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Acquired Immunity
Defensive mechanisms include :
1) Innate immunity (Natural or Non specific)
2) Acquired immunity (Adaptive or Specific)
Cell-mediated immunity Humoral immunity
Two mechanisms
1) Humoral immune response:
- Antibodies are produced by B-lymphocytes
- These have the ability to recognize and bind
specifically to antigen that induced their formation
2) The cell mediated immune response (CMI)
- It is mediated by certain types of T-lymphocytes
- T-lymphocytes recognize foreign material by
means of surface receptors TCR
- T-lymphocytes attack and destroy foreign material
directly or through release of soluble mediators
i.e. cytokines
- Attack intracellular antigen
1) Highly specific for the invading organism
2) Discrimination between “self and “non self” molecules
The response only occurs to “non self” molecules
3) Diversity:
- It can respond to millions of different antigens
- Lymphoctes population consists of many different clones
(one cell and its progny)
- Each clone express an antigen receptor and responds only
to one antigenic epitope
Steps of Acquired Immune Response lymphocyte B & T:
1. Recognition of the antigen by specific lymphocytes
2. Activation of these specific lymphocytes
3. Proliferation and differentiation into effector cells;
4. The effectors cells eliminate the antigen
5. Return of homeostasis and development of memory cells
* Memory cells evoke a more rapid and long response on re-exposure to same antigen
Maturation events of T lymphocyte
Hematopoietic progenitors cells from bone
marrow move into Thymus gland
At thymus it is called thymocytes and it run
through several selection process
1. Beta selection: active proliferation and
elimination thymocytes with gross defects
introduced into the T cell receptor (TCR).
2. positive selection: selects cells with a TCR
that able to bind MHC class I or II molecules
with weakest affinity.
3. Negative selection: Killing by apoptosis T cells
with a high affinity for self peptides or MHC.
Eliminate auto reactivity towards self.
Upon maturation two types of T Lympocytes is produce which is CD4+ : T-helper cells
CD8+: T-cytotoxic cells
When antigen enter a body it will be attacked by antigen presenting cells (APC).
Then it will display antigen peptide bonded with MHC II on cells surface.
To activate CD4+ T cells, TCR on Tcells have to bind to MHC II on APC. (first signal)
Then CD28 molecule have to bind to B7 molecule (costimulation)
CLONAL EXPENSION
Upon activation the CD4+ T Cells become blast cells. 24H
IL-2 secreted and CD4+ T multiply.
CD4+ T differentiate into subset(effector cells) TH1
TH2
Effectors cell function affects CD8+ T cells (Discuss next)
B lymphocytes (Discuss next in B-lymphocytes)
Myeloid cells
Bone marrow precursor
When the antigen have been eliminated the
T cells number have to be decrease.
They are reduce by apoptosis.
Some will remain as memory cell and can be
activated without the need for CD28-B7
co-stimulation.
CD8+ T lymphocyte is also called cytotoxic T
lymphocytes (CTL) which mean it destroy
infected host cells.
CTL cell once matured is released into blood
stream.
Activation of CTL required binding of TCR to
MHC I on APC and binding of B7-CD28.
Activated CD4+ T lymphocyte can also
activated CTL by releasing IL-2.
When attached to infected/dysfunctional somatic cells, CTL release the cytotoxins perforin and granzymes.
Perforin forms pores (aqueous channels) in the target cell's plasma membrane
Allowing granzymes, to enter the target cell, which lead to apoptosis.
Other mechanisms is to induce apoptosis is via cell-surface interactions between the TC and the infected cell.
Elimination of excess CTL in absent of antigen is same as CD4+ T cells.
Humoral is mediated by B
lymphocytes
principal functions of B-cells are
make antibodies against antigens,
perform the role of antigen-presenting
cells (APCs),
Develop into memory B cells after
activation
B cells (maturation) Immature B cells are produced in the bone
marrow from hematopoietic stem cells.
Here stem cell develop into Pro-B cells
Pro-B cells develop into Pre-B cells
Then Pre-B develop into immature B cells
Any cells that failed developing into immature B
cells is destroyed by clonal deletion.
Some immature B cell develop into IgM+IgD+
mature B cells.
migrate to secondary lymphoid tissues to
matures.
B cells recognize their antigen in its native
form.
They recognize free (soluble) antigen in the
blood or lymph using their B cell receptor
(BCR) on cell surface or membrane bound-
immunoglobulin
Activation of B lymphocytes can
occur in two manner
T-dependent activation
T-independent activation
* T = Thymus
T-dependent activation
Once a pathogen is ingested by an antigen-presenting cell (APC) such as a macrophage or dendritic cell, the pathogen's proteins are then digested to peptides and attached to a class II MHC protein.
It is detected by T lymphocyte and TH helper cells (CD4+ T cells ) is generated.
TH cell then bind to specific B lymphocytes
TCR on TH cells have to bind to MHC II on APC. (first signal)
Then CD28 molecule have to bind to B7 molecule (costimulation)
TH cell secretes cytokines that activate the B
cell.
These cytokines trigger
B cell proliferation and differentiation into
plasma cells.
Isotype switching to IgG, IgA, and IgE
Memory cell generation
Some antigen known as TI antigens can
directly activate B Lymphocytes.
Two types of T-independent activation
Type 1 T cell-independent (polyclonal)
activation (more than 1 antigen bind to BCR on a
B cells)
Type 2 T cell-independent activation (in which
APC present several of the same antigen in a way
that causes cross-linking of antibodies on the
surface of B cells).
Effect of T-independent activation is
Plasma cell produce
Proliferation of B lymphocyte
Only IgM produce
No memory cells produce
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