Acquired Immunity Flashcards
(20 cards)
Lymphocytes in adaptive immunity
T-cells (develop in Thymus) are responsible for cell-mediated response
B-cells (develop in bone marrow) produce antibodies and are responsible
for humoral response
Innate vs Adaptive in specifity and memory
Innate
- General protection
(recognition of common features of the
pathogen (PAMPS))
- Does not alter on repeated exposure
(no immunological memory)
Adaptive
- Highly specific for a particular pathogen
(recognition of specific details of
molecular structure (antigens))
- Improves with each subsequent
exposure (immunological memory)
Clonal Selection Theory
- an organism first randomly generates a vast diversity of
lymphocytes - those lymphocytes that can react against the foreign
antigens are specifically selected for action - those lymphocytes that react against self antigens are inactivated
Primary organs and tissues of adaptive immunity system
(bone marrow and thymus)
- sites where lymphocytes mature and differentiate
into antigen-sensitive mature B and T cells
- Positive and negative selection takes place
Secondary organs and tissues of adaptive immunity system
(lymph nodes and spleen)
-areas where lymphocytes encounter and bind
antigen
-followed by proliferation and differentiation into fully
mature effector cells
Primary and secondary antibody responses
The secondary response induced by a
second exposure to antigen A is faster and
greater than the primary response and is
specific for A.
Indicating that the adaptive immune system
has specifically remembered encountering
antigen A
The same type of immunological memory is
observed in T-cell-mediated responses
Recognition in adaptive immunity
Mediated by specific antigen receptors expressed on the surface of lymphocytes
T-cells- T cell receptors (TCR)
B-cells- Immunoglobulins (Anti-bodies)
Both belong to a structural family of immunoglobulin proteins
Immunoglobulin structure
- All immunoglobulin molecules
have the same basic structure
– 4 polypeptide chains - 2 identical heavy chains
- 2 identical light chains (k
or L) - Heavy and light chains
connected by disulfide
bonds
both chains contain two
different regions
-constant (C) regions (CL and
CH)
-variable (V) regions (VL and
VH)
Somatic Hyper-Mutation
- Enzyme AID (Activation Induced
Cytidine Deaminase) introduces
individual point mutations in the V-
region of immunoglobulin - Resulting clones of B-cell will differ in
the specificity and affinity for antigen - Those with greater affinity will survive
and differentiate into the plasma cells
and memory cells
4 main mechanisms of antibody diversification
- Combinatorial joining of gene segments
- Junctional diversification during gene segment joining (TDT enzyme)
- Combinatorial joining of L and H chains
- Somatic Hyper-Mutation
Thymus-independent antigens
Requires 2 signals
* Extensive cross-linking of B-cell
receptors (when binds repeated
epitopes on bacterial cell)
* Second signal is provided by
recognition of a common microbial
pattern by TLRs
Thymus-dependent antigens
- B-cell acts as antigen presenting cell
CD4+ T-cells
are principally regulatory cells, which
control the functions of other
lymphocytes by secretion of cytokines
CD8+ T-cells
possess direct cytotoxic activity towards
cells infected with viruses and against
certain tumors, thus eliminating
infections caused by intracellular
pathogens or malignant transformation
T-cell receptor
Heterodimer
Recognises antigen
in the complex with
MHC molecule
Recognises
extended/unfolded
form of an antigen
CD4 and CD8 co-receptors on. mature t-cells
Cytotoxic T cells express CD8, which recognizes MHC I proteins
Helper T cells express CD4, which recognizes MHC II proteins.
T cell receptor binds to the variable
(polymorphic) parts of the MHC protein that
form the peptide-binding groove
the co-receptor binds to the invariant part,
far away from the groove.
Pathway of T-cell development
T cell precursors are born in the bone marrow and “educated” in the thymus.
Once the T-cell
repertoire is established, immunity can be sustained without the production of
significant number of new T-cells.
The pool of peripheral T-cells is maintained by the division of mature T-cells.
The thymus “involutes” with age (>14 y.o. ) and is largely degenerated in elderly.
How T cells are selected to not recognise antigens
from anywhere in the body?
Self-Tolerance
The autoimmune regulator (AIRE) is a transcription factor expressed in the medullary
thymic epithelial cells, mTECs.
Through the action of AIRE, mTECs express major proteins from elsewhere in the body
(so called “tissue-restricted antigens” - TRA) and T cells that respond to those proteins
are eliminated through cell death.
When AIRE is defective, T cells that recognize antigens normally produced by the body
can exit the thymus and enter circulation. This can result in a variety of autoimmune
diseases
T-cell selection
1.T cell progenitors enter the thymus at the
cortex/medulla border via post–capillary venules
2.In the cortex, thymocytes undergo somatic
gene recombination and positive selection by
cTECs, only those T-cells which can recognise
MHC with moderate affinity are allowed to
migrate to the medulla (others die) – Positive
Selection
3.In the medulla, thymocytes are screened for
reactivity to tissue-restricted self antigens
expressed by mTECs-(Negative Selection)
4. Mature T cells exit the thymus via blood or
lymphatic vessels
T-cell activation requires 3 signals…
- antigen-specific interactions
- co-stimulatory molecules
- instructive cytokines
