Cell-Mediated Immunity

Cell Mediated Immunity Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues. T cells regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc. Defense against: Bacteria and viruses that are inside host cells and are inaccessible to antibodies ( intracellular pathogens). Fungi, protozoa, and helminths Cancer cells Involved in harmful effects of delayed hypersensitivity reactions included in transplant rejections, contact dermatitis, skin tests, and granuloma formation.

Cell Mediated Immunity is Carried Out by T Lymphocytes

T Cells and Cell Mediated Immunity Antigens that stimulate this response are mainly intracellular. Unlike humoral immunity, cell mediated immunity is not transferred to the fetus. Cytokines: Chemical messengers of immune cells. Over 100 have been identified. Stimulate and/or regulate immune responses. Interleukins: Communication between WBCs. Interferons: Protect against viral infections. Chemokines: Attract WBCs to infected areas.

T Cells and Cell Mediated Immunity Antigen processing and presentation: T cells have an antigen receptor that recognizes and reacts to a specific antigen (TCR). T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells. MHC Class I: Found on all cells. MHC Class II: Found on phagocytes. Clonal selection increases number of T cells recognizing a specific antigen.

T Cells Only Recognize Antigen Associated with MHC Molecules on Cell Surfaces

Ag processing and presentation by APCs MHC Class II MHC Class I Antigen Presenting Cell (APC)

MHC Class II + peptide MHC Class I + peptide Antigen Presenting Cell (APC)

CD8 T cell CD4 T cell T cell receptor (TCR) TCR Class II Class I Antigen Presenting Cell (APC)

Association of peptide with an MHC II (exogenous Ag)

Association of peptide with an MHC I(endogenous Ag)

T Cells and Cell Mediated Immunity Types of T cells 1. T Helper (TH) Cells: Central role in immune response. They are CD4+ Recognize antigen associated with MHCII on the surface of antigen presenting cells (e.g.: macrophage, denteritic cells, and B cells). Activate macrophages Induce formation of cytotoxic T cells Stimulate B cells to produce antibodies.

Central Role of Helper T Cells

Types of T cells (Continued) 2. Cytotoxic T (Tc) Cells: Destroy target cells. They are CD8 positive & (CD4 -). Recognize antigens associated with MHC I on the surface of all cells: Kill host cells that are infected with viruses or bacteria. Recognize and kill cancer cells. Recognize and destroy transplanted tissue. Release protein called perforin which forms a pore in target cell, causing lysis of infected cells. Undergo apoptosis when stimulating antigen is gone.

Cytotoxic T Cells Lyse Infected Cells

Nonspecific Cellular Components 1. Activated Macrophages: They are stimulated phagocytes. Stimulated by ingestion of antigen or by cytokines. Larger and more effective phagocytes. Enhanced ability to eliminate intracellular bacteria, virus-infected and cancerous cells.

Nonspecific Cellular Components -cont. 2. Natural Killer (NK) Cells: Lymphocytes that destroy virus infected and tumor cells. Not specific. Don’t require antigen stimulation. Not MHC restricted. Not phagocytic, but must contact cell in order to lyse it.

Relationship Between Cell-Mediated and Humoral Immunity 1. Antibody Production T- Dependent Antigens: Antibody production requires assistance from T helper cells. A macrophage cells ingest antigen and presents it to TH cell. TH cell stimulates B cells specific for antigen to become plasma cells. Antigens are mainly proteins on viruses, bacteria, foreign red blood cells, and hapten-carrier molecules. T- Independent Antigens: Antibody production does not require assistance from T cells. Antigens are mainly polysaccharides or lipopolysaccharides with repeating subunits (bacterial capsules). Weaker immune response than for T-dependent antigens.

Humoral Response to T Dependent Antigens

Relationship Between Cell-Mediated and Humoral Immunity 2. Antibody Dependent Cell Mediated Cytotoxicity Target cell is covered with antibodies, leaving Fc portion sticking outwards. Natural killer and other nonspecific cells that have receptors for Fc region are stimulated to kill targeted cells. Target organism is lysed by substances secreted by attacking cells. Used to destroy large organisms that cannot be phagocytosed.

Destruction of Large Parasites by ADCC

Phases of T cell responses Ag processing and presentation by APCs Activation of T lymphocytes requires Recognition of Ag displayed on APCs Costimulators: increase the strength of adhesion between APCs and T cells Cytokines produced by APCs (IL-1,TNF-α , IL-12) and by T cells themselves (IL-2, INF-γ, LT) Clonal expansion: proliferation and differention of T cells to effector T cells: in response to autocrine growth factor IL-2 Effector functions of T cells

T cell Recognition of Antigen on an APC Endocytosis CD4+ T cell APC T Cell Receptor Peptide MHC II

T cell Activation by an Activated APC IL-1 IL-6 IL-12 IL-12 Receptor CD4+ T cell CD28 “Signal 3” B7 T Cell Receptor LPS “Signal 2” TLR4 “Signal 1” Signal 1: Specificity Signal 2: Activation Signal 3: Cytokines& differentiation Peptide MHC II Antigen Presenting Cell (APC)

APC and T cell Interactions ( Costimulatory signals) B7 (CD80/86) CTLA-4 Activation CD28 Activation B7 (CD80/86) CD4+ T Cell TCR Recognition MHC II APC CD58 (LFA-3) CD2 Adhesion Activation CD40L CD40

Clonal Selection and expansion Only those lymphocytes whose receptor recognizes the antigen become activated, and then proliferate.

CD4 T cell cytokine effects IL2,IFNγ Th1 Macrophag Activation IL12 Th0 IL4 IL2,IL4,IL12, IL13, IFN-λ IL4,IL13 Th2 B Cell Activation

Effector Functions of TH1 CD4+ T Cells (Cell-Mediated Immunity)

Effector Functions of TH2 CD4+ T Cells (Humoral Immunity)

The Control of Activated CD4+ T Cells by Regulatory CD4+CD25+ cells Apoptosis (- ) peptide/APC IL-12/ IFN-g TH1 CD4+ cells (- ) IL-10 IFN-g IL-4 (- ) Activated CD4 T cells Resting CD4 T cells (- ) TH2 CD4+ cells Regulatory immunity CD4/CD8 interactions CD8 or CD4 suppressor effector CD8 or CD4 suppressor precursor L. Chess 2002

Overview of the Immune Response

The body's second line of defense against infections is _____. active immunity inflammatory response passive immunity cell-mediated immunity humoral immunity

Tissue macrophages begin their lives as neutrophils have short life spans because they self-destruct after engulfing foreign invaders originate from monocytes that leave the circulation and enter the tissues do not attack microorganisms directly; instead, they destroy virus-infected body cells

Which of the following types of cells initiate a secondary immune response? natural killer cells immature white blood cells memory cells effector cells plasma cells

The biggest difference between cell-mediated immunity and humoral immunity is _____. how long their protection lasts whether a subsequent secondary immune response can occur whether clonal selection occurs how they respond to and dispose of invaders how fast they can respond to an invader

Helper T cells are part of cell-mediated immune response the first line of defense the complement system a group of phagocytic white blood cells

The role of cytotoxic T cells is to attack _____ body cells that have been infected antibodies proteins circulating in the body fluids specific viruses and bacteria complements

Viruses and bacteria in body fluids are attacked by _____. antibodies from B cells cytotoxic T cells complement proteins helper T cells antigens

The role of cytotoxic T cells is the secretion of _____, which plays a role in the _____ immune response. antibodies ... antibody-mediated antibodies ... humoral perforin ... cell-mediated perforin ... humoral interleukin-2 ... humoral

A T cell recognizes Ag in association with MHC molecule, causes the APC to secrete: IL-1 IL-2 1L-4 IL-6

All the following are true about CMI except: Characterized by mononuclear cell infiltration Can be transferred to non immune individual by serum Delayed in time compared to humoral immunity Initiated by intracellular Ags

B7 surface molecule on the APC can bind to ...... on Th: CD28 CTLA4 LFA-1 a & b b & c

A cytolytic T cell (Tc) may be able to kill a virally-infected antigen presenting cell (APC) True False

True Explanation All nucleated cells express class I MHC molecules. Cells infected with virus have some viral peptides associate with class I MHC molecules which are then expressed on the cell surface where they can be recognized by a cytolytic T cell and be killed. Therefore an antigen presenting cell (APC), which expresses both class I and class II MHC molecules and is infected by virus, is susceptible to killing by a cytolytic T cell.

Antigen presenting cells (APC) process superantigens True False

False Explanation  By definition, antigen processing involves the internal cellular fragmentation of proteins into peptides that can associate with class I or class II MHC molecules and then be presented on the cell surface to a T cell. Superantigens are not processed, but rather exert their effect externally by binding as an intact (non-fragmented) molecule to T cell receptor (TCR) molecule and to some portion of a class II MHC molecule on an antigen presenting cell

Th1 and Th2 cells are capable of interfering with each other's effector pathways True False

True Explanation Th1 cells produce interferon-gamma that interferes with the Th2 pathway, and Interleukin-10 (IL-10) produced in the Th2 pathway interferes with the Th1 pathway