Unit 3 Immunology Flashcards
ADCC
- HIV elite controllers may have strong ADCC response
- in ADCC, Fcgamma receptor on NK cells binds Fc region of IgG antibody that is bound to target cell, NK cell then induces apoptosis
- is not related to MHC the way CTL is
NK Cells
- cell of innate immune system
- can attack cells and directly induce apoptosis
- ADCC also
- is not MHC related the way CTL is
Flow Cytometry
- test for T cell number and function
- shows graph of CD4+ vs C8+ cells
- lasers used to illuminated cells in single file line and quantify them
Test for B Cell Function
- serum protein electrophoresis
- serum run on gel and stained for protein
- results show graph with peaks with normal gammaglobulin showing soft peak on right side
- big, wide peak is polyclonal hypergammaglobulinemia
- big, narrow peak is monoclonal hypergammaglobulinema (multiple myeloma)
- no peak is agammaglobulinemia
Test to measure individual immunoglobulin classes or subclasses
- single radial immunodiffusion
- results appear in circles that can be measured
Test for T Cell Function
- skin test
- chest x ray in infants might be helpful to check for thymus (looks like heart)
Tests for Autoimmune Diseases
- antinuclear antibodies
- rheumatoid factor
- immune complexes
- immunofluorescence
- immunohistochemistry
Tests for Specific Antibody
- precipitation
- simple ELISA (indirect only)
- passive agglutination
Tests for Measuring Antigens
- direct ELISA
- capture ELISA
- rapid screens
- reverse passive agglutination
Monoclonal Antibodies
- B cell mixed combined with myeloma cell that produce antibodies to certain inflammatory elements
- murine (mouse) -omab
- chimeric (mouse VL and VH domains only) -ximab
- humanized (mouse CDR only) -zumab
- human (made in SCID mouse with human organs) -umab
Biological Response Modifiers (BRMs)
-some are growth factors that can be used in bone marrow transplant to increase new bone marrow growth
Bispecific T Cell Engager (BiTE)
-antibodies (CD19 and CD3) that are coupled together via engineering to bring CTL cell together with B lymphoma cell
Chimerica Antigen Receptor (CAR)
- antibody to CDR of target cell that is attached to antibody for CD3 CTL cell surface molecule
- no MHC restriction
Passive Antibody Therapy in Cancer
- attach antibody to cancer cell to toxin or T cell
- this allows specific targeting of cancer cells for treatment
ABO (and bombay) Blood Types
- O>A>B>AB
- bombay- lacks transferase to add final sugar to core, so these people do not express their blood types and appear O
- bombay can only receive blood from bombay
isohemaglutinins
- IgM antibody to other blood types
- exposed to antigens in environment and do not need to be exposed to other blood types to have reaction
crossmatch test
- done before blood transfusion to test for antibody in recipient to antigens in donor blood
- donor cells are suspended in saline and plasma of recipient is added
- mixture is centrifuged and supernatant is checked for redness (hemolysis)
- pellet is then resuspended and checked for clumps
- if either test is positive, blood is not used
Coomb’s Test (indirect vs direct)
- antiglobulin test (tests for presence of antibody)
- ex. autoimmune hemolytic anemia
- direct- is there antibody present on cells that I am interested in? Add antiglobulin to pt’s cells.
-indirect- is there unexpected antibody to donor RBCs in plasma of recipient? Add antiglobulin to mixture of donor’s cells and recipient’s plasma.
heterphile antibody
- antibody to disease also happens to bind to another antibody
- cross reactive antibodies
- can test for mono or syphilis
Hemolytic Disease of Newborn
- severe disease causes high bilirubin that can cross blood brain barrier and lead to brain disease or death
- sensitization occurs in mother during pregnancy where fetus is Rh+ and mother is Rh-
- mother then makes IgG than can cross placenta in future pregnancies
- RhoGAM is IgG to Rh(D) and opsonizes Rh(D) in mother’s blood stream and destroys them before mother can develop response
ABO hemolytic disease of newborn
- when mother makes IgG instead of IgM to ABO antigens
- this can cross placenta and cause disease
- no treatment available
passive aggluination
- serial dilutions of serum (antibodies) mixed with antigen
- can measure titer amount
- uses beads to normalize antigen size
HIV
- affects Th CD4 cells
- must be below 200 to have AIDS
- HIV type 1 is more prevalent than type 2
- lentivirus- slow progression that leads to death
- virus from chimps (M), and gorillas (O) and brought to US likely from sex travel in Haiti
- 35 million people in world have HIV
- In US, 1,100,000 have HIV, 16% don’t know they have it
- incidence dec. 33% since 2001
- virus gp120 binds to CD4 on T cells, causing conformational change in gp120 that puts it in contact with CCR5 (on T cell)
- second conformational change so that gp41 is exposed on HIV that pokes through T cell membrane and virus enters cells
- cells infected with HIV can lyse quickly, become chronic, or become latent
- chronic viral producers have gp120/gp41 on surface and can fuse with other non infected cells, rendering antibodies useless
- latency is in Tfh cells in lymph node that can suppress DNA replication but cannot get rid of DNA from nucleus
- pts eventually stop making more T cells
dx: with ELISA and confirm with western blot
Infections Seen in HIV Patients
-Candida albicans
-Pneumocystis jirovecii
-Protozoan infections
-CMV
-hepatitis
-HSV
-VZV
TB
-kaposies sarcoma
-T cell mediated diseases
HIV long term survivor
- mutation in CCR5 (homozygous delta 32) on Th (CD4) cells
- mutation means no CCR5 receptor is present for HIV to bind to to enter cells
HIV elite controller
- associated with HLAB57
- esp. good at presenting HIV on MHCs
- infected with HIV but do not progress to AIDS
- ADCC or CTL response is strong
Good Target for HIV Vaccine
-target gp120 or gp41 because these portions cannot mutate to maintain function of viruses
Immune Surveillance Theory
- T cells and other immune cells may suppress cancer cells
- confirmed by research- immunosuppressed pts have more cancer
Immunoediting
- appear to not have tumor, but really have latent tumor cells
- elimination- immune system attacks cancer or cancer cells die due to overproliferation
- equilibrium- immune system kills most cancer cells but not all, some survive for many years
- escape- cancer cells mutate to resist immune system (CTLA-4 and PD1 checkpoint receptors on CTLs are engaged by cancer cells)
- autoantibodies can be made to block these receptors and prevent activation by tumor cells (PD1= nivolumab, CTLA4= ipilimumab)
Tumor Associated Antigens (TAA)
- could be normal but overexpressed
- could be mutated
- tumor rejection antigens are subclass
Tumor Rejection Antigens (TRA)
-subclass of tumor associated antigens that are recognized by immune system and allow us to attack tumor
Carcinoembryonic Antigen (CEA)
- normally expressed in bowel of fetus that is also on in colon cancer
- NOT used as routine screening
- can use in high index of suspicion or to track dec. levels after resection
CTL and Cancer
- recognize TAA on tumor cell MHC and kill tumor cell
- respond when there is high rate of MHC response
Th1 and Cancer
- Th1 cells normally recruit M1 macrophages to kill
- cancer cells create environment that is M2 friendly, and this causes tumor growth
NK and Cancer
- not MHC dependent
- can kill via direct binding or ADCC
- as tumor cells decrease MCH expression, NK cells become more crucial to response
Innocent Bystander Killing of Tumor
- inject BCG (TB shot) directly into tumor and T cells respond
- T cells then also damage surrounding tumor cells
Antibody Therapy to Cancer
- attach antibody to toxin or NK cell or radioisotope and target antibody to specifically bind cancer cells
- costly
Adoptive Cellular Transfer Therapy
- tumor infiltrating lymphocytes (TIL) and immune cells that can attack tumor cells are taken from patient and grown in culture
- pt is immunosuppressed and cells are injected back into patient to kill tumor cells
Herceptin
Monoclonal antibody (humanized) that targets HER2 -treats cancer
Simple ELISA
-tests for antibody
Capture ELISA
- tests for antigen
- antigen must have at least two epitopes
