Cell mediated immunity Flashcards
what adaptive (acquired) immunity
third line defense
-speacialized lymphocytes:
•T and B cells
-antibodies
cell mediated immunity plays a major role in
• Defense against mainly viral and other intracellular pathogens,
cancer cells
• Delayed type hypersensitivity
• Graft rejection
T-lymphocyctes
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
organs and composition of T cell networks
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.
cell mediated immune response- a sequential peocess
• 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.
T cell receptor
• 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.
What is major histocompatibility complex(MHC)
• 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.
two structurally different type of MHC exist
• 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.
What antigen presenting cells (APCs)
• 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
how antigen processing and presentation
• 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).
Different pathways for association of peptide with MHC class I and II molecules
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
Processing and presentation antigen - Exogenous antigen
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
Processing and presentation of antigen- endogenous antigen
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
T lymphocytes -Activation and effector functions
• 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.
types of effector T cells
• 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.
Effector function – Helper T cell function
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.
Effector function – Cytotoxic T cells
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.
Superantigens
• 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.
Clinically important superantigens
Clinically important superantigens include Staphylococcal enterotoxins that cause food poisoning, and the toxic shock syndrome toxin (TSST).
Other examples of Cell-Mediated Immune response:
Delayed-Type Hypersensitivity (DTH): the tuberculin test
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.
Other examples of Cell-Mediated Immune response:
Contact sensitivity
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
Other examples of Cell-Mediated Immune response;
Graft rejection
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.
