Enclonar, Kimberly / MLS 3A

Adaptive Immunity Adaptive Immunity

• Highly specific and has the ability to remember it
February 2, 2021
• Increase response upon subsequent exposure
Lean Kristin Ugdang, RMT
• Adapts - depending on the antigen encountered
• 3rd line of defense
Primary Lymphoid Organs/Central Lymphoid Organs
• Result from exposure of immunogens
Bone Marrow
• Components
• Medulla of flat bones o Cellular - T cells & B cells
• Site of B cell maturation o Humoral - Cytokines & Antibodies
• Equivalent to Bursa of Fabricus in birds • Lymphocytes (T-cells & B-cells)
• Origin of all blood cells o Tolerance - ability to distinguish "self" from
• Contain pluripotential hematopoietic stem cells "non-self"
• Antigen Independent lymphopoiesis o Specificity - refers to cell-surface receptors for
specific for a certain fragment of an antigen
Thymus (epitope)
• Small, flat, bilobed organ that overlies the heart o Memory - refers to the ability of these cells to
• Located in the mediastinum respond much faster after repeated antigen
• Site of T cell maturation exposure
• 2 regions:
o Cortex
o Medulla
• Consists of thymic stroma that contains thymic EC
• Fully developed before birth
• Diminishes in size as a person aged
• Progenitor T cells from BM migrates to the thymus
and enter via the high endothelial venules (HEV)

Secondary/Peripheral Lymphoid Organs (Antigen-

Dependent Lymphopoiesis) Active (infection) • Developed during
Spleen convalescence from
an infection
• Largest secondary LO
• Filter blood and destroy old or senescent old RBCs Natural • Immunity after
• Trabecula divides it to 2: chicken pox
o Red pulp - site of senescent RBC destruction infection
o White pulp - contains the lymphoid tissues Passive (maternal) Through the placenta
arranged around periarteriolar lymphatic sheet
Active (immunization) • Obtained after
(PALS)
vaccination
▪ PALS - T cells
▪ Primary follicle - Naive B cells (mature B • Booster injection -
to expand memory
cells that are not yet stimulated by
pool
antigens)
▪ Marginal zone - Contains dendritic cells Passive (antibody • After injection of
that trap antigens transfer) gammaglobulins
• Responds to IV route antigens • Serum or plasma
Artificial containing high
Lymph Nodes concentration of
• Collects lymph fluids from adjacent tissues preformed Abs
• Traps antigens in the tissues produced by
• 2 compartments another person or
o Cortex - Contains macrophages and naive B cells animals that has
▪ Secondary follicles - Antigen stimulated B been actively
cells with germinal center inside it immunized
▪ Germinal center - clonal expansion of B • Antisera
cells takes place (formation of memory &
plasma cells)
o Para cortex - T cells T cell Ontogeny
o Medulla • Cell-mediated immunity
• Maturation of T cells
• Drains in the thoracic duct and emptied in the
subclavian vein • CD - cluster of differentiation
o CD4+ T cell (T helper)
• Lymphadenopathy - enlargement due to
o CD4+ T cell (T cytotoxic)
accumulation of cells
• T cell receptor (TCR)
o Unique specificity towards antigen
Others
o Contains alpha and beta chain
• Mucosa Associated Lymphoid tissues (MALT)
o Gastrointestinal, respiratory, urogenital tract o Variable region - recognizes antigen
o CD3 - other chains that form complex with TCR;
• Cutaneous Associated Lymphoid Tissues (CALT)
o Skin responsible for intracellular signaling
• Gut-Associated Lymphoid Tissue (GALT)
o Peyer patches, tonsils
 Enclonar, Kimberly / MLS 3A
o Cells that fail to make successful rearrangement
of the gene for B chain remain in the DN3 stage
o Expression of the B chain paired with a surrogate
A chain (pre-TCR or the pT A) together with CD3
molecules
o Expression of pre-TCR arrests further B chain
rearrangement
o Pre-T cells are produced
• Double Negative Thymocytes 4 (DN4)
o DC44- & CD25-
o Rearrangement of the gene coding for the a-
chain of the TCR
o Expression of the complete A:B TCR
• Double Positive Thymocytes
o TCR stimulates CD4 & CD8 molecules
o Complexed with CD3
• Screening Tests
o Death by Neglect
▪ Thymic EC will present self antigens (MHC
class I) to the CD4/8+ thymocytes
▪ Thymocytes that lack TCR signal undergo
apoptosis
o Positive Selection
▪ T cells with functional A:B TCR are given
proliferation signal
Pre-Thymic Phase o Negative Selection
• Sites of origin of lymphoid precursor
▪ Thymocytes with strong TCR signals are
• Appear in fetal liver and shift to the bone marrow
deleted (apoptosis)
later on
• Mature T cells
• Pluripotent HSCs → multipotent progenitor cell →
• Survivors of the selection of processes exhibit only 1
lymphoid + myeloid → thymus via corticomedullary
type of marker
junction
• MHC Class II - CD4 (T helper)
• Driven by chemicals released by thymus
• MHC Class I - CD8 (T cytotoxic)
• Express other receptors: CD2, CD3, CD7
• Thus:
o T helper: CD4, CD3, CD7, a:B TCR
o T cytotoxic: CD8, CD3, CD7, a:B TCR
• Migrate to the medulla and leave the thymus via the
HEV and go the secondary lymphoid organs

Thymic Phase (Subcapsular Region)

• Progenitor T cells lack the surface molecules of a
mature T cell
• Immature, DOUBLE NEGATIVE CD3 TCR complex -
CD4/8-thymocytes
• CD3 is unexpressed (CD3-)
• CD2 - the first T cell specific surface molecule is
expressed
• Double Negative Thymocytes 1 (DN1)
o CD44+ (adhesion molecule)
Y:delta cells
o Genes encoding the B chain of the TCR are in the
• TCR is made up of y:delta chains
germline configuration
• Much less common
• Double Negative thymocytes 2 (DN2) • Abundant in the mucosa (IEL)
o CD44+ (adhesion molecule)
• Restricted TCR - acts as PRR
o CD25+ (interleukin 2 receptor) - important in T
cell proliferation T-regulator Cells
o Cytoplasmic markers start to appear
• CD4+ & CD25+
o Thymocyte becomes committed T cell
• 5% of all CD4+ T cells
o Rearrangement of B receptor gene occurs at this
• Suppress cytokine production of T cells
stage →
• Prevents autoimmune cells
• Double Negative Thymocytes 3 (DN3)
o Reduce expression of CD44
T cytotoxic Cells
o CD25+
• Recognize intracellular infections
o Rearrangement of the gene coding for the B
• Recognize MHC class I
chain occur
 Enclonar, Kimberly / MLS 3A
T helper cells
• Extracellular infections
• MHC Class II
• Promotes cytokine production

Th and Tc Cell Activation

• Major Histocompatibility Complex
• MHC Class I - nucleated cells; intracellular
o Assists immune response during infection
• MHC Class II - APCs; extracellular
o Assists during extracellular infection
• APC (macrophage, B cells, antibodies)
T helper cell Activation and Clonal Expansion in Lymph
• Class II MHC holds the peptide (serving tray) - CD4
Nodes
helper
• 1-2 days after T cell maturation
• Complex provides signal transduction
• Effector Cells
• Binding of TCR to antigen is weak, therefore a more o Th Memory
stable condition must be met
▪ Recognizes same antigen; more rapid
o Performed by Integrins
response
▪ Leukocyte Function Associated antigen 1 o Th1
(LFA-1) - most common
▪ Produces IL2, Interferon gamma (most
□ Binds to ICAM-1 or ICAM-2
potent), TNF-B
□ Chemokines increase affinity of LFA1
▪ Interferon gamma stimulates antibody
to ICAM-1 or 2
production
□ Antigen recognition of T cell converts o Th2
low affinity LFA-1 towards ICAM;
▪ IL4
increases antigen binding
▪ Stimulates B cell to produce antibodies
(IgE)
o Th17
▪ IL-17 & IL-22
▪ Stimulates inflammation
o T regulatory
▪ CD4 & CD25+
▪ Acts as suppressor

Signal Two / Co-stimulation

• Essential to fully activate T cell
• Microbial antigen stimulates expression of CD80 &
CD86 (or B7)
• Work together with coreceptor
• CD40L- CD40 signal
o CD40 in APC bind with CD154 (CD40L) in T cells
Differentiation of CD*+ T cells into CTLs
o Binding stimulates CD80 which binds with CD28
• MHC Class 1 can also be expressed on APCs

Effector Functions of CTLs subsets in infection Sites

• Perforins - makes pores
• Granzymes - DNA & mitochondrial digestion
 Enclonar, Kimberly / MLS 3A
B cell Ontogeny Mature B cell
• Humoral Mediated immunity • Naive B cells move to secondary lymphoid organs for
• Immunoglobulin - receptor for B cells antigen activation
o Consists of light & heavy chain • Express IgD
• Mature in bone marrow - niches promotes
localization B cell Activation
• Growth factors are also present in bone marrow • Activates proliferate and clonal expansion
• Receptor-associated signaling molecule is activated
once there is cross-linking with Ig towards antigen
• Immunoreceptor Tyrosine-based Activation Molecule
(ITAM) is activated

T cell Dependent B cell Activation

• Binding of CD40 & CD40L (T cells)
• Activation of clonal expansion
• Activated T-cell produces cytokines which bind to B-
cell
Pro-B cell T cell Independent B cell Activation
• Earliest among B-cell lineage • Triggered by cross-linking of Ig towards antigens that
• Sequential rearrangement of heavy chains has the same isotope
• Surface proteins can be observed • Production of
o C-Kit - interacts with bone marrow stromal cells o Plasma cells - produces antibodies
• VDJh chains o Memory B cell - long life-span

Pre-B cell
• Has mu chains in its surface accompanied by
surrogate light chains
• Ig alpha and beta - signal transducing units
• Formation of pre-B receptor

Immature B cells
• Expression of IgM molecule
• Central tolerance - deletion of Ig