Immunology 2 Flashcards
Where do B and T Cells mature?
B cells mature in Bone marrow
T cells mature in Thymus
Where is the Thymus located?
In front of the heart
What is the Thymus?
A bi-loobed organ, that is the site of T cell maturation.
What two sections comprise the thymus ?
The Cortex (outer) The medulla (inner)
What separates the two lobes of the Thymus? (TradeCalais 🇫🇷)
The trabecalae
Detail the cortex of the Thymus
Tightly packed, high cell density
Consist of proliferating immature Thymocytes (from bone marrow)
It is the site of positive selection
What is positive selection?
Thymocytes are exposed to self-MHC (expressed on epithelial cells of thymus). If non-reactive then they are eliminated. If they are reactive they diffuse closer to the medulla.
Note: it is a good thing they react with MHC as this is needed in future
Detail the medulla (remember Hasan’s spot 👺)
Loosely packed with cells, fewer lymphocytes present
But higher population of mature Thymocytes
Hassalls corpuscles can be observed here
Site of negative (medusa) selection
What role do Hassalls corpuscles serve supposedly?
Might function as sites of clearance for dead/un selected Thymocytes
What is involved in negative selection of the medulla?
Dendritic and macrophages display self-antigens/peptides
If Thymocyte has too high an affinity with them then eliminated to prevent autoimmune effects
Those with intermediate affinity are selected
What is occurs when the gene (Jayne/ gene) AIRE is expressed in the medulla of the Thymus?
Thymocytes are presented with more complicated self antigens
What two MAIN classes of cells are found in the thymus?
- Stromal cells
2. Cells of hemopoetic origin
What two types of stromal cells exist in thymus
Epithelial thematic cells (nurse cells etc)
Dendrites and macrophages
When is the thymus most active?
During early stages of life, neonatal, adolescence. Not so much in adulthood
Where are double negative immature Thymocytes found in thymus?
Where are double positive immature Thymocytes found in thymus?
Where are single positive mature Thymocytes found in thymus?
Double ++ = cortex
Double – = lower cortex
Single += medulla
How do T cells acquire their unique TCRs?
Through genetic rearrangement in the thymus
Name the two primary organs of the lymphatic system
Bone Marrow and the Thymus
Name 7 secondary lymph organs
Lymph nodes, Spleen, Tonsils, Peyers Patches, Mucosal-associated Lymphoid tissue (MALT), Appendix, and Bronchus-associated lymphoid Tissue (BALT- in rats/rabbits) and INDUCIBLE BALT (iBALT- humans and mice)
Where are most lymphocytes activated?
In the lymph nodes. Where antigens are trapped and encounter lymphocytes.
How do antigens arrive in nymph nodes?
Via lymphatic vessels, where they arrive in the into the lymph node at the AFFERENT vessel
Where clusters are Lymph nodes found ?
At clusters of junctions of lymphatic vessels
In lymph nodes, where are B cells found and where are at cells found ?
B cells- Cortex
T cells - para cortex
What cells in the Lymph nodes display antigen/foreign peptides?
Dendritic cells and macrophages
What two fates are possible for naive T cells entering a Lymph Node?
- They enter and encounter an antigen presented by an APC, they are activated and thus proliferate and differentiate into specific EFFECTOR T Cells, wherein they are released via efferent vessel
- They don’t encounter a compatible antigen and re-circulate the body until they do or die naturally
Why do lymph nodes swell?
Overactivity of the immune response
Huge volume of lymphocyte proliferation at Germinal centres
What are germinal centres?
Areas of B cell proliferation, somatic hypermutation and then differentiation into plasma cells or class switch into memory cells or other.
What is the structure of a germinal centre. And what are the cells termed at each department?
Dark zone- where naive B cells enter (termed centrobalsts) and proliferate in rapid and mutative manner
Light zone- where B cells (now termed centrocytes) are subjected to selected by follicular T helper cells in the presence of follicular dendritic cells
At what structures do T and B cells enter lymph nodess?
The High Endothelial VENULE! (Venue)
How do B and T cells enter Lymph Nodes across the HEV?
- L-Selectin (on lymphocyte surface) binds to both GlyCAM-1 (Glucosylation-dependent cell adhesion molecule 1) and CD34 on epithelial cell surface of lymph node, initiating a rolling/tumble effect
- Cytokines on the Extracellular surface of HEV (lymph node) bind to cell surface receptors on the lymphocyte activating LFA-1 (lymphocyte function-associated antigen 1)
- LFA-1 binds tightly to ICAM-1 (Intracellular CAM) on surface of HEV
- DIAPEDESIS occurs (lymphocyte leaves blood and enters lymph node)
What are FDCs?
Follicular dendritic cells: unconventional Dendrite, displays Antigen to B and T cells in all secondary lymph organs e.g spleen and lymph nodes
What 2 methods do FDCs possess to activate B cell differentiation?
- Complement receptors on surface: bind to OPSONINS on antigen and present to B/T cells
- Antibodies already bound to antigen can bind (at the constant region) to specific receptors on the FDC whereupon they are engulfed and fragments of antigen are displayed on surface to form cross-links with further Lympohocytes initiating a germinal centre
The spleen is the largest secondary lymph organ in the body, true or false?
True
Compare the white and red pulps of the spleen
Red pulp:
RBC disposal
Erythrocytes, platelets, and resident macrophages occupy it
Little lymphocytes
White pulp: Rich in B cells (and T) Contains PALS (periarteriolar lymphoid sheath) T cells around central arteriolar Primary follicles found along PALS
What is GALT
It is general class of MALT belonging to the gut (mucosal associated lymph tissue).
Involves;
Tonsils, appendix, Lamina Propria and Peyers Patches
How many Peyers Patches are present in typical adult?
30/40
Where are Peyers Patches usually found?
In the Ileum
What features distinguish Peyers Patches from the rest of the intestine?
No villi, or crypts of Lieberkuhn (impressions) on the lumen
What other secondary lymph organ are Peyers patches similar to in structure?
Lymph Nodes
What is the special cell found in the centre of Peyer Patch structures? And what purpose do they serve?
M cells - microfold cells
They allow the entry of antigens into the lymph tissue via endocytosis
What general function do PP serve?
To analyse and respond to pathogens in the gut
What specialised function do PP Serve?
In the production of TH2 responses and stimulating IgA secretion (ideally suited to pathogens of the gut)
What do TH2 cells do?
They help activate B cells for the production of antibodies against an Extracellular parasite and help activate eosinophils
How is it that T cells can return to secondary organs with great efficiency and accuracy ?
- L-Selectin binds GlyCAM1 and CD34 which initiate events leading to DIAPEDESIS into Lymph nodes
- T- cells containing a4b7 bind MadCAM1 and enter Peyers patch at HEV
- These cells go onto to proliferate cells with higher expression of a4b7, thus increasing likelihood of future return
How does the replicative nature of a pathogen affect the need for greater memory lymphocytes
If the pathogen replicates fast then there is greater need for faster immune response
Which leukocyte is most efficient at presenting antigens?
Dendritic cells
What is MHC known as in humans?
HLA- human lymphocyte antigen
What is MHC?
A set of cell surface molecules belonging to a larger gene family. They mediate leukocyte-leukocyte interaction
MHC controls the immune system in every organism? T OR F?
False mofo, only in vertebretes
What lymphocytes do MHC interact with?
T cells
Each MHC is slightly different in each individual and so determines the compatibility of organ transplants and susceptibility to autoimmune diseases. Is this true?
Yup
What is the molecular fragment displayed on MHC?
The epitope of the antigen
What is somatic hypermutation?
The reshuffling and mutation process of genes responsible for the antibodies of B cells. Occurs in the germinal centres of Lymph nodes
What does the population of MHC molecules indicate about the cell it’s bound to?
Indicates to the balance of proteins within
How subgroups of MHC are there?
3
Briefly describe class 1 MHCs!
They have no beta2 subunits, and can only be recognised by CD8+ co-receptors of T cytotoxic cells
Briefly describe class 2 MHCs!
They contain beta2 subunits and can bind CD4 co-receptor of helper T cells. They form an Alpha beta subunit
How may it be said that the MHC acts as a chaperone?
It dictates which lymphocytes may form a high affinity interaction with the presented antigen
Basically what happens when a lymphocyte binds with an presented epitope on MHC?
It adapts to it
Which MHC is exclusively expressed, and by which cell type?
MHC class II and by APC
