Lymphoid Organs & Cell Migration Flashcards
Where is MALT located?
- GIT
- Respiratory tract
- Genitourinary tract
Where are mature naive B cells stored?
primary follicle
Acute Phase Response
Increase in the appearance of various proteins in circ. - cytokines and anti-microbial proteins
- IL-1β, IL-6, TNF-𝛼
Binding sites of chemokines
- to proteoglycans on blood side of blood vessels
- to chemokine receptors on leukocytes
chemokinesis
non-directional movement
Chemotaxis
- directional migration of cells up a conc. gradient of chemotactic molecules
Components of Inflammatory Response
- blood supply increases
- capillary permeability increases - allows exudation of serum proteins in surrounding tissue - abs, complement
- leukocyte migration to site:
- NFs first
- APCs
- CTLs and TH - need to be activated first by APCs in lymph nodes/spleen
- B lymphocytes
Composition of IL-2R
alpha (low affinity alone)
beta
gamma chains
*highest affinity occurs when all 3 form a receptor triggering activation of immune cells
Cytokines
- 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)
Cytokines involved in myeloid cell development
- 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)
Describe the development of the immune system
- 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)
Example of chemokine
IL-8 (CXCL7)
- produced by macrophages
- attracts NFs to site
Example of Recombinant GM-CSF and G-CSF GFs
- Leucomax - Novartis
- Neulasta (Amgen)
- application in chemotherapy
- targets rapidly dividing cells in bone marrow - neutropenia occurs (deficiency in NFs) - drugs prevent this from occuring
Examples of diseases associated with chronic inflammation
- pul diseases
- cancer
- CVD
- Alzheimers
- Diabetes
- Arthritis
- Autoimmune diseases
- Neuro disease
Examples of duality in the immune system
- 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
Function of spleen
- monitors blood-borne infections
- white pulp - contains T and B cells
- red pulp - removal of aging RBCs and platelets - phagocytosed by macrophages
Where are immune cells from the circulation homed?
high endothelial venue (HEV)
IL2 & IL2r
- production of IL2 and its interaction with IL2R - crucial for immune system activation to infection
Leukocyte migration across endothelium
- vasodilation of vasculature is vital - slows flow down and decreases prosthetic repulsion
- vasodilatory molecules
- bradykinin
- PGs
- Histamine
- Leukotrienes
Lymph journey
Arrives via several afferent lymphatic vessels
Leaves via one efferent lymphatic vessel
Name chemotactic molecules
- C5a - complement protein (chemoattractant for NFs and macrophages)
- f-met-leu-phe - bacterial tripeptide (chemoattractant for NFs)
- chemokines - small cytokines
Opsonins
- induce phagocytosis
- C-reactive protein
- serum amyloid protein
- mannose-binding protein
Primary Lymphid Organs
- haemopoietic stem cell
- bone marrow - stem cells give rise to all immune cells except T cells
- thymus - produces T cells
Production of B cells in bone marrow
- 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