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Lecture 10 - Antigens & APC 1
Antigens & APC 1
38
Immunology
Undergraduate 4
04/04/2015

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Term
Most immunogenic antigens are ______ in size
Definition
> 1000 Da
Term
Immunogenicity (increases/decreases) with size
Definition
increases
Term
What is MHC-restricted antigen presentation?
Definition
APCs process proteins, present their antigens to T-cells via MHC molecules
Term
True or False

Lipids & polysaccharides are highly immunogenic
Definition
false
Term
How are lipid-linked antigens (glycolipids, lipopeptides) processed?
Definition
CD1 molecules process them and present to antigen-specific T cells
Term
What factors affect antigen immunogenicity? (7)
Definition
-size
-genetics
-exposure route
-chemical stability
-foreignness
-antigen dose
-complexity
Term
What are epitopes?
Definition
the antigenic determinants of a protein
Term
What is an immunodominant epitope?
Definition
the epitope on an antigen that elicits the most favourable host response
Term
What is a cross-reactive T cell or antibody?
Definition
One which is involved in recognizing similar antigens found on two different types of pathogens
Term
What might cause an individual to develop an auto-immune disorder?
Definition
-failure in the negative T cell selection process
-release of immunologically protected self-antigens during injury
-loss of tolerance to self-antigens
-exposure to microbial antigens which share epitopes with self-antigens
Term
What might cause a hapten to become immunogenic?
Definition
-covalently binding to self or non-self proteins
Term
What are pro-haptens?
Definition
small molecular weight chemicals which can become activated to haptens by UV, hydroxylation, oxidation etc
Term
Why do APC typically migrate to secondary lymphoid tissue after processing an antigen?
Definition
Because they need to present the antigen to antigen-specific T cells, which are hard to find but found in greater concentrations in the secondary lymphoid tissue
Term
Which part of the lymph node is rich in B cells and macrophages?
Definition
the cortex
Term
What are germinal centers?
Definition
Regions within follicles which develop in response to antigen stimulation
-made of rapidly dividing B cells & FDCs
Term
What are FDCs?
Definition
follicular dendritic cells
Term
GCs serve as sites for.... (5)
Definition
-clonal expansion
-Ig class switching
-somatic mutation
-affinity maturation
-generation of memory B cells
Term
What is the paracortex?
Definition
region of LN rich in T cells, HEVs and APCs
Term
What do HEVs do?
Definition
supply LN with APCs, lymphocytes, soluble antigens

drain the LN of lymphocytes
Term
What is found within the medulla of LNs? (5)
Definition
B cells
T cells
macrophages
plasma cells
memory T & B cells
Term
How does lymph flow through the lymph ducts?
Definition
muscle contraction & 1-way valves to prevent backflow
Term
Which chemokines draw APCs to the lymph node? What receptor do they bind to on APC?
Definition
CCL19 & CCL21

bind to CCR7
Term
Describe the process of lymphocyte extravasation
Definition
1. Lymphocytes drawn via CCL21 and CCL19 binding to CCR7
2. L-selectin CD62L interations with endothelial CD34 for tethering & rolling
3. Rolling induces expression of lymphocytes adhesion molecules
4. Adhesion molecules adhere to EC receptors
5. Lymphocytes are extravasated into LN
Term
How are B cells drawn to follicles for interaction with APC?
Definition
CCL19 & CCL21 via CCR7

CXCL13 via CXCR5

CXCL12 via CXCR4
Term
How are T cells drawn to follicles?
Definition
CCL19 & CCL21 via CCR7

CXCL12 via CXCR4
Term
What happens to lymphocytes after antigen specific T & B cells have been activated?
Definition
EC expresses S1P1 which binds to lymphocyte S1P receptors and allows them to be released from the LN
Term
What happens to plasma cells after differentiation into antibody-secreting effector cells?
Definition
-some go to medulla, secrete Ab into circulation
-some go to paracortex, enter efferent lymphatic / circulation, take up residence in BM equivalent tissues & spleen
-most undergo apoptosis

-ones that target immune-dominant epitopes will remain many years, secreting Ab for long-term immunity
Term
How are memory B-cells able to survive long-term?
Definition
FDCs secrete BAFF which promote B-cell survival

FDCs slowly release antigen overtime, essential for B cell survival
Term
What happens during a secondary response to an antigen?
Definition
-memory T cells in periphery are immediately activated by APCs
-migrate via afferent lymph to follicles
-interact with memory B cells to promote proliferation & differentiation into effector plasma cells
Term
How is the porcine lymph node different from other mammals?
Definition
-more similar to nodules than true lymph node
-afferent lymph duct in each nodule, surrounded by paracortex
-cortex surrounds paracortex, has 1 efferent duct (poor drainage of medulla)
-lymphocytes enter via HEV & afferent but leave primarily via HEV
Term
What are the roles of the spleen (3)
Definition
-storing RBCs & platelets
-recycling iron
-capturing blood borne antigens
Term
What are the two compartments of the spleen and what does each do?
Definition
Red Pulp
-storing RBCs & recycling old ones

White Pulp
-PALS rich in T cells & follicles rich in B cells
Term
What happens after APC have presented antigen to specific T cells, activating B cells?
Definition
mature B cells (plasma cells) migrate to red pulp & release antibodies into the splenic vein
Term
Where does APC of blood-borne antigens typically occur?
Definition
liver
spleen
bone marrow equivalent tissues
Term
Where does antigen presentation at mucosal surfaces typically occur?
Definition
liver
spleen
bone marrow

also LN, Peyer's patches & tonsils
Term
Where does antigen presentation of skin antigens typically occur?
Definition
in draining lymph nodes

(or nodules in chickens, lymphoid aggregates in fish)
Term
What organs produce antibodies during the mammalian primary immune response?
Definition
plasma cells within the spleen & lymph nodes
Term
What organs produce antibodies during the mammalian secondary immune response?
Definition
memory B cells in bone marrow equivalent tissues
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