Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
160 Cards in this Set
- Front
- Back
What is diffuse lymphatic tissue?
|
Scattered lymphocytes, plasma cells. Only efferent vessels. Beneath wet epithelia.
|
|
What does a primary nodule lack?
|
A germinal center (central pale zone).
|
|
What makes up a germinal center?
|
Lymphocytes and follicular dendritic cells
|
|
Describe the blood supply of lymph nodes.
|
At the hilum arteries enter, veins leave. Postcap venules in paracortex.
|
|
Where are reticular cells found and what do they do?
|
Part of the sinus wall and in stroma. Specialized fibroblast that produce collagen III. Also produce cytokines to attract lymphocytes and dendritic cells.
|
|
Where are Dendritic cells and what do they do?
|
From bone marrow, APC to T lymph
|
|
Where is the thymus from embryologically?
|
3rd and 4th pouch endoderm
|
|
What happens in the thymus' cortex?
|
Lymphocytes undergo selection, differentiation and maturation. Macrophages phagocytosing apoptotic lymphocytes.
|
|
Where are Hassall's corpuscles found?
|
The medulla of thymus
|
|
What are the 3 types of Thymic epithelial cells?
|
Cortical epithelial cells
Thymic epithelial cells type 3 & 4 Medullary epithelial cells |
|
What 2 structures would one find in thymic epithelial cells?
|
Desmosomes and tonofibrils (keratin intermediate filaments)
|
|
Name the 2 types of Cortical epithelial cells
|
Subcapsular epithelial cells (tight junc)
Nurse cells/Inner cortical epithelial cells |
|
Which type of cell is involved in the blood-thymus barrier?
|
Subcapsular epithelial cells
|
|
What is the function of the thymic epi cells?
|
B/T barrier
Form loose meshwork Educate T lymph Make cytokines and hormones Form Hassall's corp |
|
What structures does the spleen lack?
|
Lymph sinuses and afferent lymph vessels
|
|
What covers the spleen?
|
Peritoneum
|
|
Name the encapsulated lymph organs
|
Spleen, thymus, lymph nodes
|
|
Where are central arteries found in the spleen?
|
white pulp
|
|
What are splenic cords (Billroth cords)?
|
The tissue between sinusoids in the spleen red pulp that contain many MO and RBCs
|
|
What are the branches off of the central arteries in the spleen called?
|
Penicillar (straight arteries). Terminate into arterial cap (ensheathed by MO, reticular cells and lymphatic cells)
|
|
Describe the open theory.
|
In the spleen the arterial cap empty into the splenic cord spaces then passes between the endo cells of sinusoid to re-enter circ.
|
|
What is the function of the spleen?
|
Filter blood
Produce lymphocytes (B cells make antibodies) Destroys old blood cells Hematopoiesis in embryo Blood storage |
|
What kind of lymph vessels do tonsils have
|
Efferent
|
|
Tonsils are collectively known as...?
|
Waldyer's ring
|
|
Which is the largest tonsil?
|
Palatine
|
|
Where are Peyer's patches found?
|
Ileum
|
|
What are M cells and what do they do?
|
Cover Peyer's patchesand they endocytose macromolecules and transport them to underlying lymphocytes
|
|
Name the cells involved in the Triumvirate
|
Lymphocytes
Phagocytes APC |
|
How do T cells recognize foreign fragments?
|
Via epitopes presented to them by APCs via MHC
|
|
Which cells are the only ones to possess Specificity, Discrimination, and Memory?
|
B & T cells
|
|
Where do B & T cells originate from?
|
Hematopoietic Stem Cells (HSC)
|
|
True or False: B cell education, differentiation, and maturation require the presence of exogenous antigen
|
False
|
|
What is important to note about the maturation, education, and differentiation of T cells?
|
It occurs in the absence of exogenous antigen.
|
|
What happens upon the "graduation" of B & T cells?
|
They acquire cell membrane specific receptors for antigen and migrate and seed secondary lymph tissues
|
|
What is Clonal expansion?
|
When Ag interacts with the receptor, cell activates and divides --> clone of identical progeny whose receptors bind the same epitope. Also yields memory cells.
|
|
What 3 things must an Ag be in order to be effective?
|
1) Foreign (non self or altered self)
2) High Mol weight 3) complex & preferably protein |
|
What is a complete Ag?
|
Protein
High mol weight Chemical complexity Degradability |
|
What kind of bond is there between an epitope and MHC?
|
Noncovalent
|
|
Any molecule that is not itself antigenic but when conjugated to a carrier protein becomes antigenic and induces Ab
|
Hapten (incomplete Ag)
|
|
Antigenic without the participation of T lymphocytes
|
T-independent Ag
|
|
What is characteristic about T-independent Ag?
|
Having a structure that consists of repeating chemical units (ex: bacterial flagella) Antibody usually produced: IgM
|
|
How is a superAg different than a regular Ag?
|
Unlike regular Ag that bind to MHC cleft, the superAg bin the MHC-TcR independent of the cleft- they are not processed by APC
|
|
What is the importance of superAg?
|
Ability to non-specifically activate T cells resulting in abnormal amount of cytokines.
|
|
Describe adoptive immunity
|
Transfer of lymphoid cells (not Ab) from an actively immunized donor. T cells major player.
|
|
What 4 things does Acquired immunity possess?
|
1) Specificity
2) Adaptive 3) Discrimination 4) Memory (anamnestic response) |
|
What is the function of the MHC molecule?
|
Function as antigen presenting structures for T cells
|
|
Small fragments of cut up Ag
|
Epitope
|
|
MHC I: Ag?
To? Need? Important for...? |
Endogenous Ag
To Tc cells Need CD8 Viruses (intracellular pathogens) |
|
MHC II: Ag?
To? Need? Important for..? |
Exogenous Ag
To Th cells CD4 Pathogens that replicate outside cell |
|
MHC is found on what chromosome in humans?
MHC aka...? |
Chromosome 6
aka: HLA (Human Lymphocyte Ag) |
|
Which MHC Class is expressed on nearly all nucleated cells?
|
MHC Class I
|
|
What are the major regions in the human genome coding for Class I
|
A, B, C
|
|
Class I and II encode what type of proteins?
|
Glycosylated
|
|
MHC Class II is expressed on what type of cells?
|
APCs
|
|
What are the major regions in the human genome coding for Class II?
|
DP, DQ, DR
|
|
How are MHC genes inherited?
|
Usually inherited as a group (closely linked).... One haplotype from mom, one from dad
*Polymorphic* |
|
How are MHC genes expressed?
|
Codominantly
*progeny will generally not be able to accept grafts from parents since only have half from each* |
|
Describe the MHC Class I molecule
|
Alpha chain: large, 3 external domains (1,2,3), transmembrane domain, cytoplasmic segment
Beta chain: invariant protein, gene not part of MHC |
|
Which portion of the MHC Class I molecule forms the Ag/peptide binding domain?
|
alpha1 and alpha2
|
|
Describe the "hotdog bun" of MHC Class I
|
form a platform of 8 antiparallel B strands with 2 alpha helices forming borders... Groove holds 8-10 aa
|
|
The MHC Class I Beta and Alpha chains look similar to what?
|
Immunoglobin fold structure... They are considered part of the Ig Superfamily
|
|
Which part of the MHC molecule is recognized by CD8?
|
alpha3
|
|
Describe the MHC Class II molecule
|
Alpha chain and Beta chain associate via noncovalent bonds... 2 external domains alpha 1 and 2; beta 1 and 2....
|
|
What region on the MHC Class II are considered Ig Superfamily members?
|
alpha2 and beta2
|
|
What region of the MHC Class II bind Ag?
|
alpha1 and beta1
|
|
What region of the MHC Class II is recognized by CD4?
|
beta2
|
|
How many different Class I molecules can each human express?
|
Up to 6
|
|
Describe the "promiscuity" of MHC molecules
|
Can bind large # of peptides.... some peptides can bind more than one molecule
|
|
In what form does the peptide bind in Class I and II?
|
extended conformation inside the groove between the 2 alpha helices
|
|
Of Class I and II molecules, which can hold more aa?
|
Class II (13-25 aa)... Class II is more open, Class I is blocked at ends (8-10 aa)
|
|
Which portion of the epitope/peptide makes more direct contact with the TCR and why?
|
The middle portion of the peptide because the middle tends to hunch up and not make direct contact with the groove
|
|
True or false:
Hunching is seen only in MHC Class I |
True
|
|
True or false:
MHC Class II can bind and unlimited variety of peptides |
False... limited variety
|
|
Describe the sequence in which MHC Class I presents Ag
|
Ubiquitin attached--> degraded into peptides by proteasome--> IFN-gamma substitutes parts of proteasome to create immunoproteasome --> Peptide transported into RER by TAP--> peptide loaded into MHC assisted by calnexin, calreticulin, and tapasin --> trimer goes through golgi to surface
|
|
Which cells can present endogenous Ag?
|
Almost all cells since all nucleated cells have MHC Class I
|
|
What does an immunoproteasome do?
|
produce peptides with a hydrophobic or basic residue at the C terminus
|
|
What happens when one lacks functional TAP?
|
Bare lymphocyte syndrome.... immuno compromised
|
|
What does the MHC Class I bind to until they can bind to the Beta segment?
|
Calnexin
|
|
Where does MHC Class I first bind on the peptide?
|
C terminus
|
|
What does ERAP do?
|
(ER aminopeptidase) can cut off aa from the other end of the peptide to make it fit
|
|
What are the most effective APCs?
Which need to be activated before expressing MHC Class II? |
Dentritic Cells
Macrophage |
|
Where do exogenous Ag come from?
|
phagocytosed bacteria, Ag bound to Ab on surface of B cell
|
|
What cells constitutively express MHC Class II?
|
B cells
|
|
Describe Ag presentation by MHC Class II
|
Internalized--> degraded as it passes through acidic endosomal compartments--> Class II chains made and enter ER--> invariant chain associates with to fill groove (dummy)--> moves to golgi and join endosomes with peptide--> invariant chain degrades into CLIP--> CLIP exchanged for peptide with help of HLA-DM--> goes to surface
|
|
What degrades the invariant chain?
|
acidic pH and proteases
|
|
Describe Cross Presentation
Advantage? |
APCs can present exogenous Ag to Tc in the context of MHC Class I... Ex: Dendritic cells
Advantage: can help get immune response to viruses faster |
|
Where is the diversity in MHC genes clustered?
|
In parts of molecule that actually bind the peptides... specifically where the Ag actually binds
|
|
Marek's Disease
|
in chickens with MHC B19
|
|
Akylosing spondylitits
|
inflammatory disease leading to the stiffening of the vertebral joints in the spine
|
|
What turns on and proliferates a B lymphocyte?
|
Cytokines from T cells
|
|
What synthesizes and secretes specific Ab?
|
Plasma Cells
|
|
What are the 3 major ways Ab protect the host?
|
Neutralization
Opsonization (C3b) Complement activation |
|
What percentage of serum is IgG
|
~80%
*migrates in the gamma globulin fraction of serum protein sep* |
|
What are the 5 isotypes of Ig?
|
IgG
IgA IgM IgD IgE |
|
How are the 5 Ig Isotypes distinguished?
|
Distinguished on the basis of aa structural differences in the C heavy chain
|
|
How are Ab and BcR related?
|
Antibodies are the SOLUBLE form of the BcR
|
|
Which 2 isotypes are involved with the BcR?
|
sIgM
sIgD |
|
True or false:
Each Ab differs in it's basic structure |
False:
All Ab have the same basic structure, they just differ in the regions that bind epitope |
|
The site associated with Ag recognition and binding
|
Paratope
|
|
What is the specificity of the Ab based on?
|
The hypervariable regions within the paratope called CDR
|
|
What are the 3 hypervariable regions within the VL and VH chains?
|
HV1, HV2, HV3 aka (CDR1, CDR2, CDR3)
|
|
Describe the composition of an Ab
|
2 light and 2 heavy chains held together by inter-chain S-H bridges
|
|
About how many aa make up the looped domains and how are they held?
|
90-100 aa... Held in configuration by intra-chain disulfide bonds
|
|
What is the N-term of the Ab characterized by?
|
VH and VL
|
|
POINT TO NOTE
|
Arms of Ab identical --> V and C heavy and light chains composed of same aa sequences--> paratopes will bind identical epitopes--> Bivalent
|
|
What is the hinge region composed of and what are their functions?
|
Cysteine-- form the inter-chain disulphide bonds that hold heavy chains together
Polyproline-- allow flexibility of the 2 arms of Ab |
|
What is the Fc?
|
The "tail" 2 heavy chain constant regions... Important for the biologic activity related to the Ab
|
|
What is Fab?
|
Describes each arm of the Ab made of L and H chains. Fab binds only one epitope...
*F(ab)2 describes both arms together --> bind 2 epitopes* |
|
Why is Fc important?
|
1) Binding MO, PMNs, NK cells
2) Binding or fixing Complement 3) Transport Ab across membrane 4) Bind B cells during "education" and cR formation 5) Identify Ab isotype |
|
What is ISOtypic?
|
Differences in the aa composition of H constant regions... 5 isotypes... gamma, alpha, mu, delta, epsilon
|
|
Describe Allotypic
|
Refers to allelic aa differences in the Ab C regions...serve as genetic markers (Gm, Am, Km)
|
|
What is IDIOtypic?
|
Within the L and H chains are hypervariable regions called CDRs (uniquely differ)...Remainder framework is the same for each Ab)
|
|
An Ab directed against the Ag specific part of the sequence of an ab or TcR thus recognizing binding sites of other Abs or TcRs
|
Anti-idiotypic Ab
|
|
In principle, what should Anti-IDs do and when are they used?
|
The should inhibit a specific immune response... important to Regulation of immune system... used in IVIG
|
|
Where does Pepsin cleave an what are the resulting pieces?
|
Cleaves below the disulphide bonds of H chain... leaves one F(ab)2 fragment and subfragments of Fc
|
|
Where does Papain cleave and what are the resulting pieces?
|
Cleave above the disulphide bonds of H chain... leaves 2 Fab fragments and 1 Fc
|
|
How many isotypes do the L chains have?
How are they seen in the Ab? |
2: k and lambda
An Ab can have either kappas OR lambdas, never both |
|
What Chromosomes are Kappa and lamda from?
|
Chromosomes 2 (k) & 22 (l)
*chromosome 14 H chain* |
|
What is Multiple myeloma?
|
The most common gammopathies... results from malignant proliferation of plasma cells secreting a lot of monoclonal Ig (M proteins) of any given isotype
|
|
What is special about IgA?
|
It has a secretory component that protects it from enzymatic digestion at mucosal surfaces
|
|
Where are CDRs found?
|
Within the variable regions of both H & L chains
|
|
True or false:
Each B cell produces Ig of a single Ag specificity |
True
|
|
True or false:
Ab are capable of binding diverse configurations of epitope |
True
|
|
What is the first step in B cell activation?
|
Cross-linking of BcR with epitopes.
|
|
What does 'capping' of sIgM BcR do?
|
Sends a message to the co-receptors Ig-alpha and Ig-beta and initiates intracellular signaling pthwys
|
|
How many subisotypes does IgG have?
|
4... Predominant is IgG1
|
|
True or false:
The variable regions of the paratopes don't differ for each subisotype of IgG |
True
|
|
Which Ig is the only capable of crossing the placenta and how does it accomplish that?
|
IgG... crosses via the Fc region on a protection receptor FcRn
|
|
What is FcRn similar to?
|
MHC Class I
|
|
How many FcRn are needed to transport an IgG molecule?
|
2
|
|
IgG: Half-life...?
how is it recirculated? |
~23 days
re-circulated via an endosomal FcRN receptor (FcRP) |
|
Which Ig is capable of agglutination as well as precipitation?
|
IgG
|
|
How does IgG participate in opsonization?
|
IgG binds Ag and facilitates phagocytosis via the Fc binding to receptors on PMNs and others
|
|
When an Ab Fc binds to NK cell
|
Antibody-dependent cell-mediated cytotoxic cell----- ADCC
|
|
Major functions of IgG
|
Activates Compliment
Neutralizes Immobilizes Opsonization |
|
Serum concentration upper limit IgG
|
1600
|
|
Number of subisotypes for IgA
|
2: IgA1 IgA2
|
|
What is the importance of IgA
|
Important in the primary immunologic defenses of the GI and respiratory tracts *MALT*
|
|
IgA in serum is a...?
in secretions...? |
Serum as a monomer
Secretions as a dimer |
|
How, where, and when is IgA2 dimer joined?
|
by cystein-rich J chain intra-cellularly before secretion
|
|
True of false:
IgA complement |
False!
|
|
True or false:
IgG is an efficient antiviral antibody |
False: IgA is!
|
|
What is the importance of secretory dimeric IgA?
|
Important defense in mucous secretions
|
|
How is IgA stabilized against proteolysis?
|
By combination with a Secretory Component synthesized by local epithelial cells
|
|
The secretory component that stabilizes IgA is a portion of...?
|
the Poly-Ig receptor that mediates the transport of the dimer to the luminal surface.
|
|
Secretory IgA upper limit concentration
|
400
|
|
Which Ig is Pentameric?
|
IgM
|
|
Which Igs have an extra heavy chain?
|
IgM and IgE (CH4)
|
|
How many epitopes can IgM theoretically bind?
|
10
|
|
How are Fc chains in IgM joined?
|
disulfide bonds and a j chain
|
|
IgM naturally occur against what?
|
They are natural isohemagglutinin Ab that naturally occur against RBC Ag of the ABO blood groups
|
|
What is the first isotype to be synthesized after Ag exposure?
|
IgM
|
|
What do elevated levels of IgM indicate?
Serum upper limit |
recent infection
200 |
|
Which Ig is uniquely susceptible to proteolytic degradation?
|
IgD
|
|
Which Ig is the allergy Ab?
Aka...? |
IgE
cytotrophic or reaginic Ab |
|
What cells do IgE attach to and what is it responsible for?
|
Binds via Fc region to mast cells and basophils and is responsible for immediate hypersensitivity and allergies... Also protects against worms (Helmiths)
|
|
What denotes an Ig Superfamily?
|
molecules found on cell surfaces with polypeptide chains with folded regions or domains (similar to Ab)
|
|
Name the 4 phases in Primary Humoral Response
|
1) Lag Phase (1-2 weeks)
2) Exponential Phase (rapid increase) 3) Steady Phase (production/degradation balanced) 4) Decline Phase (shut down) |
|
Describe the Booster/Anamnestic response
|
2nd exposure to same Ag triggers memory B cells... shorter lag phase... IgM still first but higer longer [IgG]
|
|
Which 2 Ab can fix or bind complement?
How many of each is needed? |
IgG (2 needed)
IgM (1) |