[mtle] immunosero pt. 2

(1) MHC class I

(1) type of MHC; VIRALLY infected cell is recognized by T cytotoxic cell (CD 8)

T cytotoxic cell activated by IL 2 produced by T helper cell; activated Tc kill virally infected cell by PERFORINS and GRANZYMES

(2) MHC class I

(2) type of MHC; located on ALL nucleated cells; presents antigen to CD8 cells (T cells) destruction of cirally infected cells, tumor cells, graft rejection

(1) MHC class II

(1) type of MHC; antigen presenting cells present antigenic fragements through this MHC and is recognized by T helper cell

T helper cell produces IL 2 and becomes activated; IL 12 stimulates activated Th cells to become Th 1; IL 4 stimulates activated Th cell to Th2

(2) MHC class II

(2) type of MHC; located on antigen-presenting cells (MAC, monocyte, B cells, dendritic cells); presentation of antigen to CD4 cells (T helper cells)

T helper 1 cells

type of Th cells; produce IFN-y which activates phagocytes to kill ingested microbes; mediate TYPE IV hypersensitivity reaction and CELLULAR immunity

IFN-y

produced by Th1 cells; stimulates production of antibodies that promote ingestion of microbes by phagocytes which increases opsonization and phagocytosis

T helper 2 cells

type of Th cells; produce IL 4 which stimulates production of IgE and Il 5; mediates TYPE I hypersensitivity and HUMORAL immunity

IL 4

produced by Th2 cells; stimulates production of IgG4

IL 5

stimulates production by IL 4; activates eosinophils

IgE

stimulates production by IL 4; activates mast cells by and coats helminths for destruction by eosinophils

HLA-B27

this type of major histocompatibility complex are associated with ANKYLOSING SPONDYLITIS (has STRONGEST correlation) or BAMBOO SPINE DISEASE

HLA-DR3

this type of major histocompatibility complex are associated with SYSTEMIC LUPUS ERYTHEMATOSUS, DIABETES MELLITUS, GRAVE'S DISEASE, ADDISON'S DISEASE, MYASTHENIA GRAVIS

HLA-DR4

this type of major histocompatibility complex are associated with RHEUMATOID ARTHRITIS and DIABETES MELLITUS

HLA-B8

this type of major histocompatibility complex are associated MYASTHENIA GRAVIS, ADDISON'S DISEASE, CELIAC DISEASE, INCREASED RESISTANCE to HIV

major histocompatibility complex

HIGHLY polymorphic; HLA gene has many forms in population and makes compatibility difficult

chromosome 6

which chromosome is associated with MHC genes?

class I genes

HLA-A, HLA-B (B27 & B8), HLA-C

class II genes

HLA-D, HLA-DP, HLA-DQ, HLA-DR (DR3, DR4)

class III genes

C2, C4, factor B, TNF

serologic tissue matching

tests for MHC; donor and recipient cells are reacted with HLA antibodies; SIMPLE nad FAST

cellular tissue matching (mixed lymphocyte reaction)

tests for MHC; recipient lymphocyte proliferates; best for BONE MARROW GRAFTS and LIVING RELATED DONORS; tests for HLA-D (CLASS II)

mitomycin C or irradiation

in mixed lymphocyte reaction; used to INACTIVATE donor lymphocyte

thymidine

in mixed lymphocyte reaction, used to measure amount of proliferation

molecular tissue matching (restriction fragment length polymorphism)

tests for MHC; enzymes that cleave DNA are used to obtain patterns; DNA sequences are amplified by PCR; genetic disparity is assessed; FASTEST and SUPERIOR

HLA class I typing

tissue typing

a. requires only 1-2 mL of serum

b. lymphocytes are incubated with panel of HLA-antibodies and complement is added

c. if HLA antigen specific to HLA antibody is present, complement is activated and kills cells

ACD or heparinized blood

type of sample used in HLA class I typing

ficoll-hypaque centrifugation

obtains purified lymphocyte suspension in HLA class I typing

eosin Y or trypan blue

dye used to visualize in HLA class I typing

uninjured cells

in HLA class I typing; small, bright, refractile; NEGATIVE reaction -> NOT lysed

injured cells

in HLA class I typing; flattened, large, dark, nonrefractile; POSITIVE reaction -> LYSED meaning antigen present

HLA class II typing

tissue typing; HLA-DR typing requires identification of B lymphocytes; B cells adhere to NYLON WOOL and can be eluted

nylon wool separation (elution)

in HLA class II typing, prepares B lymphocyte suspension

antigen

substance that triggers an immune response and reacts with antibody

hapten

part of antigen; non immunogenic materials (when combined with carrier will create new antigenic determinants); INcomplete antigen

schlepper molecule (carrier molecule)

part of antigen; IMMUNOGENIC; coupled with haptenic groups which will confer new antigenic specificities

immunogen

substance that can induce immune response

foreignness

factors influencing immunogenicity; greater the difference between substance and host, MORE potent is its antigenic qualities

<1 kilodalton

size of NON immunogenic molecule

6 kD or more

size of STRONG immunogen molecules

at least 1 kD or 10,000 Daltons

size of molecule to be immunogenic

chemical composition

factors influencing immunogenicity; MORE COMPLEX the substance, MORE IMMUNOGENIC; protein have HIGH molecular weight therefore they are GOOD immunogens

dose

factors influencing immunogenicity; method of administration wherein there is a dose of antigen above or below which immune response will NOT be optimal

route

factors influencing immunogenicity; method of administration wherein subcutaneous or intramuscular route is BETTER than intravenous or intragastric routes

adjuvants

factors influencing immunogenicity; substances that can ENHANCE immune responses

alum precipitate

used in human vaccines; used to complex with immunogen to increase its size and prevent rapid escape from tissues

squaline or Mf59

type of adjuvant; obtained from shark's oil (HIV vaccine development)

freund's complete adjucant

type of adjucant; water in oil emulsion of killed MTB or B. pertussis, enhances cell mediated immunity; NOT used for human vaccines because it produces large granuloma

autoantigen

antigen from SAME individual

alloantigen

antigen from DIFFERENT individual but SAME species

heteroantigen

antigen from DIFFERENT species

heterophile antigens

heteroantigens that exist in unrelated plants or animals but are either identical or closely related in structure so that antibody to one will cross-react with antigen of the other

autograft

graft of tissue from one's own body

isograft (syngraft)

graft from DIFFERENT but identical individual

allograft

graft from DIFFERENT individuals but SAME species (fetus on mother's womb)

heterograft (xenograft)

graft from DIFFERENT species (pig's heart valves)

bone marrow

MOST IMMUNOGENIC organ that can be transplanted

cornea

LEAST IMMUNOGENIC organ that can be transplanted

hyperacute graft rejection

-type of graft rejection occurring WITHIN MINUTES

-mechanism is HUMORAL; caused by preformed cytotoxic antibodies to donor antigens

accelerated graft rejection

-type of graft rejection occurring 2-5 DAYS

-CELL-MEDIATED; caused by previous sensitization to donor antigens

acute graft rejection

-type of graft rejection occurring 7-21 DAYS

-CELL-MEDIATED; caused by allogeneic reaction to donor antigens

chronic graft rejection

-type of graft rejection occurring more than 3 MONTHS

-CELL-MEDIATED; caused by disturbance of host vs. graft tolerance

antibodies

specialized proteins that aid in destroying infectious agents; SPECIFIC glycoproteins referred to as IMMUNOGLOBULINS; produced in response to antigenic stimulation

immunoglobulins

antibodies that neutralize toxic substance, facilitate phagocytosis (opsonization), kill microbes, combine with antigen on cell surfaces and cause destruction of cells

heavy chain

gamma, alpha, mu, epsilon, and delta; each chain combines equally well with any light chain

light chain

lambda and kappa; antibodies will always have two identical type of this chains

kappa

type of light chain found in chromosome 2

lambda

type of light chain found in chromosome 22

disulfide bonds

type of bonds that connects heavy chain to heavy chain and heavy chain to light chain

bence jone proteins

proteins with light chain to light chain connection

hinge region

located between constant heavy 1 and constant heavy 2; allows immunoglobulin to take on different shapes

proline

high content of this substance in hinge region gives immunoglobulin flexibility

variable domain

part of region; responsible for binding antigen; varies to allow B cells to produce antibodies to many different antigens; UPPER portion of Fab which binds to SPECIFIC antigen

constant domain

part of region; LOWER portion of FAB and activates compliment cascade

isotype

-type of antibodies found in all different individuals in related species

-HEAVY chain of each immunoglobulin class

allotype

-type of antibodies found within one species

-VARIATION in CONSTANT region

idiotype

-type of antibodies found within one individual

-variations in VARIABLE region

valence

number of binding sites

papain

cleaves immunoglobulin into 3 fragments; cleaves ABOVE hinge region; has 2 Fab and 1 Fc

pepsin

cleaves immunoglobulin into 2 fragments; cleaves BELOW hinge region; has F(ab)2 and Fc'

F(ab)2

fragment of immunoglobulin molecule obtained by pepsin cleavage that consists of two light chains and two heavy-chain halves held together by disulfide bonding; MAJOR fragmentation product of pepsin

(1) IgM

(1) immunoglobulin; PRIMARY response to antibody; FIRST to appear after antigenic stimulation and maturing infant; synthesized only as long as antigen remains present (has NO memory cells

(2) IgM

(2) immunoglobulin; function as complement fixation, agglutination, opsonization, toxin neutralization; MOST efficient at triggering classical complemnt activity; potent AGAINST gram (-) bacteria

(3) IgM

(3) immunoglobulin; efficient at AGGLUTINATION which causes CLUMPING together of LARGER particles (RBCs) and cytolytic response; MOST PRIMITIVE; responds to CARBOHYDRATE antigens

(1) IgG

(1) immunoglobulin; functions by providing immunity for newborn (can cross placenta), fix complement, coat antigen for enhanced phagocytosis (opsonization), neutralize toxin and viruses, participate in agglutination and precipitation reactions

(2) IgG

(2) immunoglobulin; macrophage, monocytes, neutrophil have receptors for this Ig; ENHANCE contact between antigen and phagocytic cells and INCREASE efficiency of phagocytosis

(3) IgG

(3) immunoglobulin; better at PRECIPITATION reactions because precipitation involves small soluble particles which are more EASILY brought together by relatively small IgG

(4) IgG

(4) immunoglobulin; MAJOR immunoglobulin in NORMAL serum and in ANAMNESTIC RESPONSE; LONGEST half-life of any immunoglobulin class; targeting VIRALLY infected cell for destruction by ADCC; responds best to PROTEIN antigens

IgG3

type of IgG; LARGEST hinge region and LARGEST number of interchain disulfide bonds and MOST EFFICIENT at binding complement

IG2 and IgG4

type of IgG; SHORTER hinge region which are POOR mediators of complement activation

IgG1 and IgG3

type of IgG; GOOD at initiating phagocytosis (bind most STRONGLY to Fc receptors)

(1) IgA

(1) immunoglobulin; functions to patrol mucosal surfaces and acts as first line of defense leading to neutralizing toxins produced by microorganisms and helps to prevent bacterial adherence to mucosal surface

(2) IgA

(2) immunoglobulin; found in BREAST MILK for breastfeeding helps maintain health of newborns; complexes of IgA and antigen are easily trapped in mucus and eliminated by ciliated ECs which prevents pathogens from colonizing mucosal epithelium

(3) IgA

(3) immunoglobulin; PREDOMINANT immunoglobulin in SECRETIONS; present as DIMER in secretions; binds to SECRETORY COMPONENT produced by epithelial cells which prevents enzymatic degradation forming SECRETORY IgA

(1) IgD

(1) immunoglobulin; present on surface of B cells (plats a role on B cell activation) and plays a role in regulating B cell maturation and differentiation; SUSCEPTIBLE to proteolysis -> SHORT life (1-3 days)

(2) IgD

(2) immunoglobulin; cell membrane found on surface of B cells in association with IgM; serves function in immunoregulation; helps in differentiation and maturation of B cell to plasma cell

(1) IgE

(1) immunoglobulin; mediates some type of hypersensitivity (allergic) reactions, allergies, anaphylaxis; responsible for immunity and invading PARASITES

(2) IgE

(2) immunoglobulin; originally called REAGIN; binds strongly to receptor on MAST CELLS and BASOPHILS and together with antigen, mediates release of HISTAMINE and HEPARIN from these cells

monoclonal antibodies

antibodies fused activated B cells with MYELOMA CELL (cancerous plasma cell) that can be grown indefinitely in laboratory

george kohler and cesar milstein

discover monoclonal antibodies in 1975 and was awarded the nobel prize in 1984

myeloma cell line

in monoclonal antibody, incapable of producing antibody and also deficient of HGPRT and thymidine kinase which are needed for DNA synthesis