PATH 3610 Lecture Notes - Lecture 5: Mantoux Test, Cell-Mediated Immunity, Transplant Rejection
14 May 2018
School
Department
Course
Professor
Cell mediated immunity (CMI)
- depends on presence of Tc cells specifically reactive to an antigen on the
surface of infected or transformed host cells
- the Tc cell antigen receptor (TCR) recognizes foreign antigens which are
presented on the surface of infected or transformed host cells by surface
molecules called Major histocompatibility (MHC) markers
- recognition of the antigen MHC complex by Th1 (CD 4+) cells results in
release of soluble mediators, cytokines (IL2, IFN –y) which stimulate other
cells (CD8+ Tc and macrophages) to enhance killing of the intracellular
organism or infected cells
- in transplantation, unmatched donor MHC may be recognized as foreign
antigen by the recipient; this matching MHC markers between donors and
recipients is essential to avoid rejection
- many Th1 cytokines enhance macrophage function
o cytokine or T-cell activated macrophages have increased ability to
phagocytize and kill organisms
o although initial activation of macrophages requires specific
interaction of antigen with specialized pathogen recognition
receptors and later reaction T-cells
- activated Tc (CD8+) lymphocytes recognise antigen complex with MHC on a
target cell surface and are directly cytotoxic resulting in antigen-specific lysis
of target cells. These include foreign cells (graft rejection) or host cells with
viral, bacterial, parasitic or tumour antigens on their surface
- CMI particularly important in immunity to organisms which multiply
intracellularly (i.e. all viruses, some bacteria such as Listeria, Brucella,
Mycobacteria and many parasites)
- Detection of CMI: tests for CMI are at present technically more difficult and
more expensive than tests for antibodies, used less frequently for
diagnosis/disease surveillance
- In vivo: Delayed type hypersensitivity (DTH) skin test tests for Th1
reactions (most common CMI test)
o Ex. the tuberculin skin test for TB
▪ Injection of antibody intradermatally in a sensitized (reactive)
animal → results in swelling (induration) and erythema after
24-48 hours (delayed)
▪ Reaction due to infiltration of mononuclear cells (lymphocytes,
macrophages) to site of injection by the release of chemotactic
(cell attracting) cytokines from activated antigen-specific Th1
cells
- Less common IN VITRO tests
o 1) Culturing lymphocytes in presence of antigen and measuring
cytokine production, usually by ELISA
o 2) Fluorescence activated cell scan (FACs) measures changed in the
proportions of CD4+ or CD8+ cells in circulation, in response to
antigen exposure (monitoring CD4+ T-cells during HIV infection)
find more resources at oneclass.com
find more resources at oneclass.com
o 3) Lymphocyte proliferation (blastogenesis): culturing
lymphocytes in the presence of antigen and determining the degree of
proliferation in response to said antigen by the incorporation of
tritiated thymidine into new DNA (quantifies mitotic events)
Dysfunctions of Immunity
- Two broad categories
o Overly active or misdirected immune responses
▪ Allergies/asthma
• Allergy- type 1 hypersensitivity: interaction will
activate allergen specific T cell, the allergen specific IgE
on the mass cell can bind to the allergen
• Causes cross blinding, which activates a signalling
cascade
▪ Autoimmune disease eg. Multiple sclerosis, Crohn’s disease
o Immunodeficiency
▪ Primary (genetic) loss of immune function
▪ Secondary (acquired) loss of immune function
- Autoimmunity
o Result of a failure in tolerance toward inactivation/elimination of self-
reactive lymphocytes
o Enables T or B-cells to attack self tissue
o May be organ specific or systemic
o May involve antibodies, T-cells, immune complexes, or a combination
of these elements
- Tolerance
o Tolerance = prevention of an immune response against self structures
(central or peripheral)
▪ Central: deletion of self-recognizing lymphocytes before they
mature
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Many th1 cytokines enhance macrophage function phagocytize and kill organisms: although initial activation of macrophages requires specific. Activated tc (cd8+) lymphocytes recognise antigen complex with mhc on a target cell surface and are directly cytotoxic resulting in antigen-specific lysis of target cells. These include foreign cells (graft rejection) or host cells with viral, bacterial, parasitic or tumour antigens on their surface. Cmi particularly important in immunity to organisms which multiply intracellularly (i. e. all viruses, some bacteria such as listeria, brucella, Detection of cmi: tests for cmi are at present technically more difficult and more expensive than tests for antibodies, used less frequently for diagnosis/disease surveillance. In vivo: delayed type hypersensitivity (dth) skin test tests for th1 reactions (most common cmi test: ex. the tuberculin skin test for tb. Injection of antibody intradermatally in a sensitized (reactive) animal results in swelling (induration) and erythema after.
