5 - Adaptive immunity (Cell mediated immune responses) Flashcards
Why are there more CD8 cells than CD4 cells during an infection
Because CD8 cells kill the infected cell directly, whereas CD4 cells produce cytokines which travel throughout the body so less is needed
Thymocyte
T cells originating in bone marrow, go to thymus to differentiate.
T cell negative selection
Death by neglect (no recognition of MHC peptide) or strong recognition of self antigen
T cell positive selection
T cell differentiates into CD8 or CD4 in the medulla of the thymus
Immunologic tolerance
lack of response to antigens that is induced by exposure of lymphocytes to these antigens
What is the underlying cause of autoimmune diseases
Failure of self tolerance
Principal mechanisms of central tolerance in T cells
Death of immature T cells (negative selection) and the generation of CD4 + regulatory T cells
What does peripheral tolerance lead to
Functional inactivation (anergy) or death, or when the self reactive lymphocytes are suppressed by regulatory T cells
Where does central tolerance occur
Generative lymphoid organs (bone marrow and thymus)
Central tolerance
Lymphocytes with receptors specific for self-antigens are deleted at an early stage in development.
Peripheral tolerance
Peripheral tissues
Two types of TCR
αβ TCRs and γδ TCRs
Different regions of a TCR
- Antigen recognising domains = Variable (V) regions
- Conserved portions = constant (C) regions
function of invariant membrane proteins
- Deliver intracellular signals following antigen
recognition - Associated with antigen receptor chains
Subsets of CD4 helper T cells
Th1, Th2, Th17, Tfh and Treg
Th17 cells
develop in response to extracellular bacterial
and fungal infections and induce inflammatory reactions that destroy these organisms
Regulatory T cells
Suppress immune responses
What causes Th0 cells to differentiate into Th1
DCs produce IFN-γ and IL-12
Th1
Acting through CD40 ligand and IFN- γ , increase the ability of macrophages to kill phagocytosed microbes
Response of macrophages to Th1 cells
- Killing of phagocytosed bacteria
- Increased expression of MHC and costimulators
- Secretion of cytokines (TNF, IL-1, IL-12, chemokines)
End result of Th1 cells
- Killing of phagocytosed bacteria
- Increased expression of MHC
IFN- γ
- Produced by Th1 cells
- contribute to the recruitment of monocytes and granulocytes
- activate the antimicrobial activity of macrophages
- phagosome maturation
- production of reactive nitrogen intermediates
- antigen presentation
CD4 T cells deficiency (e.g. HIV+)
Increases susceptibility to both primary and reactivation tuberculosis as T cells participate in granuloma formation
Granuloma
hallmark of TB
What causes Th0 cells to differentiate into Th2
DCs produce IL-4
Th2
- Acting through IL-4, IL-5 and IL-13, stimulate antibody responses and defend against helminth parasites
- Involved in allergic reactions to environmental antigens
End result of Th2 cells
- Alternative macrophage activation (tissue repair) (IL-4 and IL-13)
- Eosinophil activation (IL-5)
- Intestinal mucus secretion and peristalsis (IL-4 and IL-13)
- Mast cell degranulation (IL-4)
- Antibody production (IL-4)
Cytotoxic T lymphocytes (CTL)
Uses perforin and
granzymes to destroy infected cells
CD8+ T cells
Activated upon binding to
non-self antigen presented by DC in the context of MHC-I
Perforin
- Disrupts the integrity of the target cell plasma and endosomal membrane
- Facilitates the delivery of granzymes into the cytosol
Granzymes
Major function is to induce
apoptosis
CD4+ and CD8+ T cell cooperation
- CD4 + T cells recognise antigens derived from the vesicular microbes and activate the macrophage to kill the microbes in the vesicles
- CD8 + T cells recognise antigens derived from the cytosolic bacteria and are needed to kill the infected
cell, thus eliminating the reservoir of infection
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