Chapter 28: Adaptive Immunity & Diagnostics (Exam 4) Flashcards
MHC I
present peptides of 8-11 amino acids
from endogenous (intracellular) foreign antigens
alerts immune system it has been infected
cell gets destroyed by T cell excreting perforins and granzymes
MHC II
present 10-20 amino acids
from exogenous (extracellular) pathogens
after endocytosis of pathogens,
alerts immune system to antigens presence
does not kill presenting kills
other terms for antibody
immunoglobulin (IG)
B cell receptor (BCR)
antibody production
B cells contain antibodies on surface (~100k per cell)
1. BCR recognizes epitope on pathogen, B cell phagocytoses antigen
2. presents antigens of enclosed pathogen on surface (MHC II) to T helper cells
3. T helpers produce cytokines that stimulate division of antigen reactive B cells –> differentiate into plasma cells
4. Secretion of large amounts of antibodies specific to the antigen
Functions of antibodies
mark pathogen surface
inhibit infection
neutralize toxins
Marking a pathogen’s surface
most common function of antibodies
phagocytes have unspecific antibody recognizing receptors, phagocytosis of IG-coated cell or virus
inhibiting infection
interferes with pathogen’s outer structures
e.g. antibodies in mucous membranes hinder influenza
neutralizing toxins
binds to toxins
e.g. antibodies in blood and lymph block toxins from binding with host cells
cytotoxic T cell
kills cells that have the antigen
T helper cell
binds MHC II
produces cytokines & interleukins
natural active immunity
getting a disease and recovering
natural passive immunity
passing antibodies to infants through breast milk
artificial passive immunity
receiving a vaccination and developing immunity
artificial passive immunity
receiving pre-formed antibodies (antiserum)
properties of innate immune system
targets common pathogens
responds within hours
non-inducible
doesnt require pre-exposure
does not generate memory
driven by phagocytes
phagocytes
white blood cells able to ingest kill and digest pathogens
properties of adaptive immune system
targets specific pathogens
responds after days
induced by innate
requires pre-exposure
generates immunity
driven by lymphocytes
lymphocytes
white blood cells that make antibodies & mark pathogens for destruction
immune system hypersensitivity
inappropriate immune response that results in host damage
two major types: antibody mediated and cell mediated
type I hypersensitivity
immediate
IgE sensitization of mast cells
latency- minutes
ex. reaction to bee sting
type II hypersensitivity
cytotoxic
IgG interaction with cell surface antigen
latency- hours
ex. drug reactions
type III hypersensitivty
immune complex
IgG interaction with soluble or circulating antigen
latency- hours
ex. systemic lupus erythematpsus
type IV hypersensitivity
delayed type
Th1 inflammatory cell activation of macrophages
latency- 24-48 hrs
ex. poison ivy
type I (immediate) allergies
increase or decrease bp or hr
mild or life threatening
ex. pollen, mold, shellfish, insect venom
immune system alert through mucous membranes of lungs or gut
antibody mediated
type IV (delayed) allergies
often after contact skin (contact dermatitis)
itchiness, reddening, edema, tissue damage, blisters
ex. jewelry, cosmetics, poison ivy, latex
cell mediated
Type I diabetes
organ: pancreas
mechanism: cell mediated immunity and autoantibodies against surface and cytoplasmic antigens of beta cells or pancreatic islets (II and IV)
tissue/cell specific
Myasthenia gravis
organ: skeletal muscles
mechanism: autoantibodies against acetylcholine receptors on skeletal muscle (II)
Goodpasture’s syndrome
organ: kidney
mechanism: autoantibodies against basement membrane of kidney glomeruli (II)
rheumatoid arthritis
organ: cartilage
mechanism: autoantibodies against self IgG antibodies which form complexes deposited in joint tissue, causing inflammation and cartilage destruction (III)
systemic
systemic lupus erythematosus
affects: DNA, cardiolipin, nucleoprotein, blood clotting proteins
mechanism: autoantibody response to various cellular constituents results in immune complex formation (III)
multiple sclerosis
unknown cause
body’s immune system attacks its own tissues, destroys fatty substance that coats and protects nerve fibers in the brain and spinal cord (myelin)
superantigens
proteins capable of elicitng a strong response because they activate more t cells than a normal immune response
produced by many viruses and bacteria that interact with t cell receptors
may produce systemic diseases
characterized by systemic inflammatory reactions
some influenza, toxic shock, graft vs host, cytokine storm covid, immunotherapies
immunodeficiency
active adaptive immunity is critical for infectious disease resistance
animals with deficiencies in B cells are prone to bacterial infections
t cell deficiencies prone to viral infections and cancers
severe combined immune deficiency syndrom (SCID)
serious, congenital deficiency in both B and T cells
patients live a restricted life to limit exposure to pathogens
adenine deaminase
X-SCID interlukin receptor missing, expresses on T, B and NK cells
omenn syndrome rag gene mutations (recombination activating gene)
acquired immunodeficiency syndrome (AIDS)
caused by HIV infection that progresses and kills CD4 & T cells
patients are prone to opportunistic infections and cancer since deficienct in T cell help
Avastin
immunotherapy
anti VEGF antibody
tumors produce protein VEGF which binds to receptors on blood vessels which helps it grow and spread
Avastin attaches to VEGF, preventing it from binding to receptors, existing blood vessels may shrink away from tumor, prevents new vessels from forming
herceptin anti her2 ab
immunotherapy
normal: her2 receptors send signals telling cells to grow and divide
breast cancer: too many her2 receptors send signals too quickly, causing rapid cell growth
herceptin: stops her2 from signaling growth
immunotherapy
type of cancer treatment designed to boost body’s natural defenses to fight cancer
uses substances either made by body or in lab to improve or restore immune function
opdivo keytruda anti PDL abs
immunotherapy
-PD-1 expressed on antigen stimulated T cells & induces downstream signaling that inhibits T cell proliferation, cytokine release & cytotoxicity
-many tumors (melanoma) suppress cytotoxic T cell activity by expressing PD-1 ligand on cell surface
-anti-PD-1 and PD-L1 antibodies can reverse T-cell suppression and induce long lasting antitumor responses
CAR T-cell therapy
Chimeric antigen receptor (CAR) T-cell therapy is a way to get immune cells called T cells (a type of white blood cell) to fight cancer by changing them in the lab so they can find and destroy cancer cells
two forms of relapse after CAR-T cell infusions
antigen-positive relapse
antigen escape
antigen-positive relapse
occurs in early phase
closely related to car-t cell persistance
antigen escape/loss
occurs in later phases
alternative splicing primary cause, gradually develop into dominant clusters under strong immune pressure
trogocytosis
Trogocytosis occurs when one cell contacts and quickly nibbles another cell and is characterized by contact between living cells and rapid transfer of membrane fragments with functional integrity. Many immune cells are involved in this process, such as T cells, B cells, NK cells, APCs
cytokine release syndrome
a condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies and CAR-T cells
caused by large, rapid release of cytokines into blood from immune cells affected by the immunotherapy
immunotherapy and the gut microbiome
composition of each persons gut microbiota plays significant role in efficacy of given treatments
goal is to determine as precisely as possibly which microbes confer beneficial effect and formulating a probiotic suspension of just those organisms
historical spontaneous regressions of cancer
rhodenburg: 185 cases in 1918
fauvet: 202 cases 1960-1964
boyd: 98 cases 1966
everson & cole: 176 1900-1960
challis: 489 1900-1987
hobohm: meta analysis of 1000 cases, frequency estimated to be 1 in 100,000 cancers
why study malignant melanoma in tumor immunology
visible
model for melanoma regression
occurs with auto-immunity to melanocyte self-antigens (vitiligio)
specific t-cell and humoral responses occur
vitiligo patterns may be template of antigen repertoire
immune system can recognize any tumor
immonoassays and disease
serological reactions used for many diagnostic immunology tests and often use monoclonal antibodies (MBAS)
clinical diagnostic tests that use MBAS include typing of bacterial pathogens, identification of cells containing foreign surface antigens and highly specific blood and tissue typing, detect and treat cancer
monoclonal antibodies
produced by isolating single clones of B cells that are fused with cancer cells to make immortalized cell lines that produce a single type of antibody
direct agglutination
results when soluble antibody causes clumping due to interaction with an antigen that is an integral part of the surface of a cell or other insoluble particle
used for classification of antigens found on surface of RBCs
passive agglutination
the agglutination of soluble antigens or antibodies that have been absorbed or chemically coupled to cells or insoluble particles
reactions can be up to 5x more sensitive than direct agglutination
enzyme immonoassay (EIA) or enzyme linked immunosorbent assay (ELISA)
very sensitive immunological assay
widely used in clinical diagnostic & research
EIAS employ covalently bonded enzymes attached to antibody molecules
rapid tests similar to EIAS
both allow detection of antigen-antibody complexes
rapid tests
similar to EIAS but results can be recorded in minutes not hours
provide point of care diagnostics
not as specific or sensitive
reagents absorbed to support material
body fluid applied to support matrix
matrix contains soluble antigen conjugated to colored molecule (chromophore) & line of fixed antigen which antibodies bind to, detect color change
ex. pregnancy, strep, hiv, covid, rsv tests
immunoblot / western blot
electrophoresis of proteins, followed by transfer to a membrane & detection by addition of specific antibodies
immunoblot methods detect antibodies to specific antigens or antigens themselves
ex. hiv antibodies, confirmatory test for hiv rapid test
