The Immune System: Cells, Functional Anatomy and Lymphocyte Homing Mechanism Flashcards
Purpose of immune system
protecction against pathogens
viruses
bacteria
fungi
protozoa
worms
Which of the following. cells is NOT part of the immune systerm
Macrophages
Basophi;s
Epithelial cells
Lymphocytes
ALL OF THE ABOVE ARE PART OF THE IMMUNE SUSTEM
The key cellular actors
Sentinel Cells in the tissues
Dendritic cells, macrophages, and mast cells
Circulating phagocytes and granulocytes
Neutrophils, monocytes, and eosinophils
(also natrual killer cells (actually lymphocytes)
Lymphocytes
B and T cells
Immune response to influenza virus
inflammation (innate immunity)
1) Pathogen evades physical and chemical barriers
2) Tissue resident macrophages sense presence of pathogens via TLR receptors
3) Macrophages secrete cytokines including chemoattractants (CXCL8 or IL8) Which indue neutrophoil trafficking to inflammatory site
Migration of DCs to lymphoid organs
Dendritic cells are activated when they recognise certain characteristic features of microbes
Once activated, DCs migrate to regional lymphoid tissue to initiate lymphocyte (adaptive immune) response
Note free antigen is also delivered to lymphoid organs through the lymphatic system
Activation of lymphocytes
B and T lymphocytes with different antigen specificities circulate through lymphoid organs (including the lymph node)
Free antigen can activate antigen-specific B cells
Activated dendritic cells activate antigen specific T cells
CALLED CLONAL SELECTION
Activated lymphocytes divide and expand
B lymphocute effector functions
activated B cells produce antibody. Antibodies circulate, bind to microbial antigens, and have anti-microbial activities
These include: neutralization, opsonization, and complement actication
T lymphocyte effector functions
T cells come in 2 flavors: hyelper T cells and cytotoxic T cells
Cytotoxic T cells migrate back to the site of infection and kill microbe infected cells
Helper T cells either
a) stay in lymphoid organs and help B cells differentiate into antibody-producing cells, or
b) migrate to site of infection and help activate macrophages to become more effective phagocytes
Helper T cells are a major source of cytokines
Macrophage: initiators of the immune response
Sentinels in tiessie, express pattern recognition receptors that recognize pathogens
Specific pathogenic stimuli can lead to differential responses by macrophages
Major function: ingest and kill microbes
after activation, secrete cytokines that induce specific responses to clear specific pathogens
Induce repair or wounded tissue
Major function of macrophages
ingest and kill microbes
Macrophage
Monocyte
Monocytes
Bean or U shaped nucleus with abundant cytoplasm
2-8% of circulating WBCs
become macrophages in tissues
phagocytosis, antigen presentation, microbial killing
Monocytes differentiate into…
activated macrophages
Neutrophils
Neutrophils
Multilobes nucleus (PMN); granules do not stain with acidic or basic stains
60-70% of EBCs
Major functions: phagocytosis, bacterial killing
Filled with granules that have microbial properties
Immediate responders to inflamed tissues
Major function of neutrophils
phagocytosis and bacterial killing
Eosinophils
Eosinophils
Bilobed nucleus, granules stain with acidic dye (eosin)
2-4% of WBCs
Remove foreign material bound to antibody
Mast cells
Mast cells
IgE crosslinking induces mast cell degranulation
granules contain histamines and other cytokines that previde anti-helminth or allergic repsonses
mostly resides in tissues
Innate response to helminths (worms)
Involve innate cells that contain granules containing inflammatory and antimicrobial mediators
same mediators as allergic reactions
(eosinophils and mast cells)
Basophils
Basophils
bilobes nucleus obscured by granules that stain with basic dyes (hematoxylin)
<1% circulating WBCs
release histamine
may be involved in T cell responses
Lymphocytes
Lymphocytes
Sherical nuclei, small amount of cytoplasm
25-30% circ WBC
B cells 25-30% of circ lymphocytes
AR (antigen receptor) - Ig (immunoglobulin or antibody)
T cells 65-75% of circulating lymphocytes
AR= T cell receptor
NK cells-innate-but look like lymphocytes
Lymphocytes are distinguished by their history of antigen exposure
Naive cells
No prior antigen exposure or stimulation via receptors; T: TCR B:BCR
Requires cytokine for survival T:IL7 B:BAFF
Express cell surface proteins that facilitate migration to secondary lymphoid organs (SLOs) T and B: L selectin (CD62L) CCR7; B:CXCR5
Effector
Antigen exposure via activation of antigen receptors leads to cellular proliferation (enlargement of cells)
Acquire effector functions, including expression of cytokine (T) and antibody (B: plasma cell)
Express cell surface proteins that facilitate migration to inflammatory sites (T) and bone marrow (PC)
Memory
maintains antigen specificity; long lived
Pathogen clearance takes advantage of different adaptive responses
Antibody is a molecule so it can circulate through blood, tissues, at mucosa
Cell mediated is dependent on LN strucure and cytokine mediated
On the L, you see that the virus is inside the affected cell. Have to kill of infected cell.
Cytotoxic T cells kills of the infected cell
T cell cant recognise free floating pathogen
B cell produces antibodies that recognise free floating pathogen
True or false
The anatomy of the immune response, ie where the immuneresponse occurs, is important for optimized immune responses
TRUE
Immune response is temporarily and spatially regulated
Innate immunity is the rapid response
First responders: innate immunity. Rapid, nonspecific.
Adaptive immunity
Specialty physicians: adaptive immunity. Takes longer, specialy responses.
Hematopoesis: bone marrow
The process of turning stem cells into immune cells
yolk sac/paraaortic mesenchyme (early fetal) -> liver/spleen -> bone marrow
Stem cells mobilization: plerixafor
(AMD3100)
Adaptive immunity: Lymphocytes
B and T cells
Maturation of lymphocytes occurs in the bone marrow (B cells) and thymus (T cells) and involves theexpression of antigen receptors and the acquisition of functional/phenotypic characteristics of mature cells
Naive lymphocytes recirculate between blood and secondary lymphoid organs
Where do B cells mature
bone marrow
where do T cells mature
thymus
T cell origins: Thymus
Thymus- a bilobes structure in the anterior thoracic cavity
Cortex- maturation of thymocutes (TCR rearrangement and acquisision of mature phenotype) and development of tolerance
Mature T cells migrate into medulla, enter curculation, seed secondary lymphoid organs
The lymphatic system
lymph is a plasma filtrate present in th einterstitium of tissues throughout body
Lymph nodes are small nodular structures situated in chains along lymphatic vessels throughout the body. Lymphatic vessels drain lymph from the skin, mucosal surfaces, and internal organs through LNs, ultimately returning lymph back to circulation
Antigen is carried to LNs via lymph
Lymph nodes are
small nodular structures situated in chains along lymphatic vessels throughout the body. Lymphatic vessels drain lymph from the skin, mucosal surfaces, and internal organs through LNs, ultimately returning lymph back to circulation
Lymph nodes: sites of adaptive immune activation
Afferent lymphatics carry lymph to the LN and efferent lymphatics carry lymph away from the LN… to the nect LN in chain
ultimately lymph is delivered from the thoracic duct to the blood via anterior vena cava
Waht carries lymph to the LN
afferent lymphatics
What carries lymph away from LN
efferent lymphatics
Lymph is delivered from the thoracic fuct to the blood via
anterior vena cava
Fuctional segregation: B cell and T cekk areas of a lymph node
Cotrex: follicles- B cells, folicular DCs (CXCL13: CXCR5)
Paracortex: T cells, DCs, HEVs (CCL19, CCL21: CCR7)
DCs actually not dendritic cells
Spleen
LUQ of the abd, filters blood
Red pulp-reticular stromal cells, macrophages, DC, RBCs in vascular sunuses- removed spent bloods cells and particulates from blood
White pulp- B and T cells in follicles and PALS-major site of immunne respinse to blood borne antigens
laive lymphocutes arrive via blood and home to T cells and B cell area based on chemokine signals (CCL19/21- secreted by PALS stoma, and CXCL13- secreted by folicular stroma)
White pulp functions to
mount immune responses to blood borne antigens
Cutaneous and mucosal immune systems
skin and mucosal surfaces are in continuous contact with the external environment
High level exposure to pathogenic and nonpathogenic foreign antigens
regional immune responses can occur at tissue associated lymohoid structures such as MALT ( mucosa associated lymphoid tissue) GALT (gut associated lymphoid tissue) BALT (bronchial associated lymphoid tissue) ect
How do immune cells get to all of the places that they need to go?
Lymphatic vessels and peripheral blood vessels
Leukocytes traffic using classes of cell-cell surface molecules
Leukocyte comes along with selectin ligand
Rolling happens
Bouncing/rolling happens by selectins. Allows them to slow down
Integrin activation by chemokines
Stable adhesion
Migration through endothelium
Different selectins, chemokines, and integrins regulate LN versus inflammatory site homing
Naive T cell in high endothelial venule in LN has l selecin and CCR7 expressed on the molecule
Activated T cell in peripheral shows different things on surface
Integrins
Humans with defects in integrins suffer from leukocyte adhesion deficiency (LAD). Immunodeficient.
Therapeutics against integrins (Nataluzumab- anti VLA4) approved for use in multiple autoimmune disorders including MS and crohns dz
Bent- low affinity
Extended (high affinity)
