy, b/c mother's immune system will not encounter the fetal red blood cells until the time of birth when the placenta ruptures -problem in subsequent pregnancies, b/c the mother's immune system has produced antibodies against the Rh+ blood cells -T dependent response generating IgG -RhoGam (human, anti-RhD IgG) at 28 weeks and within 24 hours after birth: binds to Rh+ -also given to any Rh- woman following termination of pregnancy

Erythroblastosis Fetalis -Type _____ Hyper-Sensitivity -Rh- mother gives birth to an Rh+ fetus -transport of maternal IgG specific for Rh across the placenta -not much of a problem during the _______ pregnancy, b/c mother's immune system will not encounter the fetal red blood cells until the time of ________ when the placenta ruptures -problem in subsequent pregnancies, b/c the mother's immune system has produced antibodies against the Rh+ blood cells -T ___________ response generating IgG -_____________ (human, anti-RhD IgG) at 28 weeks and within 24 hours after birth: binds to Rh+ -also given to any Rh- woman following termination of pregnancy

Grave's Disease -non-cytotoxic Type II HS -IgG auto-antibodies are formed against the TSH receptor -the antibodies bind to the TSH receptor and stimulate the unregulated production of thyroid hormones -thus, there was a change in tissue function and not lysing of blood cells

Grave's Disease -__________________ Type _____ HS -IgG auto-antibodies are formed against the ______ receptor -the antibodies bind to the TSH receptor and stimulate the unregulated production of thyroid hormones -thus, there was a change in tissue function and ______ lysing of blood cells

Histamine -binds to histamine receptors (H1, H2, and H3) -binds to H1 on nearby smooth muscle cells and endothelial cells lining blood vessels -induces vascular permeability and eventually causes inflammation Smooth Muscle Contraction -constricts airways -increase secretion of mucous due to increased vasodilation -if all the fluid is removed from vasodilation and increased permeability, this could lead to organ failure due to lack of oxygen

Histamine -binds to histamine ___________ (H1, H2, and H3) -binds to H1 on nearby smooth muscle cells and endothelial cells lining ___________ ___________ -induces vascular ___________ and eventually causes inflammation Smooth Muscle Contraction -constricts airways -increase ___________ of mucous due to increased vasodilation -if all the fluid is removed from vasodilation and increased permeability, this could lead to organ failure due to lack of oxygen

Through the HEV

How do T cells enter the lymph node?

Live Injected Vaccines -first dose usually provides coverage -second dose ensures seroconversion Inactivated Vaccine -first dose usually doesn't provide protection -may not develop until 2nd or 3rd dose -antibody titer wanes over the years (not lifelong immunity)

How many doses do live injected vaccines and inactivated vaccines usually require? Why?

Hyper IgM Syndrome (HIM) -X linked -mutation in CD40L on T cells -CD40L is necessary for T cell communication with B cells and the formation of specific antibodies, therefore there is no class switching (to antibodies other than IgM) and no germinal centers formed -increased levels of IgM and no IgA, IgG, or IgE -patients usually have recurrent bacterial infections and severe diarrhea

Hyper IgM Syndrome (HIM) -X linked -mutation in ___________ on T cells -CD40L is necessary for T cell communication with B cells and the formation of specific antibodies, therefore there is no _________ ________ (to antibodies other than IgM) and no ____________ ___________ formed -increased levels of IgM and no IgA, IgG, or IgE -patients usually have recurrent __________ infections and severe _________

IgE -in normal individuals, serum IgE range is very low (0.1-0.4 microgram/mL) -in severely allergic individuals, serum IgE range is rarely greater than 1 microgram/mL -half life of IgE is only 2-3 days, but if it's bound to an FcR on a mast cell/basophil, the IgE is stable for weeks to months (but not forever, which is why people can outgrow an allergy)

IgE -in normal individuals, serum IgE range is very ________ (0.1-0.4 microgram/mL) -in severely allergic individuals, serum IgE range is rarely greater than 1 microgram/mL -half life of IgE is only 2-3 days, but if it's bound to an ________ on a _________/__________, the IgE is stable for weeks to months (but not forever, which is why people can outgrow an allergy)

Immunosuppressed Persons -should never receive live, attenuated vaccines -inactivated vaccines can be given, but responses may be decreased -cancer patients may receive live vaccines 3 months after chemotherapy has been discontinued HIV+ -MMR and varicella can be given to those who are asymptomatic or mildly immunosuppressed -those who are symptomatic or in full blown AIDS should never receive MMR

Immunosuppressed Persons -should never receive _______ _________ vaccines -inactivated vaccines can be given, but responses may be decreased -cancer patients may receive live vaccines ___________ after chemotherapy has been ___________ _________ -MMR and varicella can be given to those who are asymptomatic or mildly immunosuppressed -those who are symptomatic or in full blown AIDS should never receive MMR

Chediak-Higashi -granules unable to fuse together, affecting neutrophils, NK cells, and monocytes -melanocytes are also granular, and so are unable to fuse, affecting the patient's skin pigment

In which immunodeficiency disease do the patients present albinism? Why?

Inactivated Vaccines -kill the pathogen by heat or chemical means -pathogen can no longer replicate in host -critical to maintain the structure of epitopes on the surface antigens during inactivation -heat not usual method (denature proteins) -chemical inactivation with alkylating agents -require repeated boosters (3-5 doses) -produce humoral (antibody) response predominantly

Inactivated Vaccines -_______ the pathogen by heat or chemical means -pathogen can no longer __________ in host -critical to maintain the structure of ________ on the surface antigens during inactivation -heat not usual method (denature proteins) -chemical inactivation with alkylating agents -require repeated ___________ (3-5 doses) -produce humoral (antibody) response predominantly

Innate Immunity Meets Adaptive -within a few hours of the acute inflammatory response, APCs + antigen leave the area via lymphatics -activated dentritic cells begin to express CCR7 (chemokine receptor) -chemokines bind to CCR7, allows them to exit tissue -dentritic cell's focus shifts from antigen capture to antigen presentation -activated dentritic cell's concentrate in the draining lymph nodes in the paracortex -naive T cells also express CCR7, home to lymph nodes

Innate Immunity Meets Adaptive -within a few hours of the acute inflammatory response, APCs + antigen leave the area via __________ -activated ________ ________ begin to express CCR7 (chemokine receptor) -chemokines bind to CCR7, allows them to _______ tissue -dentritic cell's focus shifts from antigen capture to antigen ___________ -activated dentritic cell's concentrate in the draining lymph nodes in the ___________ -naive T cells also express CCR7, home to lymph nodes

Intraepithelial Lymphocytes -lamina propria houses a large concentration of activated T cells with a CD4:CD8 ratio of 7:3, B cell blasts and IgA+ plasma cells -intraepithelial lymphocytes are mostly T cells, but 10-40% are TCR gamma-delta, which don't need the thymus for development and can be found in patients with DiGeorge's

Intraepithelial Lymphocytes -lamina propria houses a large concentration of activated T cells with a CD4:CD8 ratio of 7:3, B cell blasts and IgA+ plasma cells -intraepithelial lymphocytes are mostly T cells, but 10-40% are ______ ________, which don't need the thymus for development and can be found in patients with _________

Leukocyte Adhesion Deficiency (LAD) -rare autosomal recessive -absence of CD18 (common beta-2 chain of integrins) -leukocytes cannot migrate -omphalitis -chronic recurrent bacterial infections -no abscess or pus formation -patients suffer with recurrent pyogenic infections, impaired wound healing, and severe gum inflammation -CBC reveals leukocytosis and flow cytometry can determine the presence or absence of cell adhesion molecules -treatment of choice is bone marrow transplant, antibiotics, and IFN-gamma

Leukocyte Adhesion Deficiency (LAD) -rare autosomal recessive -absence of ________ (common beta-2 chain of integrins) -leukocytes cannot _________ -omphalitis -chronic recurrent __________ infections -no abscess or ______ formation -patients suffer with recurrent pyogenic infections, impaired wound healing, and severe ______ inflammation -CBC reveals leukocytosis and flow cytometry can determine the presence or absence of _________________ -treatment of choice is bone marrow transplant, antibiotics, and IFN-gamma

-composed of primary follicles containing small, resting B cells and follicular dentritic cells -after contact with antigen, form secondary follicles with a corona of concentrically packed resting B cells surrounding a germinal center -germinal centers consist of follicular dentritic cells, and dividing B cells which can differentiate into plasma cells and memory cells

Lymph Node Cortex -composed of primary follicles containing small, resting B cells and __________ ____________ cells -after contact with antigen, form __________ follicles with a corona of concentrically packed resting B cells surrounding a _________ _________ -germinal centers consist of follicular dentritic cells, and ____________ B cells which can differentiate into plasma cells and memory cells

Lymph Nodes -encapsulated lymphoid organs found throughout the body, connected via lymphatics -antigens check in any time they like, but can never leave -separate compartments for B and T cells (cortex and paracortex) -when antigens are delivered to specific lymph node areas and the lymphocyte specific to that antigen is present, an immune response will be mounted

Lymph Nodes -___________ lymphoid organs found throughout the body, connected via lymphatics -antigens check in any time they like, but can __________ leave -separate compartments for B and T cells (cortex and paracortex) -when antigens are delivered to specific lymph node areas and the lymphocyte specific to that antigen is present, an immune response will be mounted

Lymphocyte Trafficking -lymphocytes (B or T cells) must be able to continuously circulate through the secondary lymphoid tissues in order to increase the chances that they will come in contact with antigen -once a lymphocyte recognizes antigen, within 24 hours of antigen localizing in the lymph nodes, antigen-specific lymphocytes are depleted from circulation, localized in the LN or spleen, and become activated -the flow of B and T cells through the secondary lymphoid tissues is directed by cell adhesion molecules (CAMs) and specialized endothelial cells called high endothelial venules (HEV)

Lymphocyte Trafficking -lymphocytes (B or T cells) must be able to continuously circulate through the ___________ lymphoid tissues in order to increase the chances that they will come in contact with antigen -once a lymphocyte recognizes antigen, within 24 hours of antigen localizing in the ________ _________, antigen-specific lymphocytes are _________ from circulation, localized in the LN or spleen, and become ___________ -the flow of B and T cells through the secondary lymphoid tissues is directed by _________________ and specialized endothelial cells called high endothelial venules (HEV)

Mast Cells and Basophils -mucosa and epithelial surfaces lining body surfaces -all vascularized tissue (extending CNS and retina) -contain granules with pre-formed (primary, immediate) pharmacologically active mediators (i.e. histamine) -once the FcR has been cross-linked, degranulation occurs in seconds

Mast Cells and Basophils -mucosa and epithelial surfaces lining body surfaces -all ________________ tissue (extending CNS and retina) -contain ____________ with pre-formed (primary, immediate) pharmacologically active mediators (i.e. histamine) -once the __________ has been cross-linked, degranulation occurs in seconds

Mucosal Associated Lymphoid Tissue (MALT) -diffuse collections of lymphocytes, plasma cells, and phagocytes -found in lung and intestine -tonsils, Peyer's patches, and appendix are more organized -forms a separate secretory system in which plasma cells secrete large amounts of IgA

Mucosal Associated Lymphoid Tissue (MALT) -diffuse collections of lymphocytes, plasma cells, and phagocytes -found in _________ and intestine -tonsils, Peyer's patches, and appendix are more organized -forms a separate secretory system in which plasma cells secrete large amounts of _________

Mucosal Immunity -antigen enters Peyers patches across specialized cells called M cells -dome areas/follical associated epithelium are between the villi and beneath the dome area is where the immune system lies within the mucosa -M cells sample the environment of the lumen of the gut and instead of phagocytosing the antigen, the M cells transport the antigen into a pocket of waiting T and B cells -after activation, lymphocytes enter lymph, go through MLN and thoracic duct, pass from the blood and back into the lamina propria (via CAM) to become IgA secreting plasma cells -IgA's primary function is neutralization of the antigen

Mucosal Immunity -antigen enters _________ _________ across specialized cells called M cells -________ ________/follical associated epithelium are between the villi and beneath the dome area is where the immune system lies within the mucosa -______ ________ sample the environment of the lumen of the gut and instead of phagocytosing the antigen, the M cells transport the antigen into a pocket of waiting ________________ -after activation, lymphocytes enter lymph, go through MLN and _________ __________, pass from the blood and back into the lamina propria (via CAM) to become ________ secreting plasma cells -IgA's primary function is ______________ of the antigen

Secondary Lymphoid Tissue -lymph nodes, spleen, and loosely associated clusters of lymphoid tissue (MALT, BALT, and GALT) -secondary lymphoid organs are where the immune cells respond to antigen

Once antigens enter the body, where are they taken?

Phagocytic Deficiencies -phagocytosis is a primary means for the removal of extracellular bacteria from the body, therefore defects reveal an inability to clear infections -can result from a reduction in the numbers of phagocytic cells or from a reduction in their function -in each case, the hallmarks are recurrent bacterial or fungal infections that range from mild skin infections to life threatening systemic infections -frequent infections with S. aureus, S. pneumoniae, E. coli, pseudomonas, candida, and aspergillus -ex. chronic granulomatous disease (CGD)

Phagocytic Deficiencies -phagocytosis is a primary means for the removal of extracellular bacteria from the body, therefore defects reveal an inability to _______ infections -can result from a reduction in the numbers of __________ cells or from a reduction in their function -in each case, the hallmarks are recurrent _________ or fungal infections that range from mild skin infections to life threatening systemic infections -frequent infections with S. aureus, ____________, E. coli, ___________, candida, and aspergillus -ex. chronic granulomatous disease (CGD)

S. aureus, S. pneumoniae, E. coli, Pseudomonas, candida, and aspergillus

Phagocytic deficiencies present frequent infections with which organisms?

Polysaccharide Vaccines -virulence factor of many organisms -composed of long chains of sugar molecules -inability to activate T Helper cells -IgM, no class switching, no affinity maturation, no memory -neutrophils have trouble attacking encapsulated vaccines, b/c polysaccharide capsules are slippery -Pneumococcal Vaccine - 23 serotypes: just the capsules

Polysaccharide Vaccines -virulence factor of many organisms -composed of long chains of sugar molecules -inability to activate __________ cells -________, no class switching, no affinity maturation, no memory -___________ have trouble attacking encapsulated vaccines, b/c polysaccharide capsules are slippery -_____________ Vaccine - 23 serotypes: just the capsules

Primary Mediators -primary or (immediate) reactions are the direct result of IgE cross-linking and degranulation -pre-stored in the granules and effects are immediate but short lived -ex. histamine, heparin, TNF-alpha, proteases, degradative enzymes, inflammatory mediators -ECF (eosinophil chemotactic factor) and NCF (neutrophil chemotactic factor) -if there's nothing to get rid of, the neutrophils and eosinophils cause damage -ECF associated with late stage asthma

Primary Mediators -primary or (immediate) reactions are the direct result of IgE _________-_______ and degranulation -pre-stored in the granules and effects are immediate but _________ lived -ex. __________, heparin, TNF-alpha, proteases, degradative enzymes, inflammatory mediators -ECF (____________ chemotactic factor) and NCF (_____________ chemotactic factor) -if there's nothing to get rid of, the neutrophils and eosinophils cause damage -ECF associated with late stage ___________

Recombinant Antigen Vaccines -any gene for an immunologic protein can be isolated and cloned in bacteria, yeast, or mammalian cells -primarily induces humoral immunity -antibodies made against the surface antigens -HBV: HBsAg (surface antigen) grown in yeast -HPV -MenB

Recombinant Antigen Vaccines -any gene for an immunologic protein can be isolated and cloned in bacteria, yeast, or mammalian cells -primarily induces humoral immunity -antibodies made against the _________ antigens -HBV: HBsAg (surface antigen) grown in _______ -HPV -MenB

Serum Sickness (Systemic) -Type III HS -many of the classic treatments for infectious diseases has been to generate antiserum in horses and administer to patients as immediate treatment -seven to ten days following administration of horse serum, the patient would get chills, fever, vasculitis, and occasional glomerulonephritis -due to horse serum forming complexes with human antibodies -Today, serum sickness can be caused by anti-venom, streptokinase, and large doses of penicillin

Serum Sickness (Systemic) -Type ______ HS -many of the classic treatments for infectious diseases has been to generate antiserum in _________ and administer to patients as immediate treatment -seven to ten days following administration of horse serum, the patient would get chills, fever, _________, and occasional glomerulonephritis -due to horse serum forming complexes with human antibodies -Today, serum sickness can be caused by anti-venom, streptokinase, and large doses of __________

Secondary (Late) Mediators -Il-4 -Platelet Activating Factor (PAF) -chemotactic for leukocytes -activates neutrophils, eosinophils, and platelets -prostaglandins and leukotrienes -effects are felt after the primary, but are more potent and longer lasting

Secondary (Late) Mediators -Il-________ -_________ __________ ___________ (PAF) -chemotactic for leukocytes -activates neutrophils, eosinophils, and platelets -prostaglandins and _____________ -effects are felt after the primary, but are more _________ and longer lasting

Selective IgA Deficiency -most common of the immunodeficiency diseases (1:800) -genetic component not known -in some patients, can detect anti-IgA, in others the IgA+ B cells don't differentiate into plasma cells -patients can be asymptomatic to presenting with an increased incidence of respiratory tract infections and infections at mucosal surfaces -lack of IgA often means overproduction of IgE, so patients would NOT be given gamma-globulins, b/c these might trigger an allergic reaction and an increase risk of anaphylaxis

Selective IgA Deficiency -most common of the immunodeficiency diseases (1:800) -genetic component not known -in some patients, can detect anti-IgA, in others the IgA+ B cells don't differentiate into plasma cells -patients can be _______________ to presenting with an increased incidence of _____________ _________________ infections and infections at mucosal surfaces -lack of IgA often means overproduction of __________, so patients would NOT be given gamma-globulins, b/c these might trigger an ___________ reaction and an increase risk of anaphylaxis

Spleen -large, encapsulated organ situated high in the left abdominal cavity -not supplied by lymphatic vesicles -antigens are carried in by the splenic artery -blood borne antigens -Red Pulp: RBCs -White Pulp: WBCs B Cells -found in the marginal zone -arranged in follicles -after antigen contact, B cells can form secondary follicles T Cells -surround the artery in the periarteriolar lymphoid sheath (PALS), which contains white pulp

Spleen -large, encapsulated organ situated high in the left abdominal cavity -_______ supplied by lymphatic vesicles -antigens are carried in by the _______ ________ -________ borne antigens -Red Pulp: RBCs -White Pulp: WBCs B Cells -found in the ________ _________ -arranged in follicles -after antigen contact, B cells can form ____________ follicles T Cells -surround the artery in the _________ ________ _______ (PALS), which contains white pulp

Systemic Anaphylaxis -occurs when allergens enter the blood Organ Specific Anaphylaxis -occurs when allergens effect target organs -most commonly effected are the respiratory, GI, and connective tissues

System vs. Organ Specific Anaphylaxis

Systemic Anaphylaxis -allergens in blood -widespread activation of mast cells -increased vascular permeability -widespread constriction of smooth muscle -fluid leaving the blood leads to a rapid drop in blood pressure and anaphylactic shock -many organ systems are damaged, b/c they're functionally impaired -mortality usually associated with asphyxiation due to airway constriction and epiglottal swelling

Systemic Anaphylaxis -allergens in ___________ -widespread activation of __________ cells -increased vascular _____________ -widespread constriction of _____________ muscle -fluid leaving the blood leads to a rapid drop in blood pressure and _______________ __________________ -many organ systems are damaged, b/c they're functionally impaired -mortality usually associated with asphyxiation due to airway constriction and ________________ swelling

T Cell Deficiencies -because T cells orchestrate the immune response, T cell deficiencies can affect both the humoral and cell-mediated responses -much more severe than B cell disorders -patients usually have increased incidence of fungal and viral pathogens -IgM still present b/c that's T cell independent Examples -DiGeorge's -Bare Lymphocyte Syndrome

T Cell Deficiencies -because T cells orchestrate the immune response, T cell deficiencies can affect both the humoral and cell-mediated responses -much more severe than B cell disorders -patients usually have increased incidence of ________ and ________ pathogens -_________ still present b/c that's T cell independent Examples -DiGeorge's -Bare Lymphocyte Syndrome

Timing and Spacing of Vaccines -if received live vaccine: wait 2 weeks before antibody so that the immunotherapy doesn't disrupt or bind to the vaccine -if received antibody: wait more than 3 months before giving vaccine -inactivated vaccines are generally not affected by circulating antibody to antigen

Timing and Spacing of Vaccines -if received live vaccine: wait ___________ before antibody so that the immunotherapy doesn't disrupt or bind to the vaccine -if received antibody: wait more than __________ before giving vaccine -inactivated vaccines are generally not affected by circulating antibody to antigen

Transient Hypogammaglobulinemia of Infancy -aka "early onset agammaglobulinemia" -delayed onset of normal IgG synthesis usually seen in the 5th and 6th month of life -transient, low levels of gammaglobulins in infants -usually resolves by 2-6 years of age -patients usually have recurrent respiratory infections -can be caused by malnutrition in fetuses

Transient Hypogammaglobulinemia of Infancy -aka "early onset agammaglobulinemia" -delayed onset of normal _____ synthesis usually seen in the _________ and _______ month of life -transient, low levels of gammaglobulins in infants -usually resolves by ______-_____ years of age -patients usually have recurrent ___________ infections -can be caused by malnutrition in fetuses

1. IL-4 2. Platelet Activating Factor (PAF) 3. Prostaglandins 4. Leukotrienes

What are four examples of secondary (late) mediators?

Type I Hypersensitivity Reaction -induced by certain types of allergens and has all the hallmarks of a normal immune response except -secretion of IgE from plasma cells distinguishes Type I Hypersensitivity from normal immune response -IgE binds to a high affinity FcR on the surface of tissue mast cells and blood basophils -IgE coated mast cells/basophils are said to be sensitized -future exposure to the same allergen cross-links the mIgE on sensitized mast cells/basophils and causes the degranulation of these cells, resulting in the release of pharmacologically active mediators

Type I Hypersensitivity Reaction -induced by certain types of allergens and has all the hallmarks of a normal immune response except -secretion of ________ from plasma cells distinguishes Type I Hypersensitivity from normal immune response -IgE binds to a high affinity _______ on the surface of tissue mast cells and blood __________ -IgE coated mast cells/basophils are said to be ________ -future exposure to the same allergen __________-__________ the mIgE on sensitized mast cells/basophils and causes the _____________ of these cells, resulting in the release of pharmacologically active mediators

Type II Hypersensitivity -antibody mediated HS against our own cells or receptors or membranes -mediated by IgG or IgM -antibodes against tissue antigens Causes -local complement activation -influx of leukocytes -tissue destruction via ADCC, degranulation, and oxygen radicals

Type II Hypersensitivity -antibody mediated HS against our own cells or receptors or membranes -mediated by _______ or IgM -antibodes against ______ antigens Causes -local ______________ activation -influx of _________ -tissue destruction via ADCC, degranulation, and oxygen ___________

Type II -antibodies binding to cells or tissues -cytotoxic -IgM and IgG Type III -immune complex mediated destruction of tissues -IgM and IgG

Type II vs Type III Hyper-Sensitivity

Type III Hypersensitivity -caused by high levels of circulating immune complexes (IgG or IgM) -systemic, rather than organ specific damage -circulating immune complexes overwhelm the immune system's ability to remove them -deposits in various tissues (skin, glomeruli, blood vessels, synovium, and lungs) and activate complement -neutrophils try to remove the complexes and this results in degranulation and tissue damage

Type III Hypersensitivity -caused by high levels of circulating _____________ _______________ (IgG or IgM) -__________, rather than organ specific damage -circulating immune complexes overwhelm the immune system's ability to remove them -deposits in various tissues (skin, glomeruli, blood vessels, synovium, and lungs) and activate __________ -____________ try to remove the complexes and this results in degranulation and tissue damage

Type IV Hypersensitivity Reaction -only HS reaction that is T cell mediated -reactions typically take 24-48 hours -classic examples are contact dermatitis and the TB skin test -non-harmul components (pentadecacetechol from poison ivy) complex with proteins in the skin and get taken up by APCs and presented to T cells -TH1 response develops resulting in activation of macrophages via IFN-gamma resulting in an inflammatory response that is unwarranted

Type IV Hypersensitivity Reaction -only HS reaction that is ________ ________ -reactions typically take 24-48 hours -classic examples are contact dermatitis and the _______________ -non-harmul components (pentadecacetechol from _______ ________) complex with proteins in the skin and get taken up by ___________ and presented to T cells -______ response develops resulting in activation of macrophages via _______________ resulting in an inflammatory response that is unwarranted

Allergens -most common is penicillin -insect stings -peanuts and Brazil nuts Treatment -rapid administration of epinephrine (EpiPen) -stimulates reformation of tight junctions -reduces permeability -prevents fluid loss from blood -decreases swelling -increases blood pressure

What are some common allergens that cause systemic anaphylaxis? What's the treatment?

Urticaria/Hives -allergens that activate mast cells in the skin -can acquire hives from food allergies if the allergen gets carried through the blood -most common cause is insect bites -atopic dermatitis (eczema): chronic itching with skin rash, erruption and history of increased IgE and allergies

Urticaria/Hives -allergens that activate _______ cells in the ________ -can acquire hives from food allergies if the allergen gets carried through the _______ -most common cause is ______ -______ -atopic dermatitis (eczema): chronic itching with skin rash, erruption and history of increased _______ and allergies

1. X-Linked Agammaglobulinemia 2. X-Linked Hyper IgM 3. Selective IgA Deficiency 4. Common Variable Hypogammaglobulinemia 5. Hypogammaglobulinemia of Infancy

What are five examples of B cell deficiencies?

-not consistently immunogenic in children younger than two years of age -repeat doses do not cause a booster response (enhanced immune response) -predominant antibody is IgM with little to no IgG -phased out with conjugate vaccines

What are some concerns with polysaccharide vaccines?

Cholera, Plaque, Pertussis, Typhoid, Influenza, Polio (IPV), Rabies, and Hepatitis A

What are some examples of Inactivated (dead) vaccines?

Advantages -mimic natural infection (replication in all the places it normally would) -builds better memory response -individuals who are seroconvert become immune with just one dose Disadvantages -reversion to virulent form (1 in 4 million): MMR vaccine uses RNA viruses that lack proofreading -contaminated viruses: ex. Simian virus in oral polio vaccine --> cancer in humans -complications similar to natural disease: fetus and mother may not be perfect immunological match, which is why pregnant women don't receive attenuated vaccines -measles: Subacute Panencephalitis

What are the advantages and disadvantages of attenuated vaccines?

1. Defects in Phagocytic Cell Function 2. Defects in Complement 3. Defects in B Cell Development or Function 4. Defects in T Cell Development or Function 5. Combined B and T Cell Deficiencies

What are the five types of immunodeficiencies?

Rolling -selectins on the lymphocyte bind CD34 on the vascular endothelium -force of blood pressure rolls the lymphocyte along the vascular endothelium Attachment -above interaction activates beta-2 integrins Arrest and Adhesion -beta 2 integrins change conformation and bind very strongly to ICAM molecules on the surface of the vascular endothelium (tight binding) Transendothelial Migration

What are the four steps of transmigration?

Smooth muscle contraction and increase vascular permeability

What are the two major effects of histamine?

1. Capsular Polysaccharide 2. Inactivated Toxins (DTaP) 3. Recombinant Surface Antigens

What are three purified macromolecules?

1. Serum Sickness (Systemic) 2. Arthus Reaction (Localized)

What are two examples of Type III Hyper-Sensitivity?

Cell Adhesion Molecules (CAMs) like CD18 and High Endothelial Venules (HEVs) of the postcapillary venules

What directs the flow of B and T cells through the secondary lymphoid tissues?

Arthus Reaction (Localized) Type III Hypersensitivity

What dis?

Chediak-Higashi -presence of giant granules -neutropenia

What disease is the blood smear indicative of?

Mucosal Associated Lymphnoid Tissue Bronchial Associated Lymphoid Tissue Gut Associated Lymphoid Tissue -secondary lymphoid tissues where immune cells respond to antigen

What do MALT, BALT, and GALT stand for? Why are they important?

Paracortex -primarily T cells and IDC (increased class II) -neighbors to B cell area (good for activation) Medulla -plasma cells secreting antibody -where mature/effector cells concentrate before leaving through the efferent lymphatic -effector cells

What do the paracortex and medulla of the lymph nodes contain?

Plasma Cell

What is an effector B cell?

Diagnosis for Chronic Granulomatous Disease (CGD) -WBCs separated from blood sample and placed with NBT -if NBT turns blue for positive, this means NADPH oxidase is present and the patient is negative for CGD -if the NBT turns yellow for negative, this means NADPH oxidase is lacking and the patient is positive for CGD

What is nitroblue tetrazolium reduction (NBT) used as a diagnosis for? How are the results read?

X-Linked Agammaglobulinemia -mutation in tyrosine kinase important in the development of pre-B cells to mature B cells

What is the only humoral defect condition in which there are no B cells?

Mutations in RAG-1/2, ADA are autosomal recessive whereas mutations in the IL-2R gamma chain (shared by several cytokines) are X-linked -recurrent infections with bacteria, fungi, and viruses

What mutations can cause SCID?

Men x-linked recessive immunodeficiency increased frequency of infection from catalase positive organisms

What population is most susceptible to chronic granulomatous disease (CGD)?

Toxoid Vaccine

What type of vaccine protects against a specific disease, but not against the bacteria?

A cell that actually does something. Effector B cell = plasma cell Effector Tc Cell has been activated by IL-2 and kills stuff An effector helper cell would be a subset of the T cells (TH1 or TH2) that releases cytokines to have a specific effect on the immune system

What's an effector cell?

DTaP: Diptheria, Tetanus, acellular Pertussis -inactivated; toxoid -exotoxins -prevents the disease, but not the infection, b/c the vaccine protects against the toxin -ex. the vaccine protects against tetanus, but not other C. tetani infections -anti toxoid antibodies bind to toxin and neutralize effects -difficult to make in high quantities -cloning

What's an example of a toxoid vaccine? How do they work?

-failure of the immune system -reactions that are unwarranted and harmful to the host -the immune response itself is responsible for induction of disease -requires sensitization and is antigen specific -classified by Gell and Coombs (4 types)

What's hypersensitivity?

They're TCR delta-gamma instead of alpha-beta -delta-gamma T cells don't develop in the thymus and are thought to instead develop in the gut -can be found in patients with DiGeorge's

What's special about intraepithelial T cells?

-B cells located in the marginal zones -T cells located in the Periarteriolar Lymphnoid Sheath (PALS; sheath of lymphocytes that surround the splenic artery); PALS composed of white pulp

Where are B cells and T cells located in the spleen?

-if the antigen penetrates the tissues, it will be cleared by the draining lymph nodes -if antigen enters the blood, it will be cleared by the spleen, which contains an end artery -if antigens enter the GI or respiratory tract, they will be cleared by the mucosal associated lymphoid tissue (MALT)

Where do antigens go when they enter the body?

Immunocompromised individuals and pregnant women.

Which populations should never receive a live, attenuated vaccine?

-polysaccharide vaccine, so T Helper cells aren't involved, meaning no memory response can be formed

Why are adults administered the pneumococcal vaccine?

Prostaglandin and leukotriene are not prestored, they are made de novo from arachidonic acid during the inflammatory response The effects of prostaglandin and leukotriene are similar to histamine, but more potent and longer lasting

Why are the effects of prostaglandin and leukotriene not felt immediately, like histamine?

All the WBCs head to the secondary lymphoid tissues in search of the antigen

Why does the circulating WBC count drop a day or two after someone is sick?

-prevents invasion -protects against the most virulent strains, but still allows children to build their own immunity

Why does the pediatric pneumococcal vaccine only protect against 14 capsular serotypes?

Serotype B's capsule is not immunogenic Separate vaccine for serotype B, which is the most common strain of N. meningitidis

Why is N. meningitidis Serotype B not included in the MCV4 vaccine?

No, infants are largely protected with maternal IgG until about 6 months of age, so the maternal IgG would just bind to the vaccine. This is why most live, attenuated vaccines are administered between 12 and 15 months when maternal IgG has been depleted.

Would a vaccine like MMR be effective if administered to a 4 month old infant? When are most live, attenuated vaccines administered?

X-Linked Agammaglobulinemia -mutation in a tyrosinase kinase important in the development of pre-B cells to mature B cells -only humoral defect with no B cells -patients have difficulty with encapsulated bacteria like H. influenzae, S. pneumoniae, S. pyogenes, and S. aureus -patients exhibit increased severity of viral infections that effect the gut (enteroviruses) -recurrent mucosal infections -usually appears around 6 months of age and 80% present with pneumonia and other sinopulmonary infections -B cells CD19 negative -pre B cells in the bone marrow, but none in the periphery

X-Linked Agammaglobulinemia -mutation in a _________ kinase important in the development of ________ cells to mature B cells -only humoral defect with ________ ________ _________ -patients have difficulty with __________ bacteria like H. influenzae, S. pneumoniae, ________________, and S. aureus -patients exhibit increased severity of _______ infections that effect the _______ (enteroviruses) -recurrent _________ infections -usually appears around 6 months of age and 80% present with __________ and other sinopulmonary infections -B cells ________ negative -pre B cells in the ________ _________, but none in the periphery