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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