Cell mediated immunity

Question 1

what adaptive (acquired) immunity

Answer 1

third line defense
-speacialized lymphocytes:
•T and B cells
-antibodies

Question 2

cell mediated immunity plays a major role in

Answer 2

• Defense against mainly viral and other intracellular pathogens,
cancer cells
• Delayed type hypersensitivity
• Graft rejection

Question 3

T-lymphocyctes

Answer 3

T-lymphocytes – “Cellular arm” of acquired/adaptive immunity.
- recognize foreign antigens on the surface of cells or tissues.
- regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc

Question 4

organs and composition of T cell networks

Answer 4

etcThe T cell-mediated immune response begins in the secondary lymphoid organs: spleen, lymph nodes, and organized lymphoid tissues associated with mucosal surfaces including Peyer’s patches, tonsils and gut-associated lymphoid tissues.

Question 5

cell mediated immune response- a sequential peocess

Answer 5

• Mature T lymphocytes, known as naïve T cells, circulate through blood and the lymphatic system, and reside in secondary lymphoid organs. (Naïve T cells are those that have not yet encountered foreign Ag and have not yet been activated).

• Antigen presenting cells (APC) generate antigenic peptides from a pathogen by antigen processing, and display them on the cell surface.

• Antigenic peptides are presented to the naive T lymphocyte in secondary lymphoid organs by APC.

• Triggers a cascade of intracellular signaling events, resulting in activation of the naïve T cell.

The activated T cells rapidly proliferate (clonal expansion), migrate through the tissues to the sites of Ag presence, and perform effector functions such as cell-mediated cytotoxicity and production of various cytokines.

CD8+ T (cytotoxic) cells are very effective in direct lysis of infected or malignant cells.

CD4+ T helper cells produce cytokines • that can be directly toxic to the target
cells or
• can stimulate other T cell effector
functions and B cell antibody production, • also can mobilize powerful inflammatory
mechanisms.

Question 6

T cell receptor

Answer 6

• The T-cell receptor, or TCR, is a molecule found on the surface of T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules.
• Most T cells have antigen receptors composed of alpha and beta chains, each with variable and constant regions (V and C regions).
• It recognizes antigen associated with MHC and is responsible for T cell activation.

Question 7

What is major histocompatibility complex(MHC)

Answer 7

• Cell mediated immune responses are regulated by MHC.
• The major histocompatibility complex (MHC) is a set of specialized
proteins expressed on surface of host cells.
(In humans – HLA, large genetic locus present on Chromosome 6).
• MHC molecules have two key functions:
• to selectively bind to peptides produced when proteins are processed
inside host cells
• to present peptides on the surface of a host cell to a T cell
• Importantly, they allow T cells to distinguish self from non-self.

Question 8

two structurally different type of MHC exist

Answer 8

• Two structurally different types of MHC exist
• Class I MHC – present on most nucleated cells.
• Class II MHC – present on dendritic cells, macrophages and B cells.
The critical role played by MHC molecules in binding processed antigen and presenting it in T-cell responses is referred to as the MHC restriction of T-cell responses.

Question 9

What antigen presenting cells (APCs)

Answer 9

• Pathogens and other exogenous antigens are internalised into the vesicular compartments of antigen presenting cells (APCs), by phagocytosis, endocytosis or macropinocytosis.

Monocytes : Peripheral blood
Macrophages : Tissues
Dendritic cells : Lymphoid tissues
Langerhans cells : Epidermis

Question 10

how antigen processing and presentation

Answer 10

• The protein is broken down to peptides—linear fragments—of varying length.
• Some of these peptides bind to an MHC molecule inside the cell.
• The MHC molecule with bound peptide moves to the cell surface for expression.
• The combination of peptide bound to an MHC molecule is recognized at the cell surface by a T cell that expresses the “appropriate” or “correct” TCR.

• MHC class I molecules interact with CD8+ T cells
(responses of CD8+ T cells are restricted by MHC class I molecules).
• MHC class II molecules interact with CD4+ T cells
(responses of CD4+ T cells are restricted by MHC class II molecules).

Question 11

Different pathways for association of peptide with MHC class I and II molecules

Answer 11

Endogenous antigen processing pathway
Generate Ag fragments that associate with MHC class I molecules on cell surfaces

Exogenous antigen processing pathway
Generate Ag fragments that associate with MHC class II molecules on cell surfaces

Question 12

Processing and presentation antigen - Exogenous antigen

Answer 12

Exogenous antigens – e.g. bacterial, parasitic
⬇️
hydrolysed in endosomes to linear peptides
⬇️
presentation on the cell surface together with class II MHC to CD4+ T lymphocytes

Question 13

Processing and presentation of antigen- endogenous antigen

Answer 13

Endogenous antigens – e.g. autoantigens, foreign antigens from viral, intracellular parasites or tumourous antigens
⬇️
hydrolysed to peptides
⬇️
transportation into ER
⬇️
in Golgi complex they are associated with class I MHC
⬇️
presentation on the cell surface to CD8+ T lymphocytes

Question 14

T lymphocytes -Activation and effector functions

Answer 14

• Recognize antigens (on dendritic cells) in peripheral lymphoid organs, resulting in expansion of Ag-specific lymphocyte pool.
• Differentiate into effector cells and memory cells.
• Activation of T cells requires recognition of antigen displayed on APCs, co- stimulators, and cytokines produced by both APC and T cell.

Question 15

types of effector T cells

Answer 15

• CD4 (T helper cells)
• CD8 (Cytotoxic T cells)

Each type
• responds to different types of antigens.
• activated by different antigen presentation. • has different effector function.

Question 16

Effector function – Helper T cell function

Answer 16

Role of TH cells in macrophage activation
• Macrophages routinely engulf invading microbes resistant
to lysosomal killing.

• TH cells recognize macrophage with engulfed microbes resistant to killing.

• TH cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms.

Question 17

Effector function – Cytotoxic T cells

Answer 17

Activation of CD8 T cells = cytotoxic T cells (CTLs)

• Binding of TCR + CD8 to MHC-I of APC
• TCR recognizes foreign protein in self MHC molecule. • Specific clone expands by ~100,000.
• Activated CTLs bind with target cell.
• Granulysin, granzymes and perforin released from granules = apoptosis.

Question 18

Superantigens

Answer 18

• Classical antigens generate peptides that bind the peptide-binding groove of MHC Class II. In contrast superantigens bind directly to MHC without processing.

• This type of response causes a massive production of CD4 T cell cytokines resulting in systemic toxicity and suppression of adaptive immunity.

• Compared to a normal antigen-induced T-cell response where 0.001 to 0.0001% of the body’s T-cells are activated, these superantigens are capable of activating up to 20% of the body’s T-cells.

Question 19

Clinically important superantigens

Answer 19

Clinically important superantigens include Staphylococcal enterotoxins that cause food poisoning, and the toxic shock syndrome toxin (TSST).

Question 20

Other examples of Cell-Mediated Immune response:
Delayed-Type Hypersensitivity (DTH): the tuberculin test

Answer 20

Delayed-Type Hypersensitivity (DTH): the tuberculin test

• The Mantoux test or tuberculin test or PPD test is a screening test for latent TB infection.
• About 0.1 mL of tuberculin is injected intradermally.
• In 48 hours, a hard, red nodule develops at the site of the injection if the person is or had been infected earlier with MTB. This nodule is densely packed with lymphocytes and macrophages.
• DTH is a cell-mediated response and the T cells responsible for DTH are members of the CD4+ subset.

Question 21

Other examples of Cell-Mediated Immune response:
Contact sensitivity

Answer 21

Contact sensitivity
• Many people develop rashes on their skin following contact with certain chemicals such as nickel, certain dyes, and the active ingredient of the poison ivy plant.
• The response usually takes some 24 hours to occur, and like DTH, is triggered by CD4+ T cells.
• After the antigen is engulfed by dendritic cells in the skin, they migrate to +
nearbylymphnodeswheretheypresentfragmentsoftheantigentoCD4 T cells .
• The activated T cells migrate from the lymph nodes to the skin to elicit the inflammatory response

Question 22

Other examples of Cell-Mediated Immune response;
Graft rejection

Answer 22

Graft rejection
• Grafts of a kidney, heart, lung, liver, etc. from one human to another always (unless donated by an identical twin) are seen by the recipient’s immune system as antigenic and elicit an immune response.

• If unchecked, this response will eventually lead to destruction of the graft. Both CD4+ and CD8+ T cells participate in graft rejection. They are responding to differences between donor and host of their MHC class II and class I respectively.