Week 11 - Mucosal Immunity + HLA + Chemotaxis Flashcards by Guy Ben Arie

What are the kinds of Infections that cause the most death every year?

Respiratory Mucosa Acute infections

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What are the the associated lymphoid tissues on the mucosal surfaces?

MALT, GALT, NALT

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What is percentage of the lymphocytes in mucosal surfaces relative to all?
What does this mean for antibody production ?

75%

IgA is the most abundant in body (not serum) - 2/3 of Ab

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What is the job of M cells? Where are they located ?

Transport of antigen to APC by transcytosis (Microfold cells)
Mucosal epithelium above the Peter patches

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SED of Peyer Patch

Subepithelial dome

Transportation of Antigens from M cells

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Dendritic cells can __________ ________ across the epithelial layer to ________ antigen from the lumen of the gut.

Dendritic cells can extend processes across the epithelial layer to capture antigen from the lumen of the gut. (Skipping the M cell part)

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What is the route of the Lymphocyte that was presented by Gut DC an antigen?

Proliferation in Mesenteric Lymph node to Thoracic duct to Blood stream and Back to Gut for attack.

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Effector Lymphocyte homing back to the GALT - How?

Retinoic acid from inducing DCs causes the Lymphocyte to express the correct Integrin molecules and CCRs which leads lymphocytes to go back to gut.

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IEL

Intraepithelial lymphocytes - Primary Protection

Half of them are the gamma delta T cells an NKT cells (rest is usual Lymphocytes)

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Active receptor mediated transport along the Gut wall - Transport material

Dimer IgA

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Which signals cause the Isotype switch to IgA?

IL5, IL2, TGF-Beta

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T Independent B cells of Lamina Propria - Activation 2 stimulus

Antigen from Lumen on capture

DC activated signaling - BAFF, TGF-Beta

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What is the importance of the CD40-CD40L costimulation of te T cell in TD of Gut B cells?

Allows for somatic Hypermutation that leads to VDJ recombination and allows better avidity IgA produced in comparison to TI B cells.

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What is the component that allows for IgA transcytosis in epithelium of Gut?

Poly-Ig receptor binding the J chain of IgA Dimer

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Where else do we have the IgA transcytosis with Poly-Ig receptor? (Not Gut)
What does this allow?

Hepatocytes - allow for Bile to contain IgA and Recirculate to Gut

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Where are the PRRs of the Gut found?

Inside the Epithelial cells (e.g. TLR9 in vesicles) and the Lamina Propria (e.g.NLR).
Also on the subepithelial DCs.

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Inflammasome components and function

NLR, Caspase 1, ASC

Together cleave Pro-IL1 to IL1 and initiate Inflammation

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DC that recognizes bacteria that are not a danger for the body what is the consequence?(non cytokines components)

TH17 differentiation - CD11b with DCs

T regulatory - CD103 with DCs

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Fusobacterium Nucleatum promotes the formation of

Defensin in the oral cavity

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Porphyromonas Gingivalis causes the formation of Citruline from Arg in the humen proteins - what could be the result of this? (Citrulinated Protein response)

Activation of B cells with ACPA production and systemic IC accumulation as in Autoimmunity but also other systemic diseases like Atherosclerosis (Keep your mouth clean)

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MALT

Mucosa associated lymphoid Tissue

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NALT

Nasopharynx associated lymphoid Tissue

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GALT

Gut associated lymphoid Tissue

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TDA of Peyer Patch

T-dependent Area - Surrounding the follicular area that contains B cells.

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Effector Lymphocyte homing back to the GALT - What are the 2 Chemokines that attract them there?

CCL25 and MADCAM

In what forms does IgA stand in Active and Passive Transport across the mucosa?

Active Receptor Mediated Transport - Dimer | Passive Paracellular diffusion Transport - Monomer (also IgG)

``` Upon recognition of antigen on the mucosal lining by dendritic cells a TI class switch happen on B1 cell by the DC stimulation. a Low affinity IgA is produced. What is the utility of that? Why isn't it better to have a TD class switch here? ```

FIRST LINE OF DEFENCE. | TD is with higher affinity but takes longer.

The NLRs (inside the enterocytes) are very sensitive in detecting the activity of _______ ______ such as ______ or secretion systems.

The NLRs (inside the enterocytes) are very sensitive in detecting the activity of virulence factors such as toxins or secretion systems.

The Intestinal/Bronchial epithelial cells _________ the immune cell function - depending on the _______ of the microbe it can detect if it is normal flora or not and transfer the input.

The Intestinal/Bronchial epithelial cells regulate the immune cell function - depending on the location of the microbe it can detect if it is normal flora or not and transfer the input.

CD11b+ DC was collecting an antigen in the GALT. After Synapse with a naive T cell -What is the outcome?

TH17 cell differentiation - Inflammation

CD103+ DC was collecting an antigen in the GALT. After Synapse with a naive T cell -What is the outcome?

Treg cell differentiation - Tolerance

Distinctive features of the mucosal immune system: | Anatomical Feature -

Permanent Ag uptake

Distinctive features of the mucosal immune system: | Effector Mechanism of B cells-

Permanent IgA production

Distinctive features of the mucosal immune system: | Effector Mechanism of T cells-

Activated/Memory T cells predominate - even in absence of infection

Distinctive features of the mucosal immune system: | Immunoregulatory Environment-

Active downregulation of Immune responses (e.g for food particles) Predominates

HLA Typing and HLA Related Diseases: | What is a Haplotype?

a combination of alleles (DNA sequences) at adjacent locations (loci) on the chromosome that are transmitted together (linked).

HLA Typing and HLA Related Diseases: | What is the Chromosome from which the Paternal and Maternal HLA are arriving from?

Chromosome 6

HLA Typing and HLA Related Diseases: | What is the extra subunit that makes the 4th part of the MHC-I molecule? From Which Chromosome?

β-Microglobulin from Chromosome 15

HLA Typing and HLA Related Diseases: What is the difference in collection of the information regarding each HLA type in the OLD Vs. NEW systems of nomenclature?

Old nomenclature - Serological Markers | New nomenclature - Genetic

HLA Typing and HLA Related Diseases: What is the difference in presentation of the information regarding each HLA type in the OLD Vs. NEW systems of nomenclature?

Old nomenclature - HLA+CAPITALS+2 digits (HLA-B27) | New nomenclature - HLA+CAPITALS*+4 digits (HLA-B*0801)

HLA Typing and HLA Related Diseases: | What is the information provided in the 4 digits NEW system of nomenclature?

1) Allele group 2) Specific Allele 3) Proteins with silent mutations in the coding sequence 4) Differences in the noncoding region

HLA Typing: What is the name of the test that allows for determination of HLA sensitization with a panel of reactive antibodies? What it can serve for?

``` Microtoxicity test (Terasaki) Similar patterns that cells express are indicative of similar HLA antigens - DONOR-RECIPIENT Histocompatibility ```

HLA Typing Methods:Microtoxicity test (Terasaki) | How are the patterns of the HLA phenotype detected?

Specific Antibody Binding HLA with Complement Lysis of cell later triggers a staining of damaged cells. HLA specific Stain.

HLA Typing Methods - Mixed lymphocyte culture: | It is used only for detection of HLA-_ in MHC-_.

HLA Typing Methods - Mixed lymphocyte culture: | It is used only for detection of HLA-D in MHC-2.

``` HLA Typing Methods - Mixed lymphocyte culture: If the Recipient T cells are lacking the class II MHC of the Donor - What will be the outcome? ```

Activation and Proliferation of the recipient T cells following by incorporation of radioactive nuclear DNA. Positive Result! (Reaction Occurred)

``` HLA Typing Methods - Mixed lymphocyte culture: If the Recipient T cells are sharing the same class II MHC of the Donor - What will be the outcome? ```

No reaction - Negative Result!

HLA Typing Methods - Mixed lymphocyte culture: | Before transplantation these test are performed with both Recipient and Donor T cells - Result for both must be _______.

HLA Typing Methods - Mixed lymphocyte culture: Before transplantation these test are performed with both Recipient and Donor T cells - Result for both must be Negative.

HLA in Tissue transplantation: | In kidney transplantation : both HLA-I and HLA-II antigens are important but the HLA-__ is the most important.

HLA in Tissue transplantation: | In kidney transplantation : both HLA-I and HLA-II antigens are important but the HLA-DR is the most important.

HLA in Tissue transplantation: | In bone marrow transplantation the MHC ____ are the most important.

HLA in Tissue transplantation: | In bone marrow transplantation the MHC genes are the most important.

HLA Related Diseases: | HLA-DQ2 is associated with Sjogren syndrome, Coeliac Disease and ____.

HLA Related Diseases: | HLA-DQ2 is associated with Sjogren syndrome, Coeliac Disease and IDDM.

HLA Related Diseases: | HLA-DRB1 is associated with ______ ______.

HLA Related Diseases: | HLA-DRB1 is associated with Rheumatoid Arthritis.

Chemotaxis and Diseases: | What Infections cause Increased and Decreased Chemotaxis?

Increased Chemotaxis - General Infections | Decreased Chemotaxis - AIDS, Brucellosis

Chemotaxis and Diseases: | What diseases are caused by Chemotaxis abnormalities? are they causing Increased/Decreased Chemotaxis ?

Chediak-Higashi syndrome and Kartagener syndrome. | Always Decreased.

Chemotaxis and Diseases: | What non-infectious diseases cause Increased Chemotaxis?

Atherosclerosis ,Arthritis, Periodontitis, Psoriasis , Reperfusion syndrome, Metastatic tumors

Chemotaxis and Diseases: | What non-infectious diseases cause Decreased Chemotaxis?

Sclerosis multiplex, Hodgkin disease, Male infertility

Order the steps of Lymphocyte Extravasation: | Adhesion, Attachment, Transendothelial migration, Rolling, Activation

1) Attachment 2) Rolling 3) Activation 4) Adhesion 5) Transendothelial migration

Lymphocyte Extravasation: | Name the Interaction in Rolling

L-Selectin and P/E-selectin

Lymphocyte Extravasation: | Name the Interaction in Adhesion

Integrins: LFA-1 to ICAM

How many transmembrane domains are there in MHC I and MHC II?

MHC I - 1TM Domain | MHC II - 2TM Domains

What are the Antigen binding subunits of MHC I? What are the ones that doesn't bind it? (Overall Tetramer)

MHC I Antigen binding - α1 and α2 | subunits that doesn't bind it - α3 and β2-Microglobulin

What are the Antigen binding subunits of MHC II? What are the ones that doesn't bind it? (Overall Tetramer)

MHC II Antigen binding - α1 and β1 | subunits that doesn't bind it - α2 and β2

Integrins for homing are Heterodimers an example for it is Integrin ____ which interacts with MADCAM to recirculate back to GALT.

Integrins for homing are Heterodimers an example for it is Integrin α4β7 which interacts with MADCAM to recirculate back to GALT.