Immunology Flashcards
IL 2 is produced primarily by _____
Helper T cells
What is the major growth factor for T lymphocytes (Interleukin ___)
IL2
______ binding to t cell receptors stimulates the secretion of IL2 and the expression of IL2 receptors
Antigen
IL2 promotes growth and differentiation of T and B cells as well as activates ____ and _____ .
Natural killer cells
Monocytes
What are IL2 anticancer effects as treatment for metastaticmelanoma and renal cell carcinoma
IL2 increases natural killer cell and T cell activity
Why is the H. Flu vaccine administered as a capsular polysaccharide from H. Flu conjugated to a tenanous toxoid
Polysacharides only elicit B cell responses which do not elicit memory resulting in short relative duration of immunity
Polysaccharide-protein conjugate vaccine ellicits a B and T cell response –> memory -> longer immunity
Why are polysacharide vaccintions not effective in children <2?
They have immature humoral immunity (polysaccharide capsule rovokes an antibody-mediated immune response)
T-cell dependent antigen stimulates which two effects that increase the efficacy of protein conjugated vaccine compared to polysaccharide capsule vaccines?
T cell dependent stimulation of B lymphotcytes
Production of memory B lymphocutes
Type I (alpha and beta) interferons are synthesized by most human cells in response to _____
Viral infections
Secrete alpha and beta type one interferons bind receptors on __________
Neighboring cells (paracrine and autocrine signaling)
Binding of alpha and beta interferons to interferon I receptors leads to the transcription of what enzymes?
Antiviral enzymes (halt protein synthesis): RNase and protein kinase R
Antiviral enzymes transcribed by alpha and beta interferon activity during viral infections become active only in the presence of ______
Double stranded RNA
Effect of alpha and beta interferons during viral infection:
Supress viral replication by haltingprotein synthesis
Promote apoptosis of infected cells
Each molecule of MHC class I protein consists of __________ and an associated beta 2- microglobulin
Single heavy chain
Each molecule of MHC class I consists of a single heavy chain and an associated _____________
Beta 2 microglobulin
Heavy chains are highly _______ which allows them to present a large variety of antigens
Polymorphic
Viral polypeptides are processed in the host cell and combined with MHC class I in the __________
Endoplasmic reticulum
Structural features of MHC class II include ____ and ______ polypeptide chains
Alpha and beta
MHC class ______ has alpha and beta polypeptide chains
II
MHC class I is found on the surface of what cell type
All nucleated cells
MHC class II is found on what cell type
Antigen presenting cells (B cells, macrophages, dendritic cells, langerhans cells
What type of antigens are presented by MHC class I
Virus and tumor proteins
Where are antigens that are presened on MHC class I molecules processed
Cytoplasm
What antigens are presented on MHC class II molecules
Bacteria
Where are antiges presented on MHC class II molecules processed
They are phagocyosed and digested by lysosomes within which antigen binds to MHC II
Antigen presentation by an MHC class I molecule results in
Apoptosis of hte presenting cell
MHC class I present endogenous antigens to ___ cells
Cytotoxic T cells (CD8)
How do reactive T lymphocytes appear differetly than normal T lymphocytes
reactive are larger
Abundunt cytoplasm
Scalloped edge
Reactive lymphocytes are activated, pathogen-specific _____ and ______that form in response to certain intracellular infections
Cytotoxic T cells
Natural killer cells
Reactive lymphocytes are associated to certain intracelullar infections such as HIV, CMV, and toxoplasmosis but are particularly linked to
Infectious mononucleosis (primary Epstein-Barr virus) (Reactive lymphocytosis is a diagnostic feature of infectious mononucleosis)
Reactive lymphocytes are effector cells that contain cytotoxic granules composed of ____ and _____
Perforin
Granzymes
Function of perforin
Creates holes in the infected cell’s membrane
Granzyme function
Enter the cytoplasm of infected cells and trigger cell death
History of recurren respiratory infections and dextrocardia suggest what diagnosis
Kartagener syndrome (primary ciliary dyskinesia (PCD))
Mode of inheritence for kartagener syndrome
Autosomal recessive
Eukaryotic flagella and ciliar are composed of central core known as the _______
Axoneme
The axoneme of flagella an motile cilia consists of a circular array of microtubule doublets surrounding 2 central microtubules called what kind of arrangement
9 + 2 arrangement
The axoneme of flagella and motile cilia is anchored to the cell by a _______
Basal body
Each microtubule doublet in cilia and flagella have A and B subunits that are connected to adjacent doublets via
Dynein arms
What is the function of dyenin arms?
Contain ATPase that generates energy to slide microtubules past each other –> ciliary movement
Failure of dyenin arm to develop normally can result in ______
Primary ciliary dyskinesia
Ankylosing spondylitis has increased production of what cytokines
Il-17
TNF alpha
Prostaglandins
Ankylosis sonylitis has increased risk with what HLA?
HLA-B27
Pain presentation of ankylosing spondylitis
Back and buttock pain that is relieved with exercise and worse at night
Clinical findings in ankylosing spondlitis
Redced chest expainsino, enthesitis (tenderness at tendon insertion sites), dactylitis (swelling of fingers and toes), anterior uveitis
What is “bridging syndesmophytes”? (A finding in ankylosing spondylitis)
Ossification at vertebral body margins (“bamboo spine”)
Where is ankylosing spondylitis thought to originate from? (Whats the cause)
The gut: defects in mucosal barrier and an abnormal intestinal microbiome –> inflammation
IL-17 mediates an inflammtory response via which cell type
Innate lymphoid cells and helper T cells (Th1, Th17)
IL-17 stimmulates production of which additional inflammatory factors
TNF alpha and prostaglandins
What is the effect of high IL-17, TNF-alpha, and prostaglandings in the joints of someone with ankylosing spondylitis?
Bony erosions and abnormal bone growth
Bone erosion –> subchondral sclerosis –> ankylosis (bony fusion
Treatment for ankylosing spondylitis
NSAIDS (inhibit prostaglandin formation)
Anti-TNF alpha agents (etanercept, infliximab)
Anti-IL-17 agents (secukinumab)
Neoantigens are displayed on MHC class ____ molecules and subsequently recognized by _____ cells
I
Cyotoxic T cells
Over expression of programmed death ligand 1 (PD-L1) on cancer cels surface binds PD-1 receptor on T cells to what result
Supresses T cells ability to induce apoptosis: “T cell exhaustion”
Pembrolizumab mechanism of action
Monoclonal antibody that blocks PD-1 (restores cytotoxic t cell response (disinhibition) in cancers that overepress PD-L1)
Cells and humoral components involved in type I hypersenstivity reactions:
IgE
Basophils
Mast cells
Humoral components and cellular components involved in type II hypersensitivity reactions
IgG and IgM autoantibodies Complement NK cells Eosinophils Neutrophils Macrophages
Goodpasture and autoimmune hemolytic anemia are examples of what type of hypersensitivity reaction?
Type II (cytotoxic)
What humoral and cellular components are involved in type III hypersenesitivity responses
Deposition of antibody-antigen complexes
Complement
Neutrophils
Serum sickness, PSGN, and lupus nephritis are examples of what type of hypersensitivity reaction
Type III (immune complex)
anaphylaxis and allergies are examples of what type of hypersensitivty reaction
Type I (immediate)
Type 4 hypersensitivity reactions include what humoral and cellular components
T Cells
Macrophages
(No humoral components)
Contact dermatitis and tuberculin skin test are examples of what type of hypersensitivity reaction
Type 4 (delayed type)
What changes occur on initial exposure to an allergen in a patient who will eventually develop an allergic response
Antibody class switching to IgE which bind IgE receptors on basophils (blood) and mast cells (tissues)
What changes does a second exposure to an allergen illicit
Allergen interacts with cell bound-specific IgE which crosslik and cause degranulation of mast cells
Major antibody for mucosal immunity:
IgA
Plasma cells synthesize IgA linked by ______
J chain
IgA dimers bind to ________ on basolateral surface of intestinal epihelial cells and undergo transcytosis.
Polymeric immunoglobulin receptor (pIgR)
As the linked IgA dimer is released into the intestinal lumen, a portion of pIgR remains attached to the antibody (called _______ )
Secretory component
Live attenuated vaccines generally produce a ________ immune response than killed vacines by acting as a persistent stimulus that better activates helper and cytotoxic T cells
Stronger
Live attenuated oral vaccine will have a significantly higher IgA response in the __________ than a inactivated injected vaccine
Oropharyngeal and intestinal mucosa
Increase in mucosal IgA offers immune protection where
At site of viral entry by inhibiting attachment to intestinal epithelial cells
Name for the live attenuated oral poliovirus vaccine
Sabin
Name for the inactivated poliovirus vaccine
Salk
In _______________ donor T cells from the graft migrate into host tissues where they recognize host MHC antigens and become sensitized —> CD4 and CD8 donor cell activation —> destruction
Graft versus host disease (GVHD)
Graft versus host disease is a condition that usually occurs after allogeneic bone marrow transplantation but can occur following transplantation of organs rich in ________
Lymphocytes (or transfusion of non irradiated blood)
Patients affected by GVDH are generally severely ______ which allows donor T cells to survive
Immunodeficient (due to primary disease process or result of immunosuppressive therapy)
What organs are most commonly affected by graft versus host disease
Skin (maculopapular rash, especially palms and soles of feet) GI tract (diarrhea, intestinal bleeding, abdominal pain) Liver (abnormal liver function tests)
Sialyl lewis X or PSGL-1 bind what on neutrophils to induce rolling in leukocyte accumulation
L-selectin
Selectins are involved in which phase of leukocyte accumulation
Rolling
Integrins (activated by chmokines) change to high affinity state in which phase of leukocytosis adhesion cascade
Activation
Neutrophils bcome firmlia attached to the endothelium via binding of ________ to ________ on endothelial cells
CD 18 beta 2 integrins (MAC-1 and LFA-1)
Intercellular adhesion molecule 1 (ICAM-1)
Transmigration of the nutrophils is accomplished by squeezing between the cells via integrin attachments and adherence to ______________
Platelet endothelial cell ahesion molecule 1 (PECAM-1)
In ____________ disease leukocytes cannot leave the vasculature to migrate into tissue under conditions of inflamation
Leukocyte adhesion deficiency (LAD)
LAD type 1 is the absence of _______
CD18
In LAD type 1, there is an absence of CD18 which leads ot inability to synthesize _________ , affecting tight adhesion, crawling, and transmigration
Beta 2 integrins: MAC-1 and LFA1
Clinical manisfestation of LAD type 1
Recurrent skin infections without pus formation
Delayed detachment of umbilical cord
Poor wound healing
LAD type 2 is due to impaired fucosylation of sialyated carbohydrates ligands which prevents binding to ______
Selectin
LAD 3 is due to impaired cytokine signaling which prevents ______ activation
Integrin
What in the HBV vaccine generates protective immunity against the virus?
Recombinant HBsAg
How are people with the HBV vaccine immune?
Patient will generate anti-HBs antibodies which bind circulating viral partcles and prevents attachment ot and penetration of hepatocytes
During sensitization to an allergen, the antigen is presented on MHC II which activates what cell type
Helper T cells
During sensitization to an allergen, helper T cells are activated by allergen antigen on MHC II and epithelium release of ______ and _______ to become a Th2 cell
IL-25 and IL-33
Th2 cells secrete what cytokines to induce B cell classs switching to IgE produciton
IL-4, IL-13
Which immune cells are responsible for the destruction of cells with decreased or absent MHC class I proteins on their surface
NK cells
Cells markers on NK cells
CD16 or CD56
Do NOT express CD 4, 8, or3
Do NK cells require the thymus for maturation?
No (present in athymic patients)
Do NK cels have antigen specific activities/require antigen for activation?
No
What cytokines activate NK cells
Interferon gamma and IL-12
Duing a parasitic infection, Th 2 induces eosinophil prolferation via release of what cytokine
IL-5
How are hemilinths destroyed by the immmune system?
Antibody dependent cell mediated cytotoxiity
IgG and igA antibodies coating the helminth bind the Fc receptors on eosinophil cell surface –> degranulation and release of cytotoxic proteins and reactive oxygen intermediates o destroy the paraste
What cyctotoxic protein is released from eosinophils
Major basic protein
What cell contributes to the late phase of a type 1 hypersensitivity reaction
Eosinophils (release prostaglandins, leukotrienes, and cytokines)
How does macrophage response to TB infection change over a few weeks once infected?
Initially the pathogen escapes phaolysosome s in alveoar macrophages
After a few weeks APCs start to display mycrobacterial antigens on MHC II and release IL-12 –> Th1 differentiation –> interferon gamma secretion –> macrophage activation –> fully maturephagolysosomes destroy intracellular bacteria and differentiat e into epitheliooid and langhans giant cells to surround extracellular bacteria forming a granuloma
What is released from APCs to differentiate naive CD4 cells into Th 1 cells
IL-12
What is released from Th1 cells to activate macrophages
Interferon gamma
How do granulomas limit myobacteria proliferation
Their acidic and hypoxic central environment limits proliferation (but usually does not eliminate the infection)
Tuberculin skin test is what type of hypersensitivity reacion
Delayed type/T-cell mediated
Why may some people have a negative tuberculin skin test if they were recently exposed to TB but a positive test a few weeks later
The cell mediated response takes several weeks to form
What is a Ranke complex
Calcified lower lobe nodule and ipsilateral hilar lymph node
Often seen in TB patients even when asymptomatic
Takes several months to form
What tranfusion reactions occur minutes to hours after transfusion
Allergic and acute hemolytic
What causes an allergic transfusion reaction
Preformed antibodies against blood product component
What causes an acute hemolytic transfusion reaction
ABO incompatibility (often clerical error)
How does an allergic transfusion reaction present
Anaphylaxis and urticaria within minutes-hours of transfusion
How does acute hemolytc transfusion reaction present
Fever, flank pain, hemoglobinuria, DIC, positive Coombs test minutes - hours after transfusion
How does a febrile nonhemolytic transfusion reaction present
Fever and chills hours after transfusion
What causes a febrile non hemolytic transfusion reaction
Cytokine accumulation during blood storage
How does a transfusion-related acut lung injury present following a blood transfusion
Respiratory distress and bilateral pulmonary edema hours after trnsfusion
How does delayed hemolytic transfusion reaction present
Often asymptomatic, labratory evidence of hemolytic anemia, and + Coombs test days-weeks following blood transfusion
What is the cause of transfusion related acute lung injury
Donor antileukocyte antibodies
What is the cause of delayed hemolytic transfusion reaction
Anamnestic antibody response
What is required for a patient to have an anamnestic response (delayed hemolytic transfusion reaction) to a blood transfusion
A previous exposure to a foreign minor red blood cell antigen (non-ABO) such as pregnancy, prior blood transfusion, or intravenous drug use
Activation of Fas receptor leads to what?
Extrinsic pathway of apoptosis
Upon binding Fas ligand, Fas receptors trimerize to allow their death domains to form a binding site for ______
Fas-associated death domain
Receptor bound Fas associated death domain (FADD) stimulated activation of __________
Initiator capsoses 8 and 10
Initiation caspases 8 and 10 begin an activaion cascade culminating in the activation of _________
Executioner caspases 3 and 6
Executioner caspases 3 and 6 initiate terminal processesof apoptosis such as:
Cleavage of DNA
Fragmentation of the nucleus
Organelle autodigestion
Plasma membrane blebbing
What cells express Fas receptors
T lymphocytes
Activation-induced cell death is apoptosis of T lymphocytes due to constant presence of what stimulating self-antigens
Fas L
Mutations involving Fas or FasL result in excessive accumulation of ____________ and development of autoimmune diseases such as systemic lupus erythematosus
Autoreactive T-cells
Is parapneumonic effusion fluid in the pleural space exudative or transudative
Exudative
Why do infections and inflammtory tissue injuries cause pleural effusion
They increase vascular permeability (allows protein rich exudates to cross)
What is the most potent chemotactic eicosanoid
Leukotriene B4
Which leukotrienes cause bronchospasms and increas bronchial mucus secretion, playing a large role in asthma pathogenesis
LTC4, LTD4, LTE4
5-HETE (leukotriene precursur), C5a, and IL-8 are all important __________ agents
Chemotactic
What type of necrosis is seen in TB
Granulomas with caseating necrosis
In TB, granuloma with caseating necrosis consist of what cells
Large epithelioid macrophages
The most specific cell surface marker of the monocyte-macrophage cell is _______, which binds to bacterial lipopolysaccharide
CD14
The most specific cell surface marker of the monocyte-macrophage cell lineage is CD14, which binds to bacterial _________
Lipopolysaccharide
The caseating granulomas of tuberculosis are almost alway surrounded by large epitheliod macrophages with __________ cytoplasm
Pale pink granular
Classic features of melanoma: (5)
Asymmetry Border irregularity Color varegation Diameter > 6 mm Evolution over time (A, B, C, D, E)
What is color variegation (common feature of melanoma)
Different colors representing different areas of activity within the tumor
In color variegation in melanoma, what do red areas indicate
Vessel ectasia (dilation) and local inflamaiton
In color variegation in melanoma, what do brown or black areas indicate
Flared areas along the border due to advancing, neoplastic melanocytes
In color variegation in melanoma, what do white and gray areas indicate
Cytotoxic lymphocytes recognize tumor antigens (melan-A) and induce apoptosis –> malignant melanocyte regression
Pembrolizumab mechanism of action
Programmed cell death receptor 1 inhibitor (PD-1 inhibitor)
Tryptase is an enzyme that is relatively specific to _____ cells
Mast
Elevated serum levels of tryptase are oten used to support clinical diagnosis of__________
Anaphylaxis
What is the receptor found on mast cells and basophils that normally binds the Fc portion of circulating IgE, coating the cell with various antigen specific IgE molecules
High affinity IgE receptor (Fc epsillon RI)
Crosslinking of multiple membrane bound IgE antibodies by a multivalent antigen results in ____________, causing degranulation and the release of preformed mediators that initiate an allergic response
Aggregation of the high-affinity IgE receptor
IgE class switching is initiated by ____ and _____ which is released by the Th2 cells
IL-4, IL-13
IgE class switching is initiated by IL-4 and IL-13 which are released from which cells
Th2
Cell mediated adaptive immunity (targetting intracellular pathogens) and type IV (delayed type) hypersensitivity reactions mainly involve Th___ cells
Th1
Excess of what cell type my underli the pathogenesis of asthma
Th2 (relative to Th1)
Th2 secretes IL- 5 which activates _____
Eosinophils
Th2 cells release ____ which activates eosinophils
IL-5
___ cells release IL-5 which activates eosinophils
Th2
_______ is a condition with a mutation in the bruton tyrosine kinase gene which casuses failure of bone marrow pre-B cells to develop into mature B cells
X-linked agammaglobulinemia (XLA)
X-linked agammaglobulinemia is a mutation in ________
Bruton tyrosine kinsae gene
Patients with X-linked agammagobulinemia have low or absent ____ in blood and lymphoid tissues and what other serum findin
B cells
Pan-hypogammaglobulinemia (very low IgG, IgM, and IgA)
Patients with x-linked agammaglobulinemia have increased risk for infections with ______ bacteria, and viral and parasitic infections such as enteroviruses and Giardia lamblia de to absence of opsonizing nd neutrolizing antibodies
Pyogenic (encapsulated)
B cell surface protein cell markers
CD19
CD20
CD21
B lymphocytes aggregate in the cortex of lymph nodes to form lymphoid ______
Follicles
In the lymph node: ______ follicles are dense and dormant.
Primary
Secondary follicles have a plae __________ containing proliferating B cells in response to antigenic stimulus
Germinal center
Secondary follicles have a plae germinal center containing proliferating ______ cells in response to an antigeenic stimulus
B
Maternally derived antibodies wane how long after birth?
3-6 months
Superantigens interact with __________ on antigen presenting cells (macrophages) and with the _____ region of TCR
MHC
Variable
Superantigens interact with MHC molecules on _____ and variable region on _____ receptors
Antigen presenting cells (ie macrophages)
T-cell
Widespread activation of T lymphocytes by superantigens is responsible for release of _____ from T cells and _____ and ____ from macrophages which causes capillary lek, circulatory collape, hypotension, shock, fever, skin findings, and multi organ failure
IL-2
IL-1 and tumor necrosis factor
A few weeks after infection with TB, ____ cells release interferon gamma which activated macrophages
Helper T cells
What is required, and happen a few weeks after a TB infection, inorder for helper T cells to release interferon gamma and activate amcrophages
Infected macrophages in draining lymph system display mycobacterial antigens on MCH II
CD4 cells release ____ that activates macrophages and increases their ability to kill phagocytosed organisms
Interferon gamma
Activated macrophagescan differentiate into _____ and coalesce into multinucleated langhas giant cells that wall of mycobacteria withing granuloma
Epithelioid histocytes
Activated macrophages can differentiate into epithelioid histpcytes and coalesce into __________ that wall off myobacteria within granulomas
Multinucleated langhans giant cells
The center of caseating granulomas is ____ and ____ which causes it to appear acellular, necrotic, and “cheese like” (caseating)
Acidic
Hypoxic
Horse-shoe shaped, fused, activated macrophages = _______
Multinucleated Langhans giant cells
What type of burn has erythema that blanches without blistering
Superficial burn (1st degree)
Superficial (1st degree) burns damage only the ______
Epidermis
Superficial partial-thickness burns (2nd degree) damage the __________
Epidermis and upper dermis
Deep partial-thickness burns (2nd degree) damage the
Epidermis and most of the dermis
Full-thickness burns (3rd and 4th degree) damage ________
Entire dermis (And may extend into fat, muscle, and/or bone)
Release of _____ from _____ cells results in blanching erythema that extends to the area surounding the initial burn
Histamine
Mast cells
Damage to venules can resultin fluid extravasation through gaps between injured _________ cells –> blister
Venule endothelial cells
A blister is formed from a collection of serous fluid between the ___ and ____-
Dermis and epidermis
What is the earliest morphologic change that occurs after a superficial thermal burn
Erythema due to release of preformed mediators (histamine) from mast cells
Clostridium tetani poduces an exotoxin (tetanospasmin/ tetanus toxin). It travels by retrograde axonal transport through LMN and acts on the anterior horn cells to block _______
Inhibitory neurotransmission
Opisthotonos
Limb spasms
Hyperextension of back and neck
Due to blocked inhibitory neurtransmission from tetanus
What type of vaccine is tetanus vaccine
Tetanus toxoid vaccine (formaldehyde-inactivated tetanus toxin)
The tetanus toxoid vaccine (a formaldehyde inactivated tetanus toxin) stimulates ______ response against tetanus toxoid
Humoral antibody response
The tetanus immunization with an inactivated toxoid triggers production of antitoxin antibodies: _____ immunity
Active
Most common systemic vaculitis in children that presents with palpable purpura over buttocks and thighs
Henoch-Schonlein purpura (HSP)
Henoch-schonlein purpura (HSP) is caused by circulating _______
IgA-antigen immune complexes
What type of hypersensitivity reaction is henoc-schonlein purpura (HSP)
Type III (immune complex)
How does Henoch-schonleini purpura (HSP) cause hematuria
Deposition of immune complexes in renl mesangium
Wheal and flare lesions usually result from what type of hypersensitivity reactions
Type I
Sarcoidosis will have what finding on lung biospy
Non caseating granulomas
Non caseating granulomas are characterized by a central collection of tightly clustered _________ with abundant pink cytoplasm surrounded by a rm of mononuclear cells
Epithelioid macrophages
Sarcoidosis is thought to result from a dysregulated _____ immune respponse to an unidentified antigen which causes the formation of granulomas
Cell mediated
Cell mediated immunity is stimulated by _____ from antigen presenting cells which stimulate CD4 cells to differentiate into ____ cells
IL-12
Th1
Th1 cells release ___ which stimulates the autocrine proliferation of Th1 cells
IL-2
Th1 cells secrete _______ which activated macrophages and promotes granuloma formation
Interferon gamma
Activated macrophages and T cells produce _______ which assists in leukocyte recruitment and granuloma maintenance
Tumor necrosis factor
Antigen presenting cells present extracellular antigens on MHC class ___
II
After phagocytosis or endocytosis, proteins are degraded in acidified _____
Lysosomes
Phagocytosed or endocytosed proteins are degraded in lysosomes and loaded onto MHC class ___
II
Proteasomes degrade proteins then the peptide fragments are sent to ______ where they are attached to MHC class I
ER
Acute rejection most often occurs within weeks or up to 6 months after transplant and is predominantly cell- mediated, involving sensitization of __________ against ________
Host T lymphocytes
Donor MHC antigens
What cells are distinguished by presence of abundant basophilic cytoplasm, perinuclear paleness (large Golgi apparatus), and nucelei with “clock face” (peripheral) chromatin)
Plasma cells
Presence of >10% plasma cells in the bone marrow raises strong suspicion for ____________
Multiple myeloma
In multiple myeloma, neoplastic _____ cells crowd the bone marrow leading to impaired hematopoiesis
Plasma
People with multiple myeloma have limitted generation of targeted immunoglobins but have high levels of circulating ________ which does not provide immunity against diverse range of pathogens
Monoclonal immunoglobulin
Multiple myeloma is associated with renal insufficiency due to clogging of tubules with _________
Immunoglobulin light chains
HBsAg persisting over 6 months indicates ____
Chronic hepetitis B infection
A patient wih a traumatic ocular injury later developed a granulomatous inflammation of the contralateral eye. What condition is this
Sympathetic ophthalmia
Sympathetic opthalmia occurs when the contralateral eye of a traumatic ocular injury develops granulomatous inflammation due to robust ____ response to previously sequestered antigens in the eye
T cell
In order to limit potential organ damage that may result from robust inflammatory response, inflammaiton is inhibited by multiple mechanisms in certain anatomic sites. What is this called
Immune privilege
What may be released following traumatic eye injury (inherent immune privilege zone) causing immune response
Previously sequestered antigens that T cells recognize as foreign
The _______ of the Fc portion of the heavy immunoglobulin chains represents the site that binds to the Fc receptors on neutrophils and macrophages
Carboxy terminal
The carboxy terminal of the Fc portion of the _____ immunoglobulin chains represents the site that binds the Fc receptors on the neutrophils an macrophages
Heavy
Early phase of type I hypersensitivity reaction happens minutes after an exposure and presents as ____
Dermal edema and erythema(wheal and flare reaction) due to vasodition and increased capillary permeability
Late pase of type 1 hypersensitivity reaction presents as _____ , 2-10 hours after the early phase reaction
Indurated lesion
The late phase of a type I hypersensitivity reaction is caused by type 2 helper T cells releasing cytokines that activate eosinophils which release ______, causing tissue damage
Catioinic proteins (major basic protein, eosinophil peroxidase)
Following traumatic eye injury, granulomatous inflamation of both the injured and noninjured eyes is a condition known as ______
Sympathetic opthalmia
Sympatheticopthlmia occurs when there is a robust _______ response to previously sequestere antigens in the eye, an area that displays immune privilege
T - cell
Bradykinin is a potent vasodilator that ultimately increases vascular permeability and can cause what potentially fatal adverse effect?
Angioedema
What can present as tongue, lips, or eyelid swelling and less frequently, laryngeal edema and difficulty breathing and can be exacerbated by ACE inhibitors
Angioedema
_________ is a condition resulting from decreased expression of complement inactivating proteins on the surface of red blood cells–> increased formation of MAC —> anemia due to complement-mediate hemolysis
Paroxysmal nocturnal hemogobinuria
Treatment for paroxysmal nocturnal hemoglobinuria
Monoclonal antbody (exulizumab) to a terminal complement component (ie. C5) which inhibits formation of MAC
Inhibition of MAC formation from eculizumab monoclonal antibody treatment for example results in loss of rapidcomplement -mediated killing of gram negative bacteria making patients espcially at risk to ______ infection
Neisseri meningitidis
Mechanism of action for etanercept in RA treatment
Tumor necrosis factor alpha inhibitor: fusion protein that links TNF alpha receptor to Fc component of hummon immunogloblin G1 (acts as decoy receptor)
Suffix “mad” meaning
Monoclonal antibody
Suffix “cept” meaning
Receptor molecule
suffix “nib” meaning
Kinase inhibitor
Wound healing requires formation of grunaltion tissue which is impaired by inflammation, therefore, release of ant-inflammatory cytokines such as ______ from macrophages and regulatory T cells supresses inflamation response and facilitates fibroblast proliferation and reepithelialization of the wound
IL-10
In patients with diabetes mellitus, constitutively elevatd blood glucose increases inflammation by stimulating the release of proinflammatory cytokines and _______ from neutrophiles
Reactive oxygen species
Elevated glucose leads to marked decrease in ____ production which contributes to an incerased susceptibility for chronic non healing wounds and ulcers
IL-10
In systemic lupus erythematosus, hematologic abnormalities are due to what type of hypersenitivity reaction while lupus nephritis is due to type ____ hypersensitivity reaction
Type I: autoantibodies against blood cell antigens –> pacytopenia
Type III: imune complex deposition –> lupus nephritis
A ________ uses specific antibodies and a fixed quantity of radiolabeled antigen to determine the amount of antigen present in an unknown sample
Radioimmunoassay
What is the function of TH1 cells
Activate macrophages and CD8 T cells
What immunity are Th1 cells involved in
Cell mediated
What cytokines are released from Th1 cells
IL-2. IFN-gamma, and lymphotoin beta
What immunity are Th2 cells involved in
Humoral
What are the roles of Th2 cells
Activate B cells and promote class switching
Cytokines released from TH2 cells
IL-4, 5, 10, and 13
Th1 cell diferentiaion is stimulated by a macrophage presenting an antigen and secreting ______
IL-12
Patients with IL-12 receptor deficiency are sysceptible to severe mycobacterial infections due to inability to mount a strong cell-mediated granulomatous immune response, therefore they require treatment with _____
IFN-gamma
Acute hemolytic transfusion reactions are examples of what type of hypersensitivity reaction
Type II (antibody-mediated)
The polysaccharide vaccine for strep pneumoniae covers how many serotypes
23
The conjugate vaccine for strep pneumoniae covers how many serotypes
13
Why is the 13 valend pneumococcal vaccine given to children instead of the 23 valent vaccine
The23 valent is polysaccharide vaccine and children under 2 have immature humoral anitbody response , also the antibody levels decline over 5 years in the 23 valent (bc no memory cells)
The 13 valent is a conjugate vaccine and allows for the development of memory B cells
What is the term for age-related immune decline
Immunosenescence
Why does immunosenscence occur
Loss of etlomere length during aging –> decreased produciton of rapidly providing cells such as naive B and T lymphocytes
Wht patients are at risk for a life threating infection of enterovirus
Infants with primary humoral immunodeficiency (ie x linked agammaglobulinemia) (enterovirus usually self limited)
Most activated B cells migrate to _______located in the lymph node cortex where they form germinal centers that are the site of B cell proliferation during the immune response
Lymphoid follicles
What is the main serum immunoglobulin of the secondary response to an antigen
IgG
Why do approximately 25% of patients with active TB have false negative TST test
Impaired lymphocyte response, immunocompromise (ie HIV), improper injection , or recent infection (it takes 8 wks ofo infection for cell mediated response to form)
Activation of complement by IgM prior to antigen binding is prevented how?
The C1 binding site is hidden while unbound IgM is circulating in its planar form
Adalimumab is a recombinant human IgG that binds ______ to prevent it from associating with cell surface receptors, thus blockng its pro-inflammatory effects, making it useful in treating Crohns, psoriasis, and rheumatoid arthritis
TNF alpa
Use of adalimumab can induce formation of _____ which reduces activity and increases drug clearance. Patients will show declining effectiveness of the treament
Antidrug antibodies (ADAs)
A positive C-ANCA vasculitis that primarily attaacks the upper/lower respiratory tracts, kidneys, and skin is what ?
Granulomatosis with polyangitis
Rituximab mechanism of action
Deplete B cell populations by binding CD20 –> Fc receptor mediated B cell cytotoxicity
hereditary angioedema is characterized by a deficiency or dysfunction of_______
C1 inhibitor
poor C1 inhibitor function leads to elevated _______
bradykinin
elevated brakykinin leads to what physical exam finding
edema (increases vasodilation and vascular permeability)
Complement level testing in hereditary angioedema will show ____
low C4
in the absence of C1 inhibitor, unregulated C1 activation leads to ____
unchecked cleavage of C4
3 characteristic findings of wiskott-aldrich syndrome
eczema
recurrent infections
thrombocytopenia
3 characteristic features of ataxia-telangiectasia
ataxia
telangiectasia
sinopulmonary infections
3 characteristic features of chediak higashi syndrome
oculocutaneous albinism
pyrogening infections
progressive neurologic dysfunction
2 characteristic features of chronic granulomatous disease
severe bacterial and fungal infections
granuloma formation
3 characteristic features of DiGeorge syndrome
congenital heart disease
dysmorphic facies
hypocalcemia
3 characteristiv features of severe comnined immunodeficiency
severe bacterial and viral infections in infancy
chronic diarrhea
mucoccutaneous candidiasis
name a characteristic feature of terminal complement deficiency
recurrent neisseria infections
name 3 characteristic features of wiskott aldrich syndrome
reccurent infections that worsen with age
easy bleeding
ecxema
mode of inheritence of wiskott aldrich syndrome
X linked recessive
wiskott aldrich syndrome is caused by a mutation in cytoskeleton proteins that are critical for normal cell structure and cell to cell interactions required for activation of _______
hematologic cells
in patients with wiskott aldrich syndrome _____ are abnormally shaped and deficient leading to petechiae, purpura, hematemesis, and epistaxis
platelets
a deficiency of B cells such a in wiskott aldrich syndrome results in recurrent pyogenic infections due to inability to mount a humoral immune response against organisms with ______
polysaccharide capsule (neisseria meningitidis, haemophilus influenzae, strep pneumo)
what is the treatment for wiskot aldrich syndrome
transplantation with HLA matched bone marrow
severe combined immunodeficiency (SCID) is characterized by defective ____ cell development which causes ____ cell dysfunction
T
B
severe combined immunodeficiency mode of inheritence
x linked recessive and autosomal recessive
what is the treatment for severe combined immunodeficiency
stem cell transplant
the candidal antigen skin test used to determine the presence of cellular immunity via delayed type hypersensitivity reaction involves what cell types
macrophages (present ag)
CD4 t cells
CD8 t cells
CD4 and CD8 cells both secrete _____ which stimulates phagocytosis of candida by macrophages
interferon gamma
failure to generate a response to the candida skin test for example is reffered to as
anergy
describe the morphology in a hyperacute transplant rejection
gross mottling and cyanosis
arterial fibrinoid necrosis and capillary thrombotic occlusion
defective signaling between CD4 T cells and B cells is consistent with what diagnosis which presents as recurrent infections and failure to thrive
hyperimmunoglobulin M syndrome
class switching occurs by splicing out DNA coding for different types of the _____ region
heavy chain constant region
class switching occurs when an activated CD4 t cells’ ______ binds _____ on B cell
CD40L
CD40
adenosine deaminase converts adenosine into _______
inosine
if adenosine deaminase in inhibited, metabolism of deoxyadenosine through an alternate pathway is phosphorylated into deoxyadenosine triphosphate which is a _______
toxic metabolite
build up of deoxyadenosine triphosphate activates the caspase system and inhibits _____________ which depletes cells of DNA precursors
ribonucleotide reductase
what cells are highly mitotically active and thus highly sensitive to inhibition of adenosine deaminase
lymphocytes
ADA inhibitors are best for treating ______ cancers
lymphocyte derived (hairy cell leukemia)
gene mutations in ADA lead to the autosomal recessive disease _________
sever combined immunodeficiency
numerous cytokines are released in sepsis, resulting in widespread systemic inflammation. one of the most important mediators of sepsis is _____
tumor necrosis factor
cytokines responsible for inducing systemic inflamatory response in spesis inclue TNF alpha, _______, and _______
iL-1
IL-6
foreign bodies can elicit a ________ response, seen clinically as a tender, eythematous, borwn or purple papule, nodule or plaque
granulomatous
what form of immunoglobins form the immune complexes that deposit in the glomerular basement membrane in PSGN
IgG
what characteristic finding is seen on electron microscopy in PSGN
electron dense subepithelial humps
what type of hypersensitivity reaction is PSGN
type III
history of recurrent pneumonia infections, a diagnosis of celiac disease and anaphylactic reaction during transfusions is suggestive of what primary immunodeficiency
slelective IgA deficiency
why do patients with selective IgA deficiency have anyphylaxis during blood transfusions
their IgE antibodies with detect IgA from the transfused blood as foreign
________ selsction is the process by which only T cells expressing a TCR that is able to bind self MHC are allowed to survive
positive
during positive selection t cells interact with ________ cells expressing self MHC
thymic cortical epithelial cells
which happens first: positive or negative selection
positive
_____ selection is the proccess by which T cells possessing TCRs that bind with high affinity to self antigen or self MHCclass I or II are eliminated by apoptosis
negative
during negative selection, T cells interact with ______ cells
thymic medullary epithelial and dendritic cells
after ____ ocurs, subsequent pregnancies with Rh-positive fetuses with be at risk for hemolytic disease of the newborn
Rh alloimmunization (formation of B lymphocytes in the mother due to previous exposure)
what can be administered to pregnant mothers to avoid Rh alloimunizaiton
anti- Rh(D) immunoglobulin: a poluclonal antibody consisting of IgG ant-D antibodies
Sirolimus prevents T cell growth and proliferation by inhibiting _______ that leads to interuption in IL-2 signal trnasduction
mTOR (by binding FKbinding protein)
calcineurin inhibitors (tacrolimus, cyclosporine) are commonly used immunisoppression medications that function by blocking the translocation of NFAT resulting in reduced transcription of ______
IL-2
what do normal numbers of CD3 cells in flow cytrometry indicate
normal levels of circulating T cells
what do normal levels of CD19 cells in flow cytrometry indicate
normale levels of circulating B cells
HLA- ____, HLA-____, and HLA-____ genes encode MHC class II molecules on APC
DP
DQ
DR
HLA-___, HLA-____ and HLA-_____ genes encode MHC class I mo
A
B
C
recurring skin and mucosal infections with absence of purulences suggest what immune feficiency disease
leukocyte adhesion deficiency (LAD)
leukocyte adhesion deficiency is characterized by absence of ______
CD18
CD18 is necessary for the formation of _____ which are essetial for leukocyte adhesion to endothelial surfaces and migration to peripheral tissues in response to infection or inflammation
integrins
what is a single-celled buddy yeast with pseufohyphae and forms “germ tube” hyphal structures when grown in nutritionally rich serum
candidemia
how is superficial candida infection prevented by the the imune system
T lymphocytes (in particular helper T cells)
how is hematogenous spread of candida prevented by the immune system
neutrophils
which joint is spared in RA?
DIP
In RA, B CD4 T cells induce B cells to synthesize rheumatoid factor and _____
anti-citrullinated protein antibodies
rheumatoid factor is an antibody (usually IgM) specific for _______
Fc component of IgG
why do mothers with blood types A or B rarely have children with hemolytic disease of fetus and newborn
maternal antibodies (anti A or anti B) are of IgM type and cannot cross placenta
mothers with blood type O produce _____ antibodies (anti-A and anti B) which cause fetal hemolysis more commonly than in mothers who have type A or B blood
IgG
poison ivy dermatitis is what type of hypersensitivity reaction
type IV (delayed)
On flow cytrometric analysis of a sample of fetal thymus, a certain population of cells is identified that is positive for both CD4 and CD8 cell surface antiges. These cells are best characterized as ______
Immature cortical T lymphocytes
Pro-t cells arrive at the thymus as ______ cells: cells that lack both CD4 and CD8 antigens
Double negative
After TCR gene rearrangement of the beta chain genes, production of both the CD4 and CD8 antigens are simultaneously expressed , and these cells are referred to as _________ or immature T lymphocytes
Double positive T cells
Positive selection of T cells occurs in the of thymus
Cortex
Negative selection of T cells occurs in the _____ of thymus
Medulla
Which chain on the TCR undergoes rearrangement after CD4 and CD8 cell markers are expressed
Alpha chain
How is does IL-10 produce anti inflammatory effects
Reduces il-2 and IFN-gamma release from TH1 cells
Decreased MHC class II expression
Inhibits activated dendritic cells and macrophages
Macrophages infected with TB present mycobacterial antigens to CD4 cells and secrete IL-12 to induce activated which type of helper cells
TH1
Th1 cells secrete ____ to activate macrophages
IFN gamma
Neutrophil counts increase following administration of corticosteroid due to ________
Demargination (nutrophils previously attached to the vessel wall)
Which white blood cell count is acutely increased following administration of high dose prednisone shot
Neutrophils
Inactivated influenza vaccination stimulate formation of neutralizing antibodies against the ______ antigen of included strains
Hemagglutinin
In the influenza virus, Hemagglutinin attaches to sialic acid receptors on host respiratory cells inorder to _____
Viral entry into cells
Inactivated (killed or component) viral vaccines primarily generate a humoral immune respnose against extracellular viral antigens, preventing _____
Viral entry into the cell
Live attenuated viral vaccines can generate strong cell mediated immune response that _________ in addition to providing humoral immunity
Can kill virally infected cells
Ankylosing spondylitis is associated with a specific _______ serotype
Human leukocyte antigen cass II
What allele has a higher incidence in seronegative spondyloarthropathies than the general population
HLA B27
_________ results form destruction of fetal red blood cells by maternal antibodies directed against fetal erythrocyte antigens
Hemolytic disease of the newborn (erythroblastosis fetalis
What antibodies are involved in erythroblastosis fetalis
Maternal anti-Rh(D) IgG antibodies
Indication of a positive Coombs test
Autoimmune hemolysis
In chronic renal allograft rejection, Chronic cell mediated and antibody mediated response against donor antigens leads to obliteratie vascular wall thickening, tubular atrophy, and __________
Interstitial fibrosis
Macrophages produce ______ as a chemokine to induce chemotaxis and phagocytosis in neutrophils
IL-8
Pus consists of a thin, protein rich fluid, known as liquor puris, and dead leukocytes. primarily which leukocyte?
Neutrophils
In normal T cells, TCR activation –> _____ activation –> NFAT activation –> IL-2 gene trancription
Calcineurin
Calcineurin activates NFAT which stimulates ____ production which promotes gorwth and differentiation of T cells
IL-2
Cyclosporine and tacrolimus are used as immunosuppressants in transplant patients to inhibit _____ activation
Calcineurin
Patient with deficiencies in _______ often experience recurrent infections by Neisseria species
Complement factors that form the membrane attack complex (MAC)
A 3 month old girl is brought to the ED for fever, irritability, and vomitting for past 2 days. On exam she is ill-looking, lethargic, and febriel. Blood cultures grow TB. One of her brother died from disseminated mycobacterial infection during infancy. Impairment of which of the following protective mechanisms is most likely contributing to this patients infection: Antibody production Complement production Interferon signaling Isotype switching Leukocyte adhesion
Interferon signaling
If a patient’s neutrophils fail to turn blue on nitroblue tetazolium testing, what disease do they have
Chronic granulomatous disease
Mode of inheritance chronic granulomatous disease
X-linked
Inactivain mutations affecting what are present in chronic graulomatous disease
NADPH oxidase
NADPH oxidase is present in activated phagocytes and is responsible for producing ______ and activating __________
Reactive oxygen species
Granule proteases
Patients with chronic granulmatous disease are at risk for recurrent infections with _____ positive organisms because they can destroy the hydrogen peroxide produced by their own metabolic activity
Catalase
When cellular proteins (or pathogen derived proteins) are degraded by proteasomes, some of the resulting peptide fragments are transported into the endoplasmic reticulum by _____ proteins adn loaded onto ______ molecules
TAP (transporter associated with antigen processing) MHC class I
Acute cardiac transplant rejection shows endomyocardial biopsy with dense _____ infiltrate and cardiac myocyte damage
Mononuclear lymphocytic infiltrate
____ encodes a transcriptional regulator that converts activated CD4 cells into regulatory T cells, a population of T lymphocytes that inhibit immune activation
FOXP3
FOXP3 encodes a transcriptional regulator that coverts activated CD4 cells into ______
Regulatory T cells
Expression of FOXP3 drives the production of ____ which inhibits macrophage function, blocks inflammatory cytokine releases by CD4 cells, and downregulates expression of MHC cls II on APCs
IL 10
FOXP3 expression drives the production of ____ which inhibits B lymphocyte proliferation/activation and promotes Treg differentiation
TGF beta
FOXP3 expression drievs the production of ___ which binds with high affinity to CD80/86 on APCs making it less availible to activate T cells
CTLA-4
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, and X linked transmission) is a genetic disorder that is due to a mutation in _____
FOXP3
Fluticasone drug class
Glucocorticd
How are intranasal glucocorticoids (fluticasone) helpful in treating allergic rhinitis
Inhibit transcription of genes that encode for inflammatry mediators –> suppress function of all leukocyte cell lines
Glucocorticoids decrease tissue production of proinflammatory prostaglandins and leukotrienes through the inhibition of ____
Phospholipase A2
Glucocorticoids decrease synthesis of almost all proinflammatory cytokines and increase what anti inflammatory cytokine
IL 10
What effect do glucocorticoids have on eosinophils, T cells,and monocytes, perhaps by decreasing Bcl-2 expression
Increase apoptosis
Most immunotherapy regimens use a fragment of the immunoglobuline with 1 valence (binding) site rather than the full immunoglobulin with 2 valence sites, because fragments are significantly smaller than the full immunoglobin, what function of the drug is improved
Improved tissue/tumor penetration and medication pharmakinetics
Antigen binding fragments (Fab) contain a variable domain and the first constant region of a heavy and light chain. Beause they do not contain a ___ region, they do not activate complement or trigger phafgocytosis
Fc
Why are Fab fragments no generally used in applications that require cell death such as cancer immunotherapy
Fab fragments lack Fc portion and do not activate coplement or trigger phagocytosis
List the required components of classical pathway of complement
C1 complex (C1q,r,s)
Fc portion of an IgM or IgG antibody that is bound to an antigen
C4
C2
List the required components of the lectin pathway of the complement cascade
Host pattern recofnition receptors bind carbohydrates produced only by foreign pathogens
Binding produces proteases
C4
C2
List the requirements of the alternative pathway of the complement cascade
Autoactivated C3b
Factor B
Factor D
Classical complement pathway activation with show high, low, or normal levels of the following: C4, C3, factor B
C4: low
C3: low
Factor B: normal
What are autlogous donor cells?
Cells obtained from the patient
What are allogenenic donor cells
Cells obtained from a related or an unrelated donor
A patient who has a history of ebstein barr virus that undergoes hematologic stem cell transplantation is at risk for what?
EBV reactivation
A patient who develops erythema and pruritus on the scalp, face and neck 2 days after reexposer to hair dye is likely experiencing what type of reaction
Allergic contact dermatitis (type iv, delayed-type, hypersensitivity reaction)
In the sensitization phase of allergic contact dermatitis (type IV sensitivity), cutaneous ____ cells take up haptens and present hapten-peptide complexes to CD4 and CD8 cells in lymph nodes
Langerhans cells
In the 2nd phase of contact dermititis, eicitation, what are the main effector cells
CD8
2 concerns following a vaccination are vasovagal syncope and anaphylaxis. How can they be differentiated?
Vasovagal: palor, absent respiratory symptoms, bradycardia
Anaphylaxis: urticaria/flushing, upper airway edema/bronchospasm, tachycardia
