4. T-Cells and Antigen Presentation Flashcards
Describe T-lymphocytes (origin, types, activation).
Precursors from pluripotent bone marrow stem cell via lymphoid lineage, migrate to thymus. CD4 (helper) and CD8 (cytotoxic). Must have antigen presented to them. First presentation should be by dendritic cell for activation.
Describe dendritic cells.
Describe what happens when an exogenous antigen meets an APC.
Descended from monocytes. Motile, phagocytic, chemotactic. Antigen receptors: toll-like receptors, lectins e.g. mannose-binding lectin. Cooperation receptors for elements of immune system: Fc receptors (for Ab), C3b receptors (for complement). Can present to both CD4 and CD8 T-lymphocytes.
Endocytosed by APC via antigen receptors/Ab/C3b. Decides whether self/nonself. Endosome merges with lysosome and contents digested by enzymes. Oligopeptide fragments inserted into groove of class II HLA molecules in wall of endosome, pass to cell surface in wall of vacuole where they may be recognised by a CD4 T-cell.
EXOGENOUS ANTIGEN RECOGNISED BY CD4 ON CLASS II HLA
Describe what happens between an endogenous antigen and an APC.
Synthesised within the APC, may be self (usually cellular proteins) or nonself (virus etc.) Sample of proteins manufactured within APC broken up by proteosomes in cytoplasm. Oligopeptide fragments transported into endoplasmic reticulum and inserted into groove of class I HLA molecules, which pass to cell surface in wall of vacuole, where may be recognised by CD8 T-cell
ENDOGENOUS ANTIGEN RECOGNISED BY CD8 ON CLASS I HLA
Describe antigen recognition by CD4 and CD8 T-lymphocytes.
Both endogenous and exogenous antigens can be self. How do T-cells eliminate self-reactive T-cell clones?
TCR (T-cell receptor) recognises antigen (diff for each clone of T-cells). CD4 molecule ensures only antigens recognised on class II HLA molecules. CD8 ensures only antigens recognised on class I HLA molecules. CD3 molecular complex signals recognition to interior of T-cell. Other accessory molecules: CD28-CD80 and 86 activation signals, CD2-CD58 adhesion. IL12 stimulates.
Clonal deletion in thymus eliminates many. Others eliminated at first antigen recognition if dendritic cells don’t express accessory molecules. If dendritic cell detects danger, expresses: IL1, necrosis, microbial products via innate receptors
Describe macrophages as APCs.
How do B cells interact with T cells?
Present oligopeptides from phagocytosed material on class II HLA molecules. If they are recognised by experienced CD4 T-cells: activation and clone expands, and macrophage activated via cytokines (IFNγ) - becomes more destructive (enzymes, free radicals, giant cell formation, granuloma etc.)
B-lymphocytes endocytose material they recognise by their Ab, present oligopeptides from endocytosed material on class II HLA molecules. If recognised by experienced CD4: T-cell activation and clone expands, and B-cell activated and clone expands. Some B-cells form plasma cells - secrete Ab.
What presents to CD8 T-lymphocytes?
What is the difference between CD4 and CD8 cell behaviour when presented with an antigen?
Almost all cells (including macrophages and B-lymphocytes) present oligopeptides derived from proteins they synthesise on class I HLA molecules. If recognised by experienced CD8 T-cell, the cell presenting the antigen will be killed (apoptosis/pores implanted in membrane). Thus cells harbouring viruses, bacteria or protozoans are killed.
CD4: help activate cells on which they recognise antigen. CD8: kill cells on which they recognise antigen.
Describe the 3 subsets of CD4 T-lymphocytes.
1) Th1 CD4: help activate macrophages. Produces cytokines IL2, interferon gamma, TNF beta. Differentiate from mature naive CD4 on first activation if dendritic cell secrete IL12.
2) Th2 CD4: help activate B-lymphocytes. Produces cytokines IL4, IL5, (IL13). Differentiate from mature naive CD4 on first activation if dendritic cell expresses Notch ligand and does not secrete IL12 or IL23
3) Th17 CD4: pro-inflammatory. Secretes IL17. Differnetiate from mature naive CD4 if dendritic cell secretes IL23, in presence of IL6.
What are cytokines, and what are their 3 modes of action?
What 6 things do macrophages secrete?
Why do all cells secrete interferon alpha and bata if virally infected?
What do most cells of the immune system, many connective tissue and epithelial cells secrete when damaged and/or exposed to products of damage?
Polypeptide inflammatory mediators, often act locally. Autocrine action (on cell that secreted the cytokine), paracrine action (on neighbouring cells), endocrine action (on cells all over body). Endothelial cell activation, chemotactic and activation of phagocytes. Secreted by many cells (immune and CT) IRT activation and damage.
IL1, IL2, inferferon-alpha, TNF-alpha, chemokines, prostaglandins and leukotrienes
Puts cells into virally resistant state, increases HLA class I molecule expression
IL6, chemokines, leukotrienes and prostaglandins
What do dendritic cells secrete?
What do all T-cells secrete?
IL12, IL23. Paracrine contribution to activation of the T-lymphocyte to which antigen is being presented, and influences on which subset that T-cell will join.
Bone marrow stem cell growth factors (IL3, G-M CSF - granulocyte-monocyte colony stimulating factor), chemokines, CD4 T-cell subset cytokine secretion patterns (Th1, Th2, Th17), CD8: IL2, IFN gamma, TNF beta
What are the type 1 interferons and what do they do?
What does IL1 do?
What does IL6 do?
Alpha and Beta interferons. Put cells into virally resistant state, increases HLA class I molecule expression.
Secreted by macrophages IRT damage. Paracrine effect on other macrophages, endothelial cells etc. Inflammatory mediator. Endocrine effect: acute phase proteins, fever.
Secreted by many cells (immune system, some CT cells etc.) IRT damage. Effects: maturation and class switching of B-cells, differentiation and maturation of mature naive T-cells into Th17 subset, secretions of acute phase proteins inc CRP
What do TNF alpha and beta do?
What does IL17 do?
What do IL12 and IL23 do?
List some other inflammatory mediators.
Induce apoptosis in virally infected and neoplastic cells. Paracrine effect on other macrophages. Shock and cachexia. TNF-α secreted by macrophages. TNF-β secreted by CD4 Th1 and CD8 T-cells.
Secreted by CD4 Th17 T-lymphocytes. Inflammatory mediator: endothelial cell activation, chemotactic and activation of phagocytes.
Secreted by dendritic cells. Paracrine effect on CD4 T-cells being activated, diverting them into Th1 subset. IL23 does the same but into the Th17 subset.
Prostaglandins, leukotrienes, histamine, NO.
What does IL2 do?
Name a type 2 interferon? Describe what it does.
What do IL4 and IL5 do?
Secreted by CD8 and CD4 Th1 T-lymphocytes. Autocrine and paracrine effects on these T-lymphocytes promoting activation, and finally apoptosis.
IFN gamma. Secreted by CD4 Th1 T-cells and CD8 T-cells. Induces antiviral state. Upregulates expresison of class I and class II HLA molecules. Main macrophage activating factor.
Secreted by CD4 Th2 T-cells. Autocrine and paracrine for CD4 Th4 T-cells promoting activation and class switching of B-cells. IL5 does the same and also activation of eosinophils.
Which is right?
- Endogenous antigen moves from ribosome to endoplasmic reticulum, is inserted into class II HLA mol, moves to cell surface, and is presented to CD4 T-cells.
- Exogenous antigen moves from ribosome to the endosome, is inserted into class II, moves to cell surface, and is presented to CD8 T-cells
- Endogenous antigen moves from ribosome to endoplasmic reticulum, is inserted into Class I HLA mol, and is presented to CD8 T-cells
- Exogenous antigen moves from endosome to endo-lysosome, is inserted into Class I HLA molecule, and presented to CD8 T-cell
- Endogenous antigen moves from endosome to endolysosome, is inserted into class II HLA molecule, and presented to CD4 T-cells
- Exogenous antigen moves from endosome to endolysosome, is inserted into class II HLA molecule, and presented to CD8 T-cells
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