CPR1 - Immunology {1.03b,1.08,2.03,2.10}

What is forward scatter in flow cytometry?

Size of cells

What is side scatter in flow cytometry?

Granularity

What is the normal range of leukocytes (total WBCs)?

4500–10,500 per mm³

What is the normal range of Neutrophils in a complete WBC?

40-60%

What is the normal range of lymphocytes in a complete WBC?

20-40%

What is the normal range of monocytes in a complete WBC?

2-8%

What is the normal range of eosinophils in a complete WBC?

1-4%

What is the normal range of basophils in a complete WBC?

<1%

What does the root -cytosis mean in terms of lymphocytes?

Increased lymphocytes

What does the root -philia mean in terms of granulocytes?

increased granulocytes

What does the root -penia mean in terms of WBC count?

Decreased count

What does leukocytosis with a left shift indicate?

increased bands and less mature neutrophils are present in the blood, along with a lower average number of lobes in segmented cells

What malignancies can a left shift leukocytosis indicate?

Presence of infection or tumor

What does leukocytosis with right shift indicate?

No production of immature neutrophils in the bone marrow, Indicates bone marrow suppression

What is the result of hypersegmented neutrophils?

Increased nuclear segmentation due to slowed DNA synthesis

What is the most likely diagnosis for Hypersegmented neutrophils?

Vitamin B12 or Folic acid deficiency

What is the result of Atypical Lymphocytes?

Many lymphocytes released in the blood

What is the most likely diagnosis for atypical lymphocytes?

Viral infection

What is the result of blasts (immature neutrophils)?

Immature cells found in circulation

What is the most likely diagnosis from blasts (immature neutrophils)?

Leukemia

What is a common cause of congenital neutropenia?

Hereditary neutropenia

What is a common cause of acquired neutropenia?

Bone marrow disease

What is a common causes of acquired neutrophilia?

Bacterial infections, tissue destruction, neoplastic growth

What is the common cause of congenital lymphopenia?

Congenital immunodeficiency diseases (SCID)

What is the common cause of acquired lymphopenia?

Severe infection, Corticosteroids, HIV Immunodeficiency

What is the common cause of acquired lymphocytosis?

Viral infection (EBV, CMV, hepatitis, etc.), Some fungal, parasitic infections, Rare bacterial infection (Pertussis), Allergic reactions/drug sensitivities, Immunologic disease, Lymphoproliferative disorders

What type of shift is seen in neutrophilia?

Left shift

What type of shift is seen in lymphocytosis?

Right shift

What is the common cause of acquired monocytopenia?

Immunosuppressants

What is the common cause of acquired monocytosis?

Mycobacterial infection, Tuberculosis, syphilis, Subacute bacterial endocarditis, Inflammatory responses, Myeloproliferative disorders

What is the common cause of acquired eosinophilia?

Parasitic (helminth or worm) infections, Type I Hypersensitivity reactions, Pulmonary disease (Asthma)

What is the common cause of acquired basophilia?

Type I Hypersensitivity reactions

What do increased levels of IgM indicate?

Initial stages of infection

What do increased levels of IgG indicate?

Later stages of infections

What do increased levels of IgE indicate?

Hypersensitivity or parasitic infections

What do increased IgA indicate?

Mucosal infection

Which infections do eosinophils respond to?

Helminth or worm infection

A finding of lymphocytosis on a CBC differential may be caused by which of the following?

Infection with EBV

What is pernicious anemia?

an autoimmune disease where the body can't absorb vitamin B12 due to a lack of intrinsic factor (IF)

What cells secrete intrinsic factor (IF)?

Parietal cells

What causes loss of intrinsic factor (IF) in pernicious anemia?

Autoantibodies against IF or against parietal cells

What isotype of antibodies are against IF in pernicious anemia?

IgG

What antibody effector function is used against IF?

Neutralization

What is the antibody effector function against parietal cells?

Opsonization

Since mucosal antibodies are IgA isotype, where do the IgG antibodies come from that destroy IF?

Underlying conditions or chronic inflammation leads to IgG autoantibody production

What are some causes of chronic gastritis?

Autoimmune gastritis, helicobacter pylori infection, association with other autoimmune disorders

What type of hypersensitivity reaction is seen in pernicious anemia?

Type II hypersensitivity

How is pernicious anemia diagnosed?

Megaloblastic anemia is seen, a cause is found to be B12 deficiency, autoantibody detection through ELISA

What is the anatomical pathology of pernicious anemia?

Lymphocyte and plasma cell infiltration of gastric mucosa followed by loss of gastric parietal cells, intestinal metaplasia confined to body of stomach

What are the symptoms of pernicious anemia?

Parasthesia, anemia, sore tongue, bleeding gums, jaundice, fatigue, irritability, diarrhea, memory loss

A 42-year-old woman presents to the hospital with yellow eyes and dark urine, fatigue, and shortness of breath. On examination, she is anemic and jaundiced. Her blood work reveals a hemoglobin level of 5.4 g/dL (ref: 13– 17g/dL) and a corrected reticulocyte count (CR) of 9% (ref: 0.5–2.5%). Further testing by direct Coombs test shows that her RBCs had IgG and complement C3 on their surfaces. Her serum contains autoantibodies. What is the most likely diagnosis?

Autoimmune hemolytic anemia

What is intravascular hemolytic anemia?

hemolysis within the vasculature using complement

What is extravascular hemolytic anemia?

Hemolysis in the liver and spleen

What is intrinsic hemolytic anemia?

hemolysis of often genetic origin

What is extrinsic hemolytic anemia?

Acquired disorder due to autoimmune responses or infections

What is the Direct Coombs test?

Test to detect antibodies bound to RBCs, central to detect autoimmune hemolytic anemia (AIHA)

What complement pathway do antibodies activate?

Classical pathway

Why is complement tested in combination with antibodies in a direct Coombs test?

Antibodies activate complement by the classical pathway

What is an indirect Coombs test?

Detect antibodies against RBCs that are present unbound in patient’s serum, used in prenatal testing

Detection of which hypersensitivity reaction would an indirect antiglobulin test (IAT) be helpful in?

Type II hypersensitivity

What is autoimmune hemolytic anemia (AIHA)?

Autoantibodies directed against self RBC membrane antigens lead to accelerated RBC destruction

Why does an indirect Coombs test (IAT) not test for unbound complement?

Complement is naturally present in blood, it is only when it is activated that it binds to a surface

How are RBCs destroyed in the spleen in extravascular hemolytic anemia?

Antibody and/or complement function - opsonization and phagocytosis

What is the epidemiology of autoimmune hemolytic anemia (AIHA)?

Autoantibody production against RBCs, most patients older than 40 years, underlying lymphoproliferative malignancies, lymphoma

What is warm AIHA?

Direct Coombs test (DAT) pattern solely IgG positive or IgG and C3 positive, mainly extracellular hemolysis

at what temperature do autoantibodies bind and react optimally with RBCs?

37 degrees Celsius (35-40)

What is the pathogenesis of warm AIHA?

IgG autoantibodies bind to RBCs and destruction by splenic macrophages, incomplete phagocytosis results in spherocyte formation

What are the causes of warm AIHA?

Primary - idiopathic, secondary - lymphoproliferative disorders, other autoimmune disorders

What are the treatments for warm AIHA?

Corticosteroids, splenectomy, blood transfusion

What is cold AIHA?

Cold agglutinin disease (CAD), DAT pattern IgG negative, IgM involved, complement is the major player that forms MAC

What are the causes of cold AIHA?

Primary - idiopathic, secondary - infections like mycoplasma, viral pneumonia, infectious mononucleosis, mumps, cytomegalovirus

Why do infections cause autoimmunity?

Molecular mimicry, foreign antigen shares sequence or structural similarities with self-antigens

How is cold AIHA diagnosed?

Presence of IgM and complement on RBCs in direct Coombs test (DAT), presence of antibodies associated with infections

What is the treatment for cold AIHA?

Cold avoidance, treatment of underlying infections

What is paroxysmal nocturnal hemoglobinuria (PNH)?

Deficiency of complement regulatory protein DAF or CD59, complement-mediated intravascular RBC lysis, Coombs test negative

What is the immunodominant sugar of the A antigen?

N-acetylgalactosamine

What is the immunodominant sugar of the B antigen?

D-galactose

What does the O allele encode for?

An enzyme with no function

Why are antibodies to ABO in the serum formed naturally?

Sugars that are identical to, or very similar to, the ABO blood group antigens are found throughout nature

What are anti-A and ant-B antibodies called?

isohemaglutinins

What is the immune component of type II hypersensitivity?

IgG or IgM

Why are people with the blood group O considered universal donors for blood transfusions?

Patients with blood group O do not have any antigens on their surface, transfusion does not lead to cytotoxicity

What will happen to individuals who do not produce the D antigen if they encounter the D antigen?

They will produce anti-D

What does the RhD protein encode for?

D antigen

What happens is an Rh negative patient is transfused with Rh positive blood?

Hemolytic transfusion reaction (HTR)

What happens when an Rh negative mother is pregnant with an Rh positive child?

Mother makes antibodies against the fetal cells

What is a common cause of RHD gene deletion?

Unequal homologous recombination in rhesus boxes

What is weak D in the genetics of Rh blood group?

All antigen epitopes are present but are underexpressed, Anti-D prevented, can receive RhD-positive blood

What is partial D in the genetics of Rh blood group?

Some D antigen epitopes missing, should not receive RhD positive blood

What is the function of RhAG?

Direct Rh antigens to the RBC membrane

What happens in the absence of Rh complex?

Alters RBC shape, increases osmotic fragility, shortens lifespan

How is hemolytic disease of the newborn prevented?

anti-D (RhoGAM)

Why does HDN only occur during the 2nd pregnancy?

Initial exposure antigen recognized as foreign, immune response leads to generation of IgG or IgM, subsequent exposure IgG or IgM bind to antigen, cellular cytotoxicity and complement activation

How do Rh antibodies destroy RBCs?

Bind to RBCs and mark them for destruction in spleen (extravascular hemolysis), rarely activate complement

How do antibodies gain access to the fetus in HDN?

Generation of IgG which can cross the placenta

How can a direct Coombs test detect HDN?

Detect maternal IgG bound to fetal RBC (anti-Rh)

How can an indirect Coombs test be used to prevent HDN?

Prenatal testing to detect anti-Rh antibodies in mothers serum