Immunology Exam 1 2
Terms
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- Molds
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multinucleate
grow as hyphae - yeasts
- unicellular ovoid cells- divide through budding
- protozoa
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singe celled animals
injection by bites- Trypanosomes, Leishmania, plasmodium
ingestion of infective staged- Gardia, Entamoeba - Helminths
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-tapeworm (Cestoda)
-flukes (Trematoda)
-roundworms (Nematoda) - hi(N:C) cells
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all B cells
90% T helper cells
50% Tc cells - Gaul body
- lipid drop with primary lysosomes- found in T cells wtih hi(N:C)
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lo(N:C)
LGL morphology -
10% Th cells
50% Tc cells
all NK cells
more lysosomes in T cells - CD
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cluster designation
clusters of antibodies that recognize a particular cell marker - TCR-2
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alpha and beta polypeptides
always assoc. with CD3
positive transmembrane - TCR-1
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gamma and delta
always assoc. with CD3 - CD3
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five polypeptides always associated with 2 TCR
negative transmembrane - B cells in peripheral blood express IgM and IgD
- IgM is associated with other molecules on B cells surgace to form the B cell antigen receptor complex
- main markers to identify human B cells
- CD19, CD20, CD22
- NKRP1
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on NK cell
attaches to glycoproteins and sends + signal to kill cell- counteracted by Ly49 - Ly49
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on NK cell
attaches to MHC1 and sends - signal so cell is not killed - activated B cell expressed new markers-
- MHC2, IL-2 receptors, IL-3-6 receptors
- Mononuclear phagocytes are two types-
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1- professional phagocytic
2- APC- have Fc receptors and MHC2 - monocyte characteristics
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horse shoe shaped nucleus with azurphilic granules
large
contain peroxidase and acid hydrolases for intracellular killing - follicular dendritic cell
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in B cell areas of lymph and spleen
present antigen to B cells, lack MHC2 but have lots of comp. rec. and Fc rec. - interdigitating cells in medulla of thymus
- delete self recognizing T cells
- neutrophil
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90% of granulocytes
three lobes
primary granules- lysosomes
secondary granules- lysozyme
Kamakazi cells
comp. rec, not specific - eosiniphil
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bi-lobed
allergies- usually degranulate
parasitic worms - basophil
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allergen stimulates degran.
allergen must cross like with IgE
histamine
Fc rec. for IgE - platelets
- increase permeability of BV around injury
- Hassal's corpuscles
- in thymic medulla, contain degenerating epithelial cells
- white pulp of spleen
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surrounds central arteriole- PALS
T cells around arteriole
B cells further out in 1ary and 2ary follicles - germinal centers
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in secondary follicles of B cells in spleen and lymph nodes
contain follicular dendritic cells and phagocytic cells - marginal zone
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surrounding secondary follicles of B cells of lymph nodes and spleen
contain B cells and macrophages - red pulp of spleen
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sinuses containing macrophages, erythrocytes, platelets, granulocytes, and plasma cells
where old RBCs are destroyed - Lymph node
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Cortex- B cells
Paracortex- T cells
Medulla- T cells, B cells, plasma cells and macrophages - HEV in lymph nodes
- mostly in paracortex but some in cortex
- classes of Ig determined by..
- heavy chain type
- isotypes
- differences in CONSTANT region
- allotypes
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differences in protein expression in one individual in a population
same isotype - idiotypes
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differences in VARIABLE region
produces antigen specificity - A B cell can have more than one _____ but only one _______.
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isotype, idiotype
specific to ONE antigen - IgG
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all memory cells
four chain molecule
confers immunity to newborn - IgM
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pentamer connected by J chain and 18AA residue
first antibody released in immune response - IgD
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large amount on B cell membrane
unknown function - IgE
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scarce in serum
basophils and mast cells
allergies
short lived abs, but long lived when attached to mast cell - CDR- complement determining region
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variable region on light chain of Abs
interspered by Fr- framework - gene segments for variable chain
- variabe, joining, diversity
- papain
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cleaves into two Fab segments and one Fc region
cleaves in hinge region - pepsin
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cleaves after hinge-
one Fab2 and one pFc - CDR's -numbers
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30, 50, 95
in abs, 3 CDR's and 4 Fr's - ITAM
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portion of CD3 with tyrosine that is phosphoryated upon peptide bonding of TCR
causes IL2 and IL2 rec. to be expressed - MHC gene location
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Chr. 6 humans HLA complex
Chr. 17 mice H2 complex - Class III MHC genes
- encode soluble serum proteins, components of complement, TNF
- haplotype
- set of alleles for MHC- one from mom and one from dad
- MHC 1
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always with B2 microglobulin
binds short aa sequences
blocked cleft- anchor residue
low expression in liver, neural and muscle cells
high expression in lymphs - MHC 2
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Beta and Alpha chains- 2
up to 12 on cell
H bonding throughout binding site - ABC family of transporters
- In cell with MHC1, transport peptide to RER from cytoplasm
- antibody affinity
- strength of single bond between antigen and antibody
- antibody avidity
- all the Fab regions so more than one epitope and paratope interaction
- first interaction after antigen challenge
- APC and T cell
- Interdigitating dendritic cells
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in T cell dependent areas of lymph nodes and spleen
the most effective cells for inital activation of resting CD4 T cells
have CD80 and CD82 to stim. CD28 on T cell
highest levels of MHC2 - enzyme p56lck
- on TCR- phosphorylates tyr. on ITAM of CD3
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co stimulatory interactions
"second signal" -
ICAM-1 with LFA-1
CD80/CD82 with CD28- most potent signal to divide
LFA-3 with CD2 activates T cells - IL-1 and IL-6 by APCs
- activate T cell- induce expression for IL-2 rec. on T cell
- macrophage activating factors from T cells
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IFN gamma, GM-CSF, TNF alpha
induce expression of MHC2, Fc rec., adhesion molecules (CD80, CD82), IL6, IL1 - TNF alpha from macrophage
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can kill cell directly
causes leukocytes to adhere to bv wall and diapediesis - TNF alpha and IL-2
- stimulate NK cells
- CD40 on B cell binds to CD40L of T cell...
- most potent activator of B cell
- T cell release cytokines- affect on B cell
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IL-2- proliferation
IL-4- early on B cell activation and proliferation
IL-5- in mouse, activator
IL-6- DIFFERNTIATION
TNF alpha and beta- B cell growth - primary antigenic challenge
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lag, log, plateau, decline
mostly IgM - secondary antigenic challenge
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shorter lag
extended plateau and decline
much higher plateau
mostly IgG
memory Th cells - IL-4
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acts on B cells to induce activation and differentiation
causes TH cell differentiation - sedondary challenge higher affinity due to...
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somatic hypermutation
selective expansion of high affinity clones only - How do memory B cells differe from unprimed B cells?
- They make IgG earlier and have higher affinity for antigen
- T ind antigens
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Activate B cells without T cell help
similar weak primary and secondary response
many are products of bacteria - mitogens (lectins)
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can activate lymphocytes in a non-antigen speciic manner
bind to CD2 on T cell
ex. PHA ConA - superantigens
- activate T cells non-specifically- bind on variable B chain of TCR. Puts T cell in state of tolerance.
- cytokines
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regulate cell growth, cell activation, inflamm, immunity, tissue repair, morphogenesis.
chemokines if chemotactic - inteferons
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anti-viral CKs.
IFN alpha and beta- response to viruses
IFN gamma- response to immune stimuli, produced by NK and T cells.
-induce MHC2 molecules, and IL-1 and IL-6 - Inerleukins
- made by endothelial cells and fibroblasts
- IL-1
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made mostly by macrophages
stimulates T and B cells
fever
almost all cells have it - IL-2
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made by T cells and NKs
most powerful growth factor and activator
acts on B cells and NK's to induce growth and differentiation - IL-3
- stimulates stem cell growth, always with growth factor
- IL-6
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produced by macrophages, T cells, B cells, fibroblasts, endothellial cells
acts on B cells to differentiation into AFCs - humoral branch
- EXTRAcellular
- cell mediated branch
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INTRAcellular
depend on cytokines - bacterial endotoxin
- activates complement components
- TH select and activate effector mechanisms
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help B cells make antibody
activate or suppress effector cells- Tc, NK, macrophages, granulocytes, K cells - if organism triggers release of IL-12 and IFN gamma from macrophage, then....
- TH1 subset will develop and secrete IL-2 and IFN gamma which activate macrophages
- if organism triggers release of IL-4 and IL-10 from macrophage then...
- TH2 subset will develop and secrete IL-4-6, IL-10 to increase Abs production, increase mast cells and eosinophils
- IFN gamma from TH1 cells inhibits...
- proliferation of TH2 cells
- IL-10 of TH2 cells inhibits...
- cytokine release by TH1 cells
- effector cells of cell mediated cytotoxicity are...
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Tc cells
NK cells
K cells - most important role of Tc cell is to...
- eliminate virus infected cells
- NK cells provide....
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the first line of defense against virus infection
NK cells peak at 3 days
Tc cells peak at 7 days - Virus infected cells release IFN alpha and beta which activate...
- NK cells
- K cell
- any cytotoxic cell with Fc receptor on surface- must link to pathogen through abs made by B cell
- killing mech of T cells, K cells, NK cells
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bind target cell
degranulate releasing perforin
polyperforin channels on target cell
degredative enzymes enter - ADCC
- Antibody Dependent Cell Mediated Cytotoxity
- endotoxin (myeloid derived) killing mechanism
- LPS activate macrophage to release TNF alpha- this with IFN gamma from T cells and NK cells produces NO and kills
- myeloid cells killing mech.
- release reactive oxygen intermediates, reactive nitrogen intermediates, hydrolytic enzymes
- cytotoxicity
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virus infected essential cells are killed
ie. nerve cells - chronic inflammation
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against autoantigens resulting in inflamm.
ie. Rheumatoid, multiple sclerosis - Space occupying lesions
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T cells continue to accumulate and release lymphokines, recruiting macrophages--granuloma results--giant cell with lytic enzymes.
CD4 Th1 producing IL-2, IFNgamma and TNF alpha - Excessive cytokine release
- toxic shock syndrome