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Week 7 Immunology > The Immune System: Cells, Functional Anatomy and Lymphocyte Homing Mechanism > Flashcards

The Immune System: Cells, Functional Anatomy and Lymphocyte Homing Mechanism Flashcards

1
Q

Purpose of immune system

A

protecction against pathogens

viruses

bacteria

fungi

protozoa

worms

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2
Q

Which of the following. cells is NOT part of the immune systerm

Macrophages

Basophi;s

Epithelial cells

Lymphocytes

A

ALL OF THE ABOVE ARE PART OF THE IMMUNE SUSTEM

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3
Q

The key cellular actors

A

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

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4
Q

Immune response to influenza virus

inflammation (innate immunity)

A

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

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5
Q

Migration of DCs to lymphoid organs

A

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

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6
Q

Activation of lymphocytes

A

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

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7
Q

B lymphocute effector functions

A

activated B cells produce antibody. Antibodies circulate, bind to microbial antigens, and have anti-microbial activities

These include: neutralization, opsonization, and complement actication

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8
Q

T lymphocyte effector functions

A

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

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9
Q

Macrophage: initiators of the immune response

A

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

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10
Q

Major function of macrophages

A

ingest and kill microbes

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11
Q
A

Macrophage

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12
Q
A

Monocyte

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13
Q

Monocytes

A

Bean or U shaped nucleus with abundant cytoplasm

2-8% of circulating WBCs

become macrophages in tissues

phagocytosis, antigen presentation, microbial killing

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14
Q

Monocytes differentiate into…

A

activated macrophages

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15
Q
A

Neutrophils

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16
Q

Neutrophils

A

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

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17
Q

Major function of neutrophils

A

phagocytosis and bacterial killing

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18
Q
A

Eosinophils

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19
Q

Eosinophils

A

Bilobed nucleus, granules stain with acidic dye (eosin)

2-4% of WBCs

Remove foreign material bound to antibody

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20
Q
A

Mast cells

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21
Q

Mast cells

A

IgE crosslinking induces mast cell degranulation

granules contain histamines and other cytokines that previde anti-helminth or allergic repsonses

mostly resides in tissues

22
Q

Innate response to helminths (worms)

A

Involve innate cells that contain granules containing inflammatory and antimicrobial mediators

same mediators as allergic reactions

(eosinophils and mast cells)

23
Q
A

Basophils

24
Q

Basophils

A

bilobes nucleus obscured by granules that stain with basic dyes (hematoxylin)

<1% circulating WBCs

release histamine

may be involved in T cell responses

25
Q
A

Lymphocytes

26
Q

Lymphocytes

A

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

27
Q

Lymphocytes are distinguished by their history of antigen exposure

A

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)

28
Q

Memory

A

maintains antigen specificity; long lived

29
Q

Pathogen clearance takes advantage of different adaptive responses

A

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

30
Q

True or false

The anatomy of the immune response, ie where the immuneresponse occurs, is important for optimized immune responses

A

TRUE

31
Q

Immune response is temporarily and spatially regulated

A

Innate immunity is the rapid response
First responders: innate immunity. Rapid, nonspecific.

Adaptive immunity
Specialty physicians: adaptive immunity. Takes longer, specialy responses.

32
Q

Hematopoesis: bone marrow

A

The process of turning stem cells into immune cells

yolk sac/paraaortic mesenchyme (early fetal) -> liver/spleen -> bone marrow

Stem cells mobilization: plerixafor

(AMD3100)

33
Q

Adaptive immunity: Lymphocytes
B and T cells

A

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

34
Q

Where do B cells mature

A

bone marrow

35
Q

where do T cells mature

A

thymus

36
Q

T cell origins: Thymus

A

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

37
Q

The lymphatic system

A

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

38
Q

Lymph nodes are

A

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

39
Q

Lymph nodes: sites of adaptive immune activation

A

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

40
Q

Waht carries lymph to the LN

A

afferent lymphatics

41
Q

What carries lymph away from LN

A

efferent lymphatics

42
Q

Lymph is delivered from the thoracic fuct to the blood via

A

anterior vena cava

43
Q

Fuctional segregation: B cell and T cekk areas of a lymph node

A

Cotrex: follicles- B cells, folicular DCs (CXCL13: CXCR5)

Paracortex: T cells, DCs, HEVs (CCL19, CCL21: CCR7)

DCs actually not dendritic cells

44
Q

Spleen

A

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)

45
Q

White pulp functions to

A

mount immune responses to blood borne antigens

46
Q

Cutaneous and mucosal immune systems

A

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

47
Q

How do immune cells get to all of the places that they need to go?

A

Lymphatic vessels and peripheral blood vessels

48
Q

Leukocytes traffic using classes of cell-cell surface molecules

A

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

49
Q

Different selectins, chemokines, and integrins regulate LN versus inflammatory site homing

A

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

50
Q

Integrins

A

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)

Week 7 Immunology (2 decks)

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