Immunology Exam 4 Flashcards
Primary immunodeficiency disorders are caused by defects in the humoral immunity that include _________ & _________.
Complement
&
antibodies (B cells)
Primary immunodeficiency disorders are caused by defects in components of cellular immunity that includes _________ & ________.
T cells
&
Phagocytes
Phagocytes and complement are a part of what type of immunity?
Natural Immunity
T cells and antibodies (B cells) are a part of what type of immunity?
Acquired immunity
Immunodeficiency disorders that are X-linked affect primarily what gender?
Males
What is the primary symptom present with patients that have immunodeficiency disorders?
Recurrent infections
This B cell deficiency causes pyogenic bacterial infections - especially in the upper and lower respiratory tract.
-There is not enough or any production of antibodies to specific antigens.
Agammaglobulinemia
Immunoglobulin blood levels vary with age in normal individuals.
At birth we have low levels of ___ & ___ but adult levels of ___ because they come from the mom.
Low levels of IgA and IgM
adult levels of IgG that cross the placenta from mom
Immunoglobulin blood levels vary with age in normal individuals.
At 2-3 months, what happens to IgG?
IgG drops as maternal antibodies are metabolized
What immunodeficiency disorder usually corrects itself by 9-15 months of age?
Transient Hypogammaglobulinemia of Infancy
This immunodeficiency disorder is X-linked causing it to be seen almost exclusively in males. Development is blocked at the pro-B-cell stage. The blocked development causes no antibodies to be made.
X-linked Bruton’s Agammaglobulinemia
Cause of X-linked Bruton’s Agammaglobulinemia
Deficiency of enzyme Bruton’s tyrosine kinase
Deficiency of enzyme Bruton’s tyrosine kinase results in a failure of what not being added to heavy chain rearrangement?
Variable gene
With this immunodeficiency disorder patients may have recurrent otitis and areas of cellulitis in the diaper area. Pseudomonas aeruginosa and Staphylococcus aureus may be isolated from the skin lesions.
X-linked Bruton’s Agammaglobulinemia
What is the most common primary immunodeficiency?
IgA Deficiency
TRUE or FALSE:
Most patients with IgA deficiency are asymptomatic
TRUE
How is IgA deficiency typically discovered?
A patient with IgA deficiency forms Anti-IgA antibodies that cause anaphylaxis following a blood transfusion
What immunodeficiency is a result of having a normal number of mature B cells but they cannot differentiate into plasma cells for a variety of reasons?
Common Variable Immunodeficiency (CVI)
The following are manifestations of which immunodeficiency:
- Malabsorption
- Diarrhea
- Malignancies
- Autoimmune disorders
Common Variable Immunodeficiency
(CVI)
A patient between the ages 20 & 30 that has a low serum IgG with recurrent bacterial infections.
What immunodeficiency is this?
Common Variable Immunodeficiency
(CVI)
B cell deficiencies:
Slow development of the immune system that subsides around 2 years old
Transient hypogammaglobulinemia
B cell deficiencies:
- Development of B cells arrested at pro to pre-B cell
- Deficiency in enzyme results in failure of VH gene rearrangement
X-linked Bruton’s agammaglobulinemia
B cell deficiencies:
- Antibodies to IgA form
- Most common deficiency
- Blood transfusion anaphylaxis
IgA deficiency
B cell deficiencies:
- Development arrested at mature B cell, differentiation to plasma cells isn’t possible
- Hypogammaglobulinemia results
Common variable immunodeficiency
Which type of immunity deficiencies have manifestations of recurrent infections with intracellular pathogens such as viruses, fungi (Candida), and intracellular bacteria?
Cellular immunity deficiency
(T cells)
TRUE or FALSE:
T cell deficiencies affect cellular immunity but can also affect humoral immunity
TRUE
Which are more difficult to manage:
Cellular immunity deficiencies
or
Humoral immunity deficiencies?
Cellular immunity deficiencies
Developmental abnormality of the third and fourth pharyngeal pouches that develop in the neck region.
DiGeorge Anomaly/Syndrome
What is missing in most patients with DiGeorge Anomaly?
Portion of chromosome 22 on the QII region
DiGeorge Anomaly causes and insufficient number of what cells? Why?
T cells - maturation occurs in the thymus but DiGeorge Anomaly affects the thymus and other neck region organs/structures
What is the treatment for DiGeorge Anomaly?
Fetal thymus and bone marrow transplant along with thymic hormones to stimulate the thymus
TRUE or FALSE:
Purine-nucleoside phosphorylase deficiency is rare autosomal recessive deficiency that can cause UTIs and Candida infections
TRUE
Which immunodeficiency causes the number of T cells to decrease as toxic purine metabolite deoxyguanine triphosphate accumulates?
Purine-nucleoside phosphorylase (PNP) deficiency
Infants with this deficiency are often confused with having neonatal HIV infection due to their symptom similarities.
PNP defieciency
What are the T-cell deficiencies discussed?
DiGeorge Syndrome/Anomaly
Purine-nucleoside phosphorylase (PNP) deficiency
What are the B-cell deficiencies discussed?
X-linked Bruton’s agammaglobulinemia
Transient hypogammaglobulinemia
Common variable immunodeficiency (CVI)
IgA deficiency
Most severe of the congenital immune deficiencies
Severe Combined Immunodeficiency
SCID
Which for of SCID is the most common?
X-linked SCID
What occurs in X-linked SCID?
- *-Normal signaling between cells is affected and halts maturation
- T cells, B cells, and NK cells are affected**
Deficiency similar to PNP. Toxic accumulation of purines in lymphoid cells impairs the proliferation of both B and T cells.
Adenosine deaminase deficiency (ADA)
Name other variety of defect grouped under SCID
-Autosomal recessive SCID: Adenosine deaminase deficiency (ADA)
Syndrome in which a patients presents with immunodeficiency, eczema, and thrombocytopenia
Wiskott-Aldrich Syndrome (WAS)
Cause of Wiskott-Aldrich Syndrome
X-linked protein defect
Severe deficiency of the naturally occurring antibodies to blood group antigens (isohemagglutinins)
Wiskott-Aldrich Syndrome (WAS)
DEFINITION:
Muscle incoordination
Ataxia
DEFINITION:
Capillary dilation
Telangiectasis
Defect in TCR and Ig gene recombination process that is autosomal recessive
Ataxia-Telangiectasia (AT)
First line of defense against infections, effective ingesting/killing, involved in antibody mediated killing.
Neutrophils
Treatment of this neutrophil defect involves granulocyte transfusions, cytokine administration, and bone marrow transplantation.
Chronic granulomatous disease (CGD)
This disease is the result of several neutrophil defects and death usually occurs in childhood typically because of infection.
Chronic granulomatous disease (CGD)
This neutrophil defect increases susceptibility to candidiasis and is the most common neutrophil abnormality. No treatment is needed in most cases of this deficiency.
Myeloperoxidase deficiency (MPO)
What causes Leukocyte adhesion molecule deficiency?
Defect in adhesion receptors for PMNs, monocytes, and T cells.
Abnormal adhesion, motility, chemotaxis, and endocytosis due to a defect in adhesion receptors
Leukocyte adhesion molecule deficiency
Delayed wound healing and chronic skin infections are manifestations of which neutrophil deficiency?
Leukocyte adhesions molecule deficiency
Hodgkin’s disease that results in the patient developing Herpes Zoster is an example of what?
Secondary immune deficiency
Which of the following are primary immunodeficiency defects:
- Chronic granulomatous disease
- SCID
- Myeloperoxidase deficiency
- DiGeorge Syndrome
- IgA deficiency
- *-SCID
- DiGeorge Syndrome
- IgA deficiency**
What are secondary immunodeficiency defects associated with? (10)
- *-Infections
- Malignancies
- Immunosuppressive agents
- Burns
- Diabetes mellitus
- Malnutrition
- Surgical procedures/trauma
- Renal malfunction
- Aging
- Alcoholic cirrhosis**
How many types of hypersensitivity are there?
4
DEFINITION:
Immune response which harms the host/self
Hypersensitivity
Immediate hypersensitivity
Type I
Antibody-Mediated Diseases
Type II
Immune Complex-Mediated Diseases
Type III
T-Cell Mediated (Delayed) Diseases
Type IV
Which of the hypersensitivities are considered immediate?
Type I
Type II
Type III
Symptoms develop within what timeframe for immediate hypersensitivities?
Minutes to hours
Which of the hypersensitivities is/are considered delayed?
Type IV
TRUE or FALSE:
Immediate hypersensitivity = Antibody mediated
TRUE
Antibody mediated hypersensitivity includes what type(s)?
Type I, II, and III
Cell-mediated hypersensitivity includes what type(s)?
Type IV
Symptoms develop within what timeframe for delayed hypersensitivity?
24 - 48 hours after contact with antigen
TRUE or FALSE:
Delayed hypersensitivity = Cell mediated
TRUE
What other name is type I hypersensitivity known as?
Anaphylactic
What is another name for allergens?
Atopic antigens
DEFINITION:
Substances that trigger the formation of IgE
Atopic antigens
DEFINITION:
Inherited tendency to respond to naturally occurring allergens with continued production of IgE
Atopy
Old name for IgE
Reagin
Which T cell regulates IgE production?
Th2
Which hypersensitivity:
- Allergen activates B cells to form IgE secreting plasma cells
- IgE antibodies bind to high-affinity receptors on mast cells and coat the cell (sensitization)
- Subsequent exposure to the same allergen leads to crosslinking of bound IgE antibodies on mast cells
- Results in the release of granules from mast cell
- Chemical mediators are released
Type I hypersensitivity
TRUE or FALSE:
Asthma is a Type II hypersensitivity
FALSE
Type I
Primary mediator in Type I hypersensitivity
Histamine
Secondary mediators for Type I hypersensitivity (4)
- *-Prostaglandins
- Leukotrines
- Platelet activating factor (PAF)
- Cytokines**
Symptoms that occur with Type I hypersensitivity
- *-Wheal and flare
- Asthma
- Anaphylaxis
- Skin eruptions**
Testing methods for Type I hypersensitivity
- *-RIST
- RAST
- Skin test**
Test for total IgE
RIST: radioimmunosorbent test
Test for level of specific IgE
RAST: radioallergosorbent test
RIST is what type of test?
Sandwich EIA - competitive
RAST is what kind of test method?
ELISA microarray test
Which immunoglobulins cause disease by binding to cell antigens and/or tissue antigens and inducing inflammation in Type II hypersensitivity?
IgG or IgM
Which hypersensitivity:
- Antibodies stimulated by cell antigens (foreign or self)
- Antibodies attach to antigen and potnetially fix complement
- Possible effects:
- Opsonization and subsequent phagocytosis
- Binding of complement and lysis of cell antigen
- Antibody dependent cell cytotoxicity by some WBCs
- Antibody binds to tissue = destroyed
Type II hypersensitivity
The following are examples of which hypersensitivity:
- Transfusion reaction
- Hemolytic disease of the newborn (HDN)
- Autoimmune hemolytic anemia (AIHA)
Type II hypersensitivity
What antigen is most commonly involved in severe reactions of HDN?
D antigen
TRUE or FALSE:
An Rh(-) mothers antibodies will not affect her first Rh(+) child
TRUE
When does an Rh(-) mother make IgG antibodies against a baby?
When exposed to the blood group antigens of an Rh(+) baby
When a mother makes IgG antibodies that cross the placenta and destroy fetal RBCs it is known as this disease
Hemolytic disease of newborn (HDN)
What are the different types of autoimmune hemolytic anemia? (4)
-Cold autoagglutinins
-Warm autoimmune hemolytic anemia
-Idiopathic autoimmune hemolytic anemia
-Autoimmune or idiopathic thrombocytopenic purpura (ITP)
What is the usual antibody for cold autoagglutinins?
IgM against I/i blood group
What antibody is responsible for warm autoimmune hemolytic anemia?
IgG
What infections are associated with warm autoimmune hemolytic anemia?
- *-Infectious mononucleosis
- Cytomegalovirus
- Chronic hepatitis**
Antibodies formed to platelets which are then destroyed. Occurs mainly in children following a respiratory viral illness.
Autoimmune or Idiopathic thrombocytopenic purpura (ITP)
Autoimmune disease caused by the formation of antibodies to antigens in the kidney resulting in glomerulonephritis.
Goodpasture’s syndrome
Autoimmune disease caused by the formation of antibodies to the thyroid.
Hashimoto’s disease
Autoimmune disease caused by the formation of antibodies to acetylcholine receptors resulting in no muscle contraction.
Myasthenia gravis
Formation of antibodies to beta cells of the pancreas
Insulin-dependent diabetes mellitus
Immunofluorescent stain of IgG to kidney membrane is a testing method used for which autoimmune disease?
Goodpasture’s syndrome
Hypersensitivity type in which antibody binds to antigen on cell surface causing either complement to be fixed, phagocytosis, or antigen dependent cell cytotoxicity - OR - antibody binds to tissue causing damage.
Type II hypersensitivity
The following are examples of which hypersensitivity?:
- Transfusion reaction
- HDN
- AIHA
- Goodpasture’s
- Hashimoto’s
- Myasthenia gravis
- Insulin dependent diabetes mellitus
Type II hypersensitivity
What type of testing can be done for type II hypersensitivity?
- *-Blood group antibodies
- Platelet antibodies
- Specific antibody**
Hypersensitivity that occurs when patient comes in contact with an allergen
Type I
Which immunoglobulin is produced in type I hypersensitivity?
IgE
What cell(s) are a part of type I hypersensitivity?
Basophils and Mast cells
In Type I hypersensitivity:
Contact with allergen produces ____ antibodies that bind to _______/____ cells that subsequently release ___________ mediators when ___ antibodies are cross-linked.
Contact with allergen produces IgE antibodies that bind to Mast cells that subsequently release inflammatory mediators when IgE antibodies are cross-linked.
Type ____ hypersensitivity:
Ig__ or Ig__ antibodies bind to cell-bound antigens present on various cell types leading to their destruction.
Type II hypersensitivity:
IgM or IgG antibodies bind to cell-bound antigens present on various cell types leading to their destruction.
Hypersensitivity:
Antibodies react with soluble antigen; complexes precipitate in tissues
Type III hypersensitivity
Hypersensitivity:
Sensitized T cells are responsible for symptoms
Type IV hypersensitivity
Which hypersensitivity is also known as complex mediated hypersensitivity?
Type III
This classification of hypersensitivity often manifests as vasculitis, arthritis, and nephritis
Type III
aka
Complex-mediated hypersensitivity
Mediators or anaphylatoxins associated with Type III hypersensitivity
C5a
C3a
C4a
What do the mediators do in complex-mediated hypersensitivity?
Increase vasodilation, vasopermeability, and attract macrophages and neutrophils to the site.
Arthus reaction is an example of which hypersensitivity classification?
Type III
The following are examples of which classification of hypersensitivity?:
- Arthus reaction
- Serum sickness
- Autoimmune diseases such as RA and SLE
- Associated with the following pathogens: Polyarteritis nodosa and Post-streptococcal glomerulonephritis
Complex mediated hypersensitivity
aka
Type III
The following is the mechanism of action for which hypersensitivity class?:
Immune complexes are deposited in tissue and complement is fixed
Complex mediated hypersensitivity
aka
Type III
What testing is done for type III hypersensitivity?
Specific antibody testing (Abys to DNA or nucleohistones for SLE / Rheumatoid Factor for RA)
Immune complexes in tissue
Complement levels
- Arteries inflamed
- Cause unknown
- More commonly seen in patients with HBV infection
Polyarteritis nodosa
Other names for Type IV hypersensitivity
Cell Mediated
or
Delayed hypersensitivity
Most of the common causes of contact dermatitis are _______
Haptens
What are some examples of the haptens associated with Type IV hypersensitivity?
Poison ivy
Poison oak
Poison sumac
Nickel
Rubber
Topical medications
- Hapten binds to glycoproteins on skin cells
- Langerhans cells and macrophages process antigen and present to T cells
- T cells (Th1) become sensitized; takes several days and may last for years
- Upon repeat exposure, skin eruptions occur
Type IV
Delayed
Cell mediated hypersensitivity
Treatment for contact dermatitis
- Topical corticosteroids
- Systemic corticosteroids
and
-Avoid contact with allergen
Examples of Type IV hypersensitivity
-Contact dermatitis
-Hypersensitivity pneumonitis
-Tuberculin skin test (PPD)
-Granulomatoud hypersensitivity
Diseases associated with hypersensitivity pneumonitis
-Farmer’s lung
-Pigeon breeder’s disease
Mechanism of action for cell mediated hypersensitivity
Activated T cells
Cell bound antibody reacts with antigen to release active substances such as histamine
Type I hypersensitivity
aka
Immediate
aka
Anaphylactic
Free antibody reacts with antigen on cell surface
Type II
aka
Free antibody
Antibody reacts with soluble antigen and complexes precipitate in tissues
Type III hypersensitivity
aka
Immune complex
Sensitized T cells responsible for symptoms
Type IV hypersensitivity
aka
Cell mediated
MHC Class I gene products
HLA-A
HLA-B
HLA-C
Sites on chromosome 6
TRUE or FALSE:
MHC class I is found on all nucleated cells
TRUE
Which MHC class is needed for cytotoxic T lymphocytes to interact with target cell?
MHC class I
MHC Class II gene products
HLA-DR
HLA-DP
HLA-DQ
Where is MHC class II present?
B cells
Macrophages
Dendritic cells
Endothelial cells
(APCs)
MCH class II is needed for which cells to interact with APCs and B cells?
T helper cells
DEFINITION:
Process of substituting or replacing a diseased organ or tissue with a functional one
Transplantation
DEFINITION:
Transplant tissues or organs
Graft
What is an autograft?
Donor and the host are the same
What is an syngraft?
Transplant between identical twins
Another name for syngraft
Isograft
What is an allograft?
Allogeneic donor
Between 2 individuals of the same species that are genetically different
What is the most common type of transplant graft?
Allograft
What is a xenograft?
Transfer of tissue from one species to another
Examples of xenografts used in humans
-Baboon heart to replace human heart
-Cow or pig valves used to treat aortic or mitral valve defects
This type of rejection occurs within minutes to hours after the transplantation
Hyperacute
When is hyperacute rejection typically observed?
Xenograft and ABO incompatibility
This graft rejection occurs over days to weeks and may last the life of the graft
Acute
Which graft rejection is most common during the first year post-transplant?
Acute
TRUE or FALSE:
Acute involves both cell and antibody mediated immunity.
TRUE
This graft rejection type occurs months to years after transplant
Chronic
Which graft rejection type is characterized by fibrosis and arteriosclerosis?
Chronic
Basic mechanism of acute graft rejection
CD4 produces cytokines
CD8 destroys the graft
B cells make antibodies to HLA-DR
Basic mechanism of action for hyperacute graft rejection
Preexisting antibodies
Basic mechanism of action for chronic graft rejection
Cell mediated and antibodity mediated immunity
Fibrosis and arteriosclerosis cause loss of elasticity and impaired circulation
TRUE or FALSE:
ABO compatibility is required for bone marrow transplants
FALSE
Test used for the serological detection of class I and II molecules
Lymphocytotoxicity test
Most sensitive method for MHC class II detection
PCR
Which transplant type does not need compatibility testing
Corneal transplants
Bone grafts use a combination of which type of grafts?
Autografts and allografts
What is the name of the new epidermis that is “grown to order” in the laboratory?
Epicel
Which organ transplant is most often performed in the U.S.?
Kidney
TRUE or FALSE:
HLA matching is more important than ABO typing for kidney transplants
FALSE
ABO typing must match
How long can kidneys tolerate being outside of the body?
2 days
A heart transplant has to be done within what timeframe?
4 hours
Which organ transplant requires ABO and HLA-DR to match?
Pancreas
What is Graft vs host disease?
Donor cells attack host cells causing skin leasions, diarrhea, and or jaundice.
Fatal if not treated.
This method is being used increasingly more often in place of bone marrow
Peripheral blood progenitor (stem) cells
Nonspecific immunosuppressive agents:
Decreases expression of IL-2 receptors and cytokine production by T helper cells
Cyclosporine
Nonspecific immunosuppressive agents:
Prevents cell proliferation
Azathioprine
Nonspecific immunosuppressive agents:
Anti-inflammatory that affects activated macrophages and decreased expression of HLA antigens
Steroids
UAMS requirement for Allogeneic bone marrow requires which HLA to match?
8 out of 8 for A, B, C, DR
What type of transplant occurs between twins?
Syngraft
aka
Isograft
Interpret the lymphocytotoxicity test result:
anti-B22 + patient cell = blue cells
Patient has HLA-B22 on their cells
Acute reaction is mediated by ___________ and ____________ and occurs within ______ to ________.
Acute reaction is mediated by T cells and antibodies and occurs within days to weeks.
TRUE or FALSE:
Successful kidney transplantation requires compatibility between ABO antigens and HLA antigens
FALSE
ABO compatibility is required for kidney transplantation
DEFINITION:
Our own cells that have grown out of control and are not regulated
Tumor
DEFINITION:
New uncontrolled growth derived from one’s own tissues
Neoplasm
DEFINITION:
Abnormal tissue resulting from uncontrolled growth
Tumor
DEFINITION:
More likely to stop growing spontaneously; tumor is unually confined to a single sight
Benign
DEFINITION:
Invasive tumor capable of spreading
Malignant
DEFINITIONS:
Cancer that originated from epithelial cells- occurs most frequently on skin, large intestine, lung, prostate gland, and breast
Carcinoma
DEFINITION:
Cancer that originates from connective tissue
Sarcoma
What occurs during angiogenesis?
Blood vessels are created in order for tumor cells to continue getting nutrients for proliferation
TRUE or FALSE:
Cancer can be the consequence of a failed immune system
TRUE
What type of cancer is associated with AIDS patients?
Kaposi’s sarcoma
What type of cancer is associated with transplant patients?
EBV-induced lymphoma
DEFINITION:
Cancer producing substances
Carcinogens
What hormone is associated with endometrial, ovarian, and breast cancer?
Increased estrogen levels in endometrial, ovarian, and breast cancer
What are examples of chemical carcinogens?
Tar, tobacco smoke, and benzene
What are examples of physical carcinogens?
Ionizing radiation, UV light, and asbestos
Viruses that may cause cancer:
EBV + malaria attacks (Africa)
Burkitt’s lymphoma
Viruses that may cause cancer:
EBV + unknown factors (China)
Nasopharyngeal carcinoma
Viruses that may cause cancer:
HTLV-1
(Human T-Lymphotropic Virus-1)
Adult T cell leukemia
Viruses that may cause cancer:
HPV
(Human papillomavirus)
Cervical cancer
Viruses that may cause cancer:
HBV
(Hepatitis B Virus)
Primary Hepatoma
Viruses that may cause cancer:
Human herpes virus 8
Kaposi’s sarcoma
The original classification of tumor antigens was based on what?
Patterns of expression
DEFINITION:
Antigens present only on tumor cells
Tumor specific antigens
What is another name for tumor associated antigens?
Tumor markers
DEFINITION:
Present on some tumor cells and some normal cells. Many tumor cells do not express unique antigens.
Tumor associated antigens
aka
Tumor markers
Modern classification of tumor markers is based on what?
-Molecular structure
-Source of the antigen
DEFINITION:
Genes capable of producing neoplastic transformation
Oncogenes
Genes that normally inhibit growth of tumors
Tumor suppressor genes
Mutations in _____ are the most common genetic change associated with cancer
p53
Oncogene caused by EBV-associated with lymphomas and nasopharyngeal carcinoma
EBNA-I protein
Epstein Barr virus nuclear antigen 1
Human T-cell lymphotropic virus type 1 is associated with what type of cancer?
A variant of hairy cell leukemia
Antigens expressed in a developing fetus (absent or low in adult)
Oncofetal tumor antigens
- Tumor marker found in fetal gut, pancreas, and liver.
- Associated with cancers in colon, rectum, and others.
- Promotes binding of tumor cells to one another
Carcinoembryonic Antigen
(CEA)
Oncofetal tumor antigen secreted by fetal liver and yolk sac cells
- Replaced in adults by albumin
- Elevated in patients with liver tumors and germ cell tumors (testicular)
Alpha-fetoprotein (AFP)
Oncofetal tumor antigen produced by placental cells.
- Used in men to monitor treatment and recurrence of testicular cancer
- Has low sensitivity causing many false negatives
Human chorionicgonadotropin-beta subunit (BhCG)
Tumor marker used to screen for ovarian cancer.
-High false positive results due to pregnancy, menstruation, endometriosis, etc.
Cancer antigen-125
(CA-125)
Tumor marker used to detect prostate cancer in men older than 50.
Present in normal and malignant cells.
Organ specific, NOT tumor specific
Prostate-Specific Antigen (PSA)
Tumor marker used in the diagnosis of medullary thyroid carcinoma.
Hormone (thyroid gland) that helps the body absorb cacium into bones.
Calcitonin
