immunology - Doubts regarding definition of upstream/downstream genes and cognate protein

With respect to the research paper, there are a few things I didn't understand:

1. What is upstream and downstream gene
2. This paper identifies proteins that help in secretion, but does not identify the originally secreted protein. Am I correct?
3. Does cognate protein here mean homologous protein(from common parents)?

Answer

Upstream means towards 5' direction from the reference point (conversely for downstream). Reference point can be a single position such as transcription start site (TSS) or a bigger segment such as a gene. When we say upstream of a gene, it means some region of DNA that is towards 5' direction from the TSS of the reference gene. Downstream of a gene refers to the region 3' to the transcription termination site of the reference gene.

Similar terminology is applicable to RNA but obviously, in this case your reference cannot be a gene (it can be an exon, for instance). I have not seen this terminology used in case of proteins.

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This paper is about identification of the proteins that aid in secretion (TEC) of certain proteins (effectors). They identified both the proteins that help in secretion and the proteins that are secreted

Here, we report a class of T6SS effector chaperone (TEC) proteins that are required for effector delivery through binding to VgrG and effector proteins. The TEC proteins share a highly conserved domain (DUF4123) and are genetically encoded upstream of their cognate effector genes.
[....]
We validated this approach by verifying a predicted effector TseC in Aeromonas hydrophila. We show that TseC is a T6SS-secreted antibacterial effector and that the downstream gene tsiC encodes the cognate immunity protein. Further, we demonstrate that TseC secretion requires its cognate TEC protein and an associated VgrG protein.

Cognate refers to the correct binding partner which will result in a functional complex. It basically refers to biomolecular partners with a known and validated relationship. This relationship need not be synergistic. For example:

RNA interference (RNAi) is an evolutionarily conserved process through which double-stranded RNA (dsRNA) induces the silencing of cognate genes. (Source)