Lymphoid Organs & Cell Migration Flashcards

1
Q

Where is MALT located?

A
  • GIT
  • Respiratory tract
  • Genitourinary tract
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2
Q

Where are mature naive B cells stored?

A

primary follicle

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3
Q

Acute Phase Response

A

Increase in the appearance of various proteins in circ. - cytokines and anti-microbial proteins

  • IL-1β, IL-6, TNF-𝛼
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4
Q

Binding sites of chemokines

A
  1. to proteoglycans on blood side of blood vessels
  2. to chemokine receptors on leukocytes
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5
Q

chemokinesis

A

non-directional movement

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6
Q

Chemotaxis

A
  • directional migration of cells up a conc. gradient of chemotactic molecules
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7
Q

Components of Inflammatory Response

A
  1. blood supply increases
  2. capillary permeability increases - allows exudation of serum proteins in surrounding tissue - abs, complement
  3. leukocyte migration to site:
  • NFs first
  • APCs
  • CTLs and TH - need to be activated first by APCs in lymph nodes/spleen
  • B lymphocytes
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8
Q

Composition of IL-2R

A

alpha (low affinity alone)
beta
gamma chains

*highest affinity occurs when all 3 form a receptor triggering activation of immune cells

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9
Q

Cytokines

A
  • secreted glycoproteins
  • produced mainly by T-helper cells and APCs (dendritics, Macs)
  • pleiotrophic - many functions
  • redundant - some can mediate a similar function (IL1 and IL6)
  • interact with high affinity receptors
  • only produced when immune system is activated

e.g. IL2 produced by activated Th cell which binds to IL2r (CD25)

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10
Q

Cytokines involved in myeloid cell development

A
  • CFU-GEMM (give rise to all granulocytes and monocytes)
  • IL-3
  • GM-CSF (granulocyte, monocyte, colony stimulating factor)
  • G-CSF (granulocyte)
  • M-CSF (monocyte)
  • EPO (erythropoietin)
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11
Q

Describe the development of the immune system

A
  • derived from totiopotent haemopoietic stem cell (HSC)
  • differentate based on:
  • cell to cell contact
  • presence of cytokines
  • HSCs are found in bone marrow and spleen (in mammals)
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12
Q

Example of chemokine

A

IL-8 (CXCL7)

  • produced by macrophages
  • attracts NFs to site
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13
Q

Example of Recombinant GM-CSF and G-CSF GFs

A
  • Leucomax - Novartis
  • Neulasta (Amgen)
  • application in chemotherapy
  • targets rapidly dividing cells in bone marrow - neutropenia occurs (deficiency in NFs) - drugs prevent this from occuring
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14
Q

Examples of diseases associated with chronic inflammation

A
  • pul diseases
  • cancer
  • CVD
  • Alzheimers
  • Diabetes
  • Arthritis
  • Autoimmune diseases
  • Neuro disease
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15
Q

Examples of duality in the immune system

A
  • innate & adaptive
  • innate - phagocytes & APCs
  • adaptive - B cells & T cells
  • T cells - Th & CTC
  • B cells BCR - Heavy & Light chains
  • T cells TCR - alphabeta TCR & gammadelta TCR
  • recognition of self and non self
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16
Q

Function of spleen

A
  • monitors blood-borne infections
  • white pulp - contains T and B cells
  • red pulp - removal of aging RBCs and platelets - phagocytosed by macrophages
17
Q

Where are immune cells from the circulation homed?

A

high endothelial venue (HEV)

18
Q

IL2 & IL2r

A
  • production of IL2 and its interaction with IL2R - crucial for immune system activation to infection
19
Q

Leukocyte migration across endothelium

A
  • vasodilation of vasculature is vital - slows flow down and decreases prosthetic repulsion
  • vasodilatory molecules
  • bradykinin
  • PGs
  • Histamine
  • Leukotrienes
20
Q

Lymph journey

A

Arrives via several afferent lymphatic vessels
Leaves via one efferent lymphatic vessel

21
Q

Name chemotactic molecules

A
  • C5a - complement protein (chemoattractant for NFs and macrophages)
  • f-met-leu-phe - bacterial tripeptide (chemoattractant for NFs)
  • chemokines - small cytokines
22
Q

Opsonins

A
  • induce phagocytosis
  • C-reactive protein
  • serum amyloid protein
  • mannose-binding protein
23
Q

Primary Lymphid Organs

A
  • haemopoietic stem cell
  • bone marrow - stem cells give rise to all immune cells except T cells
  • thymus - produces T cells
24
Q

Production of B cells in bone marrow

A
  • Immature cells stimulated to recombine their H and L chain genes - produces functional BCR
  • many B cells never reach circulation - fail to make a BCR - death by neglect
25
Secondary Lymphoid Organs
\*home to most non-circulating immune cells * lymph nodes * spleen * GALT/ BALT
26
Site of self/non-self T cell education
* outer cortex - immature proliferating thymocytes * inner medulla - mature thymocytes
27
Sites of leukopoiesis
* bone marrow * thymus - leukocytes differentiate from myeloid and lymphoid progenitor stem cells - proliferate - mature into functional cells
28
Symptoms of inflammation
1. redness - rubor 2. heat - calor 3. pain - dolar 4. swelling - tumor 5. altered function
29
Types of Cell Migration that take place
* to sites of infection and inflamm * from blood to lymph and vice versa * from primary to secondary lymphoid organs * between secondary lymphoid organs
30
Types of Th cells
1. **Th1 - IL2, TNF alpha** 2. **Th2 - IL4,5,13** 3. Th17 - IL17,22 4. Tfh - IL 21
31
What cells undergo hemopoiesis in bone marrow?
all immune cells except T cells
32
Which pathways deliver signal transduction from IL-2R to the nucleus ?
* Ras-MAPK * PI3K-Akt
33
𝛼CXC vs βCC
* alpha chemokines or CXC - chemotaxis or cell migration * beta chemokines or CC - cell activation
34
Leukocyte recruitment to tissues
* at site of infection, macrophage activate nearby endothelial cells of venules to produce integrins, selectins, ligands, chemokines * selectin - mediate weak tethering of blood leukocytes on endothelium * force of blood flow causes leukocytes to roll across endothelial surface * integrins activated to high affinity state by chemokines * activated integrins bind Ig ligands to endo cells causing firm adhesion * leukocytes crawl into junctions between end cells and migrate to venular wall
35
CRP production
* increases 1000x due to IL-6, IL-1 * in severe COVID patients - increased IL-6 and CRP levels