Cells And Organs Flashcards
Origin of immune system cells
Hematopoietic stem cells which are self renewing
Two branches: Myeloid progenitor and Lymphoid progenitor
myeloid: dendritic cells, granulocytes, eosinophils, basophils, megakaryocyte, erythrocyte
Lymphoid: NKC, b-cell, t-cell, dendritic cell
Two arms of immune defense
Innate and adaptive
Innate immunity
First line
Skin, cousin, membranes, chemicals
Second line
Phagocytosis, complement, interferon, inflammation, fever
Adaptive immunity
Third line
Lymphocytes, antibodies
Cells of innate immunity- first response
Granulocytes OR polymorphonuclear leukocytes are a subgroup of white blood cells characterized by the presence of cytoplasmic granules
They are produced in the bone marrow
Are classified as basophils, eosinophils, or neutrophils
They are named as such because of their distinct staining characteristics using hematoxylin and eosin histology always preparations
Basophils
Granules in basophils stain dark blue
Important for host defense against parasites and may be involved in allergic and inflammatory responses
Basophils contain toxic granules which are used to destroy pathogens during the process of phagocytosis
Basophils express several adhesion molecules which play a critical role in their circulation, including LFA-1 (CD11a/CD18), MAC-1 (CD11b/CD18) and CD44
Eosinophils
Stain bright red
Differentiate from myeloid precursor cells in response to IL-3, IL-5 and GM-CSF
Important for host defense against parasites and may be involved in allergic reactions
Respond to chemokines such as CCL5/RANTES, CCL11/eotaxin-1, and CCL24/eotaxin-2secreted by neutrophils or lymphocytes
Recruited eosinophils release the toxic substances contained in their granules to destroy pathogens and fight infection
Neutrophils
Stain neutral pink
The most numerous innate immune cell (50-70% of all white blood cells)
Immature neutrophils have a distract band-shaped nucleus which changes into a segmented nucleus following maturation
They circulate in the bloodstream looking for foreign objects to phagocytose and degrade
Number of circulating neutrophils is estimated using the absolute neutrophils count (ANC)
ANC
May be high (neutrophilia) due to kidney failure or bacterial infection
Leukemia or bone marrow damage results in a lower number of neutrophils (neutropenia) and an increased risk of infection
Granulocytes at work
Can be identified by expression of CD16, CD34 (immature state) and CD11b/CD18 (activated state)
Additionally, activated basophils can be identified by CD13/Aminopeptidase N, CD107a/LAMP1 or CD164; eosinophils by CD44, CD69, IL-5, and neutrophils by CD16, L-selection (CD62L)
Mast cells
Generated by bone marrow
Mast cells are similar to basophils leukocytes
They have a common progenitor (CD34+ precursor cells)
There are two types of mast cells:
-connective tissue mast cells — local allergic reaction
-mucosal mast cells, which are found in areas of the body that are exposed to the external environment (lung mucosa, digestive tract, mouth and nose)
Defense against parasites
Mast cells found in tissues can mediate allergic reactions by releasing inflammatory mediators like histamine
Monocytes/Macrophages
They are found in the bloodstream and in tissues
Monocytes circulate in the peripheral blood before entering tissues to replenish tissue-specific macrophage populations (osteoclasts, microglia cells, histiocytes, and Kupffer cells)
Macrophage, big eater, named for their ability to ingest and degrade bacteria
Upon activation, monocytes and macrophages coordinate an immune response by notifying other immune cells of existing infection
Macrophages can present antigens to lymphocytes
Macrophages also have important non-immune functions, such as recycling dead cells, like red blood cells
These housekeeping functions occur without activation of an immune response
Natural killer cells
Innate immune cells
Certain sub populations of NK cells have features of both innate and adaptive immunity (NKT cells)
They recognize and kill virus-infected cells or tumor cells
They contain granules, which are filled with proteins that can form hole in the target cell and also cause apoptosis
Besides their function as cytolytic effectors they are also regulators of immune response
Dendritic cells
Specialized sentinel cells that constantly sense and respond to their immediate environment
All DCs are hematopoietic bone marrow-derived cells, although they undergo maturation in either, the bone marrow, lymphoid, or non-lymphoid tissues
DCs capture, process, and present antigens to T cells and thus are crucial for bridging innate and adaptive immunity as well as promoting self-tolerance
Upon exposure and uptake of pathogens, maturing DCs travel to secondary lymphoid organs where they become potent T cell activators
DCs are classified as, classical/conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs)
pDCs have the ability to secrete large amounts of type I interferons upon activation through TLR7 and TLR9
B lymphocytes
Humoral immune response
Mature in the bone marrow or bursa of birds
Activated when they bind antigens through their receptors (BCR)
Responsible for generating antibodies to specific antigens
Antibodies coat the surface of a pathogen and Steve three major roles: neutralization, opsonization, and complement activation
Neutralization
Occurs when the pathogen is covered in antibodies and cannot further infect host cells
Opsonization
An antibody-bound pathogen serves to alert immune cells such as neutrophils and macrophages, to engulf and digest he pathogen
Complement activation
Process for directly destroying or losing pathogens
Some complement components act as opsonins— can opsonize pathogens
Bond to antibodies, cascade, holes in cell membrane created
T lymphocytes
Express an antigen specific receptor TCR
They begin as thymocytes (precursors to T cells) and end as lymphocytes
Thymocytes develop from hematopoietic stem cells in the bone marrow and then move to mature in the thymus
They undergo several stages of selection and quality control to ensure that maturation results in functional T cells
Essential component of cellular immune response
Divided into two broad categories: CD8+ T cells and CD4+ T cells based in which co-receptor protein is present on the cell surface
CD8+ T cells also are called cytotoxic T cells or cytotoxic T lymphocytes (CTLs)
Recognize and kill infected or cancer cells
CTLs have cytotoxic granules, containing cytotoxic that kill target cells
CD4+ T cell subsets
Th1
Th2
Th17
T regulatory cells
Th1
Coordinate immune espouses against intracellular pathogens
They produce and secrete molecules (cytokines) that alert and activate other immune cells, like bacteria-ingesting macrophages
Th2
Coordinate immune responses against extra cellular pathogens, like helminths (parasitic worms), by alerting B cells, granulocytes, and mast cells
Th17
Named for their ability to produce interleukin 17 (IL-17) a signaling molecule that activated immune and non-immune cells
Protect surfaces (skin, guy) against extra cellular bacteria (recruitment of neutrophils)
Regulatory T cells (Tregs)
Monitor and inhibit the activity of other T cells
Communication of immune cells
Immune cells communicate in a number of ways, either by cell-to-cell contact or through secreted signaling molecules
Receptors and ligands are fundamental for cellular communication
Receptors are protein structures that may be expressed on the surface of a cell or in intracellular compartments
The molecules that activate receptors are called ligands, which may be free-floating or membrane-bound
By altering the expression and density of various receptors and ligands, immune cells can dispatch specific instructions tailored to the situation at hand
Molecules involved in immune cell communication
Cytokines Toll-like receptors B-cell and T-cell receptors Major histocompatability complex (MHC) Complement
Cytokines
Small proteins with diverse function such as cell growth, activation, etc
Toll-like receptors
Expressed on innate immune cells, like macrophages and dendritic cells
TLRs recognize general microbial patterns and they are essential for innate immune-cell activation and inflammatory responses
B and T cell receptors
Expressed on B cell and T cells.
Recognize foreign antigens
Major histocompatibility complex
MHC proteins function as carriers to present antigens on cell surfaces
Also signal whether a cell is a host cell or a foreign cell
Complement
Particularly C3a and C5a
Consists of a series of proteins found in blood
Punches small holes into the pathogen, creating leaks that lead to cell death
Also serve as signaling molecules that sort immune cells and recruit them to inflammatory sites
Organs of the immune system
Lymphoid cells are first produced in the yolk sac, fetal one yum, and liver
In older fetuses and adults, lymphoid cells are mainly produced in bone marrow
Bone marrow is a hematopoietic organ that gives rise to all blood cells
Types of lymphoid organs
Primary: bone marrow, thymus, bursa of fabricius
Secondary: spleen, lymph nodes, non-encapsulated lymphoid tissue, peyer’s patches
Primary lymphoid organs
Organs that regulate the development of lymphocytes
T lymphocytes develop in bone marrow and mature in the thymus
B lymphocytes develop and mature in different primary lymphoid organs depending on species
Bursa in birds
Bone marrow in primates and rodents
Intestinal lymphoid tissue in rabbits, dogs, ruminants, and pigs
Primary lymphoid organs are usually not sites of lymphocyte interaction with microbial antigens
Thymus
Located in the thoracic cavity in front and below the heart
Large in newborns but small to invisible in adult animals-undergoes involution
Covered by a connective tissue capsule and consists of lobules
The outer part of each lobule, called the cortex contains thymocytes
The inner part of the lobule,medulla contains only few lymphocytes
No lymphatic vessels leave the thymus
Thymus function
Function: maturation of T lymphocytes
T lymphocytes learn to recognize self antigens
Thymocytes with receptors that bind strongly to self antigens are destroyed through a process called apoptosis
Thymocytes that cannot bind any MHC II molecules are also removed
Thymocytes that recognize MHC II/Ag complexes with moderate affinity are allowed to live- positive
The positively selected cells leave the thymus as mature T lymphocytes and populate the secondary lymphoid organs
The maturation process is highly regulated by a mixture of cytokines and thymic hormones such as thymosins, thymopoietins, thymulin, and thymostimulins
Bursa of fabricius
In birds only
Round sac located just before the cloaca
Like the thymus- undergoes involution
Epithelium embed the lymphocytes and lines a hollow sac connected to the cloaca by a duct
Epithelium makes folds that extend into the sac called follicles
Each follicle has a cortex and medulla
The cortex contains lymphocytes, plasma cells, and macrophages
Bursa function
Maturation of B lymphocytes
Negative and positive selection of B lymphocytes
Differentiation of antibody-forming cells
Secondary lymphoid organs
Divided into:
Encapsulated organs: lymph nodes, spleen
Non-encapsulated tissue: mucosal lymphoid organs
They develop late in fetal life and persist in adult life
Enlarge in response to antigenic stimulation
Surgical removal does not impair immune capability
They contain dendritic cells which trap and process antigens, and later present these antigens to lymphocytes to initiate an adaptive immune response
Lymph nodes
Round shaped or bean shaped encapsulated organ
Act as filters of lymph to trap antigens
Contain two important regions: outer cortex and inner medulla, between these two is the paracortex
B lymphocytes are found in the cortex in germinal centers surrounded by capsules
T cells and DCs are mainly found in the paracortex
The medulla contains mainly different types of cells
Afferent lymph flows into the node from local tissue and carries lymphocytes, DCs and antigens
Lymph enters the subcapsular sinus and then percolates through the node to the medullary sinus
Lymph exits through the efferent lymphatic vessel
Lymph nodes have arterial and venous blood supply
Principle function is to facilitate the interaction between dendritic cells and antigen sensitive T and B lymphocytes
Spleen
A large encapsulated organ found in almost all vertebrate animals
Structured by a network of connective tissue trabeculae
Structural differences exist between animals (non-sinusal spleen in cats)
Consists of two types of tissue:
—red pulp: blood filtering and RBC storage
—white pulp: where immune induction occurs, rich in lymphocytes
Primary immune function: filters blood for blood-borne antigens, cellular debris, and aged blood cells
Stores RBCs, platelets, recycles iron
Peyer’s patches
Non-encapsulated lymphoid tissue located in the wall of the small intestines
In ruminants, pigs, dogs, and rabbits- PP are found in the ileum = primary lymphoid organ for B cell development
In young ruminants the PP may be as long as two meters
Contain densely packed lymphoid follicles containing only B lymphocytes
Covered by an epithelial layer containing specialized cells called M cells which have characteristic membrane ruffles
Undergo involution
In rabbits and rodents- PP are located at random intervals in the ileum and juju I’m
In rabbits and rodents PP develop 2-4 weeks after birth and do not undergo involution
Function similar to bursa
Non-encapsulated lymphoid aggregates
Scattered throughout the muscosal surfaces of the body
Makes up a large portion of the total lymphoid tissue
Mostly located in the intestinal mucosal
Generally called mucosal-associated lymphoid tissue (MALT) which includes:
Gastrointestinal (GALT): best known MALT. It is inductive site of intestinal immune response and effector site of intestinal immune response
Bronchial p (BALT)
Nasal (NALT)
Conjunctiva (CLAT)
