Glossary of Immunology Exam 1

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IFN-alpha, IFN-beta
made by cells in response to viruses
Much less antiviral activity

made in response to immune stimuli;

produced by T cells and NK cells;

activate APCs partly by inducing MHC II molecules and they in turn can activate T cells by secreting IL-1 and IL-6 (positive feedback)
Made by macrophages (and B cells and endothelial cells);

Stimulates T and B cells and induces inflammatory responses;

Induces fever;

Virtually all cells in body have IL-1 receptors
Produced by T cells and LGLs (NK cells);

Most powerful activator and growth factor;

Acts on LGLs and B cells to induce growth and differentiation
Stimulates growth of precursors of all hematopoetic lineages (RBCs, granulocytes, macrophages, lymphocytes)
Acts on B cells to induce activation and differentiation;

Acts on T cell to promote differentiation of TH2 cells
Produced by T cells, macrophages, B cells, fibroblasts, and endothelial cells;

Acts on B cells to differentiate into antibody-forming cells (AFCs)
Lymphoid lineage
Produces lymphocytes (B cells, T cells, NK cells)
Myeloid lineage
Produces phagocytes (monocytes, macrophages and neutrophils) and other cells.
Where do T cells develop?
(primary lymphoid organ)
Where do B cells develop?
fetal liver and adult bone marrow
(primary lymphoid organs)
Resting T cells
majority are small, non-granular with a high N:C ratio

Carry a "Gall body"-consists of a cluster of lysosomes associated with a lipid droplet

about 10% of TH and 35% of Tc cells diplay LGL morphology with primary lysosomes dispersed in the cytoplasm and a well developed golgi apparatus
Resting B cells
do not display Gall bodies or LGL morphology,

cytoplasm scattered with ribosomes

activated B cells have developing rough endoplasmic reticulum (RER)

plasma cells are cell blasts that are producing antibody
NK cells
Have no antigenic receptors on their surface;

Characterized by LGL morphology
CD (cluster designation) system
a system of nomenclature,

CD refers to clusters of antibodies that recognize a particular cell marker.
What are the types of T cell antigen receptors (TCRs)?
Two types:
TCR-1 ~ a heterodimer of two disulfide-linked polypepitdes gamma and delta (5-10% of T cells)

TCR-2 ~ a heterodimer of two disulfide-linked polypepitdes alpha and beta(90-95% of T cells)
CD3 complex
Both receptors TCR-1 and TCR-2 are associated with a set of five polypeptides, collectively known as the CD3 complex, to give the T-cell receptor complex (TCR-CD3)
What marker is on the surface of a TCR-2 TH cell?

Helps or induces immune response
What marker is on the surface of a TCR-2 TC cell?

Predominantly cytotoxic functions
What class of MHC can a CD4 cell recognize?
MHC class II
What MHC class can a CD8 cell recognize?
MHC class I
What cytokines do TH1 cells secrete?
IL-2 and IFN-gamma

Important in combating viruses, bacteria and parasites

In response to intracellular pathogens
What cytokines do TH2 cells secrete?
IL-4, IL-5, IL-6, and IL-10

stimulate B cells to proliferate and produce

In response to extracellular pathogens
What constitures the B cell receptor complex (BCR)?
B cells in peripheral blood express two immunoglobulin isotypes on their surface, IgM and IgD

the surface IgM is associated with other molecules on the B cell surface to form the 'B cell antigen receptor complex' (BCR)
B cell markers
Majority of B cells have MHC class II antigens on their surface (important for B and T cell interactions)

CD19, CD20 and CD22 are the main markers used to identify human B cells
Natural Killer cell markers and function
express neither TCR nor BCR antigen receptors

NK cell function is to recognize and kill certain tumor cells and virus-infected cells
Activation of T cell
T cells 'see' the antigen in association with an MHC molecule on antigen-presenting cells
Activation of B cell
B cells can bind free antigen but generally need help from the T cells to become activated
Activated B cell
Antibody forming cells;

Following B cell activation, the B cell matures into an antibody -forming cell (AFC) and eventually to terminally differentiated plasma cells.

short-lived, surviving only a few days

activated B cell expresses new surface markers upon activation, such as MHC class II markers, IL-2R, as well as, IL-3, IL-4, IL-5 and IL-6 receptors
Monocyte characteristics
large in comparison to lymphocytes

has a horse-shoe shaped nucleus, often contains azurophilic granules

they contain peroxidase and several acid hydrolases (important for intracellular killing)
Macrophage/Monocyte cell markers
Fc receptors for IgG -trigger extracellular killing, opsonization (complement binds to immune complexes), and phagocytosis

Complement receptors

Class II MHC molecules

Receptors for cytokines, IL-2, IL-4 and IFN-gamma

their functions can be enhanced by T cells through these receptors
Antigen Presenting Cells
heterogeneous population of leucocytes

cells other than leucocytes, such as endothelial or epithelial cells can also acquire the ability to present antigens when stimulated by cytokines

found primarily in the skin, lymph nodes, spleen and thymus

mechanism of carrying antigens from the skin to the T cells in the lymph nodes

are rich in class II MHC molecules; important for presenting antigen to T cells

B cells are also considered APCs
Langerhans cells
archetypical APC

located in the skin

travel as 'veiled cells' into the lymph nodes
Follicular dendritic cells
Antigen presenting cell

found in the B cell areas of the lymph nodes and spleen.

they present antigen to B cells and lack class II MHC molecules

express high levels of FcR and complement receptors for interaction with immune complexes.
Interdigitating cells
Antigen presenting cells

Located in thymus

play a role in deleting T cells that react against self antigens
Granulocytes and Mast cells
polymorphs are referred to as granulocytes or PMNs

produced in bone marrow;

short-lived (2-3 days) compared to monocytes and macrophages

PMNs can adhere to endothelial cells lining blood vessels and squeeze through the cells to enter the tissue (diapedesis)

show no specificity for antigens but synergize with antibodies and complement in protection against microorganisms
PMNs can adhere to endothelial cells lining blood vessels and squeeze through the cells to enter the tissue
90% of granulocytes;

multi-lobed nucleus

The primary granules are lysosomes containing acid hydrolases, myeloperoxidase and muramidase

The secondary granules contain lysozyme

the ingested organisms are contained within vacuoles termed phagosomes, which fuse with lysosomes to form phagolysosomes
Bi-lobed nucleus and many cytoplasmic granules

ability to phagocytose and kill ingested microorganisms

Usually degranulates instead

play a specialized role in immunity to parasitic worms using this mechanism
involves fusion of the intracellular granules with the plasma membrane and release of the granule contents into the surrounding area;

this is the way that large targets are phagocytosed
are found in circulating blood;

characterized by deep blue-violet granules
Mast cells
are not found at all in circulation and are indistinguishable from the basophil in its properties
Basophil and Mast Cell actions
the stimulus for basophil and mast cells degranulation is often an allergen

the allergen must cross link with IgE that is bound to the basophil and mast cell via Fc receptors for IgE

all granules are released; histamine is released by degranulation giving the adverse symptoms of allergy.

they play a role against parasites
an antigen that causes an allergic reaction
involved in the immune response and especially in inflammation

following injury to endothelial cells, they adhere to surface of the damaged tissue

the platelets release substances that increase permeability, in addition to factors that activate complement
Primary Lymphoid organs
Thymus - T cells

Fetal liver, adult bone marrow - B cells
bilobed organ located in the thoracic cavity

each lobe is organized into lobules separated by connective tissue trabeculae

within each lobule the lymphoid cells are arranged into an outer cortex and an inner medulla

in thymic lobules, are also present interdigitating cells (IDCs) and mactrophages

the thymus involutes with age; atrophy begins at puberty and continues throughout life
Outer cortex of Thymus
contains relatively immature proliferating thymocytes
Medulla of Thymus
contains more mature cells, suggesting a differentiation gradient from the cortex to

Hassals' corpuscles are found in the thymic medulla, its function is unknown (contains degenerating epithelial cells)
High Endothelial Venules (HEVs)
traffic of cells into and out of the thymus occurs through these
Hassals' corpuscles
found in the thymic medulla,

its function is unknown (contains degenerating epithelial cells)
Bursa of Fabricius
modified section of the intestinal and genitourinary tracts of birds

organized in cortex and medulla
Fetal liver and Bone marrow
islands of hemapoetic cells in the fetal liver and in the fetal and adult bone marrow give rise to B lymphocytes

adult bone marrow contains mature T cells, thus, making the bone marrow an important secondary lymphoid organ (provides an environment for interactions between B and T cells)
Secondary Lymphoid Organs

Lymph Nodes

Mucosal-associated lymphoid tissues (MALT)
is responsive to blood-borne antigens

it has two main types of tissue: white pulp and red pulp
White pulp (of spleen)
consists of lymphoid tissue that surrounds a central arteriole and it is called periarteriolear lymphoid sheath (PALS)

T cells surround arteriole

B cells are arranged into primary "unstimulated" follicles and secondary "stimulated" follicles (posess a germinal center with memory cells)

the germinal centers contain follicular dendritic cells and phagocytic cells

macrophages and B cells are found in the marginal zone-area that overlying the
secondary follicles
Red pulp (of spleen)
consists of sinuses containing macrophages, erythrocytes, platelets, granulocytes and plasma cells

site where aged erythrocytes and platelets are destroyed

capillaries that ended at the PALS extend and open freely to the red pulp cords. Thus, circulating cells enter and become trapped at the cords where they can be phagocytosed
Lymph nodes
form a network that filters fluid derived from blood in the tissue spaces

frequently found at branches of the lymphatic vessels
strategically placed in areas of the neck, groin, and abdominal cavity which drain superficial and deep regions of the body

lymph nodes are 2-10mm in diameter, are round or kidney shaped

fluids enter through several afferent lymphatic vessels and leaves the node through one efferent lymphatic vessel at the hilus
Cortex of Lymph Node
contains aggregates of B cells as primary or secondary follicles
Paracortex of Lymph Node
T-cell area
Central Medulla of Lymph Node
consists of T cells, B cells, plasma cells and macrophages
Mucosal Associated Lymphoid Tissue(MALT)
aggregates of non-encapsulated lymphoid tissue are found in the lamina propria and submucosal areas of the gastrointestinal, respiratory and genitourinary tracts

lymphoid cells are present in aggregates containing germinal

antibody IgA is the most common antibody present at mucosal surfaces

it transverses mucosal membranes and helps prevent entry of infectious microorganisms
Action of IgA
plasma cells secrete IgA into the intestinal space

IgA binds to a receptor on the internal surface of the epithelial cells is then endocytosed and transported across the cell

IgA is released to the luminal surface (outside) of the cell where it can protect the mucosal surface from antigens
Lymphocyte Traffic
the main exit route of lymphocytes from blood is through the high endothelial venule (HEV)

in the lymph nodes, HEVs are primarily found in the paracortex and some in the cortex

Lymphocyte trafficking exposes antigen to a large number of lymphocytes

Lymphocytes within lymph nodes return to blood circulation by efferent lymphatic vessels, which pass through the thoracic duct into the left subclavian vein
What happens to Lymphocyte traffic when antigen is encountered?
when antigen enters the lymph nodes all traffick shuts down for 24 hours, so that antigen-specific lymphocytes are retained in the lymph node where antigen is drained
Adaptive Immune Response
2 molecules involved:
1) immunoglobulins
2) T cell antigen receptors
group of glycoproteins present in the serum and tissue fluids

some are carried on the surface of B cells where they act as receptors

some (Ab) are free in blood and lymph

the membrane bound Ig has the same antigen binding specificity as does the antibody produced by the plasma cell.
Five classes of Immunoglobulins
IgG, IgA, IgM, IgD, and IgE

differ in size, charge, amino acid composition and carbohydrate content
Why are Immunoglobulins bi-functional molecules?
One region binds to antigen while a different region mediates effector functions

effector functions include binding of the Ig to host tissues, binding to cells of the immune system, and to the first component (C1q) of the complement system
Structure of Immunoglobulins
The basic structure of all immunoglobulin molecules is a unit consisting of two identical light polypeptide chains and two identical heavy polypeptide chains
major immunoglobulin in normal human serum

It consists of a single four-chain molecule

Maternal IgG confers immunity to neonates- it crosses the placenta giving passive immunity to the newborn
it is a pentamer of the basic four-chain structure

it is confined in the intravascular pool

It is predominantly the "early " antibody,- it is the first immunoglobulin class produced in a primary response to antigen

because of steric hindrance it can only bind to 5 molecules of antigen even though it has 10 binding areas
less than 1% of the total plasma Ig

present in large quantities on the membrane of many B cells

function is unknown
scarce in serum, found on surface membrane of basophils and mast cells

plays role in immunity against parasitic helminths

associated with allergic diseases such as asthma and hay fever
found in external secretions, such as breast milk, saliva, tears, mucosal surfaces

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