25 terms

Cellular Immunity

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Cellular (Cell-mediated) Immunity
Mediated by T cells

T cells only recognize "processed" Ag fragments displayed on surface of cells
Endogenous antigens
- Proteins synthesized by body cells
- Degraded by protease into Ag fragments
- Ag fragments are then displayed on the surface of body cells by Class I MHC proteins
Endogenous antigens are processed and displayed on class I MHC of all cells
1. Endogenous antigen is degraded by protease.
2. Endogenous antigen peptides enter ER via transport protein.
3. Endogenous antigen peptide is loaded onto class
I MHC protein.
4. Endogenous antigen peptide is loaded onto class
I MHC protein.
Exogenous antigens
Extracellular Ag's are engulfed & degraded into fragments in phagolysosomes of antigen-presenting cells (APCs)
- Ag fragments are then displayed on the surface of APCs by Class II MHC proteins
Exogenous antigens are processed and displayed on class II MHC of antigen-presenting cells (APCs).
1a. Class II MHC is synthesized in ER.
1b. Extracellular antigen (bacterium) is phagocytized.
2a. Class II MHC is exported from ER in a vesicle.
2b. Phagosome merges with lysosome, forming a phagolysosome; antigen is degraded.
3. Vesicle fuses with phagolysosome. Invariant chain is removed, and antigen is loaded.
4. Vesicle with loaded MHC migrates to the plasma membrane.
Antigen-presenting Cells
APCs include:
dendritic cells
- most important
- present in connective tissue
- present in epidermal layer of skin (called Langerhans cells)
- phagocytic cells
- migrate to secondary lymphoid organs to present processed antigens to T cells
macrophages (phagocytic)
B cells (receptor-mediated endocytosis)
Class I MHC
Found on surface of almost all cells in the body (including APCs)
- If it has a fragment of a "self" protein attached to it, then T cells know to leave the cell alone
- If it has an endogenous foreign Ag attached to it, then T cells will react
Class II MHC
- Found on surface of APCs
- If the APC has an exogenous Ag fragment attached to it, then the T cells will react
CD4 T cells
turn into Helper T cells (TH) when they react with Class II MHC/Ag complexes on APCs
CD8 T cells
turn into Cytotoxic T cells (TC) when they react with Class I MHC/Ag complexes on tissue cells
Steps in Cell-Mediated Immunity
Processing of Ag
Presentation of Ag to T cells
Specific T cell binds to MHC/Ag fragment
- occurs in secondary lymphoid tissues
- requires double recognition:
i. recognition of nonself (Ag) by TCR
ii. recognition of self (MHC protein of body)
by CD 4 or CD8
- activates T cells!
Activated T cells:
- proliferate (few => thousands)
- differentiate into:
TH or TC (effector cells)
CD4 => TH
CD8 => TC
Memory T cells- ready for repeat exposures (secondary responses)
TH or TC enter circulation to go do battle
Note: Primary T cell response peaks within a week after 1st exposure
Clonal selection of T cells involves simultaneous recognition of self and nonself.
1. Dendritic cell engulfs an exogenous antigen, processes it, and displays its fragments on class II MHC protein.
2. Immunocompetent CD4 cell recognizes antigen MHC complex.
Double recognition:
T cell Ag Presenting Cell
i. TCR Processed Ag
ii. CD4 Class II MHC protein
3. CD4 cells are activated, proliferate (clone), and become memory and effector cells.
Cytotoxic T Cell (Tc)
Directly attacks and kills Ag's
- Perforins and granzymes used to kill target
Circulate throughout the body searching for Ag that activated it
Cytotoxic T cells attack infected and cancerous cells
1. TC binds tightly to the target cell when it identifies foreign antigen on MHC I proteins.
2. TC releases perforin and granzyme molecules from its granules by exocytosis.
3. Perforin molecules insert into the target cell membrane, polymerize, and form transmembrane pores (cylindrical holes) similar to those produced by
complement activation.
4. Granzymes enter the target cell via the pores. Once inside, these proteases degrade cellular contents, stimulating apoptosis.
5. The TC detaches and searches for another prey.
Helper T Cells (TH)
Stimulate proliferation of other T cells

Stimulate B cell proliferation + Ab production
Many antigens require TH co-stimulation to activate B cells

Stimulate nonspecific killers
- Macrophages, NK cells

Use interleukins to help stimulate these other immune cells
Cytokines
Protein hormones released from leukocytes that stimulate/inhibit growth + differentiation of lymphocytes (enhance immune response)
Interleukin-1:
Released by macrophages
Stimulates Helper T cells

Interleukin-2:
Released by Helper T cells
Costimulates other immune cells
TH cell help in humoral immunity
1. TH cell binds with the self-nonself complexes of a
B cell that has encountered its antigen and is displaying it on MHC II on its surface.
2. TH cell releases interleukins as co-stimulatory signals to complete B cell activation.
TH cell help in cell-mediated immunity
1. Previously activated TH cell binds dendritic cell.
2. TH cell stimulates dendritic cell to express co-stimulatory molecules (not shown) needed to activate CD8 cell.
3. Dendritic cell can now activate CD8 cell to become TC cell with the help of interleukin 2 secreted by TH cell
Importance of TH Cells
Without TH, the immune response is very weak because they direct and/or help complete the activation of all other immune cells
Regulatory T cells (Treg)
Regulatory function to keep T and B cells in check => helps limit autoimmunity
- Release inhibitory cytokines
Vaccines
Stimulate primary immune response with dead or attenuated (weakened) pathogens
Activates T + B cells w/out disease symptoms
Promotes memory of Ag
Exposure to live Ag later - secondary immune response
Tissue Transplants
Transplanted tissues are recognized as "non-self"
Prevent rejection w/immunosuppressive drugs (corticosteroids)
Disadvantage: depress patient's immune system so it cannot fight off foreign agents
AIDS (Acquired Immune Deficiency Syndrome)
Caused by Human Immunodeficiency Virus (HIV)
Viruses transmitted via body fluids - blood, semen, and vaginal secretions (blood transfusions, contaminated needles, intimate sexual contact, including oral sex)
Virus destroys TH cells - Binds to CD4 receptors
Allergic reactions
Some TH cells that stimulates B cells to turn into IgE-producing plasma cells.

IgE binds to basophils (circulating) or mast cells (in CT)

Next exposure: IgE interaction with Ag results in release of chemicals (histamine + others) from basophils/mast cells

Result: Inflammatory response (symptoms depend on where chemicals are released)
- Example: inhaled allergen causes constriction of airways and it's harder to breathe
Mechanism of an acute allergic (immediate hypersensitivity) response
1. Antigen (allergen)invades body.
2. Plasma cells produce large amounts of class IgE antibodies against allergen.
3. IgE antibodies attach to mast cells in body tissues (and to circulating basophils).
4. More of same antigen invades body.
5. Antigen combines with IgE attached to mast cells (and basophils), which triggers degranulation and
release of histamine
(and other chemicals).
6. Histamine causes blood vessels to dilate and
become leaky, which promotes edema; stimulates
secretion of large amounts of mucus; and causes
smooth muscles to contract. (If respiratory system
is site of antigen entry, asthma may ensue.)