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160 Cards in this Set

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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)